Utilization and Bio-Efficacy of Carotenoids, Vitamin A and Its Vitaminoids in Nutricosmetics, Cosmeceuticals, and Cosmetics’ Applications with Skin-Health Promoting Properties

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The Utilization of Carotenoids, Vitamin A, and its Vitaminoids from various sources in several Nutricosmetic, Cosmeceutical, and Cosmetic Applications with Skin-Health Promoting Properties.

Abstract

Following the significant advancement in the cosmetic field over the past few decades, carotenoids, vitamin A, and vitaminoids have emerged as pivotal components in the formulation of cosmetic products due to their diverse bioactive properties. Delving into a general approach on vitamin A and its derivatives’ structure, activity, biochemical way of action, and benefits, their role towards promoting mainly skin health is thoroughly detailed. For this purpose, vitamin A, vitaminoids, and carotenoids of animal, marine, plant, herb, and microorganism sources were extensively reviewed in order to evaluate their health benefits regarding skin protection. Vitamin A and its derivatives of any source heavily contributed to specific skin-related functions, including their anti-aging, skin regeneration, wound healing, hyperpigmentation, and acne treatment activity, by primarily supporting hydration, skin elasticity, and barrier repair. This review also entails recent advances in the delivery systems of these compounds, such as microencapsulation and nanoemulsions, while their potential side effects are addressed as well. Ultimately, limitations and future perspectives of vitamin A, vitaminoids, and carotenoids, considering their utilization in nutricosmetic, cosmeceutical, and cosmetic products, are further discussed.

1. Introduction

According to ancient Egyptian writings, the study upon vitamin A’s significance dates back to around 1500 BC. The year 1913 has specifically marked the beginning of the contemporary study on vitamin A, while in the year span of 1913 to the 1950s, many important findings led the scientific community to delve more into this compound’s unique profile. Because of the colored plant lipids’ and colorless liver extracts’ biological activity, Steenbock [1,2] proposed the interconversion of two vitamin types (1919), and it was only ten years later when Moore [3] exhibited how liver tissue changed the plant pigment β-carotene into vitamin A’s colorless form [1,3]. Those research findings were enough for scientists to shortly after discover that a vitamin A shortage also existed in children and that the retinene present in the eye’s visual pigments was the same compound as the chemical substance retinaldehyde [1,3]. Moreover, in the 1940s, Otto Isler and his colleagues [1,4] synthesized the all-trans vitamin A from the less expensive precursor β-ionone, which led to a decrease in its price in the global market, while in the 1950s, the discovery of the radioactive vitamin A isotopes further clarified its metabolic pathways and behavior. Once the specifics of the rhodopsin-related visual cycle in the eye were introduced, scientific research shifted to vitamin A’s potential biological role in cellular differentiation and growth, promoting skin’s well-being [1,4].

As apparent, the pursuit of youthful and healthy skin has long been a driving force in cosmetic science. As consumers increasingly seek formulations that are both effective and natural, bioactive compounds such as carotenoids, vitamin A, and its vitaminoids have gained substantial attention in the cosmetic industry. These compounds, derived from natural or synthetic sources, have several biological effects and have offered multifaceted benefits, such as antioxidant protection, skin repair, and anti-aging properties. Their integration into cosmeceuticals reflects a growing alignment between dermatological science and consumer expectations for more effective skincare solutions [5,6,7]. A glimpse of these bioactives’ skin health-related activity is depicted in Figure 1.

Figure 1. The beneficial use of carotenoids, vitamin A, and vitaminoids in cosmetic products.

Carotenoids, mainly found in plants and algae, including β-carotene, lutein, and lycopene, have the ability to neutralize reactive oxygen species (ROS), hence to protect skin cells from oxidative damage induced by environmental factors like ultraviolet radiation (UV) and pollution. Furthermore, carotenoids may enhance skin tone and radiance in plant-based, eco-conscious formulations [1,5,6,7,8,9]. Following, vitamin A and its derivatives, such as retinol and retinoic acid, are responsible for regulating cell turnover, stimulating collagen production, and addressing several skin concerns, like fine lines, wrinkles, and hyperpigmentation [3,4,10,11]. However, challenges such as irritation and photosensitivity have recently been managed by advancements in vitamin A encapsulation and slow-release delivery systems [1,11]. Lastly, vitaminoids, mainly in the form of retinoids, are integral factors to skin hydration, barrier function, and repair mechanisms, being compatible with many skin-related formulations [12,13,14].

Recent innovations in cosmetic science have focused on improving the stability, bioavailability, and delivery of these active ingredients by investigating their structure, molecular activity, biochemical behavior, and skin-health benefits [1,6]. By examining bioactives like vitamin A, vitaminoids, and carotenoids of animal, marine, plant, and microorganism origin, their skin regeneration, wound healing, hyperpigmentation, and acne treatment activity, as well as their ability to promote hydration, skin elasticity, and barrier repair, have been quite supported [6]. Interestingly, newly emerged techniques such as nanoemulsions and microencapsulation have enhanced their efficacy and synergistic effects in skincare while minimizing any adverse reactions [1,6,15].

This review aims to provide a comprehensive overview of the roles of carotenoids, vitamin A, and vitaminoids in cosmetic formulations. By delving into their mechanisms of action and recent advancements, without overlooking any safety considerations, this review highlights their potential to revolutionize skincare. As the demand for natural, effective, and sustainable products grows, these bioactives stand at the forefront of innovations that merge science and consumer preferences.

2. Materials and Methods

The Scopus database was predominantly utilized for obtaining relevant literature. Some of the main keywords and key phrases used in this review are the following: “vitamins”, “vitamin A”, “vitaminoids”, “carotenoids”, “provitamins”, “vitamin A derivatives”, “β-carotene”, “retinol”, “retinal”, “retinoic acid”, “cosmetics”, “cosmeceuticals”, “nutricosmetics”, “nutraceuticals”, “pharmaceuticals”, “anti-aging”, “antioxidant”, “skin health”, “acne treatment”, “skin regeneration”, “hyperpigmentation”, “adaptive immunity”, “health benefits”, “metabolism”, “wound healing”, “microencapsulation”, “nanoemulsions”, “animal sources”, “marine sources”, “plant origin”, “microorganism sources”, “side effects”, “precautions”, with the use of combinations of these keywords by using the AND and/or OR terms in each query so as to retrieve information from relevant scientific databases, like Scopus, Science Direct, Google Scholar, PubMed, and Research Gate.

This search process was concluded during September–December 2024, considering the last 5–10 years, and the selection criteria were determined by applying the available metadata from these databases, with the eligible review studies meeting the corresponding criteria: (i) being exclusively research articles; (ii) written in the English language; and (iii) being published between 2018 and 2024. Moreover, articles’ quality and relevance were evaluated by reviewing their titles, abstracts, and keywords and then excluding duplicates retrieved from different databases unrelated to the topic.

Subsequently, the selected articles were extensively analyzed in order to determine whether they met the predefined inclusion criteria and provided pertinent information. Conference papers, books, old reviews, and short surveys, as well as publications written in other languages, were excluded. A limited number of important articles prior to 2018 were also included, since they had not been previously reviewed thoroughly.

3. Vitamin A, Its Vitaminoids and Carotenoids’ General Profile and Health Benefits

Vitamin A, vitaminoids, and carotenoids are fat-soluble hydrocarbons that act as micronutrients and antioxidant factors, primarily functioning against oxidative stress and its consequences, with a profound impact on human health. Such bioactives are integral to several physiological processes (e.g., vision, immune function, cellular communication, and antioxidant defense). While vitamin A refers to a group of retinoids (e.g., retinol, retinal, retinoic acid), carotenoids like β-carotene serve as provitamins able to be converted into active vitamin A. Vitaminoids plus encompass compounds structurally or functionally related to vitamins, often acting as precursors or analogs with distinct activity [16,17,18,19]. The dietary sources of these compounds range from animal sources rich in retinoids to plant-based sources abundant in carotenoids. Also, they exhibit therapeutic benefits such as decreasing chronic diseases like cancer risk, supporting skin health, and mitigating oxidative stress [16]. This section explores the general profile of vitamin A, vitaminoids, and carotenoids, emphasizing their biochemical and health-related significance.

3.1. Chemical Structures, Origin, and Isolation of Vitamin A and Its Vitaminoids

The vitamin A group is comprised of compounds of several origins and a basic structure of an unsaturated isoprenoid chain that provides them with the same functional abilities. It is a 20-carbon (C) molecule comprised of a cyclohexenyl ring with methyl substitution (β-ionone ring) and a conjugated polyene (isoprenoid side chain) chain structure (-C=C-). Vitamin A compounds are, in fact, retinoids (vitaminoids) that own four isoprenoid units of natural or organic origin and share a mutual interaction with retinoid receptors [3,20]. First-generation retinoids are dietary-derived metabolites, including retinol (vitamin A), retinal (all-trans-retinaldehyde), all-trans-retinoid acid (ATRA, tretinoin, or all-trans-RA), all-trans-retinyl ester, 9-cis-retinoic acid (alitretinoin), and 13-cis-retinoic acid (isotretinoin), while 2nd (etretinate and acitretin), 3rd (adapalene, tazarotene, and bexarotene), and 4th (trifarotene) generation ones are used in many diseases’ treatments. Vitamin A is either obtained from animals (retinol and retinoids) or as provitamin A, otherwise carotenoids, from consumable plant sources [3,20]. Moreover, it is mostly associated with retinol, and its main oxidized derivatives are 11-cis-retinal and ATRA. Other well-known retinoids with clinical significance in skin-protection cosmetics are 3,4-didehydroretinol, 11-cis-retinal, 5,6-epoxyretinoic acid, retro anhydroretinol, 4-oxoretinol, and retinoyl-β-glucoronide (retinylglucoronide) (Figure 2) [3,20,21].

Figure 2. The structure of vitamin A and retinoids of the 1st, 2nd, 3rd, and 4th generations.

A common vitamin A source derives from its preformed form and is obtained via animal-based food. Major retinol contributors include milk [22], dairy products [23], meat [24], chicken [25], eggs (mainly egg yolks) [3,26], and fish [27], while its general concentration ranges from 20 to 80 μg/100 mL of whole milk (the higher the fat content in the dairy product, the higher the retinol content) [3,20]. Retinol and ATRA are primarily obtained during breastfeeding, since vitamin A is responsible for mammary gland development and lactation, not only for the offspring but also for maternal health [22,28].

Considering vitamin A content in meat and poultry, tens of mg of retinol and its esters have been reported (per 100 g), and the highest content was recorded in pigs’ liver [3,20,29,30]. It must be noted that the amount of vitamin A traced in such foods, is dependent on the amount of β-carotene included in the feed or food supplements the animal is provided with [3]. Vitamin A is also obtained by consuming fish, with predator species such as carnivorous fish (e.g., sharks) and liver oil from various marine species, owning the highest levels of retinol and retinoids [27,31,32]. Egg yolks, especially chicken egg yolks, are stated to contain almost up to 1 mg of vitamin A per 100 mg, in contrast to duck and quail eggs, which comprise it in lower and elevated amounts, respectively [25,33]. Furthermore, retinoids also derive from several dietary groups like animal (e.g., chicken, egg yolks), marine (like salmon), and plant sources (e.g., broccoli, spinach, avocado, sweet potatoes), as well as whole grains, cereal, dry nuts, and other similar sources [34,35].

In the early 20th century (1932), after the discovery of its all-trans-retinol structure, scientists had focused on isolating vitamin A from several natural sources [36,37]. However, specialized analytical methods had to overcome various obstacles, such as the multiple isomeric retinol forms. Traditional chromatographic and spectroscopic methods concerning vitamin A, vitaminoids, and carotenoids were improved over the years. This is apparent from the development of advanced quantitative analysis techniques, including high-performance liquid chromatography (HPLC) [38,39,40,41], high-resolution mass spectrometry (HRMS) [42], tandem mass spectrometry (MS/MS) [38,43,44], gas chromatography (GC) or coupled with mass spectrometry (GC–MS) [45,46], UV/Vis spectrometry [41,47,48], and liquid chromatography coupled with mass spectrometry (LC–MS) [40,44,49,50,51] and qualitative, non-destructive ones, like the nuclear magnetic resonance (NMR) spectroscopy [18,52,53], near-infrared spectroscopy (NIRS) [54,55], solvent extraction [21,40,49,56,57,58], crystallization [59,60], and antioxidant estimation [47,61,62,63,64,65] methods, widely utilized in several related experiments since [20,56]. More specifically, fat-soluble vitamins like vitamin A, according to the U.S. Food and Drug Administration (FDA), are commonly clinically analyzed via nutrient analysis methods such as UV, HPLC, HPLC-UV, and LC–MS/MS [66]. Plus, enzyme-linked immunosorbent assays (ELISA) are also utilized for the detection and quantification of such bioactives, offering mainly simplicity, compactness, and low analysis costs for routine quality control benefits [3,20]. Interestingly, for retinyl palmitate analysis in fortified oils, a rapid, direct HPLC method was developed, ensuring no time-consuming sample preparation [67].

Due to its ester form, vitamin A is highly soluble in organic solvents but practically insoluble in aqueous solutions, similarly to β-carotene. Liver tissue is rich in vitamin A, due to the high retinol amounts discovered mainly in liver oil, which is derived from marine mammals and fish. Nowadays, by exploiting molecular distillation at extremely low pressure, a widely employed technique in the commercial preparation of vitamin A-rich oils, the ester compounds can be effectively isolated from such oils [68]. Alternatively, vitamin A is easily extracted directly using chloroform or a different solvent mixture like hexane and ethanol and then purified by advanced chromatographic methods [57,58]. Saponification with KOH, followed by organic solvent-assisted extraction, is also used for hydrolyzing esters such as vitamin A, carotenoids, triglycerides, and other lipids [40], while at low temperatures retinol and/or its esters may be crystallized by a variety of organic solvents (e.g., methanol, propylene oxide, ethyl formate) [21,40,49,56].

3.2. Vitamin A-Related Bioactive Compounds: Provitamins (Carotenoids)

Carotenoids are vibrant yellowish–orange–red organic pigments mainly isolated from plants, with remarkable antioxidant activity (only 40 are traced in the diet). These metabolites are tetraterpenoids but may also be metabolized to retinol. In carotenoids, two 20-carbon structures with β-ionone rings and a poly-isoprenoid side chain are linked together, tail-to-tail [16]. Carotenoid molecules can be converted into retinol (provitamin A derivatives) due to having at least one unsubstituted β-ionone ring and are β-carotene, α-carotene, and β-cryptoxanthin, while those unable to be transformed by any metabolic pathway to vitamin A but also owning vital activity are xanthophylls like lutein, lycopene, astaxanthin, zeaxanthin, canthaxanthin, fucoxanthin, phytoene, phytofluene, and capsanthin (Figure 3), with oxygen atoms in their containing hydroxyl groups [3,20].

Figure 3. The structure of carotenoids able and unable to be converted into vitamin A.

Carotenoid content in vegetables, fruits, and plant species is strongly influenced by flesh color, degree of ripeness (fully ripe fruits display higher carotenoid content), method and location of cultivation, post-cultivation modification, storage techniques (sun favors carotenoid loss, while storage in dry places at high temperatures favors their perseverance), intracellular carotenoids’ position, purification method, cooking way, and heat treatment [3,29,30]. Photosynthetic organisms, including plants, herbs, animals, marine organisms, and microorganisms (e.g., bacteria, fungi), may produce carotenoids in different amounts. Red and orange vegetables on a great scale (tomato, red chili pepper, red pepper, carrots, pumpkins, sweet potatoes, etc.), green vegetables (like kale, spinach, broccoli, parsley, lettuce, etc.), mushrooms, fruits such as apricots and mango, herbs like basil, cereals, grains, and spirulina entail high carotenoid levels, with β-carotene being mostly present. α-carotene is similarly to β-carotene obtained via carrots, sweet potatoes, pumpkin, mangoes, broccoli, oranges, and spinach [69], while β-cryptoxanthin, either as a free compound or esterified with fatty acids (lauric, myristic, palmitic), is administered via the same sources as β-carotene and α-carotene (Figure 3) [3,70].

3.3. Indicative Role and Functions of Vitamin A, Its Vitaminoids, and Carotenoids—Vitamin A Deficiency, Hypervitaminosis, and Toxicity

Vitamin A is an essential bioactive metabolite with multiple biological functions in the human body. Initially, it plays a vital role in the cycle of vision primarily in the form of retinal, which partakes in several enzymatic and isomerization reactions. In fact, loss of night vision (night blindness) is associated with vitamin A deficiency [71]. Retinol and ATRA act as signaling molecules for gene expression in vertebrates (i.e., of growth hormones) and are involved in cell growth and differentiation [72]. Retinol is crucial for normal immune system function of both innate and adaptive immunity, while it is an immune booster resulting in antibodies vast response, preserving and reestablishing integration of all mucosal surfaces [73,74]. Moreover, minimal amounts of vitamin A and β-carotene synergistic effects may prevent cancer and scavenge ROS. β-carotene’s anti-cancer and anti-proliferation properties especially delve from its antioxidant profile and conversion into vitamin A [3,75]. Plus, red blood cells require retinoids and vitamin A for proper differentiation, while retinol contributes to spermatogenesis, glycoprotein synthesis, taste and hearing function, and retinoids partake in maintaining normal epithelial homeostasis by promoting the differentiation of keratinocytes into mature epidermal cells [3,10].

Carotenoids, vitamin A, and vitaminoids have emerged as pivotal components in synthesizing nutraceuticals, nutricosmetics, cosmeceuticals, and cosmetics. β-carotene, lutein, and astaxanthin act as potent antioxidants by combating oxidative stress, reducing photoaging, and promoting a healthy complexion. On the other hand, retinoids such as retinol and retinoic acid accelerate skin renewal, reduce hyperpigmentation, and mitigate aging impact. Such vitaminoids extend the scope of cosmetic applications by supporting hydration, skin elasticity, and barrier repair [76]. Their role in the cosmetic field and importance in cosmetic formulations will be further discussed in Section 4.

Intake recommendations on vitamin A differ by age and are typically measured in retinol activity equivalents (RAE). Reportedly, one RAE corresponds to 1 μg of retinol, 12 μg of β-carotene, or 24 μg of α-carotene/β-cryptoxanthin [3,77]. For infants and children, the suggested intake ranges from 400 to 500 RAE; adult males are advised to consume 900 RAE daily, and females, pregnant, and lactating women should consume 700 to 1300 RAE, with lactating women requiring the highest doses. Sufficient vitamin A levels are crucial for proper fetal development and ensuring adequate nutrition for the newborn [3,77].

Vitamin A deficiency impairs vision, and in severe cases, prolonged deficiency may lead to xerophthalmia and even irreversible blindness [71,78]. Such deficiency affects various body systems (inadequate plasma retinol (<0.52 μm) or liver levels (<5–20 μg/g)). The respiratory system displays increased susceptibility to infections due to epithelial changes, skin keratinization, and dryness [3,77], while impaired sperm production and testicular degeneration are observed in the reproductive system [79]. Reduced intestinal goblet cells and alterations in the epithelium lead to poor digestion (gastrointestinal system) [80], while nerve lesions and diminished taste/smell (nervous system) [81], weakened immunity and risk of infection due to malnutrition (immune system) [73], iron metabolism disruption [82], and anemia, particularly in children and pregnant women [83], are only a few indications implying vitamin A deficiency. Either because of a poor diet (primary), malabsorption, or chronic diseases (secondary), hypovitaminosis affects around one-third of children worldwide [3,77]. Vitamin A supplementation [84], biofortification (i.e., transgenic golden rice and fortified samples (e.g., sweet potatoes)) [85], and a balanced diet are effective solutions against hypovitaminosis [3,77].

Hypervitaminosis, otherwise known as vitamin A toxicity, on the contrary, is rare but can occur due to excessive vitamin A or retinoid intake (plasma retinol levels > 2.09 μm). Toxicity plus arises from supplement overuse or vitamin A-rich food overconsumption and may be either acute or chronic. Retinoid acid syndrome, hypertriglyceridemia, teratogenicity, impaired bone health, skin redness, peeling, irritation, and allergic reactions [3,77,86] may follow vitamin A’s toxicity. Plus, excess carotenoid intake can subsequently cause a range of comorbidities, from harmless, easily dissolved carotenoderma (yellow/orange skin) to complications like nephrotic syndrome, cancer, or liver issues [3,25,71,77].

4. Vitamin A, Vitaminoids, and Carotenoids as Nutricosmetic and/or Cosmeceutical and Cosmetic Factors: Absorption, Conversion, Storage, Distribution, Metabolism, and Biochemical Mechanisms of Action

As the human body is unable to produce vitamin A, it is of great importance to obtain it from the diet either in its preformed version (70–90% absorption) or as provitamin A in the form of carotenoids (≤3% absorption), and mainly β-carotene, α-carotene, and β-cryptoxanthin [3,16]. Vitamin A is implicated in several mechanisms of absorption and mainly partakes in oral, skin, parenteral, sublingual, and rectal absorption, which means that additional administration routes, like intramuscular and topical ways besides one’s diet, are also possible. Oral and topical administration pathways of vitamin A are common and will be described in further detail [3,16,77].

4.1. Mechanisms of Absorption, Conversion, Storage-Distribution, and Metabolic Pathways of Vitamin A, Its Vitaminoids, and Carotenoids

4.1.1. Oral Absorption and Metabolism of Vitamin A, Its Vitaminoids, and Carotenoids

Vitamin A is primarily absorbed through the gastrointestinal (GI) tract when consumed orally, while vitamin A and its vitaminoids’ absorption highly differs from that of carotenoids, indicated by the fact that animal-derived retinyl esters are almost completely absorbed, while plant-based carotenoids’ absorption is notably lower [3,87].

As for animal-derived vitamin A and its vitaminoids, predominantly retinyl esters, they reach the intestine, where their metabolization into retinol by a triglyceride lipase or phospholipase B in the intestinal lumen of the GI tract occurs. After being metabolized, retinol and retinoids penetrate into enterocytes along with β-carotene, associate with chylomicrons (ChM), and are finally secreted into the lymphatic system. The uptake of retinol may be initiated either by active transport or by passive diffusion, while fat-soluble retinol’s absorption is increased after consuming fatty meals and micronutrients like zinc, as micelle formation encourages it. Both preformed retinol and retinol occurring from β-carotene transform into retinal, then to retinyl esters, and lastly to retinol, binding to a specific protein, namely cellular retinol-binding protein (CRBP), which is responsible for their intracellular transport and is acquired in two forms: CRBPI (widely expressed) and CRBPII, exclusively expressed in intestinal cells [3,87,88].

Retinol bound to CRBP while in the enterocytes may either be transformed back to retinyl esters bound to ChM and continue its path in the lymphatic system (cascade 1) or be transported directly in the blood systemic circulation via ChM’s assistance, with retinol binding to the retinol-binding protein (Retinol-RBP) (cascade 2). More specifically, following cascade 1, ChM-bound retinyl esters first enter the lymphatic system and then the bloodstream as remnant chylomicrons-retinyl esters (RChM-retinyl esters), where again two different vitamin A pathways are likely to be induced: In the first pathway (cascade 3), RChM-retinyl esters enter the liver, the main retinoid storage body organ with the most vital retinoid-storing tissues/cells. Inside the liver, in the presence of hepatocytes and via the assistance of the RBP, retinyl esters are transformed into retinol and vice versa (“recycling”). Liver-derived retinol and preformed enterocyte-derived retinol are directly secreted into the bloodstream, where they bind to the RBP, transthyretin (thyroid hormone transport function) [89], or later on to other transport proteins like ATRA-bound albumin. Retinols’ transportation in the target tissues is facilitated by the RBP receptor (RBPR), basically the “gate” to the target cell. Vitamin A deficiency is able to be maintained due to stored reserves in the liver (~90%), while circulating retinoids are usually bound to proteins like albumin via the mediation of lipoprotein receptors or stimulation by the retinoic acid 6 receptor (STRA6) [3,87,88].

During the second pathway (cascade 4), RChM-retinyl esters bind directly to the lipoprotein receptor (LR), which is reportedly another “gate” to the target cell, and undergo another conversion to retinol. RBPR and LR-acquired retinol are further oxidized to ATRA, and via the nuclear receptors (NRs), all necessary genetic body functions of vitamin A are initiated (the biochemical vitamin A-related function will be clarified in Section 4.2) [3,16,77,87,88,90]. The cellular and metabolic pathway of orally given vitamin A and its transportation to target cells is depicted in Figure 4.

Figure 4. The cellular pathway of orally given vitamin A and its transportation to target cells.

Retinyl esters, primarily retinyl palmitate, before even entering the enterocytes while in the intestinal lumen, are reversibly converted by esterase into retinol. Retinol, in order to biochemically participate in gene regulation and ROS scavenging, must be previously transformed into ATRA, which interacts with the NRs. Retinol, prior to binding to the CRBP, is similarly metabolized into retinal by retinol dehydrogenases, and then retinal dehydrogenases further oxidize irreversibly retinal into acidic ATRA, the final product of vitamin A oxidation that finally binds to the cellular retinoic acid-binding protein (CRABP). ATRA is not able to be reduced back into retinal and retinol or be stored but can be ultimately isomerized into 9-cis-retinoic acid and 13-cis-retinoic acid (Figure 5) [3,16,77,87,88,90,91].

Figure 5. Vitamin A’s conversion pathway from retinyl palmitate to retinoic acid.

Considering the plant-derived carotenoids, β-carotene is absorbed from the intestinal lumen, predominantly through a passive diffusion cascade or by the mediation of the scavenger receptor class B1 (SCARB1) transporter [92] and the cluster of differentiation 36 (CD36) [93]. Almost one-half of carotenoids are reportedly absorbed unaltered, while the rest are metabolized into retinol, regarding the body’s retinol levels and the diet’s fat content. More specifically, β-carotene, after being absorbed in the intestinal lumen, is transferred in the enterocytes, where either it directly binds to the ChM, surpasses the lymphatic system, and enters the blood flow, or is converted to retinal by β-carotene 15,15′-oxygenase (β-carotene oxygenase 1 (BOC1)) central cleavage (black arrows), which is then either further oxidized into ATRA by aldehyde dehydrogenase 1 family of enzymes (ALDH1s or RALDHS) or reduced to retinol by different forms of alcohol dehydrogenase (ADH) or retinol dehydrogenases (RDH), a process likely to happen in several GI tract locations. ATRA may be further oxidized into a more polar counterpart, namely 4-oxo-retinoic acid (4-oxo-ATRA), by cytochrome P450 (CYP) 26 family enzymes, which is believed to be transcriptionally inactive, while retinol can be further esterified into retinyl esters by the enzyme lecithin retinol acyltransferase (LRAT) [94,95]. ATRA finally, biochemically, partakes in the retinoic acid receptor (RAR) genetic expression [1,3,16,29,77,87,88,91,96]. When β-carotene intake is high, there is only a small conversion rate, and most of its quantity is stored in the adipose tissue and other fat reserves. At this point, it must be clarified that some retinyl esters are metabolized back into retinol, and the remaining are further transported along with the very-low-density (VLDL) and low-density (LDL) lipoproteins (Figure 6 and Figure 7) [3,87,88,97,98].

Figure 6. The cellular pathway of orally given carotenoids and their transportation to target cells.

Figure 7. β-carotene’s conversion and metabolic pathways (the central cleavage is depicted with the black arrows and the eccentric cleavage with the purple arrows).

Apart from the usual cellular pathway depicted in Figure 6, an alternative cleavage procedure occurs with ATRA as the end product, where β-carotene is enzymatically metabolized into β-apo-carotenals (able to ultimately be converted into one molecule of retinaldehyde (purple dashed arrow) and β-ionone by β-carotene 9,10′-oxygenase (or β-carotene oxygenase 2 (BOC2)), eccentric cleavage (purple arrows)) (Figure 7) [98,99]. Although the metabolic cascades are similar for β-carotene, α-carotene, and β-cryptoxanthin, their conversion efficiencies differ due to mainly structural differences, as β-carotene is symmetric and highly efficient (two retinal molecules per molecule), in contrast to α-carotene and β-cryptoxanthin, which are asymmetric and less efficient (1 retinal molecule per molecule) [98,99]. Apart from the main retinoids present in all metabolic pathways concluding in the target cells, namely retinol, retinal, and retinyl esters, ATRA, isotretinoin (“Accutane”), etretinate, and acitretin are also used in oral therapy [3,87,88]. For instance, ATRA has shown great potential towards dermatological conditions like skin cancer, psoriasis, acne, and ichthyosis [100]; isotretinoin is used for treating moderate to severe acne vulgaris [72], while etretinate and acitretin offer UV damage protection and have been suggested as potent therapy for squamous cell carcinoma (SCC) [101]. Isotretinoin, however, may also cause adverse effects such as cell apoptosis by altering the expression of specific genes, an important issue for those suffering from chronic hand eczema, while its isomer, alitretinoin, has not displayed the same impact [3,100]. Excess ATRA is oxidized and slowly evacuates the body via the kidneys or the liver into bile or urine, since retinoids are fat-soluble [3,87,88].

4.1.2. Topical Absorption of Carotenoids, Vitamin A, and Its Vitaminoids

In contrast to oral vitamin A, its vitaminoids, and carotenoid absorption, topically applied vitamin A and its derivatives are absorbed through the skin, targeting the epidermis and dermis. There are several pathways of penetration, involving the transcellular (via keratinized cells of the stratum corneum), intercellular (between cells via lipid bilayers), and appendageal (via hair follicles and sweat glands, which bypass the stratum corneum barrier) routes [102,103]. Retinoids like retinol and tretinoin are often stabilized in formulations with liposomes or nanocarriers for enhanced penetration, due to the fact that skin absorption is boosted by occlusion, hydration, and the presence of penetration enhancers such as ethanol, in order to influence gene transcription, promote collagen synthesis, and improve skin elasticity. The conversion, storage-distribution, and metabolism of vitamin A and its derivatives also differ depending on the absorption route because of the distinct cascades via which orally ingested and topically applied vitamin A compounds enter the body and their subsequent metabolic fates. Skin metabolism is localized, prioritizing direct biochemical action [15,102,103].

Retinol skin-absorbed via any of the above routes is enzymatically converted to retinal and then ATRA in local skin cells, according to the oral route. ATRA directly acts at the site of absorption, binding both to RARs and retinoid X receptors (RXRs) by CRABPs, which are strong modulators of apoptosis, proliferation, differentiation, and cell cycle, influence gene transcription and keratinocyte proliferation, promote collagen synthesis, and improve skin elasticity and barrier function. If ATRA binds to CRABPI, it is transferred to CYP26 to be degraded, while if bound to CRABPII, it is relocated in the nucleus so as to interact with RARs and RXRs, along with several co-activators, and promote transcriptional activity of ATRA target genes [104]. This conversion mainly occurs in the epidermis and dermis, with minimal systemic involvement, and this conversion takes place locally, primarily yielding ATRA for immediate use, in contrast to oral absorption, where this conversion takes place in the intestine and liver [11,100,104]. Meanwhile, carotenoids, including β-carotene, are less commonly utilized topically and are not enzymatically cleaved to vitamin A in the skin [7,19,105]. Retinol, retinoids, and carotenoids are retained locally in the skin cells (and peripheral tissues) and metabolized in situ, while minimum systemic distribution—unless high retinoid concentrations are applied, causing overflow into circulation—occurs (Figure 8) [7,15,19,102,103,106].

Figure 8. The cellular pathway of topically administered vitamin A.

4.1.3. Other Absorption Pathways of Vitamin A, Its Vitaminoids, and Carotenoids

Vitamin A can be delivered intramuscularly (IM) as well, with a view to achieving rapid systemic effects, during a parenteral absorption (via injection) pathway [3,21]. IM injections bypass the GI tract, delivering vitamin A directly to the bloodstream, commonly in cases of a malabsorption syndrome or severe deficiency. Once in circulation, retinol binds to the RBP and transthyretin in order to be transported to the target tissues. Liquid formulations provide a convenient way of rapidly addressing vitamin A deficiency, especially when oral supplementation through water or parenteral administration is inefficient, via promoting bioavailability and micronutrient use [3,21].

Vitamin A in sublingual drops (sublingual absorption) bypasses the GI tract by direct absorption into systemic circulation through the sublingual mucosa. Sublingual absorption is remarkably effective for individuals with impaired digestive systems [3,107]. Furthermore, vitamin A suppositories or enemas deliver the nutrient via the rectal mucosa following the rectal absorption pathway, suitable for patients unable to take oral or injectable forms in cases of vitamin A deficiency [3,108].

4.2. Biochemical Mechanisms of Action of Vitamin A, Its Vitaminoids, and Carotenoids: Gene Regulation and Mediation in Thromboinflammatory Pathways

Once metabolized, vitamin A, its vitaminoids, and carotenoids partake in several biochemical pathways and thrombo-inflammatory manifestations, crucial for cellular and physiological functions. Carotenoids and vitamin A derivatives scavenge excessive free radicals during oxidative stress cases and inflammatory manifestations from several genetic, epigenetic, age-, UV-, or dietary-related, photo-oxidative, or concomitant factors. Hence, they provide enhanced antioxidant and anti-inflammatory shielding by affecting the binding, inhibiting the associated signaling, or modulating the metabolism of thrombotic and inflammatory mediators (reduction), reducing inflammatory/oxidative, and increasing anti-inflammatory/antioxidant genes [3,77,88,109].

ATRA, as the end product of the vitamin A, retinoids, and carotenoids’ metabolism, acts as aforementioned, as a ligand via several co-activators and CRABPII binding for NRs, namely RARs that regulate gene expression involved in cell differentiation, proliferation, and apoptosis and RXRs that partner with other receptors (e.g., peroxisome proliferator-activated receptor (PPARs) and VDRs), modulating diverse pathways. Such a pathway of gene expression regulation is vital for embryonic development, immune function, and skin renewal [3,77,87,100]. ATRA is involved in cellular differentiation and apoptosis in epithelial tissues, prevents keratinization disorders, aids in tissue regeneration, and induces apoptosis in aberrant cells, with implications for anti-cancer therapy [3,77,87,100]. Furthermore, ATRA promotes immune homeostasis by regulating T-regulatory cells (T-regs), hence enhancing anti-inflammatory responses and type 1T helper/type 2 T helper (Th1/Th2) balance, by supporting adaptive immunity and affecting pro-inflammatory cytokine formation as well [110]. Lastly, ATRA, when retinol-bound protein 4 (holo-RBP4) is bound, triggers the retinoic acid 6 (STRA6) gene. Once STRA6 is boosted to relocate in the cell membrane, it catalyzes the transport of RBP4’s retinol release. Thus, it sets off tyrosine phosphorylation on the C-terminal tail, which attracts signal transducer and activator of transcription 3 and 5 (STAT 3/5) and Janus kinase 2 (JAK2). Notably, STRA6 partakes in the intrinsic mechanism of p53-mediated apoptosis, occurring after cellular DNA damage or elevated intracellular ROS [111].

Concerning the visual cycle, retinal is a key molecule where it combines with opsin in the retina to form rhodopsin, essential for low-light vision. The cycle involves the conversion of 11-cis-retinal to all-trans-retinal upon light activation and recycling via the retinoid cycle in the cytoplasm of retinal cells, by the aid of several enzymatic reactions, such as retinol dehydrogenase and isomerase enzymes [92]. All-trans-retinal is then reduced by nicotinamide adenine dinucleotide (NADH) to NAD⁺ and, via ADHs in the liver, is converted to all-trans-retinol. All-trans-retinol is subsequently transformed through isomerases (liver) to 11-cis-retinol, which is then again converted by NAD⁺ to NADH transformation and ADHs to 11-cis-retinal during the Wald’s visual cycle [112].

As for the antioxidant activity, retinoids and carotenoids like β-carotene scavenge ROS, protecting cells from oxidative stress and damage, supporting cardiovascular (CV) health, skin protection, and immune defense, while also being able to combat oxidative modification of LDLs (oxidized LDLs), thereby mitigating thrombo-inflammatory stimuli and atherogenesis, as well as supporting CV health, through inhibiting the inhibitor of κΒα (IκΒα) pathway [19,113]. Moreover, platelet activating factor (PAF) inhibition is induced by both retinoids and carotenoids, able to counteract the pro-inflammatory effects of PAF, which is implicated in skin inflammation, allergic responses, and vascular changes. PAF via binding to the G-protein-coupled membrane receptors (GPCMRs) and PAF-receptor (PAF-R/PAR signaling), via pro-inflammatory genes and proteins like phospholipase Cβ (PLCβ), phosphatidylinositol 4,5-biphosphate (PIP2), and Gq protein i, γ and β subunits (Gq,i/γ/β) and via partaking in mitogen-activated protein kinase (MAPK), inhibits PAF-cholinetransferase (PAF-CPT) and lysophosphatidylcholine (LPC) acyltransferase (LPCAT) thrombo-inflammation [114,115,116]. Thrombin, eicosanoids (cyclooxygenases (COX)), collagen (type I and II), and adenosine diphosphate (ADP), implicated in several inflammatory cascades, are restrained by carotenoids action against the nuclear factor κ light-chain enhancer of activated B cells (NF-κΒ) and gene expression [105,111,117,118].

Another biochemical pathway retinoids influence is the phosphatidylinositol 3-kinase (PI3K)/protein kinase (Akt) pathway, implicated in cell survival, metabolism, and proliferation. By regulating this cascade, vitamin A, retinoids, and carotenoids contribute to tissue repair (wound healing) and protection against ROS formation and oxidative stress. More specifically, via the kelch-like ECH-associated protein 1 (keap1), an adaptor subunit of cullin 3-based E3 ubiquitin ligase, the activity of the nuclear factor erythroid 2-related factor 2 (Nrf2) that acts as a sensor for oxidative/electrophilic stress via PI3K/Akt is regulated [110,119,120]. All the above biochemical mechanisms of the beneficial action of vitamin A, retinoids, and carotenoids are thoroughly depicted in Figure 9.

Figure 9. Biochemical mechanisms of action of vitamin A, its vitaminoids, and carotenoids.

The metabolism of carotenoids, retinoids, and vitamin A prepares and regulates the availability of vitamin A by converting it into active or stored forms, while biochemical cascades describe how these active forms exert their physiological effects. Both processes are interdependent but have distinct purposes in preserving health and cellular function.

5. Vitamin A, Vitaminoids, and Carotenoids’ General Role in Nutricosmetic, Cosmeceutical, and Cosmetic Applications

As aforementioned, both retinoids and carotenoids have a lot of beneficial impact on human health. Regarding carotenoids, more specifically, both their bioactive groups, carotenes and xanthophylls, depending on the presence of oxygen in their structure, own an antioxidant and anti-aging effect, sometimes working synergistically with other antioxidants too. Vitamin A, along with its derivatives, namely retinoid esters and carotenoids, is consumed via dietary supplements or food, providing a variety of sources that could benefit the general growth and maintenance of the immune system. Retinal, for example, a retinoid aldehyde, is responsible for the normal function of the eyes, while retinoic acid acts as a hormone-like growth factor in cells. Other retinoid esters have anti-aging activity, as they are used in the cosmetic field for treating skin’s fine lines and wrinkles [3,16,77]. Deficiency of vitamin A is linked with post-natal growth retardation in children, while in adults it can cause problems for the eyes, immune, or reproductive system [121]. On the other hand, carotenoids, such as zeaxanthin and α/β-carotene, have exhibited bio-functional activity against chronic diseases, like diabetes, cardiovascular diseases (CVDs), cancer, and obesity incidents [122]. They can also be photo-protective, as they are experts in protecting the skin from ROS and lipid peroxyl radicals induced by UV radiation A and B (UV_A and UV_B, respectively), species that damage cells when incorporated in the DNA, causing mutations and early aging, wrinkles, skin cancer, melanoma, ichthyosis, acne, and other skin-associated issues [123].

Because the human body cannot produce vitamin A de novo, all needed bioactive compounds are obtained following a diet rich with animal- and marine-sourced products but also comprised of fruits and vegetables. Preformed vitamin A (retinol and retinyl esters) is mostly found in animals, while provitamin A carotenoids, including α- and β-carotene, come from colored plants and fruits [69]. In Western countries, a percent bigger than 70% of the daily dose of vitamin A comes from preformed vitamin A in animals, while less than 30% derives from carotenoids in plants, fruits, and vegetables. On the other hand, in developing countries, the opposite prevails [124]. Lately, nutraceuticals, nutricosmetics, and cosmeceuticals have grown an upward interest in providing several bioactive ingredients, like carotenoids and vitamins, as an alternative, healthier way of supplementation instead of drugs for preventing several health conditions, such as skin cancer, or delaying others, like skin aging. The term “nutraceutical” was discovered in 1989 by Dr. Stephen De Felice, as a compound from the words “nutrition” and “pharmaceutical”, while the term “cosmeceutical” originated from Raymond Reed in 1962 but became famous in 1984 from a dermatologist professor named Albert Kligman, in research of retinoic acid as an anti-aging ingredient [125,126]. These categories are placed between nutrition/beauty and pharmaceuticals to provide the bioactive ingredients to the consumers for the cure or prevention of several health issues, with no need for synthetic medications and their potent side effects. Carotenoids in nutraceuticals and/or nutricosmetics provide the same effect as in functional foods, presenting an anti-aging and photo-protective role against UV_R in the skin. Interestingly, a supplement mixture of α- and β-carotene as well as lutein has been proven beneficial in photo-protection, while a combination of β-carotene, lutein, and lycopene has been reported as an effective treatment against erythema [125].

However, β-carotene is generally unstable; hence, other vitamin A forms (retinoids) are frequently utilized in cosmetic formulations in the skincare industry. Either applied topically, orally, or systemically, vitamin A, its retinoids, and carotenoids actively participate in protein synthesis, cell division, and cellular metabolism. Normalization of keratinization and plus growth and differentiation control of epithelial cells have been declared as the main advantages of vitamin A (retinol) and its retinoids, including retinyl palmitate, retinyl acetate, retinal, and ATRA, which are widely exploited in the cosmetic field at different concentrations [100,127]. ATRA, otherwise known as tretinoin, is the most bioactive retinoid for modifying skin function, prescribed commonly at high doses, due to the fact that all vitamin A forms metabolize into ATRA, known for reducing inflammation in the sebaceous glands, inhibiting keratosis, and triggering epidermal cell proliferation during psoriasis and/or chronic inflammation-related disorders. ATRA is reported to activate genes that trigger keratinocytes, namely the precursors of immature skin cells, to differentiate into mature epidermal ones [100,127].

Concurrently, other retinoids are also essential counterparts in the nutricosmetics, cosmeceuticals, and cosmetics generation and production department. Retinol reportedly inhibits collagenase, restrains matrix metalloproteinases (MMPs) expression, stimulates glycosaminoglycans’ (GAGS) and collagen type I’s synthesis, and treats skin dyspigmentation, dryness, and anti-wrinkle cases. Finally, retinyl acetate/palmitate and retinal have been recorded to trigger epidermal cell proliferation after their conversion to ATRA as stabilizers in wrinkle treatment. Generally, retinoids downregulate a unique gene, known as cellular communication network factor 1 (CCN1), which is highly expressed in the dermis of photo-aged skin [100,127]. In the following subsections, a more detailed, clinical outcomes-based approach to the main role of vitamin A and its vitaminoids and carotenoids in nutricosmetics, cosmeceuticals, and cosmetics applications is described, while several of these clinical data are included in the comprehensive tables of Section 6.

5.1. Anti-Aging and Photo-Protective Properties of Vitamin A, Retinoids, and Carotenoids

5.1.1. Anti-Aging Effect—Skin Regeneration

Vitamin A and carotenoids have been pointed out to present remarkable anti-aging properties. Skin aging is a result of a plethora of intrinsic and extrinsic factors. Intrinsic reasons are unavoidable (i.e., genetics, the passage of time), but extrinsic factors like UV_R exposure, bad diet, stress, or toxins can be avoided. Such factors lead to the breakage of collagen fibers, resulting in early aging [128]. Vitamin A, as an immunomodulatory compound, though, is capable of regulating and proliferating several cells, like skin cells, including keratinocytes and fibroblasts, leading to collagen and elastin synthesis, which is in turn responsible for minimized wrinkles and reversed photo-aging [129]. Retinoids are capable of inhibiting MMPs and modulating gene expression while also regulating the activity of growth factors and cytokines present in complex extracellular matrix protein (ECM) exchange and inflammation [111]. MMPs present in continuous exposure to UV_R partake in breaking down the ECM in the dermis, along with collagen and elastin. This situation results in premature photo-aging, with unlikable visual skin spots such as wrinkles and fine lines, dryness, and irregular pigmentation [128]. Retinol and the other retinoids, namely retinal and ATRA, that occur via a sequential conversion (Figure 5), are able to eliminate both intrinsic and extrinsic factors by simultaneously promoting collagen synthesis and preventing collagen breakdown through RARs and RXRs (Figure 8) [111]. Regarding retinoic acid, a study conducted on ATRA confirmed that it can increase types I, II, and III collagen while reorganizing elastic fibers and modulating GAGs of the ECM [117]. Also, ATRA has the capability to enhance epidermis thickness by promoting the growth of epidermal keratinocytes and increasing the formation of endothelial cells and blood vessels in the papillary dermis, all contributing as anti-aging factors for skin protection by visibly decreasing wrinkle formation, skin roughness, and relaxation. As a result, an improvement of the skin’s elasticity, hydration, and resilience refinement, as well as a barrier function enhancement, has been observed with long-term use of vitamin A-based cosmetics [111].

Adding to retinoids beneficial impact, the application of antioxidant and anti-aging substances, like carotenoids, may also aid in the protection of the human skin from environmental factors [130]. The carotenoids present in the human skin are mostly α/β-carotene, zeaxanthin, lycopene, and lutein. In some cases, the synergistic effect of such compounds, along with some vitamins, is highly encouraged as the best way of protecting the skin from aging [123]. For example, in a study where the combination of vitamins E and C with β-carotene was examined, this conjunction of active vitamin forms concluded in an advanced scavenging ability against reactive nitrogen species (RNS), rather than this of single antioxidants [131]. Moreover, a study about the xanthophyll fucoxanthin demonstrated that it can inhibit tyrosinase activity, an enzyme whose hyperactivity leads to hyperpigmentation and skin spots, melanogenesis in melanoma, and UV_B-induced skin pigmentation, factors notably contributing to aging [132]. Astaxanthin, additionally, is believed to increase the elasticity factor and improve the skin’s texture while reducing the size of age spots [117]. Furthermore, non-colored carotenoids, namely phytoene and phytofluene, are capable of absorbing UV_A and UV_B radiation, acting as a photo-protector for the skin, while at the same time lutein and zeaxanthin, also present in the human epidermis, can protect the skin from the blue light and subsequently from early aging [117]. Lycopene, as a very strong antioxidant present mainly in tomatoes, can also act as a natural photo-protective agent towards photo/early aging [133]. The anti-aging activity of different vitamin A forms derives mainly from their antioxidant ability. Besides being photo-protective agents externally in the skin by extensive UV_R, carotenoids act as anti-antioxidants as well, by scavenging ROS and covering excited forms of singlet oxygen and triplet-state molecules that could lead to inactivation of vital antioxidant enzymes, lipid peroxidation, and DNA damage, leading to internal protection [117].

Vitamin A deficiency has long been connected to delayed epithelialization and wound healing, which is confirmed by poor wound closure, lower collagen synthesis rates, and lower levels of cross-linking of newly generated collagen. The efficacy of retinoids or carotenoids’ topical application and/or oral consumption appears to be comparable. As previously stated, retinoids function by binding to certain receptors both in the cytoplasm and in the nucleus, which remarkably impact RNA, protein synthesis, lysosome-membrane stability, cell growth, differentiation, and finally division. A widely recognizable sensitivity impact of retinoids is their exceptional capacity to counteract the anti-inflammatory steroids’ inhibitory effects on the healing process, aside from wounds’ contraction. Administering a retinoid therapy partially but significantly reverses the adverse effects of the inflammatory response, tensile strength, and collagen build-up in cutaneous wounds in individuals following steroid treatment [118].

Recent research outcomes supported that topical retinol applied to aged human skin has been pointed out to dramatically increase epidermis thickness by inducing epidermal keratinocyte proliferation, as well as to enhance endothelial cell and blood vessel proliferation in the papillary dermis, by thickening the epidermal layer and leading to the formation of new blood vessels in the dermis [111]. Type I collagen, along with tropoelastin and fibronectin expression, and the formation of collagenous ECM in aged human skin in vivo due to activating dermal fibroblasts, are drastically elevated when topical retinol therapy is applied. Reportedly, vascularity and epidermal thinning are important factors that contribute to skin weakness and restrain rapid wound healing in trauma cases in aged skin. Topical retinol improves the dermal microenvironment by encouraging the growth of vasculature via endothelial cell proliferation in aged human skin, in addition to boosting ECM’s generation. Several reports on age-related decrease in the cutaneous vasculature have been recorded, where topical retinol treatment was confirmed to promote dermal vascularity, which is able to enhance skin blood flow, as well as dermal and epidermal homeostasis [111].

5.1.2. Photo-Protective Effect

Early aging is directly linked with UV_R exposure, as aforementioned. UV_R generally consists of two categories: UV_A (~320–400 nm) and UV_B (~290–320 nm), where carotenoids specifically absorb in this spectrum due to their structure that is comprised of conjugated double bonds. Skin damage induced by UV_R, in turn, is split into two different sections: (a) acute, including cell necrosis, erythema, and inflammation, and (b) chronic, involving photo-aging with dermatological signs like wrinkles, skin spots, dryness, fine lines, and also the formation of skin cancer. UV_A penetrates the deeper dermis, and its main function is to promote early aging by activating ROS, but also inducing cell apoptosis, erythema, and carcinogenesis. UV_B is absorbed by keratinocytes in the epidermis and is more erythematogenic than UV_A, hence contributing to cancer genesis by interacting with nucleus molecules (DNA and RNA), causing mutation. Phytoene and phytofluene offer unique protection against UV radiation because of their specific absorption properties. These carotenoids are distinct from most of their counterparts that require at least seven conjugated double bonds to exhibit color and absorb light in the visible spectrum, as they possess shorter polyene chains [8,134,135]. Figure 10 explains the results of UV_R exposure to aging and demonstrates some selected carotenoids and retinoids that have been extensively studied as a cure for these comorbidities.

Figure 10. Sources, bioactivity, and skin protection properties of carotenoids.

An alternative way of treating or preventing skin damage, except by following a diet rich in carotenoids, is by using supplements, orally or topically. Clinical trials conducted in vivo with several carotenoid supplements have revealed photo-protection against the sun’s radiation. More specifically, a study on 11 men and 11 women consuming a carotenoid mixture of α-/β-carotene and lutein, by enhancing the dose to a final 90 mg per day for 8 weeks, revealed a moderate dose-dependent increase in minimal erythema dose (MED), a decrease in lipid peroxidation, and an increase in β-carotene in the serum, but not in the skin. In another similar study, 20 healthy women were administered a moderate dose of β-carotene per day for 10 weeks and then were exposed to natural sun radiation for 13 days, without stopping this administration. Study outcomes supported that an erythema reduction was observed, along with a yellow pigmentation on the skin surface. The predominant study conclusion was that pre-treatment and treatment with carotenoids during sun exposure treatment displayed a protective effect against sunburn by raising the Langerhans cells’ level and minimizing the erythema. Lastly, another similar study with two groups receiving two different supplement mixtures was tested. The first one took a mix of α-/β-carotene, cryptoxanthin, zeaxanthin, and lutein per day, while the other group was given the same mix but with the addition of vitamin E, per day for 12 weeks. After the treatment, both teams revealed yellowish skin and higher concentrations of β-carotene in their serum and skin. The level of erythema was higher in those who took only the mix of carotenoids, while those who were administered the mixture with the addition of vitamin E displayed higher protection against UV_R, revealing the possible synergistic effects of carotenoids with other antioxidants [128].

5.2. Antioxidant and Anti-Inflammatory Profile of Vitamin A, Retinoids, and Carotenoids as Immunodefensive Mechanisms

Carotenoids effectively neutralize harmful free radicals able to impair skin cells and contribute to premature aging. Such antioxidant capacity stems from their unique molecular structure, featuring a long chain of conjugated double bonds (polyene chain) that can readily donate electrons to stabilize free radicals; hence, the number of conjugated double bonds determines their antioxidant capacity [19,136,137]. Lycopene with 11 conjugated double bonds owns the highest antioxidant efficiency, followed by α-carotene, β-cryptoxanthin, β-carotene, zeaxanthin, and lutein [19]. Vitamin A and carotenoids act as very effective quenchers of singlet oxygen, both in vivo and in vitro, by reacting with free radicals, breaking them down into active degradation products [16].

Notably, dietary supplementation with carotenoids has been proved to increase the antioxidant status of the skin, resulting in a lower concentration of free radicals generated in the skin after sunlight exposure to a simulator [19,138]. Moreover, carotenoids may also enhance the activity of the skin’s endogenous antioxidant enzymes and have the ability to combat ROS and RNS [134,139]. Topical application of several carotenoids, primarily as an ingredient in cosmetic preparations, increases carotenoid levels in the stratum corneum, the outermost layer of the skin, preventing skin damage caused by free radicals from UV rays and other factors [127,139]. At this point it must be noted that the less unsaturated, colorless carotenoids, namely phytoene and phytofluene, in contrast to the more saturated lycopene, have not displayed as exceptional an antiradical ability, even though they have been proved as great skin-whitening agents [8]. As a result, β-carotene, for instance, has been confirmed as a great antioxidant candidate in sunscreens, with a great role against sun-induced lipid peroxidation [61], while a recent crossover study demonstrated that lutein capsules stabilized by 10% of the antioxidant carnosic acid may protect from photodamage by reducing UV_R-modulated gene expression like heme-oxygenase 1 (HO-1), intercellular adhesion molecule 1 (ICAM-1), and matrix metallopeptidase 1 (MMP1) genes [8,140]. Interestingly, oral supplementation with a red paprika product led to notable MED and hydration enhancement and a reduction in skin tanning in skin previously exposed to UV on the back [141].

At the same time, the anti-inflammatory properties of carotenoids stem from their ability to modulate cellular signaling pathways involved in inflammation. Carotenoids can interact with the NF-κΒ pathway, inhibiting its activation and subsequent production of inflammatory mediators. They can also reduce the expression of inflammatory markers such as interleukin 24 (IL-24) in keratinocytes [19,29,113,136]. Oxidative stress, induced by factors like UV radiation and pollution, is a major driver of inflammation in the skin. By valuably scavenging free radicals and quenching singlet oxygen, carotenoids aid in reducing oxidative stress, thereby mitigating the inflammatory cascade [142]. Additionally, some carotenoids, like β-carotene, can be metabolized into retinoids, which are known for their potent anti-inflammatory effects in the skin [8,143]. Retinoids can regulate keratinocyte differentiation, reduce sebum production, and modulate immune responses, contributing to the overall anti-inflammatory benefits of carotenoids in cosmetics. Carotenoid structure allows them to neutralize ROS and absorb UV radiation, offering protection from environmental damage such as pollution and sun exposure, benefits that translate into an enhanced skin tone and a strengthened skin barrier [8,143].

5.3. Hyperpigmentation Improvement Activity of Vitamin A, Retinoids, and Carotenoids

Following the path of this vitamin’s photo-protective and anti-aging profile, retinol has shown great potential towards several disorders and skin-related comorbidities. Hyperpigmentation is characterized by topical darkening of the skin, otherwise known as skin discoloration, resulting from excess melanin production in certain skin areas, which often appears due to excessive exposure to the sun, aging, skin inflammation, melasma, etc., and is usually a worldwide concern of women, as its appearance on the skin is not aesthetically pleasing. ATRA is one of the main adaptable solutions to this problem, while a plethora of unique mechanisms contribute to reducing the pigmentation spots on the skin. ATRA can balance the production of melanin by reducing tyrosinase activity, a valuable enzyme for melanin development and its transportation to keratinocytes. Moreover, it exfoliates pigmented cells, leaving room for fresh skin appearance with less pigmentation. Additionally, ATRA has an anti-inflammatory ability, aiding in alleviating post-inflammation hyperpigmentation spots by encouraging skin cell turnover. Lastly, it contributes to collagen activation, providing better skin texture, fewer spots, and an overall youthful complexion. Other retinoids like retinal, tretinoin, adapalene, and tazarotene have also been proved effective in topical skin treatments [111]. Also, the xanthophyll fucoxanthin can inhibit tyrosinase activity, an enzyme whose over-activity results in hyperpigmentation and skin spots, as mentioned for early aging factors [132].

5.4. Acne Treatment Activity of Vitamin A, Retinoids, and Carotenoids

Acne vulgaris is a very common skin condition, affecting many teenagers and younger individuals, that occurs because of hair follicle clogging under the skin with oil, dead skin, or bacteria and appears on the face, neck, shoulders, upper chest, and back. Reasons triggering the onset of acne include inflammation, immunological causes, hypercolonization of microorganisms, follicular hyper-keratinization, and sebaceous hyperplasia. Other factors stimulating acne may also be habitual, including smoking, bad diet patterns, or hormonal alterations [129]. Several antioxidant and anti-inflammatory sources can be valuable in treating acne vulgaris, providing better skin texture. Interestingly, blackberries, watermelon, aloe vera, and papaya preserve skin-regenerating properties, as they contain many bioactives like the carotenoids β-cryptoxanthin and β-carotene [129]. Furthermore, strong retinoid forms such as retinal, tretinoin, adapalene, and tazarotene are more effective than retinol and retinyl palmitate, providing advanced acne skin treatment [111]. Lastly, naphthalene-carbozylic acid, as another vitamin A derivative, has been applied to the skin and was confirmed as an effective acne treatment solution that reduces inflammation and hyper-keratinization in hair follicles [127].

Only severe acne that has not responded to topical treatment and adequate antibiotics, however, should be treated with isotretinoin. Isotretinoin possesses a strong anti-inflammatory profile, as it lessens the formation of comedones by effectively decreasing hyper-keratinization, sebum generation, and Propionibacterium acnes colonization of the pilosebaceous duct. P. acnes is able to induce the immune system’s inflammatory reaction. Isotretinoin treatment is thus responsible for inhibiting monocyte expression of the toll-like receptor-2 (TLR2), which lowers inflammatory cytokines’ formation in response to P. acnes, with a six-month lasting impact. Adapalene, tazarotene, and tretinoin are topically applied retinoids, authorized for moderate acne treatment as well. In addition to restraining micro-comedones’ development, the precursor lesion of comedones, they also display anti-inflammatory properties. Adapalene and tazarotene, especially, bind selectively only to the β and γ types of RARs, whereas tretinoin binds to all three types. In a clinical trial, where tretinoin 0.1% microsponges were contrasted to tazarotene 0.1% gel, tazarotene was reported to exhibit similar tolerability and better efficacy in treating facial mild-to-moderate acne vulgaris [144]. Concurrently, adapalene gels (0.3%) demonstrated superior tolerability and comparable efficacy over a ten-week period when compared with tretinoin cream 0.05% in a clinical trial evaluating the safety and performance of these products in patients with mild-to-moderate acne [145].

5.5. Psoriasis Treatment with Vitamin A, Retinoids, and Carotenoids

Psoriasis is an inflammation-associated skin condition affecting 2–3% of the global population with symptoms like itchiness, redness, burning feeling, and soreness. It is a long-lasting immune disease that appears in the skin and/or joints, with lesions mostly located on the skin surface of the knees, elbows, or scalp region. People with psoriasis were deficient in vitamins, especially D and A. The synergistic effect of these vitamins may have a better outcome in treating psoriasis than either single-treatment therapy [146]. In vivo and in vitro studies have globally taken place to examine the anti-psoriasis effect of acitretin, apremilast, and tazarotene retinoids. Acitretin reverses both increased cell proliferation and keratinization in psoriasis, resulting in skin thickness, plaque formation, and scaling reduction. Meanwhile, tazarotene is a pro-drug with a significant role in regulating skin damage, psoriasis, and acne. None of the mechanisms of action of the two retinoids, though, has been well illustrated yet [127,146]. ATRA has also exhibited anti-psoriasis activity, while astaxanthin can inhibit the production of the inducible nitric oxide (iNOS), making them possible candidates for the development of anti-psoriasis and other inflammatory skin condition drugs [130,147].

5.6. Skin and Other Cancers’ Treatment Potential of Vitamin A, Retinoids, and Carotenoids

Skin cancer is another result of over-exposure to the sun’s radiation. Photo-protection is once again the solution to avoid this undesirable and mostly irreversible condition, operated either topically or systematically. The main aim of this treatment solution is the achievement of UV light absorption by certain bioactive groups, like phenols, vitamins, and carotenoids. Such antioxidants may prevent UV_R by penetrating the skin and causing the formation of ROS, which eventually leads to skin cancer and photo-carcinogenesis, along with other side effects. Both in vivo-animal model and in vitro studies have proved the protective impact of carotenoids against skin cancer. Astaxanthin also inhibited skin cancer and tyrosinase over-activity in a rat model, while a trial among Australian volunteers showed that a diet rich in lutein and zeaxanthin was associated with a decrease of SCC in people with a family background of skin cancer (Figure 11) [8,130].

Figure 11. Activity of astaxanthin, lutein, and zeaxanthin carotenoids in skin cancer prevention.

Briefly, similar studies conducted on other retinoids and carotenoids have implied their notable potential towards several cancer disorders. Meals enriched with β-carotene were effective against esophagus cancer, lutein and zeaxanthin minimized the risk of breast cancer, and lycopene had a lower risk of prostate cancer and heart failure, while retinoid precursors prevent cancer in sunburn reactions [18]. Carotenoid and retinol treatment in human breast, cervix, prostate, colorectal, oral cancer, and leukemia has been confirmed highly effective [16]. A lower incidence of epithelial lung cancer and respiratory diseases (acute lung injury) was also observed in patients receiving a high carotenoid intake that restrains ROS and induces apoptosis in tumor cells [3,123,124].

6. Vitamin A and Its Derivatives of Several Sources: Health-Promoting Skin Benefits for Nutricosmetic, Cosmeceutical, and Cosmetic Applications

Retinoids and carotenoids have multiple benefits and have great clinical importance towards several diseases, disorders, and comorbidities. Lutein as a nutraceutical and nutricosmetic is able to mitigate the likelihood of ocular complications like cataract, retinitis pigmentosa, and age-related macular degeneration (AMD) [123,148]. Regarding hyperhomocysteinemia, coronary artery dyslipidemia, diabetes mellitus (type II mainly), hyperhomocysteinemia, atherosclerosis, metabolic disorders, CVDs, steatohepatitis, and neurodegenerative diseases, carotenoids modulate pro-inflammatory mediators (e.g., cytokines), thereby lowering blood pressure and improving insulin sensitivity [124].

Several health-related bioactive compounds are traced in functional foods, including fruits, vegetables, animal-based, marine-associated, and many microorganism-related products, naturally rich in bioactive compounds like carotenoids (e.g., tomatoes, citrus fruits, eggs, fish). Nutricosmetics, cosmeceuticals, and cosmetics are supplementary or topical formulations generated to deliver such bioactives directly via controlled dosage for health or aesthetic benefits. Carotenoids like β-carotene, α-carotene, β-cryptoxanthin, astaxanthin, zeaxanthin, lutein, lycopene, fucoxanthin, phytoene, and phytofluene are highlighted as key players in skin health [109,149,150]. A vital role of carotenoids is their antioxidant capacity, due to combating oxidative stress by neutralizing ROS and helping cellular damage. Meanwhile, these constituents are also photo-protective against harmful UV radiation, hence reducing photo-dermatoses (against Erythropoietic protoporphyria (EPP), Porphyria cutanea tarda (PCT), premature skin aging-cancer, and polymorphic light eruption (PMLE)) risk, as well as sun-induced erythema, photo-carcinogenesis, photo-aging, pigmentation, and melanogenesis disorders like melasma. Lastly, carotenoids reduce inflammatory responses, benefiting chronic inflammatory skin conditions and improving skin appearance because of their anti-inflammatory and immunomodulatory properties against conditions such as atopic dermatitis (AD) [109,149,150]. The sources of carotenoids and retinoids, their bioactivity, and their potential role towards effective skin protection are shown in Figure 12, while the most common carotenoids along with their sources and bioactive properties are displayed in Table 1, Table 2, Table 3 and Table 4.

Figure 12. Indicative sources, bioactivity, and skin protection properties of carotenoids.

At this point, it must be clarified that most animals, marine mammals, plant herbs, and microorganisms mainly produce carotenoids and not retinoids directly. However, our previous knowledge leads to the conclusion that β-carotene and other carotenoids are consumed either orally or topically and then are converted by the human body, following established metabolic pathways, to retinol and retinoids. This explains why only a few clinical trials over mainly the past decade have evaluated animal-, marine-, plant-, herb-, and microorganism-derived retinoid oral supplements or topically applied products [3].

6.1. Vitamin A, Vitaminoids, and Carotenoids of Animal Origin

Animal-sourced carotenoids found, for instance, in hens producing eggs, are namely lutein, zeaxanthin, β-cryptoxanthin, and β-carotene [122,151]. In milk, β-carotene seems to be the main carotenoid, while lutein, zeaxanthin, and β-cryptoxanthin are present in lower amounts [151]. Fried beef for human consumption displays higher bioavailability of preformed vitamin A (retinol) than that of provitamin A (carotenoids) like β-carotene in vegetables, with a range of 74% and 2–65%, respectively, while hen, chicken, or quail eggs also have displayed a notable carotenoid content [152].

Other carriers of carotenoids, which are also used for protecting the human skin, are insects. Insects receive their carotenoids like β-carotene, β-cryptoxanthin, lutein, and zeaxanthin from their food, as they cannot produce them themselves. However, aphids and whiteflies can synthesize carotenoid products de novo [153]. Birds, frogs, lizards, and snails are also carriers of carotenoids, β-carotene, β-cryptoxanthin, lutein, and astaxanthin, giving them their colored skin [153]. Similarly, in humans, β-cryptoxanthin, lutein, and β-carotene, but also α-carotene and zeaxanthin, constitute more than 90% of the total carotenoids, which mostly belong to the skin part of the palms and forehead of humans [130,153,154]. Clinical data mainly from the last decade regarding experiments conducted to prove the benefits of vitamin A, vitaminoids, and carotenoids derived from animal sources (predominantly milk, dairy, and eggs/egg yolks) in many nutricosmetics, cosmeceuticals, and cosmetics applications are demonstrated in Table 1.

Table 1. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids of animal origin in nutricosmetics, cosmeceuticals, and cosmetics applications.

Animal Source		Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results–Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year of Study	References
Milk and Dairy	Goat cheese derived from goat milk	Isolated from goat milk samples, Rhodotorula glutinis P4M422, from which the carotenoid pigments β-carotene, torulene, and γ-carotene were extracted	In vitro carotenoid synthesis process by R. glutinis from goat cheese with a view to tackling vitamin A deficiency (in vitro)	A culture medium based on goat milk whey (GMW) was optimized (Taguchi method) Ethanol, carbon and nitrogen source, and pH were evaluated Microorganism and medium selection, enzymatic hydrolysis of GMW to goat cheese, UV/Vis quantification of total carotenoids, and HPLC analysis were held	Optimized conditions were validated (urea 0.3% w/v, pH 4.5, ethanol of 10% v/v, and 6.0% glucose) The carotenoid production of 4075 μg/L was almost 200% higher than when using the un-optimized process (2058 μg/L) β-carotene, torulene, and γ-carotene were extracted under all conditions	Vitamin A deficiency tackling The hydrolyzed GMW was promising as a low-cost source for carotenoid production of carotenoid-rich matrices Useful for several purposes (nutrition, health, or skin), like food, nutricosmetics, nutraceuticals, or feeds	2020	[52]
	Cows with mastitis	Isolated from milk samples, Rhodotorula glutinis, from which the carotenoid pigment was extracted	Investigation on the antimicrobial and anti-biofilm effects of the carotenoid pigment from R. glutinis on food spoilage bacteria (Staphylococcus aureus and Salmonela typhimurium, in vitro)	R. glutinis was isolated from cow milk samples (internal transcribed spacer (ITS) sequence-based typing) Thin-layer chromatography (TLC) assessed pigment purity Broth microdilution evaluation of its antimicrobial impact Microsomal triglyceride transfer protein (MtP) assay and scanning electron microscopy (SEM) were held The sub-minimum inhibitory concentration (sub-MIC) of the pigment on the expression of quorum-sensing (QS) genes in S. typhimurium and S. aureus isolates was measured The degree of toxicity was measured by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay	ITS sequence analysis of R. glutinis revealed that isolated strains were strongly differentiated from others R. glutinis pigment had an antimicrobial impact, and its mean MIC against S. typhimurium isolates (17.0 μL/mL) was higher than the mean MIC for S. aureus isolates (4.1 μL/mL) SEM images and real-time observations revealed that sub-MIC values of the pigment suppressed biofilm generation by restraining QS gene expresssion No toxic effect on Vero cells was recorded at high MIC concentration for the pigment	R. glutinis pigment is effective in destroying the planktonic form of food spoilage and degrading food spoilage biofilm bacteria Regarding the low toxicity level of the R. glutinis pigment for eukaryotic cells, its use as a natural antibacterial preservative in many food products is strongly suggested	2022	[155]
	Animal sources and fortified foods, including margarines and dairy products	Preformed vitamin A, retinol, and provitamin A carotenoids	Evaluation of vitamin A, retinol, and carotenoids in their effect upon the risk of gastric cancer (in vivo)	A prospective cohort study was conducted to evaluate the association of vitamin A and its derivatives consumption and the risk of gastric cancer onset in Swedish adults A total of 82.002 Swedish adults aged 45–83 years who had completed a food-frequency questionnaire in 1997 were the participants of this cohort study	During a mean 7.2-year follow-up, 139 incident cases of gastric cancer were diagnosed High dietary intake of vitamin A and retinol and food- or supplement-based α- and β-carotene reduced gastric cancer risk The multivariate relative risks for the highest versus the lowest quartiles of intake were 0.53 for total vitamin A (95% confidence interval (CI): 0.32, 0.89, Pfor trend = 0.02), 0.56 for total retinol (95% CI: 0.33, 0.95, Pfor trend = 0.05), 0.50 for α-carotene (95% CI: 0.30, 0.83, Pfor trend = 0.03), and 0.55 for β-carotene 0.53 (95% CI: 0.32, 0.94, Pfor trend = 0.07) No notable association was reported for lutein, zeaxanthin, lycopene, or β-cryptoxanthin intake	Gastric cancer risk reduction	2007	[156]
	Infraspinatus muscle, liver, and kidney of goats fed with a blend of palm and canola oil	α-carotene, β-carotene, and lycopene isomers	Examination of the fatty acid composition, cholesterol, and antioxidant status of several goat parts after feeding the goats with a palm oil–canola oil blend (in vitro and ex vivo)	The blend was constituted of 20:80 (%) palm oil–canola oil A total of 24 Boer bucks were randomly assigned to diets containing 0, 4, and 8% oil blend, fed for 100 days, and slaughtered All tissues were stored for 7 days (postmortem, at 4 °C temperature)	The diet did not impact total lipid and cholesterol content in the tissues Apart from the fatty acids profile, ω-3 fatty acids were enhanced The diet had no effect on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) No impact was reported in the concentration of γ and δ tocopherol or lipid oxidation in the tissues α-Tocopherol and total carotenoids were greater in the tissues of the oil blend-fed goats than the control ones (0%) CAT and SOD were stable during storage Lipid oxidative stability, GSH-Px, tocopherol, and carotenoids in the tissues decreased as postmortem storage progressed The blend modified the fatty acids in goat meat and offal, without negatively affecting their oxidative stability	Antioxidant capacity and high food additive-functional food potential	2015	[157]
	Sheep	β-carotene including lactoferrin, immunoglobulin (Ig)A, fat-soluble vitamins, and zinc	Assessment of the impact of a cosmetic product containing 15% lyophilized sheep colostrum on acne skin (in vivo)	A group of 27 volunteers with mild or moderate acne applied the cream twice/day (8 weeks) The levels of skin hydration, sebum level, and transepidermal water loss (TEWL) were observed before and after using the cream The participants completed a survey, rating the creams’ impact on the skin	Regular application of the cream led to an objective hydration, TEWL improvement, and a sebum reduction, desirable for acne-prone skin Three quarters of participants reported that this cream reduced acne lesions like blackheads, papules, pustules, and erythema by around 40% Hydration was improved by 40%, and seborrhea was reduced by 29% in 82% of the subjects, while the skin was kept in good condition in 90% of participants	Skin condition improvement Hydrobarrier improvement Potential serving as an addition to local acne treatment, e.g., with retinoids	2024	[158]
	Cheese out of cow’s milk	Bacterioruberin	A pink-colored bacterium from the Arthrobacter agilis group, namely the strain KR32T derived from cheese, was investigated as an antioxidant (in vitro)	Apart from genome and phylogenetic analysis, chemotaxonomic analysis assigned to this strain, and several potent polar lipids were tested for their anti-radical and antioxidant capacity as well	The main carotenoid pigment was bacterioruberin grown at 10 °C for this strain The main fatty acid was anteiso-C150, and the main menaquinone was MK-9(H2) Several potent antioxidant polar lipids were existent The strain was Gram-stain-positive, catalase-positive, oxidase-positive, and coccus-shaped at optimal growth at 27–30 °C, pH 8	Potent antioxidant and anti-radical activity	2020	[159]
Eggs and Egg Yolk	(Chicken) Eggs	Lutein and zeaxanthin (1213 ± 1731 μg/day)	Examination on the hypothesis that one egg/day improves inflammation, compared with oatmeal-based breakfast without elevating other cardiometabolic risk factors in diabetic patients (Hypothesis: an egg intake would not alter plasma glucose in type 2 diabetic mellitus (T2DM) patients, as compared with oatmeal intake (in vivo))	Plasma glucose, interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were valued Glucose metabolism, dyslipidemia, oxidative stress, and inflammation were also examined A total of 29 subjects (35–65 years old) with glycosylated hemoglobin (HbA1c) values of <9% were randomly divided into groups They consumed isocaloric breakfasts with either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day during a 3-week washout period Apolipoprotein B, subfractions of VLDL, LDL, oxidized-LDL, and high-density lipoprotein (HDL), inflammatory markers, liver enzymes, and adiponectin were also measured	No significant difference was reported in plasma glucose, lipoprotein size, lipids, subfraction concentration, insulin, HbA1c, apolipoprotein B, C-reactive protein (CRP), and oxidized LDLs After gender, age, and body mass index (BMI), adjustments, aspartate amino-transferase (AST), and TNF-α, notably reduced in the egg period Compared with the oatmeal breakfast, eggs did not have any detrimental impact on lipoprotein or glucose metabolism in T2DM patients Eggs possibly due to their content of highly bioavailable lutein and zeaxanthin, decreased inflammation in diabetic subjects, as compared with an oatmeal intake	Potent anti-inflammatory and anti-diabetic character of eggs	2015	[160]
	(Chicken) egg and egg whites	Lutein and zeaxanthin	Clinical investigation on the hypothesis that two eggs/day increase plasma lutein and zeaxanthin in a pediatric population characterized by low intake of fruits and vegetables Examination on whether the inclusion of eggs in the diet increases plasma carotenoids in this population (in vivo)	A total of 54 Mexican children (25 boys and 29 girls) aged 8–12 years old were randomly divided into groups They were assigned to consume either two eggs/day (518 mg additional dietary cholesterol) (EGG period) or the equivalent amount of egg whites (SUB period) in a cross-over design (4 weeks) After a 3-week washout, children were crossed over to the alternate treatment At the end of EGG and SUB periods, 3-day records on plasma carotenoids and apolipoproteins were examined	In agreement with the lack of impact of eggs in increasing the atherogenic lipoprotein profiles, plasma apolipoprotein B levels did not alter in-between the periods Increases in plasma cholesterol were not linked to higher LDL levels Even though the values for apolipoprotein C-III were high when compared with several other pediatric populations, they were not impacted by the egg intake Low intake of carotenoids, especially during the SUB period, was recorded Plasma lutein and zeaxanthin in subjects increased during the EGG period, from 0.235 ± 0.071 to 0.280 ± 0.147 μmol/L and 0.044 ± 0.019 to 0.051 ± 0.031 μmol/L, respectively	Eggs are good sources of carotenoids lutein and zeaxanthin Better transport of carotenoids in plasma was recorded during the egg period Potent anti-atherogenic impact	2013	[161]
	Modified hen eggs and egg-yolk-based beverage	Lutein and zeaxanthin	Investigation of the impact of lutein or zeaxanthin-enriched eggs or a lutein-enriched egg-yolk-based buttermilk beverage on serum lutein and zeaxanthin concentrations, macular pigment optical density, and macular degeneration (in vivo)	Naturally enriched eggs with lutein and zeaxanthin were made with increasing xanthophyll levels in the feed of laying hens One hundred healthy volunteers were divided into five groups (90 days) Group 1: addition of a normal egg to their daily diet Group 2: lutein-enriched egg-yolk-based beverage Group 3: lutein-enriched egg Group 4: zeaxanthin-enriched egg and Group 5: control group (individuals did not modify their usual diet) Serum lutein and zeaxanthin concentrations and macular pigment density were obtained at baseline: days 45, 90	Serum lutein concentration in the lutein-enriched egg and lutein-enriched egg-yolk beverage groups vastly increased (76% and 77%, respectively) A remarkably strong increase (430%) in serum zeaxanthin levels was observed in those receiving zeaxanthin-enriched eggs No alteration in macular pigment density among subjects was recorded Daily consumption of lutein or zeaxanthin in egg yolks or egg-yolk-based beverages aids in increasing serum lutein and zeaxanthin levels, comparable with a daily use of 5 mg supplements	Increased serum lutein and zeaxanthin levels Macular pigment optical density enhancement	2014	[162]

Table 1. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids of animal origin in nutricosmetics, cosmeceuticals, and cosmetics applications.

Animal Source		Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results–Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year of Study	References
Milk and Dairy	Goat cheese derived from goat milk	Isolated from goat milk samples, Rhodotorula glutinis P4M422, from which the carotenoid pigments β-carotene, torulene, and γ-carotene were extracted	In vitro carotenoid synthesis process by R. glutinis from goat cheese with a view to tackling vitamin A deficiency (in vitro)	A culture medium based on goat milk whey (GMW) was optimized (Taguchi method) Ethanol, carbon and nitrogen source, and pH were evaluated Microorganism and medium selection, enzymatic hydrolysis of GMW to goat cheese, UV/Vis quantification of total carotenoids, and HPLC analysis were held	Optimized conditions were validated (urea 0.3% w/v, pH 4.5, ethanol of 10% v/v, and 6.0% glucose) The carotenoid production of 4075 μg/L was almost 200% higher than when using the un-optimized process (2058 μg/L) β-carotene, torulene, and γ-carotene were extracted under all conditions	Vitamin A deficiency tackling The hydrolyzed GMW was promising as a low-cost source for carotenoid production of carotenoid-rich matrices Useful for several purposes (nutrition, health, or skin), like food, nutricosmetics, nutraceuticals, or feeds	2020	[52]
	Cows with mastitis	Isolated from milk samples, Rhodotorula glutinis, from which the carotenoid pigment was extracted	Investigation on the antimicrobial and anti-biofilm effects of the carotenoid pigment from R. glutinis on food spoilage bacteria (Staphylococcus aureus and Salmonela typhimurium, in vitro)	R. glutinis was isolated from cow milk samples (internal transcribed spacer (ITS) sequence-based typing) Thin-layer chromatography (TLC) assessed pigment purity Broth microdilution evaluation of its antimicrobial impact Microsomal triglyceride transfer protein (MtP) assay and scanning electron microscopy (SEM) were held The sub-minimum inhibitory concentration (sub-MIC) of the pigment on the expression of quorum-sensing (QS) genes in S. typhimurium and S. aureus isolates was measured The degree of toxicity was measured by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay	ITS sequence analysis of R. glutinis revealed that isolated strains were strongly differentiated from others R. glutinis pigment had an antimicrobial impact, and its mean MIC against S. typhimurium isolates (17.0 μL/mL) was higher than the mean MIC for S. aureus isolates (4.1 μL/mL) SEM images and real-time observations revealed that sub-MIC values of the pigment suppressed biofilm generation by restraining QS gene expresssion No toxic effect on Vero cells was recorded at high MIC concentration for the pigment	R. glutinis pigment is effective in destroying the planktonic form of food spoilage and degrading food spoilage biofilm bacteria Regarding the low toxicity level of the R. glutinis pigment for eukaryotic cells, its use as a natural antibacterial preservative in many food products is strongly suggested	2022	[155]
	Animal sources and fortified foods, including margarines and dairy products	Preformed vitamin A, retinol, and provitamin A carotenoids	Evaluation of vitamin A, retinol, and carotenoids in their effect upon the risk of gastric cancer (in vivo)	A prospective cohort study was conducted to evaluate the association of vitamin A and its derivatives consumption and the risk of gastric cancer onset in Swedish adults A total of 82.002 Swedish adults aged 45–83 years who had completed a food-frequency questionnaire in 1997 were the participants of this cohort study	During a mean 7.2-year follow-up, 139 incident cases of gastric cancer were diagnosed High dietary intake of vitamin A and retinol and food- or supplement-based α- and β-carotene reduced gastric cancer risk The multivariate relative risks for the highest versus the lowest quartiles of intake were 0.53 for total vitamin A (95% confidence interval (CI): 0.32, 0.89, Pfor trend = 0.02), 0.56 for total retinol (95% CI: 0.33, 0.95, Pfor trend = 0.05), 0.50 for α-carotene (95% CI: 0.30, 0.83, Pfor trend = 0.03), and 0.55 for β-carotene 0.53 (95% CI: 0.32, 0.94, Pfor trend = 0.07) No notable association was reported for lutein, zeaxanthin, lycopene, or β-cryptoxanthin intake	Gastric cancer risk reduction	2007	[156]
	Infraspinatus muscle, liver, and kidney of goats fed with a blend of palm and canola oil	α-carotene, β-carotene, and lycopene isomers	Examination of the fatty acid composition, cholesterol, and antioxidant status of several goat parts after feeding the goats with a palm oil–canola oil blend (in vitro and ex vivo)	The blend was constituted of 20:80 (%) palm oil–canola oil A total of 24 Boer bucks were randomly assigned to diets containing 0, 4, and 8% oil blend, fed for 100 days, and slaughtered All tissues were stored for 7 days (postmortem, at 4 °C temperature)	The diet did not impact total lipid and cholesterol content in the tissues Apart from the fatty acids profile, ω-3 fatty acids were enhanced The diet had no effect on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) No impact was reported in the concentration of γ and δ tocopherol or lipid oxidation in the tissues α-Tocopherol and total carotenoids were greater in the tissues of the oil blend-fed goats than the control ones (0%) CAT and SOD were stable during storage Lipid oxidative stability, GSH-Px, tocopherol, and carotenoids in the tissues decreased as postmortem storage progressed The blend modified the fatty acids in goat meat and offal, without negatively affecting their oxidative stability	Antioxidant capacity and high food additive-functional food potential	2015	[157]
	Sheep	β-carotene including lactoferrin, immunoglobulin (Ig)A, fat-soluble vitamins, and zinc	Assessment of the impact of a cosmetic product containing 15% lyophilized sheep colostrum on acne skin (in vivo)	A group of 27 volunteers with mild or moderate acne applied the cream twice/day (8 weeks) The levels of skin hydration, sebum level, and transepidermal water loss (TEWL) were observed before and after using the cream The participants completed a survey, rating the creams’ impact on the skin	Regular application of the cream led to an objective hydration, TEWL improvement, and a sebum reduction, desirable for acne-prone skin Three quarters of participants reported that this cream reduced acne lesions like blackheads, papules, pustules, and erythema by around 40% Hydration was improved by 40%, and seborrhea was reduced by 29% in 82% of the subjects, while the skin was kept in good condition in 90% of participants	Skin condition improvement Hydrobarrier improvement Potential serving as an addition to local acne treatment, e.g., with retinoids	2024	[158]
	Cheese out of cow’s milk	Bacterioruberin	A pink-colored bacterium from the Arthrobacter agilis group, namely the strain KR32T derived from cheese, was investigated as an antioxidant (in vitro)	Apart from genome and phylogenetic analysis, chemotaxonomic analysis assigned to this strain, and several potent polar lipids were tested for their anti-radical and antioxidant capacity as well	The main carotenoid pigment was bacterioruberin grown at 10 °C for this strain The main fatty acid was anteiso-C150, and the main menaquinone was MK-9(H2) Several potent antioxidant polar lipids were existent The strain was Gram-stain-positive, catalase-positive, oxidase-positive, and coccus-shaped at optimal growth at 27–30 °C, pH 8	Potent antioxidant and anti-radical activity	2020	[159]
Eggs and Egg Yolk	(Chicken) Eggs	Lutein and zeaxanthin (1213 ± 1731 μg/day)	Examination on the hypothesis that one egg/day improves inflammation, compared with oatmeal-based breakfast without elevating other cardiometabolic risk factors in diabetic patients (Hypothesis: an egg intake would not alter plasma glucose in type 2 diabetic mellitus (T2DM) patients, as compared with oatmeal intake (in vivo))	Plasma glucose, interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were valued Glucose metabolism, dyslipidemia, oxidative stress, and inflammation were also examined A total of 29 subjects (35–65 years old) with glycosylated hemoglobin (HbA1c) values of <9% were randomly divided into groups They consumed isocaloric breakfasts with either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day during a 3-week washout period Apolipoprotein B, subfractions of VLDL, LDL, oxidized-LDL, and high-density lipoprotein (HDL), inflammatory markers, liver enzymes, and adiponectin were also measured	No significant difference was reported in plasma glucose, lipoprotein size, lipids, subfraction concentration, insulin, HbA1c, apolipoprotein B, C-reactive protein (CRP), and oxidized LDLs After gender, age, and body mass index (BMI), adjustments, aspartate amino-transferase (AST), and TNF-α, notably reduced in the egg period Compared with the oatmeal breakfast, eggs did not have any detrimental impact on lipoprotein or glucose metabolism in T2DM patients Eggs possibly due to their content of highly bioavailable lutein and zeaxanthin, decreased inflammation in diabetic subjects, as compared with an oatmeal intake	Potent anti-inflammatory and anti-diabetic character of eggs	2015	[160]
	(Chicken) egg and egg whites	Lutein and zeaxanthin	Clinical investigation on the hypothesis that two eggs/day increase plasma lutein and zeaxanthin in a pediatric population characterized by low intake of fruits and vegetables Examination on whether the inclusion of eggs in the diet increases plasma carotenoids in this population (in vivo)	A total of 54 Mexican children (25 boys and 29 girls) aged 8–12 years old were randomly divided into groups They were assigned to consume either two eggs/day (518 mg additional dietary cholesterol) (EGG period) or the equivalent amount of egg whites (SUB period) in a cross-over design (4 weeks) After a 3-week washout, children were crossed over to the alternate treatment At the end of EGG and SUB periods, 3-day records on plasma carotenoids and apolipoproteins were examined	In agreement with the lack of impact of eggs in increasing the atherogenic lipoprotein profiles, plasma apolipoprotein B levels did not alter in-between the periods Increases in plasma cholesterol were not linked to higher LDL levels Even though the values for apolipoprotein C-III were high when compared with several other pediatric populations, they were not impacted by the egg intake Low intake of carotenoids, especially during the SUB period, was recorded Plasma lutein and zeaxanthin in subjects increased during the EGG period, from 0.235 ± 0.071 to 0.280 ± 0.147 μmol/L and 0.044 ± 0.019 to 0.051 ± 0.031 μmol/L, respectively	Eggs are good sources of carotenoids lutein and zeaxanthin Better transport of carotenoids in plasma was recorded during the egg period Potent anti-atherogenic impact	2013	[161]
	Modified hen eggs and egg-yolk-based beverage	Lutein and zeaxanthin	Investigation of the impact of lutein or zeaxanthin-enriched eggs or a lutein-enriched egg-yolk-based buttermilk beverage on serum lutein and zeaxanthin concentrations, macular pigment optical density, and macular degeneration (in vivo)	Naturally enriched eggs with lutein and zeaxanthin were made with increasing xanthophyll levels in the feed of laying hens One hundred healthy volunteers were divided into five groups (90 days) Group 1: addition of a normal egg to their daily diet Group 2: lutein-enriched egg-yolk-based beverage Group 3: lutein-enriched egg Group 4: zeaxanthin-enriched egg and Group 5: control group (individuals did not modify their usual diet) Serum lutein and zeaxanthin concentrations and macular pigment density were obtained at baseline: days 45, 90	Serum lutein concentration in the lutein-enriched egg and lutein-enriched egg-yolk beverage groups vastly increased (76% and 77%, respectively) A remarkably strong increase (430%) in serum zeaxanthin levels was observed in those receiving zeaxanthin-enriched eggs No alteration in macular pigment density among subjects was recorded Daily consumption of lutein or zeaxanthin in egg yolks or egg-yolk-based beverages aids in increasing serum lutein and zeaxanthin levels, comparable with a daily use of 5 mg supplements	Increased serum lutein and zeaxanthin levels Macular pigment optical density enhancement	2014	[162]

6.2. Vitamin A, Vitaminoids, and Carotenoids of Marine Origin

Marine use in the cosmetic field appeared to escalate in the past few years because of their antioxidant, anti-aging, anti-wrinkle, and anti-acne properties. Several carotenoids derive from Halophilic archaea, specifically Halobacterium salinarum and Haloferax mediterranei, and have exhibited a notable anti-aging and antioxidant effect, while other animal products, like sea cucumber extracts, contain vitamins A and B, collagen, gelatin, etc., and have demonstrated a promising wound healing, antioxidant, and antimicrobial impact in treating skin issues, wrinkles, and sunburn [109,149,150]. Some carotenoids produced by halophilic organisms are phytoene, phytofluene, β-carotene, lycopene, derivatives of bacterioruberin, and salinixanthin [163].

Cyanobacteria also contain carotenoids, like astaxanthin and fucoxanthin, and thus, display antioxidant and photo-protective properties by enhancing skin elasticity and promoting collagen synthesis, respectively [109,149,150]. Brown seaweeds (Phaeophyceae), like Laminaria japonica and Laminaria digitate, and diatoms (Bacillariophyta), are also vital sources of fucoxanthin [130,132,153]. Other producers of astaxanthin seem to be the microalgae Haematococcus pluvialis and the fungus Phaffia rhodozyma [131,149,164]. Marine bacteria are also able to synthesize carotenoids, astaxanthin, and zeaxanthin, also showing anti-aging properties, preventing macular degeneration, as confirmed by Mesoflavibacter zeaxanthinifaciens, Zeaxanthinibacter enoshimensis, Muricauda lutaonensis, and several others [23]. Such marine microorganisms, along with lutein and tunaxanthin, are also traced in pink-fleshed fish like tuna and salmon, but also in shrimp, lobster, trout, and other mollusks and crustaceans [109,149,150], while β-carotene is produced as well by the microalgae strains, Dunaliella salina and Dunalielle bardawii [165]. Clinical data about the benefits of vitamin A, vitaminoids, and carotenoids from marine sources (mainly shellfish, algae, sea cucumbers, bacteria, and archaea) in nutricosmetics, cosmeceuticals, and cosmetics applications are included in Table 2.

Table 2. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids of marine origin in nutricosmetics, cosmeceuticals, and cosmetics applications.

Marine Source	Type of Marine	Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results–Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year of Study	References
Shellfish	Scallop (Chlamys nobilis)	2,2′-dihydroxy-astaxanthin from the isolated bacterium Brevundimonas scallop	Investigation of the antioxidant activity of novel carotenoids produced from this scallop (in vitro)	After serial dilutions with sterile seawater, 0.1 mL aliquot was spread on LB solid medium and was incubated at 25 °C (3 days) The genome of the isolate was analyzed, carotenoid compounds were screened by HPLC–MS, and the production was monitored Total carotenoids content (TCC), 2–2 diphenyl-1 -picrylhydrazyl (DPPH) assay	B. scallop genome was comprised of astaxanthin and hydroxy-contained astaxanthin 2,2′-dihydroxy-astaxanthin was the main constituent The highest carotenoid production of 1303.62 ± 61.06 μg/g dry cells was recorded at a temperature of 20 °C and salinity of 3% NaCl, in 10 g/L glucose as a carbon source 2,2′-dihydroxy-astaxanthin had more antioxidant effects than astaxanthin	Excellent antioxidant activity and potent industrial utilization	2020	[50]
Algae	Dunaliella salina	α-carotene, lutein, zeaxanthin, all-trans-β-carotene, and 9-cis-β-carotene	Evaluation of the beneficial activity and pro-apoptotic effects of Dunaliella salina on human KB oral SCCs	Phytochemical analysis of D. salina on KB human oral SCCs by HPLC was conducted Reducing capacity, chelating activity, DPPH assay, superoxide anion scavenging activities, anti-inflammatory properties, and anti-proliferative/cytotoxic effects were also evaluated	Different carotenoids like α-carotene, zeaxanthin, and lutein, and higher levels of all-trans-β-carotene and 9-cis-β-carotene were traced Reducing capacity, chelating activity, DPPH assay, and superoxide anion scavenging were enhanced by D. salina in a dose-dependent manner In vitro studies with KB cell line had anti-proliferative and no cytotoxic effects The anti-inflammatory property of this extract was proved via downregulating the protein expression of cyclooxygenase 2 (COX-2) in the DS-treated group The DS extract also triggered the apoptosis of KB cells in a dose-dependent manner	Antioxidant, anti-proliferative, anti-inflammatory, and radical scavenging activity Anti-carcinogenic activity of the DS extract	2017	[166]
	Dunaliella salina	β-carotene and retinol	Evaluation of enhancing the in vivo retinol bioavailability by integrating β-carotene from this microalga into prepared nanoemulsions with natural emulsifiers	Nanoemulsions were tested for their digestive stability (in vitro), digestibility (in vitro), and β-carotene bio-accessibility (in vivo) by HPLC and ultra-performance liquid chromatography (UPLC) The effect of the emulsifier’s nature on the absorption of β-carotene and its conversion to retinol was also tested in vivo Whey protein isolate (WPI) and soybean lecithin (SBL) were tested	WPI was more adequate to achieve small-particle nanoemulsion than SBL (high oil levels 10–30%) The coalescence observed in SBL nanoemulsions during GI digestion reduced digestibility and β-carotene bio-accessibility The WPI nanoemulsion displayed an aggregation in the gastric phase, redispersed in the intestinal phase, facilitating its digestibility and bio-accessibility The in vivo results proved that the WPI nanoemulsion increased the bioavailability of retinol to a higher extent (maximum concentration (Cmax) = 685 ng/mL) than SBL nanoemulsion (Cmax = 394 ng/mL), due to enhanced β-carotene absorption in rats	In vivo retinol bioavailability enhancement WPI is a promising natural emulsifier in increasing retinol bioavailability	2023	[167]
	Dunaliella salina	Phytoene and phytofluene	Evaluation of this algae’s extract to counteract skin aging under intense solar irradiation and its anti-glycation and anti-inflammatory potential (in vivo and ex vivo)	Carotenoids were produced under nutrient deprivation and adequate (to high) solar radiation Freeze-dried and extracted by supercritical CO2 (to remove colored β-carotene), the resulting oleoresin was isolated and purified, leading to colorless carotenoids The extract (0.025 mg/mL) was diluted in jojoba oil and quantified by HPLC-DAD and UV/Vis Then, the extract was incorporated into a simple cream gel chassis It was tested for over 8 weeks on 25 females aged 35–60 under daily intense solar exposure In vivo (ex vivo) anti-glycation, anti-inflammatory, and anti-aging effects were also assessed	Strongly reduced formation of N-ε-carboxy-methyl-lysine, exposed to methylglyoxal (up to −68%), was found Decreased advanced glycation end products (AGEs) receptor (RAGE) levels, notably reduced IL-6 and -8 cytokines (by 26% and 45%, respectively), and in turn increased the Nrf2 (by 19%) were observed A reduction in RAGEs (40%), glyoxalase-1 (Glo-1) (24%), and carboxymethyl-lysine (CML) confirmed the anti-glycation efficiency 1% of this extract-based cream decreased glycation scores compared with the placebo, strengthened skin’s resilience to irritation, and battled inflammation The placebo product displayed worsened red spots and wrinkling The extract also reversed all side effects observed by the placebo and reduced histamine sensitivity The key skin aging parameters, including wrinkle counts (32%) and wrinkle volume (35%), were notably improved	Anti-glycation, anti-inflammatory, anti-aging active ingredient with high photo-protection qualities	2022	[168]
	Dunaliella salina	All-trans-forms of α-carotene, β-carotene, lutein, and zeaxanthin, as well as 13-cis-β-carotene, 9-cis-α-carotene, and 9-cis-β-carotene	Suppressive impact examination regarding such extract on the production of the pro-inflammatory mediators in RAW264.7 cells via the NF-κΒ and Jun NH2-terminal kinase (JNK) activation when triggered by lipopolysaccharide (LPS) (in vitro)	Spray-dried D. saliva powder was extracted at room temperature, and 250 mL of hexane/acetone/ethanol (2:1:1, v/v/v) Saponification was performed by adding 10 mL of 40% methanolic KOH at 25 °C for 16 h The carotenoid extract was quantified by HPLC and dissolved in dimethyl sulfoxide (DMSO) Cell viability assay on the RAW264.7 cells, nitrite assay, determination of pro-inflammatory cytokines and prostaglandin E2 (PCE2), and western blotting analysis were also conducted	All-trans-α-carotene forms (28.8 mg/g), β-carotene (471.1 mg/g), lutein (7.1 mg/g), zeaxanthin (7.2 mg/g), 13-cis-β-carotene (12.1 mg/g), 9-cis-α-carotene (19.1 mg/g), and 9-cis-β-carotene (440.3 mg/g) were traced in the extract All carotenoid forms aided in the reduction in the IL-1β, IL-6, and TNF-α formation, protein expression of iNOS, COX-2, and secretion of NO and PGE2 in LPS-activated RAW264.7 cells Its attenuation of LPS-induced inflammatory responses inhibited NF-κΒ p50 subunit translocation through blocking IκΒ phosphorylation and degradation, correlated with suppressing IκΒ kinase (IKK) α/β phosphorylation and downregulating JNK action	Anti-inflammatory and suppressive impact	2013	[169]
	Haematococcus pluvialis	Astaxanthin capsules	In vivo, randomized, double-blind, placebo-controlled study for 23 healthy Japanese women (10 weeks)	Group 1 (n = 12): astaxanthin capsule Group 2 (n = 11): placebo capsule	Group 1 showed increased MED compared with placebo Group 1 presented higher moisture in the irradiated area than Group 2 No significant differences in TEWL Skin texture was improved, roughness was minimized	Skin protection and youthful complexion	2018	[170]
	Haematococcus pluvialis	Astaxanthin, astaxanthin monoester (AXME), and astaxanthin diester (AXDE) as well as retinol	Examination on the effective inhibition of skin cancer, tyrosinase, and antioxidative properties by astaxanthin and its esters from H. pluvialis (in vivo and in vitro)	AXME and AXDE were characterized for their anti-cancer action with total carotenoids (TC) and astaxanthin (AX) against UV-7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer in a rat model (in vivo) Extraction, isolation, and characterization of AX, AXNE, and AXDE; HPLC analysis of astaxanthin, astaxanthin esters, and retinols; LC–MS; measurement of tumor index; tyrosinase assay; and antioxidant enzyme presence were also measured	AT (200 μg/kg body weight (b.w.)), AXDE, and AXME reduced UV-DMBA-induced tumor incidences (96 and 88%, respectively), compared with TC (85%) and AX (66%) Approx. a 7-fold increase in tyrosinase and 10-fold decrease in antioxidant levels were normalized by AXDE and AXME, in contrast to only ~1.4–2.2-fold by AX and TC, respectively An appearance of 72 and 58 ng/mL of retinol in the serum of respective AXE-treated (AXDE and AXME) and AX-treated animals, respectively, was screened AXEs had interestingly better anti-cancer potential than AX and TC	Antioxidant, radical scavenging, anti-inflammatory, and anti-cancer activity	2013	[171]
	Haematococcus pluvialis	Astaxanthin tablets and fish collagen hydrolysate tablets	Combination of dietary astaxanthin and collagen hydrolysate as anti-aging metabolites on moderately photoaged skin (in vivo)	A total of 44 healthy aged subjects were treated with astaxanthin (2 mg/day) combined with collagen hydrolysate (3 g/day) or placebos for 12 weeks Elasticity and hydration properties of facial skin, expression of procollagen type I, fibrillin I, and MMPs 1 and 12 as well as UV-induced DNA damage in artificially UV-irradiated buttock skin before and after treatment, were thoroughly examined	The supplement group showed notable improvement in skin elasticity and TEWL in photoaged facial skin after 12 weeks, compared with the placebo group In contrast to the placebo group, in the treated group the expression of procollagen type I and fibrillin I increased, while MMPs 1 and 12 expression decreased No significant difference in the UV-induced DNA damage was recorded between groups	Improved elasticity and barrier integrity in photoaged human skin	2014	[172]
	Haematococcus pluvialis	Astaxanthin	Study on the effects of astaxanthin on the semen quality of diabetes mellitus (DM)-suffering KKAy mice (in vivo)	A total of 60 DM KKAy mice with similar body weights and initial blood glucose and serum lipid levels were assigned to four groups, one control (received the same volumes of distilled water) and three astaxanthin treatments (10, 50, or 100 mg/kg astaxanthin, twice daily), where all mice received the same high-fat diet Biochemical, testis quality, and sperm quality assessment, were also conducted	Oral astaxanthin decreased fasting blood glucose of DM mice and serum lipid levels and improved sperm quality Serum total cholesterol, LDL cholesterol, insulin, and NO levels decrease in their testis were also displayed Astaxanthin also improved the HDL cholesterol and SOD levels in DM mice testis Serum IL-11, TNF-α, and interferon-γ (INF-γ) levels were positively impacted	Impaired semen quality improvement Effective impact on serum cytokines Potential application as a promising adjuvant drug for infertility induced by DM onset	2020	[173]
	Halimeda opuntia (Linnaeus) Lamoroux green seaweed	Total carotenoid content	Evaluation on the preliminary screening of the antioxidant and cytotoxic potential of this green seaweed (in vitro)	Total phenolic content (TPC) was assessed by Folin–Ciocalteu Total flavonoid content (TFC) was determined by the aluminum chloride colorimetric method The total antioxidant capacity (TAC) was measured by the DPPH assay (200–1000 μg/m) The cytotoxic activity was evaluated against the estrogen receptor-positive human breast adenocarcinoma (MCF-7), estrogen-negative human breast adenocarcinoma (MDA-MB-231), human colorectal adenocarcinoma (HT-29), human hepatocellular carcinoma (HepG2), and mouse embryonic fibroblast (3T3) by using the MTT assay	The TPC yielded a result of 55.04 ± 0.98 mg gallic acid equivalent (GAE)/g of extract, while the TFC was 40.02 ± 0.02 quercetin equivalents (QE)/g of extract H. opuntia had the highest DPPH reduction of 63.61%, and TAC was 57.36 ± 0.004 mg ascorbic acid equivalent (AAE)/g extract at concentration of 1.0 mg/mL Total lipids in this green seaweed species were 1.60 ± 0.002%, total carotenoids were 115.57 ± 0.98 μg/g, while chlorophyll α and β were 148.73 ± 2.60 and 290.83 ± 9.46 μg/g, respectively The methanolic extract was highly cytotoxic to MCF-7 cells with a half-maximal inhibitory concentration (IC50) of 25.14 ± 1.02 g/mL and slightly less to 3T3 cells (IC50 of 65.23 ± 0.25 μg/mL)	Potential role as a natural cancer treatment Anti-cancer, anti-proliferative, cytotoxic, radical scavenging, and antioxidant activity	2022	[174]
	Sargassum hemiphyllum (brown seaweed)	Fucoidan and Fucoxanthin	Investigation on the feasibility of the synergistic effect of low molecular fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic intervention against non-alcoholic fatty liver disease (NAFLD) (in vivo)	The inhibitory impact of the LMF-HSFx or placebo capsules was evaluated on 42 NAFLD patients (24 weeks) and in a high-fat diet (HFD) mouse model and HepaRGTM Subjects took three capsules of LMF-HSFx (275 mg LMF and 275 mg HSFx per capsule), twice per day in the treatment group The placebo group received (three capsules of 550 mg/capsule cellulose powder)	LMF-HSFx decreases the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose, and HbA1c in NAFLD patients Regarding the lipid metabolism, the LMF-HSFx capsule reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression A liver fibrosis reduction in NAFLD patients was recorded as well Pro-inflammatory cytokines IL-6 and INF-γ are reduced in LMF-HSFx group patients Moreover, in HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis while regulating systemic inflammatory response index-peroxisome proliferator-activated receptor γ coactivator 1 (SIRI-PGC-1) pathway Modulation of the leptin/adiponectin axis in adipocytes and hepatocytes, regulation of lipid and glycogen metabolism, and reduction in insulin resistance against NAFLD	Efficacy towards NAFLD patients, liver fibrosis reduction (anti-fibrotic), amelioration of hepatic steatosis qualities	2021	[175]
	Marine algae-derived carotenoid	Fucoxanthin	Evaluation of fucoxanthin’s attenuative profile towards the behavior deficits and neuroinflammatory response in 1-methyl-4- phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) in mice (in vivo)	C57BL/6 mice received 30 mg/kg of MPTP (intraperitoneal (i.p.)) every day for 5 consecutive days to establish PD; subsequently, the everyday fucoxanthin treatment was intended for 7 days	The i.p. injection of MPTP concluded in impaired motor function, reduced dopamine and dopaminergic neuronal loss, tyrosine hydrolase (TH) reduction, as well as microglial activation-mediated neuroinflammation Fucoxanthin ameliorated α-synuclein abnormal accumulation and motor impairment in an MPTP-initiated chronic PD mouse model of use Fucoxanthin reversed the MPTP-mediated decline of dopamine neuron, TH, and microglial activation in the nigra pars compacta (SNpc) region by suppressing oxidative stress, gliosis, and neuroinflammation The western blot analysis showed that fucoxanthin suppressed the expression of pro-inflammatory cytokines by the MPTP treatment	Anti-inflammatory, neuroprotective, antioxidant, and anti-proliferative activity Beneficial remedy towards PD	2020	[176]
	Seaweed	Fucoxanthin	Investigation upon the seaweed fucoxanthin supplementation and its anti-obesity effect in mildly obese Japanese subjects (in vivo)	The effect of fucoxanthin (1 or 3 mg daily) was examined Capsules with fucoxanthin or placebo ones were administered for 4 weeks to male and female Japanese adults (BMI > 25 kg/m2) Before and after treatment, the body weight, composition, abdominal fat area, and circumferences of the neck, arm, and thigh were also examined	A reduction in the relative ratio after versus before treatment body weight, BMI, and visceral fat area in the 3 mg/day fucoxanthin group compared with the placebo one Relative values of the total fat mass, subcutaneous fat area, waist, and right thigh circumference were also notably reduced in the 1 mg/day fucoxanthin group than the placebo one A significant reduction in the absolute right thigh circumference was demonstrated in the 1 mg/day fucoxanthin group No abnormalities of blood pressure, pulse rate, blood parameters, and urine analysis parameters were recorded	Anti-obesity impact—Fucoxanthin may be able to improve a moderate overweight state in both males and females	2017	[177]
	Sargassum glaucescens (brown seaweed algae extract)	Fucoxanthin	Examination on the oral supplementation of fucoxanthin-rich brown algae extract upon the amelioration of cisplatin-induced testicular damage in hamsters (in vitro and in vivo)	By extracting the powder of S. glaucescens, fucoxanthin-rich brown algae extract (FXE) was obtained FXE effects in LPS-induced inflammation in RAW264.7 cells and its effects against cisplatin (CP)-induced reproductive damage in hamsters were studied on 80 male Syrian hamsters injected with and without CP and daily oral gavage with fucoxanthin (5 days) Cell viability (MTT), in vitro ROS and mitochondrial membrane potential analysis, oxidative stress markers (SOD, CAT, NO, GSH-Px, and malondialdehyde (MDA) related levels), testosterone, and α-glucosidase were assessed	Treatment with FXE reduced the level of ROS and MDA in RAW264.7 cells and the rat’s testis (cell viability) Protective effects on mitochondrial membrane potential were recorded The testosterone level was also improved along with the α-glucosidase activity The sperm count additionally increased by FXE treatment in contrast to sperm abnormality that was notably reduced Through histopathological analysis, FXE notably improved the seminiferous tubules morphology	Antioxidant and radical scavenging activity Alternative treatment of testicular or spermatogenitc damage	2020	[178]
	Chlorella sp.	β-carotene, lutein, and zeaxanthin	In vivo-in vitro study in mouse Leydig cells and MA cells treated with hydrogen peroxide (H2O2) to examine the ability of astaxanthin to rescue testosterone production under oxidation	MA-10 cells were pretreated with astaxanthin for 1 h, 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP), 22(R)-hydroxycholesterol (22R-OHC), or pregnenolone and co-treated with H2O2 for 3 more hours Same procedure to Leydig cells	Astaxanthin protected steroidogenesis against oxidative stress Antioxidant ability against H2O2	Antioxidant supplement Steroid-protective	2015	[179]
	Chlorella vulgaris	β-carotene, lutein, and zeaxanthin	In vivo study, in 11 healthy men for 14 days	Plasma concentrations of the three carotenoids were measured Pharmacokinetic metrics were held	All carotenoid concentrations were increased β-carotene had higher bioavailability of zeaxanthin and lower than lutein	Use of Chlorella vulgaris as an antioxidant carotenoid source for skin and eyes	2021	[180]
Bacteria	Gordonia Hongkongensis (EUFUS-Z928) (Isolated from the octocoral Eunicea fusca)	β-carotene	Establishment of carotenoid production and antioxidant capacity of this bacterium (in vitro)	Inoculum, carbon and nitrogen source, NaCl concentration, pH, incubation time, temperature, and stirring speed were measured (Plackett–Burman design) Screening of actinomycetota for its bioactive properties and absorbance of the pigmented crude extract by the UV-visible spectrophotometry, 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and DPPH scavenging action were evaluated LC–MS was also utilized	Results demonstrated a substantial increase in absorbance (0.091 to 0.32), DPPH (27.60% to 84.61%), and ABTS radical scavenging capacity (17.39 to 79.77%), compared with the isolation medium Six C40 and C46 carotenoids, red–orange pigments with antioxidant capacity, were identified and owned great inhibitory ability These carotenoids were namely 3-hydroxy-β,φ-carotene (limited ability as vitamin A precursor), phoeniconone, 3,3′-dihydroxyisorenieratene, 7,8-dihydroparasiloxanthin, 4,4′-dihydroxydiatoxanthin, and 3-hydroxy-β,β-caroten-3′-one	Potential use as additives for cosmetic and cosmeceutical applications of the extracts Antioxidant and inhibitory ability Free radical scavenging ability	2024	[51]
	Five cyanobacteria strains: Alkaliema aff. pantanalense LEGE15481, Cyanobium gracile LEGE12431, Nodosilinea (Leptolyngbya) antarctica LEGE13457, Cuspidothric issatschenkoi LEGE03282, and Leptolyngbya-like sp. LEGE13412	All-trans- β-carotene, zeaxanthin, echinenone, and lutein	Investigation on the biotechnological potential in the treatment of psoriasis of these five cyanobacteria extracts (in vitro)	Different extracts were examined by pigment profile using HPLC-photo diode array (-PDA) Their antioxidant potential was assessed against the superoxide anion radical Their anti-inflammatory and anti-proliferative potential was assessed in vitro by RAW 264.7 and the human HaCaT cell lines Phytochemical analysis and the effect on keratinocyte proliferation were also experimentally held	Terrestrial and freshwater strains had the highest carotenoid content (33.193–63.926 μg/g dry extract) All-trans-β-carotene, zeaxanthin, echinenone, and lutein were the most abundant carotenoids Acetone was the most effective solvent for pigment extraction, as such pigments presented the lowest IC50 values (0.29–0.38 mg dry extract/mL), concerning O2·− radical scavenging An anti-inflammatory potential was revealed for A. pantanalense LEGE15481, N. antarctica LEGE13457, and Leptolyngbya-like sp. LEGE13412, which reduced the nitric oxide (NO) in RAW 264.7 at about 25% All extracts except for A. pantanalense LEGE15481 demonstrated reduced keratinocyte proliferation and selective toxicity	Antioxidant, anti-inflammatory, and anti-proliferative potential for the topical treatment of psoriasis N. antarctica LEGE13457 and Leptolyngbya-like sp. LEGE13412 are promising for further exploitation	2020	[181]
	Cyanobium sp. (LEGE06113)	β-carotene, zeaxanthin, echinenone, and lutein	Examination of frozen-dried biomass of this cyanobacteria species for their bioactive potential (in vitro)	By frozen-dried biomass of this cyanobacteria, organic and aqueous pigment-rich extracts were obtained via classic extraction with four solvents: acetone (A), water (W), ethyl acetate (EA), and ethanol (E) For increasing extraction efficacy, the extraction was performed using W after an organic extraction (A–W, E–W, EA–W) and acetone after an aqueous extraction (W–A) Extraction yield and identification of carotenoids was held The bioactive potential of the Cyanobium sp. extracts was assessed for its antioxidant (ABTS, NI, and O2·−), anti-inflammatory COX inhibition, and cytotoxicity ability (HepG2 cell lines)	W–A had the highest antioxidant capacity and higher carotenoid content, while E–W had the highest content in phycobiliproteins and great antioxidant capacity 100 μgE/mL of the E–W extract exhibited an inhibitory potential against COX-1 and COX-2 inflammation-related enzymes In terms of cytotoxic capacity, E, W, A–W, E–W, and EA–W had no cytotoxic effects in concentrations up to 750 μgE/mL	Antioxidant, anti-inflammatory, and no cytotoxicity Valorization of this pigment-rich extract potential for biotechnological applications	2020	[182]
	Three different cyanobacteria: Pseudanabaena sp., Spirulina sp., and Lyngbya sp.	β-carotene (less amounts of Myxoxanthophyll, zeaxanthin, canthaxanthin, and α-carotene	Investigation of the antioxidant, anti-nephrolithe, and in vitro digestibility activity of three different cyanobacterial pigment extracts	Phycobiliprotein-containing water and carotenoid-containing methanolic extracts were selected Water and methanolic extracts were characterized as well The antioxidant activity (total phenolic content, total antioxidant activity, and DPPH), iso-bolographic analysis, anti-nephrolithic activity, in vitro digestibility, and calcium oxalate crystallization assay were conducted	The best half-maximal effective concentration (EC50) values for DPPH scavenging were revealed in Lyngbya water (LW, 18.78 ± 1.57 mg/mg DPPH) and Lyngbya methanol (LM, 59.56 ± 37.38 mg/mg DPPH) extracts Iso-bolographic analysis showed that most extract combinations were antagonistic, but the LM-Spirulina methanol (SM) one (1:1) had the highest synergistic rate (86.65%) In vitro digestion studies demonstrated that DPPH scavenging activity was decreased in all extracts except for the Pseudanabaena methanol (PM) and LM ones after stimulated digestion All extracts were effective in reducing calcium oxalate crystal size (nearly 60–65%) compared with the control PM and Spirulina water (SM) extracts inhibited nucleation and aggregation of calcium oxalate (~60–80%) Carotenoids are not majorly affected by digestion processes, and their antioxidant capacity stems from their assimilation	Antioxidant, anti-nephrolithic activities, and in vitro digestibility efficacy of the extracts	2015	[63]
	Phormidium sp. LEGE05292, Tychonema sp. LEGE07196, Synechocystis salina LEGE06155, and Cyanobium sp. LEGE07175	β-carotene, zeaxanthin, echinenone, canthaxanthin, and lutein	Examination of filamentous and picoplanktonic cyanobacteria for cosmetics, for improving skin structure and preserving dermal matrix components (in vitro)	With a focus on the anti-aging properties, the extracts were analyzed for their pigment profile, phenolic content, antioxidant potential, cytotoxicity against HaCaT cells, fibroblasts (3T3L2), endothelial cells (hCMEC/D3), and capacity to inhibit hyaluronidase (HAase) Phytochemical analysis, antioxidant activity assessment, and cytotoxicity assay were ultimately conducted	The TC content ranged from 118.69 to 383.89 μg/g of dry biomass, and the TPC from 1.07 to 2.45 mg GAE/g Identified carotenoids were β-carotene, zeaxanthin, echinenone, canthaxanthin, and lutein, with zeaxanthin (49.82 μg/g) and lutein (79.08 μg/g) being mostly present The highest antioxidant potential was found for Phormidium sp. LEGE05292 and Tychonema sp. LEGE07196 for superoxide anion radical O2·− scavenging (IC50 of 822.70 and 924 μg/mL, respectively) As for HAase inhibition, Tychonema sp. LEGE07196 and Cyanobium sp. LEGE07175 displayed the best IC50 (182.74 and 208.36 μg/g, respectively) Fibroblast proliferation was increased, while hyaluronic acid digestion was inhibited, and low or no toxicity was recorded	Antioxidant and anti-aging potential	2020	[183]
Archaea	Haloterrigena turkmenica	Lycopene, phytoene, and lycopersene, as well as bacterioruberin carotenoids	Identification and antioxidant activity of carotenoids from this archaea species (in vitro)	The carotenoids were extracted with methanol, separated by reverse phase (RP)-HPLC, and identified by mass spectrometry and UV/visible spectra analysis Quantification of carotenoids, analysis of the extracts by RP-HPLC and TLC, and antioxidant capacity were measured	C50 carotenoids were the main pigments, and C30, C40, and C51 were also detected, while seven geometric isomers were discerned for bacterioruberin, monoanhydrobacterioruberin, and for bisanhydro- bacterioruberin Lycopene, phytoene, and lycopersene, were found among the minor carotenoids identified Higher antioxidant power than α-tocopherol, butylhydroxytoluene, and ascorbic acid	Antioxidant activity and cytoprotective effect	2017	[184]
	Natrialba sp. M6 (haloalkaliphilic archaeon)	C50 carotenoid Bacterioruberin	Evaluation of the in vitro dual anti-cancer and antiviral activity of carotenoids produced from this archaea species (in vitro)	The isolated carotenoids were identified by Raman spectroscopy, GC–MS, FT-IR, LC–MS, and NMR Evaluation of the pigment’s compatibility with red blood cells, in vitro anti-cancer efficacy examination of the cytotoxicity on human normal and cancer cell lines, inhibitory potential on MMP-9-dependent cancer and antiviral activity against hepatitis C virus (HCV) RNA and hepatitis B virus (HBV) DNA polymerases viral replication were held Hemolytic behavior, in vitro apoptotic effect, and cytotoxicity evaluation against human virus peripheral blood mononuclear cells (PBMCs) were also conducted	C50 carotenoid bacterioruberin was the predominant compound In vitro results implied that the caspase-mediated apoptotic anti-cancer impact of this pigment and its inhibitory ability against MMP-9 were higher than those of 5-fluoracil This pigment repressed 50% of MMP-9 activity at less than 0.5 μg/mL Higher elimination capacity of HCV and HBV in infected PBMCs than currently used drugs, due to its inhibitory potential against HCV RNA and HBV DNA polymerases Therefore, HCV and HBV replication suppression was exhibited, as apparent by the high viral clearance (%) in the treated cells rather than the ones treated with antiviral drugs	Alternative source of bioactives with anti-cancer and antiviral potential Suppression of MMP-9-mediated cancer progression Inhibition of polymerase-dependent HCV and HBV replication	2020	[46]
	Halophilic Archaea	β-carotene and carotenoids in general	Carotenoids encapsulation into two oil-in-water (O/W) dispersions to increase their use as functional food applications (in vitro)	A nanoemulsion made by high-pressure homogenization and a spontaneously formed microemulsion were conceived Limonene was the dispersed oil phase, and mixtures of Triton X-100/Twen-80 (3:1) were used as emulsifiers and water/glycerol as the continuous aqueous phase Dynamic light scattering (DLS) characterized the structure of the nano- and microemulsions in the presence of carotenoids Radical scavenging ability of encapsulated carotenoids was also examined by electron paramagnetic resonance (EPR) spectroscopy	The particles size of the nanoemulsions was influenced by the emulsifiers’ concentration During storage time, a small increase in the nanoemulsion diameter size was observed due to interactions between encapsulated carotenoids and surfactants mono-layer In the microemulsion, all droplets remained unaltered The loaded dispersions had a higher antioxidant activity than those using β-carotene Using 7.25 mg/mL of carotenoids allowed notably higher radical scavenging ability (>80%) against the Tempol free radical than the microemulsion loaded with 3.62 mg/mL of carotenoids (43%, after 5 min)	Effectiveness of the delivery systems designed to encapsulate and stabilize carotenoids for food or other commercial applications Thermodynamic efficacy of such systems
	Halorubrum tebenquichense	Bacterioruberin	Investigation on the improved stability and biological activity of bacterioruberin in nanovesicles (in vitro)	Bacterioruberin extracted was loaded into liposomes (L-BR and soybean phosphatidylcholine) and archaeosomes (A-BR sn 2,3 ether-linked archaeolipids) Lipid extraction, nanovesicle characterization (size and ζ potential), generalized polarization (GP), fluorescence anisotropy (FA), transmission electron microscopy (TEM), Raman and small-angle X-ray scattering (SAXS), DPPH assay, stability (high temperature), light, pH, storage, release, anti-hemolytic action, cell viability, cellular uptake, anti-inflammatory, and antioxidant action were tested	A-BR (125 nm, −50 mV ζ potential, 9.6 μg BR/lipids) preserved the antioxidant activity of BR in front of light and high temperatures, protected its structure against acidity degradation, avoided its fast release, and retained BR within archaeolipid layers for 2 years (at 4 °C) On the contrary, L-BR (154 nm, −13 mV ζ potential, 6.9 μg BR/lipids) failed to protect and retain BR A-BR inhibited hemolysis induced by ROO* and was captured by J774A.1 cell more than L-BR However, A-RB’s anti-inflammatory (against TNF-α release) and antioxidant (ROS reduction) activity on lipopolysaccharide or H2O2-stimulated J774A.1 cells were comparable to those of L-BR SAXS revealed that archaeosomes mechanically trapped BR, making its partition more stable than in liposomal bilayers, which impaired its intracytoplasmic delivery	A-BR formulations are potent candidates for chronic inflammatory disease confrontation Further exploration in vivo is required	2022	[185]
	Halorubrum sp. BS2	Bacterioruberin and Bisanhydro- bacterioruberin	Characterization and bioprospecting of this strain along with analysis of its carotenoids (in vitro)	A set of extremely halophilic archaeal strains was isolated from seven distinct saline habitats Forty-three strains were selected based on their physiological profile and pigment production Carotenoids of the higher producer were identified by HPLC-diode array and LC–MS Mainly the antibacterial and antioxidant action was studied	Carotenoid production varied from 0.1 to 3.68 μg/mL Bacterioruberin and bisanhydro-bacterioruberin were the predominant carotenoids Their scavenging activity reached 99% at a concentration of 18 μg/mL, much higher than that of ascorbic acid High antibacterial activity against four human-pathogenic strains and four fish-pathogenic ones was also observed Variations in salinity, agitation rate, temperature, and light intensity influenced growth and carotenoid production	Halophilic archaea species are a potential carotenoid source for carotenoids of high antioxidant and antibacterial action Inhibitory effect against all tested strains Radical scavenging activity	2020	[186]
	Haloferax mediterranei		Effect of different carbon sources on cell growth and carotenoid production and their influence on the antioxidant, anti-glycemic, and anti-lipidemic activities of these archaea extracts (in vitro)	Carotenoid extract composition was characterized by HPLC–MS Antioxidant activity of carotenoid extracts obtained from cell cultures grown under several nutritional conditions was determined by ABTS, DPPH, and ferric reducing ability of plasma (FRAP) assays Antioxidant, hypoglycemic, and anti-lipidemic assays were held The ability of these carotenoid extracts to inhibit α-glucosidase, α-amylase, and lipase enzymes was also assessed	Maximum carotenoid production of 92.2 μg/mL was observed by combining 12.5% of inorganic salts and 2.5% of glucose/starch Higher carbon availability in culture media leads to alterations in extract composition, which become more bioactive Carotenoid extracts obtained from high-carbon availability cell cultures had higher proportions of all-trans bacterioruberin, 5-cis-bacterioruberin, and a double isomeric bacterioruberin, whereas 9-cis-bacterioruberin and 13-cis-bacterioruberin decreased Changing nutritional conditions optimized the production of haloarchaeal carotenoids, and the carotenoid composition altered by modifying carbon source concentration	Antioxidant, anti-lipidemic, and anti-glycemic impact Promising in food nutraceutical and nutricosmetic applications	2022	[65]
	Haloarcula sp. (several strains)	Bacterioruberin, Monoanhydro- bacterioruberin, Bisanhydro- bacterioruberin, 5-cis-26-cis- Bacterioruberin, 9-cis- Bacterioruberin, 13-cis- Bacterioruberin and 9-cis-26-cis- Bacterioruberin and 9 more in less significant amount	Antioxidant potential and biological effect on cell viability of Haloarchaea species by UHPLC-coupled with quadrupole-orbitrap (Q-Orbitrap)-MS/MC (in vitro)	The strains were cultivated and cultured for 10 days at continuous agitation at 120 rpm, 40 °C DNA extraction, amplification of 16S rRNA-encoding gene, TPC and TCC determination, and antioxidant assays (DPPH, ABTS, and FRAP) were also conducted Cholinesterases (ChE) enzyme inhibitory activity, cellular viability MTT assay, stimulation of HaCaT cells, oxidative stress: nitrite concentration assay, and docking assays of carotenoids in ChE enzymes were also tested	Six haloarchaea strains from the extreme environment of the Atacama Desert were identified, namely Halorubrum tebenquichense Te Se-85m, Halorubrum tebenquichense Te Se-86m, Haloarcula sp. TeSe-41, Haloarcula sp. TeSe-51, and Haloarcula sp. TeSe-89 Acetylcholinesterase (AChE) inhibition IC50 was 2.96 ± 0.08, and butyrylcholinesterase (BuChE) inhibition IC50 was 2.39 ± 0.09 μg/mL for the most active strain Halorubrum tebenquichense Te Se-85m Cell viability in the HaCaT cell lines showed a notable decrease at 6 h post stimuli at a concentration of 1000, 500, 250, 125, and 62,5 μg/mL with no difference after 24, 48, and 72 h Although 250 μg/mL increased cell viability, in 15 μg/mL a decrease at 6 and 48 h was observed, while after 24 and 72 h no significant cell stimulation was exhibited Apoptosis was induced by overexpression of caspase 3 (CASP3), by a reduction in pluripotency halting the SPY-box transcription factor 2 (SOX2) and causing tumor eradication	Radical scavenging and antioxidant capacity Decrease in the metabolism of cells with high proliferation rates (anti-cancer and anti-tumor action)	2021	[38,187]

Table 2. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids of marine origin in nutricosmetics, cosmeceuticals, and cosmetics applications.

Marine Source	Type of Marine	Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results–Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year of Study	References
Shellfish	Scallop (Chlamys nobilis)	2,2′-dihydroxy-astaxanthin from the isolated bacterium Brevundimonas scallop	Investigation of the antioxidant activity of novel carotenoids produced from this scallop (in vitro)	After serial dilutions with sterile seawater, 0.1 mL aliquot was spread on LB solid medium and was incubated at 25 °C (3 days) The genome of the isolate was analyzed, carotenoid compounds were screened by HPLC–MS, and the production was monitored Total carotenoids content (TCC), 2–2 diphenyl-1 -picrylhydrazyl (DPPH) assay	B. scallop genome was comprised of astaxanthin and hydroxy-contained astaxanthin 2,2′-dihydroxy-astaxanthin was the main constituent The highest carotenoid production of 1303.62 ± 61.06 μg/g dry cells was recorded at a temperature of 20 °C and salinity of 3% NaCl, in 10 g/L glucose as a carbon source 2,2′-dihydroxy-astaxanthin had more antioxidant effects than astaxanthin	Excellent antioxidant activity and potent industrial utilization	2020	[50]
Algae	Dunaliella salina	α-carotene, lutein, zeaxanthin, all-trans-β-carotene, and 9-cis-β-carotene	Evaluation of the beneficial activity and pro-apoptotic effects of Dunaliella salina on human KB oral SCCs	Phytochemical analysis of D. salina on KB human oral SCCs by HPLC was conducted Reducing capacity, chelating activity, DPPH assay, superoxide anion scavenging activities, anti-inflammatory properties, and anti-proliferative/cytotoxic effects were also evaluated	Different carotenoids like α-carotene, zeaxanthin, and lutein, and higher levels of all-trans-β-carotene and 9-cis-β-carotene were traced Reducing capacity, chelating activity, DPPH assay, and superoxide anion scavenging were enhanced by D. salina in a dose-dependent manner In vitro studies with KB cell line had anti-proliferative and no cytotoxic effects The anti-inflammatory property of this extract was proved via downregulating the protein expression of cyclooxygenase 2 (COX-2) in the DS-treated group The DS extract also triggered the apoptosis of KB cells in a dose-dependent manner	Antioxidant, anti-proliferative, anti-inflammatory, and radical scavenging activity Anti-carcinogenic activity of the DS extract	2017	[166]
	Dunaliella salina	β-carotene and retinol	Evaluation of enhancing the in vivo retinol bioavailability by integrating β-carotene from this microalga into prepared nanoemulsions with natural emulsifiers	Nanoemulsions were tested for their digestive stability (in vitro), digestibility (in vitro), and β-carotene bio-accessibility (in vivo) by HPLC and ultra-performance liquid chromatography (UPLC) The effect of the emulsifier’s nature on the absorption of β-carotene and its conversion to retinol was also tested in vivo Whey protein isolate (WPI) and soybean lecithin (SBL) were tested	WPI was more adequate to achieve small-particle nanoemulsion than SBL (high oil levels 10–30%) The coalescence observed in SBL nanoemulsions during GI digestion reduced digestibility and β-carotene bio-accessibility The WPI nanoemulsion displayed an aggregation in the gastric phase, redispersed in the intestinal phase, facilitating its digestibility and bio-accessibility The in vivo results proved that the WPI nanoemulsion increased the bioavailability of retinol to a higher extent (maximum concentration (Cmax) = 685 ng/mL) than SBL nanoemulsion (Cmax = 394 ng/mL), due to enhanced β-carotene absorption in rats	In vivo retinol bioavailability enhancement WPI is a promising natural emulsifier in increasing retinol bioavailability	2023	[167]
	Dunaliella salina	Phytoene and phytofluene	Evaluation of this algae’s extract to counteract skin aging under intense solar irradiation and its anti-glycation and anti-inflammatory potential (in vivo and ex vivo)	Carotenoids were produced under nutrient deprivation and adequate (to high) solar radiation Freeze-dried and extracted by supercritical CO2 (to remove colored β-carotene), the resulting oleoresin was isolated and purified, leading to colorless carotenoids The extract (0.025 mg/mL) was diluted in jojoba oil and quantified by HPLC-DAD and UV/Vis Then, the extract was incorporated into a simple cream gel chassis It was tested for over 8 weeks on 25 females aged 35–60 under daily intense solar exposure In vivo (ex vivo) anti-glycation, anti-inflammatory, and anti-aging effects were also assessed	Strongly reduced formation of N-ε-carboxy-methyl-lysine, exposed to methylglyoxal (up to −68%), was found Decreased advanced glycation end products (AGEs) receptor (RAGE) levels, notably reduced IL-6 and -8 cytokines (by 26% and 45%, respectively), and in turn increased the Nrf2 (by 19%) were observed A reduction in RAGEs (40%), glyoxalase-1 (Glo-1) (24%), and carboxymethyl-lysine (CML) confirmed the anti-glycation efficiency 1% of this extract-based cream decreased glycation scores compared with the placebo, strengthened skin’s resilience to irritation, and battled inflammation The placebo product displayed worsened red spots and wrinkling The extract also reversed all side effects observed by the placebo and reduced histamine sensitivity The key skin aging parameters, including wrinkle counts (32%) and wrinkle volume (35%), were notably improved	Anti-glycation, anti-inflammatory, anti-aging active ingredient with high photo-protection qualities	2022	[168]
	Dunaliella salina	All-trans-forms of α-carotene, β-carotene, lutein, and zeaxanthin, as well as 13-cis-β-carotene, 9-cis-α-carotene, and 9-cis-β-carotene	Suppressive impact examination regarding such extract on the production of the pro-inflammatory mediators in RAW264.7 cells via the NF-κΒ and Jun NH2-terminal kinase (JNK) activation when triggered by lipopolysaccharide (LPS) (in vitro)	Spray-dried D. saliva powder was extracted at room temperature, and 250 mL of hexane/acetone/ethanol (2:1:1, v/v/v) Saponification was performed by adding 10 mL of 40% methanolic KOH at 25 °C for 16 h The carotenoid extract was quantified by HPLC and dissolved in dimethyl sulfoxide (DMSO) Cell viability assay on the RAW264.7 cells, nitrite assay, determination of pro-inflammatory cytokines and prostaglandin E2 (PCE2), and western blotting analysis were also conducted	All-trans-α-carotene forms (28.8 mg/g), β-carotene (471.1 mg/g), lutein (7.1 mg/g), zeaxanthin (7.2 mg/g), 13-cis-β-carotene (12.1 mg/g), 9-cis-α-carotene (19.1 mg/g), and 9-cis-β-carotene (440.3 mg/g) were traced in the extract All carotenoid forms aided in the reduction in the IL-1β, IL-6, and TNF-α formation, protein expression of iNOS, COX-2, and secretion of NO and PGE2 in LPS-activated RAW264.7 cells Its attenuation of LPS-induced inflammatory responses inhibited NF-κΒ p50 subunit translocation through blocking IκΒ phosphorylation and degradation, correlated with suppressing IκΒ kinase (IKK) α/β phosphorylation and downregulating JNK action	Anti-inflammatory and suppressive impact	2013	[169]
	Haematococcus pluvialis	Astaxanthin capsules	In vivo, randomized, double-blind, placebo-controlled study for 23 healthy Japanese women (10 weeks)	Group 1 (n = 12): astaxanthin capsule Group 2 (n = 11): placebo capsule	Group 1 showed increased MED compared with placebo Group 1 presented higher moisture in the irradiated area than Group 2 No significant differences in TEWL Skin texture was improved, roughness was minimized	Skin protection and youthful complexion	2018	[170]
	Haematococcus pluvialis	Astaxanthin, astaxanthin monoester (AXME), and astaxanthin diester (AXDE) as well as retinol	Examination on the effective inhibition of skin cancer, tyrosinase, and antioxidative properties by astaxanthin and its esters from H. pluvialis (in vivo and in vitro)	AXME and AXDE were characterized for their anti-cancer action with total carotenoids (TC) and astaxanthin (AX) against UV-7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer in a rat model (in vivo) Extraction, isolation, and characterization of AX, AXNE, and AXDE; HPLC analysis of astaxanthin, astaxanthin esters, and retinols; LC–MS; measurement of tumor index; tyrosinase assay; and antioxidant enzyme presence were also measured	AT (200 μg/kg body weight (b.w.)), AXDE, and AXME reduced UV-DMBA-induced tumor incidences (96 and 88%, respectively), compared with TC (85%) and AX (66%) Approx. a 7-fold increase in tyrosinase and 10-fold decrease in antioxidant levels were normalized by AXDE and AXME, in contrast to only ~1.4–2.2-fold by AX and TC, respectively An appearance of 72 and 58 ng/mL of retinol in the serum of respective AXE-treated (AXDE and AXME) and AX-treated animals, respectively, was screened AXEs had interestingly better anti-cancer potential than AX and TC	Antioxidant, radical scavenging, anti-inflammatory, and anti-cancer activity	2013	[171]
	Haematococcus pluvialis	Astaxanthin tablets and fish collagen hydrolysate tablets	Combination of dietary astaxanthin and collagen hydrolysate as anti-aging metabolites on moderately photoaged skin (in vivo)	A total of 44 healthy aged subjects were treated with astaxanthin (2 mg/day) combined with collagen hydrolysate (3 g/day) or placebos for 12 weeks Elasticity and hydration properties of facial skin, expression of procollagen type I, fibrillin I, and MMPs 1 and 12 as well as UV-induced DNA damage in artificially UV-irradiated buttock skin before and after treatment, were thoroughly examined	The supplement group showed notable improvement in skin elasticity and TEWL in photoaged facial skin after 12 weeks, compared with the placebo group In contrast to the placebo group, in the treated group the expression of procollagen type I and fibrillin I increased, while MMPs 1 and 12 expression decreased No significant difference in the UV-induced DNA damage was recorded between groups	Improved elasticity and barrier integrity in photoaged human skin	2014	[172]
	Haematococcus pluvialis	Astaxanthin	Study on the effects of astaxanthin on the semen quality of diabetes mellitus (DM)-suffering KKAy mice (in vivo)	A total of 60 DM KKAy mice with similar body weights and initial blood glucose and serum lipid levels were assigned to four groups, one control (received the same volumes of distilled water) and three astaxanthin treatments (10, 50, or 100 mg/kg astaxanthin, twice daily), where all mice received the same high-fat diet Biochemical, testis quality, and sperm quality assessment, were also conducted	Oral astaxanthin decreased fasting blood glucose of DM mice and serum lipid levels and improved sperm quality Serum total cholesterol, LDL cholesterol, insulin, and NO levels decrease in their testis were also displayed Astaxanthin also improved the HDL cholesterol and SOD levels in DM mice testis Serum IL-11, TNF-α, and interferon-γ (INF-γ) levels were positively impacted	Impaired semen quality improvement Effective impact on serum cytokines Potential application as a promising adjuvant drug for infertility induced by DM onset	2020	[173]
	Halimeda opuntia (Linnaeus) Lamoroux green seaweed	Total carotenoid content	Evaluation on the preliminary screening of the antioxidant and cytotoxic potential of this green seaweed (in vitro)	Total phenolic content (TPC) was assessed by Folin–Ciocalteu Total flavonoid content (TFC) was determined by the aluminum chloride colorimetric method The total antioxidant capacity (TAC) was measured by the DPPH assay (200–1000 μg/m) The cytotoxic activity was evaluated against the estrogen receptor-positive human breast adenocarcinoma (MCF-7), estrogen-negative human breast adenocarcinoma (MDA-MB-231), human colorectal adenocarcinoma (HT-29), human hepatocellular carcinoma (HepG2), and mouse embryonic fibroblast (3T3) by using the MTT assay	The TPC yielded a result of 55.04 ± 0.98 mg gallic acid equivalent (GAE)/g of extract, while the TFC was 40.02 ± 0.02 quercetin equivalents (QE)/g of extract H. opuntia had the highest DPPH reduction of 63.61%, and TAC was 57.36 ± 0.004 mg ascorbic acid equivalent (AAE)/g extract at concentration of 1.0 mg/mL Total lipids in this green seaweed species were 1.60 ± 0.002%, total carotenoids were 115.57 ± 0.98 μg/g, while chlorophyll α and β were 148.73 ± 2.60 and 290.83 ± 9.46 μg/g, respectively The methanolic extract was highly cytotoxic to MCF-7 cells with a half-maximal inhibitory concentration (IC50) of 25.14 ± 1.02 g/mL and slightly less to 3T3 cells (IC50 of 65.23 ± 0.25 μg/mL)	Potential role as a natural cancer treatment Anti-cancer, anti-proliferative, cytotoxic, radical scavenging, and antioxidant activity	2022	[174]
	Sargassum hemiphyllum (brown seaweed)	Fucoidan and Fucoxanthin	Investigation on the feasibility of the synergistic effect of low molecular fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic intervention against non-alcoholic fatty liver disease (NAFLD) (in vivo)	The inhibitory impact of the LMF-HSFx or placebo capsules was evaluated on 42 NAFLD patients (24 weeks) and in a high-fat diet (HFD) mouse model and HepaRGTM Subjects took three capsules of LMF-HSFx (275 mg LMF and 275 mg HSFx per capsule), twice per day in the treatment group The placebo group received (three capsules of 550 mg/capsule cellulose powder)	LMF-HSFx decreases the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose, and HbA1c in NAFLD patients Regarding the lipid metabolism, the LMF-HSFx capsule reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression A liver fibrosis reduction in NAFLD patients was recorded as well Pro-inflammatory cytokines IL-6 and INF-γ are reduced in LMF-HSFx group patients Moreover, in HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis while regulating systemic inflammatory response index-peroxisome proliferator-activated receptor γ coactivator 1 (SIRI-PGC-1) pathway Modulation of the leptin/adiponectin axis in adipocytes and hepatocytes, regulation of lipid and glycogen metabolism, and reduction in insulin resistance against NAFLD	Efficacy towards NAFLD patients, liver fibrosis reduction (anti-fibrotic), amelioration of hepatic steatosis qualities	2021	[175]
	Marine algae-derived carotenoid	Fucoxanthin	Evaluation of fucoxanthin’s attenuative profile towards the behavior deficits and neuroinflammatory response in 1-methyl-4- phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) in mice (in vivo)	C57BL/6 mice received 30 mg/kg of MPTP (intraperitoneal (i.p.)) every day for 5 consecutive days to establish PD; subsequently, the everyday fucoxanthin treatment was intended for 7 days	The i.p. injection of MPTP concluded in impaired motor function, reduced dopamine and dopaminergic neuronal loss, tyrosine hydrolase (TH) reduction, as well as microglial activation-mediated neuroinflammation Fucoxanthin ameliorated α-synuclein abnormal accumulation and motor impairment in an MPTP-initiated chronic PD mouse model of use Fucoxanthin reversed the MPTP-mediated decline of dopamine neuron, TH, and microglial activation in the nigra pars compacta (SNpc) region by suppressing oxidative stress, gliosis, and neuroinflammation The western blot analysis showed that fucoxanthin suppressed the expression of pro-inflammatory cytokines by the MPTP treatment	Anti-inflammatory, neuroprotective, antioxidant, and anti-proliferative activity Beneficial remedy towards PD	2020	[176]
	Seaweed	Fucoxanthin	Investigation upon the seaweed fucoxanthin supplementation and its anti-obesity effect in mildly obese Japanese subjects (in vivo)	The effect of fucoxanthin (1 or 3 mg daily) was examined Capsules with fucoxanthin or placebo ones were administered for 4 weeks to male and female Japanese adults (BMI > 25 kg/m2) Before and after treatment, the body weight, composition, abdominal fat area, and circumferences of the neck, arm, and thigh were also examined	A reduction in the relative ratio after versus before treatment body weight, BMI, and visceral fat area in the 3 mg/day fucoxanthin group compared with the placebo one Relative values of the total fat mass, subcutaneous fat area, waist, and right thigh circumference were also notably reduced in the 1 mg/day fucoxanthin group than the placebo one A significant reduction in the absolute right thigh circumference was demonstrated in the 1 mg/day fucoxanthin group No abnormalities of blood pressure, pulse rate, blood parameters, and urine analysis parameters were recorded	Anti-obesity impact—Fucoxanthin may be able to improve a moderate overweight state in both males and females	2017	[177]
	Sargassum glaucescens (brown seaweed algae extract)	Fucoxanthin	Examination on the oral supplementation of fucoxanthin-rich brown algae extract upon the amelioration of cisplatin-induced testicular damage in hamsters (in vitro and in vivo)	By extracting the powder of S. glaucescens, fucoxanthin-rich brown algae extract (FXE) was obtained FXE effects in LPS-induced inflammation in RAW264.7 cells and its effects against cisplatin (CP)-induced reproductive damage in hamsters were studied on 80 male Syrian hamsters injected with and without CP and daily oral gavage with fucoxanthin (5 days) Cell viability (MTT), in vitro ROS and mitochondrial membrane potential analysis, oxidative stress markers (SOD, CAT, NO, GSH-Px, and malondialdehyde (MDA) related levels), testosterone, and α-glucosidase were assessed	Treatment with FXE reduced the level of ROS and MDA in RAW264.7 cells and the rat’s testis (cell viability) Protective effects on mitochondrial membrane potential were recorded The testosterone level was also improved along with the α-glucosidase activity The sperm count additionally increased by FXE treatment in contrast to sperm abnormality that was notably reduced Through histopathological analysis, FXE notably improved the seminiferous tubules morphology	Antioxidant and radical scavenging activity Alternative treatment of testicular or spermatogenitc damage	2020	[178]
	Chlorella sp.	β-carotene, lutein, and zeaxanthin	In vivo-in vitro study in mouse Leydig cells and MA cells treated with hydrogen peroxide (H2O2) to examine the ability of astaxanthin to rescue testosterone production under oxidation	MA-10 cells were pretreated with astaxanthin for 1 h, 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP), 22(R)-hydroxycholesterol (22R-OHC), or pregnenolone and co-treated with H2O2 for 3 more hours Same procedure to Leydig cells	Astaxanthin protected steroidogenesis against oxidative stress Antioxidant ability against H2O2	Antioxidant supplement Steroid-protective	2015	[179]
	Chlorella vulgaris	β-carotene, lutein, and zeaxanthin	In vivo study, in 11 healthy men for 14 days	Plasma concentrations of the three carotenoids were measured Pharmacokinetic metrics were held	All carotenoid concentrations were increased β-carotene had higher bioavailability of zeaxanthin and lower than lutein	Use of Chlorella vulgaris as an antioxidant carotenoid source for skin and eyes	2021	[180]
Bacteria	Gordonia Hongkongensis (EUFUS-Z928) (Isolated from the octocoral Eunicea fusca)	β-carotene	Establishment of carotenoid production and antioxidant capacity of this bacterium (in vitro)	Inoculum, carbon and nitrogen source, NaCl concentration, pH, incubation time, temperature, and stirring speed were measured (Plackett–Burman design) Screening of actinomycetota for its bioactive properties and absorbance of the pigmented crude extract by the UV-visible spectrophotometry, 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and DPPH scavenging action were evaluated LC–MS was also utilized	Results demonstrated a substantial increase in absorbance (0.091 to 0.32), DPPH (27.60% to 84.61%), and ABTS radical scavenging capacity (17.39 to 79.77%), compared with the isolation medium Six C40 and C46 carotenoids, red–orange pigments with antioxidant capacity, were identified and owned great inhibitory ability These carotenoids were namely 3-hydroxy-β,φ-carotene (limited ability as vitamin A precursor), phoeniconone, 3,3′-dihydroxyisorenieratene, 7,8-dihydroparasiloxanthin, 4,4′-dihydroxydiatoxanthin, and 3-hydroxy-β,β-caroten-3′-one	Potential use as additives for cosmetic and cosmeceutical applications of the extracts Antioxidant and inhibitory ability Free radical scavenging ability	2024	[51]
	Five cyanobacteria strains: Alkaliema aff. pantanalense LEGE15481, Cyanobium gracile LEGE12431, Nodosilinea (Leptolyngbya) antarctica LEGE13457, Cuspidothric issatschenkoi LEGE03282, and Leptolyngbya-like sp. LEGE13412	All-trans- β-carotene, zeaxanthin, echinenone, and lutein	Investigation on the biotechnological potential in the treatment of psoriasis of these five cyanobacteria extracts (in vitro)	Different extracts were examined by pigment profile using HPLC-photo diode array (-PDA) Their antioxidant potential was assessed against the superoxide anion radical Their anti-inflammatory and anti-proliferative potential was assessed in vitro by RAW 264.7 and the human HaCaT cell lines Phytochemical analysis and the effect on keratinocyte proliferation were also experimentally held	Terrestrial and freshwater strains had the highest carotenoid content (33.193–63.926 μg/g dry extract) All-trans-β-carotene, zeaxanthin, echinenone, and lutein were the most abundant carotenoids Acetone was the most effective solvent for pigment extraction, as such pigments presented the lowest IC50 values (0.29–0.38 mg dry extract/mL), concerning O2·− radical scavenging An anti-inflammatory potential was revealed for A. pantanalense LEGE15481, N. antarctica LEGE13457, and Leptolyngbya-like sp. LEGE13412, which reduced the nitric oxide (NO) in RAW 264.7 at about 25% All extracts except for A. pantanalense LEGE15481 demonstrated reduced keratinocyte proliferation and selective toxicity	Antioxidant, anti-inflammatory, and anti-proliferative potential for the topical treatment of psoriasis N. antarctica LEGE13457 and Leptolyngbya-like sp. LEGE13412 are promising for further exploitation	2020	[181]
	Cyanobium sp. (LEGE06113)	β-carotene, zeaxanthin, echinenone, and lutein	Examination of frozen-dried biomass of this cyanobacteria species for their bioactive potential (in vitro)	By frozen-dried biomass of this cyanobacteria, organic and aqueous pigment-rich extracts were obtained via classic extraction with four solvents: acetone (A), water (W), ethyl acetate (EA), and ethanol (E) For increasing extraction efficacy, the extraction was performed using W after an organic extraction (A–W, E–W, EA–W) and acetone after an aqueous extraction (W–A) Extraction yield and identification of carotenoids was held The bioactive potential of the Cyanobium sp. extracts was assessed for its antioxidant (ABTS, NI, and O2·−), anti-inflammatory COX inhibition, and cytotoxicity ability (HepG2 cell lines)	W–A had the highest antioxidant capacity and higher carotenoid content, while E–W had the highest content in phycobiliproteins and great antioxidant capacity 100 μgE/mL of the E–W extract exhibited an inhibitory potential against COX-1 and COX-2 inflammation-related enzymes In terms of cytotoxic capacity, E, W, A–W, E–W, and EA–W had no cytotoxic effects in concentrations up to 750 μgE/mL	Antioxidant, anti-inflammatory, and no cytotoxicity Valorization of this pigment-rich extract potential for biotechnological applications	2020	[182]
	Three different cyanobacteria: Pseudanabaena sp., Spirulina sp., and Lyngbya sp.	β-carotene (less amounts of Myxoxanthophyll, zeaxanthin, canthaxanthin, and α-carotene	Investigation of the antioxidant, anti-nephrolithe, and in vitro digestibility activity of three different cyanobacterial pigment extracts	Phycobiliprotein-containing water and carotenoid-containing methanolic extracts were selected Water and methanolic extracts were characterized as well The antioxidant activity (total phenolic content, total antioxidant activity, and DPPH), iso-bolographic analysis, anti-nephrolithic activity, in vitro digestibility, and calcium oxalate crystallization assay were conducted	The best half-maximal effective concentration (EC50) values for DPPH scavenging were revealed in Lyngbya water (LW, 18.78 ± 1.57 mg/mg DPPH) and Lyngbya methanol (LM, 59.56 ± 37.38 mg/mg DPPH) extracts Iso-bolographic analysis showed that most extract combinations were antagonistic, but the LM-Spirulina methanol (SM) one (1:1) had the highest synergistic rate (86.65%) In vitro digestion studies demonstrated that DPPH scavenging activity was decreased in all extracts except for the Pseudanabaena methanol (PM) and LM ones after stimulated digestion All extracts were effective in reducing calcium oxalate crystal size (nearly 60–65%) compared with the control PM and Spirulina water (SM) extracts inhibited nucleation and aggregation of calcium oxalate (~60–80%) Carotenoids are not majorly affected by digestion processes, and their antioxidant capacity stems from their assimilation	Antioxidant, anti-nephrolithic activities, and in vitro digestibility efficacy of the extracts	2015	[63]
	Phormidium sp. LEGE05292, Tychonema sp. LEGE07196, Synechocystis salina LEGE06155, and Cyanobium sp. LEGE07175	β-carotene, zeaxanthin, echinenone, canthaxanthin, and lutein	Examination of filamentous and picoplanktonic cyanobacteria for cosmetics, for improving skin structure and preserving dermal matrix components (in vitro)	With a focus on the anti-aging properties, the extracts were analyzed for their pigment profile, phenolic content, antioxidant potential, cytotoxicity against HaCaT cells, fibroblasts (3T3L2), endothelial cells (hCMEC/D3), and capacity to inhibit hyaluronidase (HAase) Phytochemical analysis, antioxidant activity assessment, and cytotoxicity assay were ultimately conducted	The TC content ranged from 118.69 to 383.89 μg/g of dry biomass, and the TPC from 1.07 to 2.45 mg GAE/g Identified carotenoids were β-carotene, zeaxanthin, echinenone, canthaxanthin, and lutein, with zeaxanthin (49.82 μg/g) and lutein (79.08 μg/g) being mostly present The highest antioxidant potential was found for Phormidium sp. LEGE05292 and Tychonema sp. LEGE07196 for superoxide anion radical O2·− scavenging (IC50 of 822.70 and 924 μg/mL, respectively) As for HAase inhibition, Tychonema sp. LEGE07196 and Cyanobium sp. LEGE07175 displayed the best IC50 (182.74 and 208.36 μg/g, respectively) Fibroblast proliferation was increased, while hyaluronic acid digestion was inhibited, and low or no toxicity was recorded	Antioxidant and anti-aging potential	2020	[183]
Archaea	Haloterrigena turkmenica	Lycopene, phytoene, and lycopersene, as well as bacterioruberin carotenoids	Identification and antioxidant activity of carotenoids from this archaea species (in vitro)	The carotenoids were extracted with methanol, separated by reverse phase (RP)-HPLC, and identified by mass spectrometry and UV/visible spectra analysis Quantification of carotenoids, analysis of the extracts by RP-HPLC and TLC, and antioxidant capacity were measured	C50 carotenoids were the main pigments, and C30, C40, and C51 were also detected, while seven geometric isomers were discerned for bacterioruberin, monoanhydrobacterioruberin, and for bisanhydro- bacterioruberin Lycopene, phytoene, and lycopersene, were found among the minor carotenoids identified Higher antioxidant power than α-tocopherol, butylhydroxytoluene, and ascorbic acid	Antioxidant activity and cytoprotective effect	2017	[184]
	Natrialba sp. M6 (haloalkaliphilic archaeon)	C50 carotenoid Bacterioruberin	Evaluation of the in vitro dual anti-cancer and antiviral activity of carotenoids produced from this archaea species (in vitro)	The isolated carotenoids were identified by Raman spectroscopy, GC–MS, FT-IR, LC–MS, and NMR Evaluation of the pigment’s compatibility with red blood cells, in vitro anti-cancer efficacy examination of the cytotoxicity on human normal and cancer cell lines, inhibitory potential on MMP-9-dependent cancer and antiviral activity against hepatitis C virus (HCV) RNA and hepatitis B virus (HBV) DNA polymerases viral replication were held Hemolytic behavior, in vitro apoptotic effect, and cytotoxicity evaluation against human virus peripheral blood mononuclear cells (PBMCs) were also conducted	C50 carotenoid bacterioruberin was the predominant compound In vitro results implied that the caspase-mediated apoptotic anti-cancer impact of this pigment and its inhibitory ability against MMP-9 were higher than those of 5-fluoracil This pigment repressed 50% of MMP-9 activity at less than 0.5 μg/mL Higher elimination capacity of HCV and HBV in infected PBMCs than currently used drugs, due to its inhibitory potential against HCV RNA and HBV DNA polymerases Therefore, HCV and HBV replication suppression was exhibited, as apparent by the high viral clearance (%) in the treated cells rather than the ones treated with antiviral drugs	Alternative source of bioactives with anti-cancer and antiviral potential Suppression of MMP-9-mediated cancer progression Inhibition of polymerase-dependent HCV and HBV replication	2020	[46]
	Halophilic Archaea	β-carotene and carotenoids in general	Carotenoids encapsulation into two oil-in-water (O/W) dispersions to increase their use as functional food applications (in vitro)	A nanoemulsion made by high-pressure homogenization and a spontaneously formed microemulsion were conceived Limonene was the dispersed oil phase, and mixtures of Triton X-100/Twen-80 (3:1) were used as emulsifiers and water/glycerol as the continuous aqueous phase Dynamic light scattering (DLS) characterized the structure of the nano- and microemulsions in the presence of carotenoids Radical scavenging ability of encapsulated carotenoids was also examined by electron paramagnetic resonance (EPR) spectroscopy	The particles size of the nanoemulsions was influenced by the emulsifiers’ concentration During storage time, a small increase in the nanoemulsion diameter size was observed due to interactions between encapsulated carotenoids and surfactants mono-layer In the microemulsion, all droplets remained unaltered The loaded dispersions had a higher antioxidant activity than those using β-carotene Using 7.25 mg/mL of carotenoids allowed notably higher radical scavenging ability (>80%) against the Tempol free radical than the microemulsion loaded with 3.62 mg/mL of carotenoids (43%, after 5 min)	Effectiveness of the delivery systems designed to encapsulate and stabilize carotenoids for food or other commercial applications Thermodynamic efficacy of such systems
	Halorubrum tebenquichense	Bacterioruberin	Investigation on the improved stability and biological activity of bacterioruberin in nanovesicles (in vitro)	Bacterioruberin extracted was loaded into liposomes (L-BR and soybean phosphatidylcholine) and archaeosomes (A-BR sn 2,3 ether-linked archaeolipids) Lipid extraction, nanovesicle characterization (size and ζ potential), generalized polarization (GP), fluorescence anisotropy (FA), transmission electron microscopy (TEM), Raman and small-angle X-ray scattering (SAXS), DPPH assay, stability (high temperature), light, pH, storage, release, anti-hemolytic action, cell viability, cellular uptake, anti-inflammatory, and antioxidant action were tested	A-BR (125 nm, −50 mV ζ potential, 9.6 μg BR/lipids) preserved the antioxidant activity of BR in front of light and high temperatures, protected its structure against acidity degradation, avoided its fast release, and retained BR within archaeolipid layers for 2 years (at 4 °C) On the contrary, L-BR (154 nm, −13 mV ζ potential, 6.9 μg BR/lipids) failed to protect and retain BR A-BR inhibited hemolysis induced by ROO* and was captured by J774A.1 cell more than L-BR However, A-RB’s anti-inflammatory (against TNF-α release) and antioxidant (ROS reduction) activity on lipopolysaccharide or H2O2-stimulated J774A.1 cells were comparable to those of L-BR SAXS revealed that archaeosomes mechanically trapped BR, making its partition more stable than in liposomal bilayers, which impaired its intracytoplasmic delivery	A-BR formulations are potent candidates for chronic inflammatory disease confrontation Further exploration in vivo is required	2022	[185]
	Halorubrum sp. BS2	Bacterioruberin and Bisanhydro- bacterioruberin	Characterization and bioprospecting of this strain along with analysis of its carotenoids (in vitro)	A set of extremely halophilic archaeal strains was isolated from seven distinct saline habitats Forty-three strains were selected based on their physiological profile and pigment production Carotenoids of the higher producer were identified by HPLC-diode array and LC–MS Mainly the antibacterial and antioxidant action was studied	Carotenoid production varied from 0.1 to 3.68 μg/mL Bacterioruberin and bisanhydro-bacterioruberin were the predominant carotenoids Their scavenging activity reached 99% at a concentration of 18 μg/mL, much higher than that of ascorbic acid High antibacterial activity against four human-pathogenic strains and four fish-pathogenic ones was also observed Variations in salinity, agitation rate, temperature, and light intensity influenced growth and carotenoid production	Halophilic archaea species are a potential carotenoid source for carotenoids of high antioxidant and antibacterial action Inhibitory effect against all tested strains Radical scavenging activity	2020	[186]
	Haloferax mediterranei		Effect of different carbon sources on cell growth and carotenoid production and their influence on the antioxidant, anti-glycemic, and anti-lipidemic activities of these archaea extracts (in vitro)	Carotenoid extract composition was characterized by HPLC–MS Antioxidant activity of carotenoid extracts obtained from cell cultures grown under several nutritional conditions was determined by ABTS, DPPH, and ferric reducing ability of plasma (FRAP) assays Antioxidant, hypoglycemic, and anti-lipidemic assays were held The ability of these carotenoid extracts to inhibit α-glucosidase, α-amylase, and lipase enzymes was also assessed	Maximum carotenoid production of 92.2 μg/mL was observed by combining 12.5% of inorganic salts and 2.5% of glucose/starch Higher carbon availability in culture media leads to alterations in extract composition, which become more bioactive Carotenoid extracts obtained from high-carbon availability cell cultures had higher proportions of all-trans bacterioruberin, 5-cis-bacterioruberin, and a double isomeric bacterioruberin, whereas 9-cis-bacterioruberin and 13-cis-bacterioruberin decreased Changing nutritional conditions optimized the production of haloarchaeal carotenoids, and the carotenoid composition altered by modifying carbon source concentration	Antioxidant, anti-lipidemic, and anti-glycemic impact Promising in food nutraceutical and nutricosmetic applications	2022	[65]
	Haloarcula sp. (several strains)	Bacterioruberin, Monoanhydro- bacterioruberin, Bisanhydro- bacterioruberin, 5-cis-26-cis- Bacterioruberin, 9-cis- Bacterioruberin, 13-cis- Bacterioruberin and 9-cis-26-cis- Bacterioruberin and 9 more in less significant amount	Antioxidant potential and biological effect on cell viability of Haloarchaea species by UHPLC-coupled with quadrupole-orbitrap (Q-Orbitrap)-MS/MC (in vitro)	The strains were cultivated and cultured for 10 days at continuous agitation at 120 rpm, 40 °C DNA extraction, amplification of 16S rRNA-encoding gene, TPC and TCC determination, and antioxidant assays (DPPH, ABTS, and FRAP) were also conducted Cholinesterases (ChE) enzyme inhibitory activity, cellular viability MTT assay, stimulation of HaCaT cells, oxidative stress: nitrite concentration assay, and docking assays of carotenoids in ChE enzymes were also tested	Six haloarchaea strains from the extreme environment of the Atacama Desert were identified, namely Halorubrum tebenquichense Te Se-85m, Halorubrum tebenquichense Te Se-86m, Haloarcula sp. TeSe-41, Haloarcula sp. TeSe-51, and Haloarcula sp. TeSe-89 Acetylcholinesterase (AChE) inhibition IC50 was 2.96 ± 0.08, and butyrylcholinesterase (BuChE) inhibition IC50 was 2.39 ± 0.09 μg/mL for the most active strain Halorubrum tebenquichense Te Se-85m Cell viability in the HaCaT cell lines showed a notable decrease at 6 h post stimuli at a concentration of 1000, 500, 250, 125, and 62,5 μg/mL with no difference after 24, 48, and 72 h Although 250 μg/mL increased cell viability, in 15 μg/mL a decrease at 6 and 48 h was observed, while after 24 and 72 h no significant cell stimulation was exhibited Apoptosis was induced by overexpression of caspase 3 (CASP3), by a reduction in pluripotency halting the SPY-box transcription factor 2 (SOX2) and causing tumor eradication	Radical scavenging and antioxidant capacity Decrease in the metabolism of cells with high proliferation rates (anti-cancer and anti-tumor action)	2021	[38,187]

6.3. Vitamin A, Vitaminoids, and Carotenoids of Plant and Herb Origin

Between animal-, plant-sourced, and herb-derived products, the latter engage a bigger part as suppliers of carotenoids. For humans, carotenoids are obtained through their diet, as they cannot produce them de novo and are responsible for the vibrant yellow, orange, red, and green colors of many fruits and vegetables displayed [136]. Firstly, lycopene is found in red fruits like tomatoes and watermelons, but also in pink grapefruits, apricots, papayas, and guavas [123,164]. α-carotene is a significant component in carrots, red pepper, corn, cloudberry, pumpkin, and coleslaw, and concurrently, β-carotene is present in carrots, apricot, citrus, pineapple, papaya, red pepper, red beans, celery, cucumber, lettuce, blueberry, melon, mustard, and numerous other fruits and vegetables, and β-cryptoxanthin is contained in citrus fruit like tangerine and orange but also sweet red pepper, peach, and papaya. Lutein and zeaxanthin, furthermore, are acquired from yellow fruits but also from leafy green–yellow vegetables, broccoli, corn, lettuce, parsley, etc. Lastly, the uncolored carotenoids phytoene and phytofluene are present in tomato, watermelon, papaya, peach, etc. [123,130,164].

The bioactive profile of carotenoids is mostly the same, presenting predominantly antioxidant, anti-inflammatory, and anti-aging properties. Research, however, has already shifted its focus towards displaying both their individual and synergistic effects in conjunction with compounds of the same bioactive group or other active vitaminoids, like vitamin E or K derivatives [130]. Clinical data regarding the significance of vitamin A, vitaminoids, and carotenoids from plants and herbs in nutricosmetics, cosmeceuticals, and cosmetics formulations are depicted in Table 3.

Table 3. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids of plant and herb origin in nutricosmetics, cosmeceuticals, and cosmetics applications.

Plant Source	Type of Plant/Herb	Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results–Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year of Study	References
Fruits and Vegetables	Tomato powder	Phytoene and phytofluene	In vivo study in 22 healthy women for 12 weeks	The female volunteers were given an oral supplement equivalent to phytoene and phytofluene a day for 12 weeks	MED was measured after 6 and 12 weeks, and it was increased by 10% in all panelists; 2/3% of them had an increase of 20% after 12 weeks No increase in skin color was observed Skin quality was improved to 55–95% of women	Anti-inflammatory, antioxidant activity of phytoene, phytofluene Skin photo-protection	2015	[188]
	Tomato-derived lycopene nanostructured lipid carriers (NLC)	Lycopene	In vitro physicochemical and overall characterization of lycopene-loaded NLCs for topical administration	Lycopene was loaded into NLCs with Eumulgrin® SG-orange wax-rice bran oil by high-pressure homogenization. Physicochemical estimation of lycopene’s properties, particle size, ζ potential, entrapment efficiency, X-ray diffractometry, in vitro release study, occlusion test, antioxidant capacity by ABTS and DPPH assays, and stability study were held	The lycopene-loaded NLC had a size of 150–160 nm with a relatively small size distribution A relatively fast release (first 6 h) followed by sustained release (18 h) was observed Occlusive properties of lycopene NLCs increased by increased lycopene 50% lycopene loading had a Trolox equivalent antioxidant capacity value of 36.6 ± 0.4 μM Trolox/mg NLC, higher than that of the NLC base alone (26.6 ± 0.1 μM Trolox/mg) The IC50 antioxidant activity of the 50% lycopene-loaded NLC was 14.1 ± 0.6 mg/mL and lower than that of the formulation without it (17.7 ± 0.4 mg/mL) Particle size and ζ potential of lycopene NLC stored at different temperatures of 4, 30, and 40 °C for 120 days did not change in time	Antioxidant, radical scavenging, and increased stability of lycopene-loaded NLCs	2015	[189]
	Lycopene-rich tomato nutrient complex (TNC)	Lycopene	Investigation on the protection from UVA1-induced (340–400 nm) and UVA-induced (320–400 nm)/UVB-induced (280–320 nm) upregulation of molecular markers by the carotenoid-rich TNC against UVB-induced threshold erythema formation	149 healthy volunteers were divided into two groups and subjected to a 5-week washout phase followed by a 12-week treatment, receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, and 5.6 mg tocopherols from a tomato extract and 4 mg carnosic acid from rosemary extract per day, or placebo from medium-chain triglycerides At the end of each phase, MED, UVB, chromametry biopsies, and blood samples were assessed	No difference was shown in the MED of treated and placebo groups Carotenoid-containing supplement remarkably protected against UVB-induced threshold erythema formation (Δa* after the intervention minus the Δa* after the washout phase) compared with the placebo The intake of the active supplement protected with great efficacy against the UVB-induced upregulation of pro-inflammatory markers IL-6 and TNF-α Carotenoid plasma levels notably increased	Anti-erythema formation and anti-inflammatory-related activity	2019	[190]
	Lycopene capsule and tomato paste	Lycopene	Investigation on the report that orally lycopene reduces immediate, UVB-induced threshold erythema (in vivo)	A comparative 10-week study in 20 subjects, divided into two groups: 10 for capsule—10 for tomato paste intake Blood samples were collected for serum lycopene by HPLC Chromatometer was used to measure the MED dose at 24 h after exposure of the subjects to UVB radiation Evaluations were made at baseline, 4, 8, and 10 weeks Three subjects dropped out after 4 weeks	Serum lycopene demonstrated variability, while notably higher levels for tomato paste after 4 weeks as compared with capsules and significant increases were detected No visual alteration in the MED was observed for both groups Chromatometer measures displayed no difference in the mean of MED at baseline between groups Slight color variation after 10 weeks was observed, with a tendency to be greater for capsule use and no adverse effects Lycopene regular intake was safe for systemic UVB photo-protection No correlation with serum lycopene was detected	Skin photo-protection against UVB-induced erythema	2015	[191]
	Tomato extract, lutein, and lycopene	Lycopene and lutein	Investigation on tomato extract, lutein, and lycopene’s potential in improving endothelial function and attenuating inflammatory NF-κΒ signaling in endothelial cells (in vitro)	A wide number of functional and inflammatory markers were investigated in two different cultured endothelial cell models (EA.hy926 and human umbilical vein endothelial cells (HUVECs), exposed to oleoresin, lutein, and lycopene carotenoids	All carotenoids improved endothelial function, revealed by reduced NO and endothelin release Effective attenuation of the NF-κΒ, decrease in TNF-α-mediated leukocyte adhesion, expression of ICAM-1, vascular cell adhesion molecule 1 (VCAM-1), and nuclear translocation of NF-κΒ and IκΒ ubiquitination All carotenoids were able to inhibit NF-κΒ activation in endothelial cells The oleoresin-lutein combination exerted synergistic effects on preclusion of leukocyte adhesion	Anti-inflammatory and anti-cancer potential	2013	[192]
	Tomato waste extracts	Lycopene and β-carotene	In vitro study to examine the antioxidant ability of five different tomato genotypes in cell growth activity (telomerase positive: HeLa and MCF7 and normal human embryonic lung: MRC-5 cell lines)	Pre-incubation of cells for 24 h at 37 °C in an atmosphere of 5% CO2 Extracts were added to the cells and then incubated for another 48 h	Different carotenoid content depending on the genotype Antioxidant, anti-cancer, and anti-proliferative abilities were observed Low-cost alternative of tomato waste extracts	Antioxidant and anti-cancer ingredient in health-oriented food products Application in nutraceuticals and nutricosmetics Use of agro-industrial waste into bioactive resources	2014	[193]
	Tomato capsules	Lutein and lycopene	In vivo, randomized, double-blinded, placebo-controlled study of 65 healthy people (52 men, 13 women) for a 12-week period, separated by a 2-week washout period Soft-gel lycopene capsules enriched with other TNC derivatives (phytoene, phytofluene, tocopherols) or lutein-containing capsules	Group 1 (n = 15): lycopene-rich soft gel capsules with phytoene, phytofluene, and tocopherols per day Group 2 (n = 14): lutein softgel capsules stabilized by carnosic acid, per day Group 3 (n = 14): placebo softgel capsules contained soybean oil (lycopene arm) Group 4 (n = 14): placebo softgel capsules contained (lutein arm)	Inhibition of UVA1-UVA/B induced expression of HO-1, ICAM-1, and MMP-1 genes that trigger oxidative stress	Antioxidant and radical scavenging capacity	2016	[140]
	Tomato and marine algae-derived products	Phytoene and phytofluene	Presentation of several topical in vivo and in vitro results from human toxicological studies with additional phytoene- and phytofluene-rich liquid extracts from tomato and marine algal sources	A tomato extract in squalene oil (0.75 mg/mL phytoene and phytofluene) and an extract of Dunaliella salina in hydrogenated polydecene oil (1 mg/mL phytoene and phytofluene) were utilized Culture in Dulbecco’s modified eagle medium (DMEM), treatment with fetal calf serum and penicillin/streptomycin, at 37 °C under 5% CO2, 24 h In vitro toxicology and in vivo topical toxicology in humans with a 48 h patch testing and repeat insult patch testing (HRIPT) were held	Lack of irritancy or sensitization reactions The tested sample had no genotoxic potential up to a 1/10 dilution Phytoene and phytofluene-rich extracts are classified as non-irritant, with very good skin compatibility No sensitization or allergic reactions were observed Very good toleration on human skin such products was also demonstrated	All results suggested: Antioxidant, anti-inflammatory, and anti-cancer effect Photo-protective ability Skin compatibility with no irritation, allergic, or sensitization reaction in cosmetic products	2018	[194]
	Carrots (Daucus carota L., cv. Flacoro and Nantejska)	β-carotene, phenolic acids, and flavonoids	Organic certified carrots are richer in health-promoting phenolics (including carotenoids) (in vitro) than the conventionally grown ones	Carrot roots gained from seven conventional and thirteen organic farms, characterized by similar agricultural environments (≥1 kg each root), were cut into cubes and freeze-dried at −40 °C under 10 Pa pressure, then ground in a laboratory mill and stored at −80 °C Phenolic compounds and carotenoid determination were further conducted	The samples contained 4.29 ± 0.83 mg/100 g fresh weight (f.w.) β-carotene and 9.09 ± 2.97 mg/100 g f.w. polyphenols with 4.44 ± 1.42 mg/100 g f.w. phenolic acids and 4.65 ± 1.96 mg/100 g f.w. flavonoids (on average) Slightly higher carotenoid levels were shown in conventionally cultivated roots (4.67 ± 0.88 mg/100 g f.w.) versus the organic (4.08 ± 0.74 mg/100 g f.w.) cultivars A higher polyphenol concentration in organically grown roots (9.33 ± 3.17 mg/100 g f.w.) versus the conventionally grown ones (8.64 ± 2.58 mg/100 g f.w.) and Nantejska (9.60 ± 2.87 mg/100 g f.w.) versus Flacoro ones (8.46 ± 3.03 mg/100 g f.w.) was found	Promising antioxidant potential of these carotenoids	2022	[41]
	Palmyra (Borassus flabellifer) and (soapberry (Sapindus mukorossi) and aloe vera and extraction by virgin coconut oil)	β-carotene and its isomers	Evaluation of the antioxidant capacity of a facial cream, solid soap, and liquid soap made with the carotenoid extract of the palmyra fruit pulp (in vitro)	Carotenoids in the palmyra fruit were extracted in virgin coconut oil and used for facial cream and solid and liquid soap creation Similar cosmetics were made with coconut oil (no carotenoid content), and a commercial cream and soap were used Palmyra fruit pulp was extracted by squeezing fruits with 50 mL distilled water Characterization of the pigment oil by UV/Vis, determination of β-carotene, and evaluation of the DPPH antioxidant activity were performed	UV/Vis characterization of the pigment oil extract revealed the presence of β-carotenoids by green UV fluorescence (365 nm) Cosmetic products made with the palmyra fruit pulp extract had a notably higher antioxidant activity than the control or commercial ones 1 mL of 1 mg/mL of pigment cream, solid soap, and liquid soap showed 41.58% (±2.40), 66.37% (±2.70), and 60.52% (±0.09) inhibitory activity, respectively However, as compared with the antioxidant activity of standard ascorbic acid, pigment activity was low	Great antioxidant and radical scavenging activity Potent utilization as natural antioxidant, non-toxic and healthy products	2023	[47]
	Red guava (Psidium guajava L.)	All-trans-β-carotene, all-trans-lycopene, and their isomers	Evaluation of a lycopene-rich extract from red guava for its antioxidant and anti-inflammatory profile by its activity in reducing suggestive hallmarks of acute inflammatory response in mice (in vivo)	Lycopene extract (LEG) and lycopene purified from guava (LPG) were assessed for their anti-inflammatory action in paw edema induced by carrageenan/dextran (48/80), histamine, and PGE2 A peritonitis model was used The effect on the expression of iNOS, COX-2, and NF-κB was evaluated Leukocyte migration, MPO action, and GSH levels were also assessed	Oral and i.p. administration of LEG and LPG inhibited inflammation caused by carrageenean LPG of 12.5 mg/kg p.o. notably inhibited edema formation, which was induced by several phlogistic agents and immunostaining for iNOS, COX-2, and NF-κΒ Leukocytes migration in paw tissue and peritoneal cavity decreased MPO concentration decreased, and GSH in turn increased Beneficial effect on acute inflammation and oxidative stress protection Inhibition of genes involved in thrombo-inflammatory responses was observed	Anti-inflammatory and antioxidant potential	2017	[195]
	Pink guava (Psidium guajava L. Cv. ‘Criolla’)	All-trans-β-carotene, all-trans-lycopene, and 15-cis-lycopene	Assessment of the carotenoid profile, antioxidant potential, and chromoplasts of pink guava during fruit ripening (in vitro)	Two days after being harvested, the fruits were prepared for microscopy and physicochemical analysis of fruit at ripening stages RG1, RG2, RG3, and RG4 Total soluble solids and moisture content assessment, extraction and identification of carotenoids by HPLC-DAD and LC–MS, antioxidant capacity evaluation, light, and TEM usage were also performed	Seventeen carotenoids were identified, and alterations in their profile during fruit ripening were observed All-trans-β-carotene, all-trans-lycopene, and 15-cis-lycopene were present in all RG stages All-trans-lycopene was the main carotenoid traced from 63 to 92% of the total carotenoids All-trans-lycopene was responsible for the lipophilic antioxidant capacity as exhibited by spectrophotometry used All-trans-β-carotene and all-trans-lycopene were detected by the formation of large crystalline chromoplasts	Potential of pink guava being considered as a functional food High antioxidant value	2017	[43]
	Sweet Orange	β-carotene	In vivo study in β-carotene-modified orange fed to Caenorhabditis elegans to improve the antioxidant ability of the fruit	Group 1: Caenorhabditis elegans fed to the carotenoid alone Group 2: Worm fed with the unmodified orange Group 3: Worm fed with enriched orange	Modified orange had 26 times more β-carotene Group 3 had 71.67% survival rate under oxidative stress compared with 52% of the other two groups Enriched pulp had a better antioxidant action because of the synergistic effect of β-carotene with the other antioxidants	Antioxidant and anti-inflammatory capacity	2014	[196]
	Red bell pepper extract (RBPE) (Capsicum annum L.)	β-carotene, β-cryptoxanthin, and capsanthin	Investigation in the nanoencapsulation efficiency of red bell pepper carotenoids and their application as natural food pigments or colors (in vitro)	RBPE was encapsulated by four different agents: calcium caseinate (ECC), bovine gelatin (EBG), and whey proteins isolate (EWPI) and concentrate (EWPC) to find the most effective coating and water dispersibility enabling material Formulations were obtained by O/W emulsification, followed by freeze-drying Samples were characterized for their encapsulation efficacy, HPLC, FT-IR, DLS, atomic force microscopy (AFM), thermogravimetric analysis (TGA), dispersion stability, and CIElab color	Nanoemulsions presented carotenoid encapsulation efficacy of 54.0% (ECC), 57.6% (EWPI), 56.6% (EWPC), and 64.0% (EBG) Recovered carotenoids from nanoformulations had a similarity to the RBPE, indicating the efficacy of encapsulation Average particle sizes~109 nm (ECC), 71 nm (EWPI), 64 nm (EWC), and 173 nm (EBG) were found AFM revealed that all samples were dispersed in water (8 mg/mL) and presented an intense color and sedimentation stability for 48 h In TGA analysis, all samples had a similar thermal behavior and lower decomposition speed than RBPE, implying an improved thermal stability All formulations effectively increased the carotenoid dispersibility in water, presenting their potential application as natural food pigments	Potential application as natural food pigments or colors Potential increase of shelf-life in their application in food matrices	2022	[197]
	Avocado (Persea americana)	Mostly the xanthophyll lutein and then zeaxanthin	Examination on the effect of systemic avocado consumption on cognitive function among adults with overweight complications and obesity and retinal lutein accumulation (in vivo)	A total of 84 adults (25–45 years, 31 males/53 females) were divided into a treatment group (n = 47) receiving a 12-week daily meal with fresh Hass avocado and a control (n = 37) receiving an isocaloric meal Serum lutein and macular pigment optical density (MPOD) were utilized Attention and inhibition were assessed via the Flanker, Oddball, and Nogo tasks with accompanying electroencephalographic (EEG) assessments	The treatment group exhibited notable improvement in serum lutein and accuracy There were no associations, however, between performance and changes in the lutein status or neuroelectric variables No significant alterations in the MPOD were observed, but notable ones were presented during the attentional inhibition task Cognitive benefits were independent of changes in lutein concentration Diet improvements have the potential to improve cognitive function	Improved performance in attentional inhibition Increase in serum lutein levels associated with improved cognitive control	2020	[198,199]
	Avocado (Persea americana) cv ‘Hass’	β-carotene, all-trans-lutein, all-trans-lutein-5,6-Epoxide, all-trans- violaxanthin, all-trans-Neochrome, and Chrysanthemaxanthin	Evaluation on the effect of the ripeness stage of Hass avocado on the profile and content of lipophilic and hydrophilic phytochemicals and their in vitro cytotoxic activity	Quantitative and qualitative analysis of phytochemicals was conducted in four ripeness stages by GC- and LC–MS Avocados were obtained, sanitized with chlorinated water (200 ppm) for 2 min, and dried at 25 °C for 1 h A-60 fruit lot was chosen and ripened for 14 days at 15 °C, RS1, 2, 3, and 4 (15-fruit lot each), at days 0, 4, 8, and 12 Analysis of phenolics, carotenoids, tocopherols, and phytosterols was conducted The cytotoxic activity of the methanolic avocado extracts was measured against RAW264.7 and HeLa cells	Phenolics, carotenoids, tocopherols, and phytosterols increased during the ripening stage Decrease of individual phytochemicals β-carotene was found at 0.9 to 0.4 mg/100 g d.w., while a decrease in the protocatechuic acid (0.36 to 0.03 mg/100 g d.w.), δ-tocopherol, and quercetin was traced At the end of the ripening stage, lutein at 0.5 mg/100 g was recorded The ripening stage had a dose-dependent effect, hence, it influenced the concentration of specific compounds in each group of phytochemicals, as well as the in vitro cytotoxic activity Extracts from RS1 and RS2 were the most effective against HeLa and RAW264.7 cells	Mexican ‘Hass’ avocados have similar phytochemical profiles during ripening Cytotoxic, anti-proliferative, and antioxidant potential of the avocado extracts	2020	[198,200]
	Avocado (Persea americana)	Lutein, α-carotene, β-carotene, and retinol	Evaluation of a moderate-fat diet with one avocado/day on whether it increased plasma antioxidants and decreased small and dense LDLs (sdLDLs), susceptible to in vivo oxidation and linked to increased risk of CVDs in adults with overweight and obesity	This trial was conducted with 45 male and female subjects, aged 21–70 years, overweight or obese and with high LDL 3 cholesterol-lowering diets were provided for 5 weeks, randomly: a lower-fat (LF) diet (24% calories from fat-7% saturated fatty acids (SFAs), 11% MUFAs, and 6% poly-unsaturated fatty acids (PUFAs)) and two moderate-fat (MF) diets (34% calories from fat-6% SFAs, 17% MUFAs, and 9% PUFAs): the avocado diet (AV) included one Hass avocado (~136 g/day), and the MF diet utilized oleic acid (OA) oils to match the fatty acid profile of 1 avocado	Compared with the baseline, the AV diet notably decreased circulating oxidized LDLs (−7.0 U/L, −8.8%), and both changes differentiated remarkably after the MF and LF diets The alteration in the oxidized LDLs caused by AV was correlated with number changes in sdLDLs (decreasing) but not large, buoyant LDLs The high-carbohydrate LF diet did not increase oxidized LDLs, although increasing sdLDLs An increase in fruit, vegetables, and whole grains in the diet may protect one from atherogenic lipoprotein oxidation	Antioxidant and anti-atherogenic impact against oxidized LDLs Potential inhibitory effect towards CVDs	2020	[198,201]
	Field Pumpkin (Cucurbita pepo L. (CpL)	Lycopene, b-carotene, and lutein	In vitro study in human keratinocyte cell line (HaCaT) affected by ROS In vivo, randomized, double-blind, placebo-controlled study on healthy women (n = 40, age 35–55) with visible wrinkles and skin dryness for 4 weeks	In vitro: ROS production by H2O2 and UVB radiation measurement CpL was administered in several doses to examine its bioactivity In vivo: Group 1’s skin explants were treated with CpL emulgel twice/day for 4 weeks to evaluate its effect on epidermal hydration, collagen production, and wrinkle reduction Group 2 was administered placebo as control	In vitro: CpL reduced ROS in the cells and protected against UVB; hydration factor and ceramide synthases were increased In vivo: CpL increased hydration on the skin, TEWL and wrinkles were minimized, and collagen production was enhanced	Photo-protective and Anti-aging Anti-wrinkle and hydrating ability of CpL on its use in cosmetics	2024	[42]
	Sweet Potato (Ipomoea batatas (L.) Lam) TNG66	β-carotene, violaxanthin, lutein, zeaxanthin, α-carotene, and β-cryptoxanthin and their isomers	Investigation on the inhibition of breast cancer cells and tumors in mice by a prepared carotenoid extract from sweet potato peel integrated in an ideal nanoemulsion (in vitro)	The sweet potato peel was freeze-dried, powdered, and stored at −20 °C Cell culture and animal studies, HPLC, quantification of carotenoids, stability test, in vitro release test, MTT assay, and determination of caspases 3, 8, and 9 were held The nanoemulsion was prepared by mixing a carotenoid extract, Tween 80, polyethylene glucol (PEG) 400, soybean oil, and deionized water	A total of 10 carotenoids were separated β-carotene was mainly present (638.8 μg/g) 97% nanoemulsion encapsulation efficacy High stability was recorded after 90 days of storage (25 °C) and heating (100 °C, 2 h) The release percentage of TCC under intestinal or gastric conditions: 49.1 and 18.3%, respectively The carotenoid nanoemulsion was more effective than the extract in inhibiting the growth of MCF-7 breast cells Paclitaxel (10 μg/mL), carotenoid nanoemulsion (20 and 10 μg/mL), and extract (20 and 10 μg/mL) reduced tumor volume by 75.4, 65.0, 49.7, 46.7, and 36.5% and weight by 77.4, 56.2, 40.3, 36.1, and 18.7%, respectively Both the carotenoid nanoemulsion (better) and extract decreased the epidermal growth factor (EGF) and vascular EGF (VEGF) serum levels	Anti-cancer and anti-proliferative potential	2022	[202]
	Spinach (Spinachia oleracea)	Lutein	Evaluation of the inhibitory activity of lutein against breast cancer cell growth by suppressing antioxidant and cell survival signals and induction of apoptosis (in vitro)	A molecular mechanism of growth inhibitory potential of lutein in MDA-MB-231 and MCF-7 was depicted Spinach lutein was identified by HPLC and LC–MS Cell viability measured by tetrazolium-1 assay 2′,7′-dichloro-fluorescein assay, measured ROS levels Western blot analysis of protein expression of antioxidant defense markers Lutein-induced apoptosis was measured by 4′,6-diamidino-2-phenylindole staining and caspase 3 activity assays	Purified lutein inhibited the viability of MCF-7 and MDA-MB-231 cells Lutein suppressed protein expression of SOX-2 and HO-1 and its transcription factor Nrf2 Lutein blocked cell survival proteins, NF-κΒ, phosphorylated protein kinase B (PKB), and phosphorylated extracellular-regulated kinase ½ (ERK1/2) Lutein induced apoptosis by elevating caspase-3 and downregulating the expression of B-cell lymphoma protein 2 (Bcl-2) and poly-adenosine diphosphate (ADP) ribose polymerase	Inhibition of human breast cancer cell growth, anti-cancer activity Antioxidant ability	2020	[203]
	Broccoli (Brassica oleracea)	β-carotene and other carotenoid phenolics	Investigation concerning the revalorization of broccoli by-products for cosmetic uses via supercritical fluid extraction (SFE) (in vitro)	By-products were cut, crushed, and dried at 55 °C for 24 h (moisture content 4%) A quantification of the bioactive compounds in the extracts: chlorophylls, carotenoids, phytosterols, TPC, and α-tocopherol The antioxidant ability, cytotoxic evaluation, and cell viability assay were held	SFE extracts were rich in phenolics, chlorophylls, β-carotene, and phytosterols In the bioactivity assays, the SFE extracts had high antioxidant activity and cytoprotective effects SFE extracts were far richer in total bioactive compounds than the conventional ones Antioxidant activity and attenuation of the adverse effect of UVB light on HaCaT cells	Antioxidant and cytoprotective activity Potent cosmeceutical ingredients	2020	[204]
	Waste apricot flesh (WAF)	Phytoene at the highest content of total carotenoids	Investigation on the recovery of carotenoids from WAF for determining their types, content, and potential applications (in vitro)	WAF was washed, freeze-dried, crushed, and refrigerated at 4 °C Extraction of carotenoids by ultrasound-assisted corn oil method, TCC, color assay, UPLC-atmospheric pressure chemical ionization (APCI)-MS/MS analysis, GC–MS for fatty acids analysis, and antioxidant assay were also conducted	The TCC was 42.75 mg/100 g d.w. (60 min time, 41.53 °C, 200 W power, liquid to solid (LS) ratio of 0.10 g/mL) Phytoene had the highest content of in the corn oil extracts (COE), and COE carotenoids degraded at high temperatures The green-red chromaticity axis (a*) of COE fries was 7.31 times higher than corn oil ones The natural carotenoids in the extract notably improved the a* of French fries in frying	Guidance for green recovery of carotenoids and WAF valorization The extract can be used at high temperatures and may have potent applications to reduce the use of industrial colors in food, nutraceuticals, and nutricosmetics	2023	[44]
	Pineapple (Ananas comosus L. Merr.)	α-carotene, β-carotene, lutein, β-cryptoxanthin, lycopene, neoxanthin, violaxanthin, zeaxanthin, and retinol, as well as other constituents like tocopherol and vitamins C and E	Evaluation on the impact of UV-C radiation on the bioactives of pineapple and potent antioxidant valued action (in vitro)	The amounts of vitamins C and E, as well as the aforementioned carotenoids, were analyzed before and after treatment with UVC radiation Moisture content estimation and extraction of carotenoids was also performed	All treated and un-treated pineapple by-products contained β-carotene as the main carotenoid (rind, 2537–3225 μg, and core, 960–994 μg/100 g d.w. Pineapple rind also contained lutein (288–297 μg/100 g d.w.) and α-carotene (89–126 μg/100 g d.w.)	Potent antioxidant and photo-protective activity Potential valorization as pharmaceuticals, cosmetics, and food industries	2015	[205]
	Kernel oils from sour cherry (Prunus cerasus L.)	All-trans-β-carotene (mainly) and total carotenoids, along with fatty acids, total tocochromanols, tocopherols, sterols, and squalene	Investigation on the composition of bioactives in kernel oils recovered from sour cherry by-products and the impact of the cultivar on potential applications (in vitro)	Sour cherries of six cultivars were grown in three independent batches for each cultivar Kernels were frozen (−18 °C) and freeze-dried at −51 ± 1 °C (0.055–0.065 mBar, 48 h), Undamaged kernels were milled and powdered Oil extraction, fatty acid composition by GC or GC–MS, tocopherol, TCC, tocotrienol, sterols, and squalene by UV/Vis or MS were also examined	Emphasis on carotenoids and fatty acids results: Oil yields ranged between 17.5 and 37.1%, with an average of 31.8% The main fatty acids were linoleic (35.59–46.06%), oleic (25.25–45.30%), α-eleostearic (7.43–15.76%), and palmitic (5.06–7.38%), with 94–96% of total traced fatty acids (TFAs) in the oil TCC was between 0.51 and 1.75 mg/100 g oil, with the main carotenoid traced being β-carotene The cultivar has a significant impact on the amount of the bioactive compounds in kernel oil α-Eleostearic acid was found for the first time in sour cherry kernel oils (7–16% of TFAs)	Potent antioxidant and anti-cancer potential	2016	[206]
	Mango (Ataulfo)	β-carotene	Evaluation of mango fruit intake on facial wrinkles and erythema in postmenopausal women (in vivo)	16 weeks of either 85 g or 250 g mango intake in healthy postmenopausal women with Fitzpatrick skin type II or III were evaluated Participants were given frozen mangoes prepackaged into 85 g (0.5 cup) or 250 g (1.5 cups) and consumed one cup four times/week (without heat) Facial photographs (weeks 0, 8, and 16), wrinkles at the lateral canthi, and erythema at the cheeks were qualified by Reflection spectroscopy measured skin carotenoids	Deep wrinkle severity decreased notably in the 85 g group after 16 weeks compared with baseline measures On the contrary, women in the 250 g group had an increase after 16 weeks in average wrinkle severity, average wrinkle length, and fine and emerging wrinkle severity Erythema in the cheeks elevated by 85 g intake 85 g intake reduced wrinkles in fair-skinned postmenopausal women An intake of 250 g had the opposite effect	Skin photo-protection against erythema and facial wrinkle reduction on postmenopausal women with 85 g mango feeding	2020	[207]
	Cantaloupe melon (Cucumis melo L.)	β-carotene, α-carotene, lutein, and zeaxanthin	Evaluation of the vital antioxidant stability enhancement of carotenoid-rich extract (CE) from cantaloupe melon (EPG), nanoencapsulated in gelatin under several storage conditions (in vitro)	In the pulp and melon flour processing, grain flour size was determined, and 50 g of melon flour was utilized CE and EPG stability were evaluated at 25 and 5 °C, with or without light (1600lx) β-carotene–CE concentration was determined by UHPLC and UV-Vis and antioxidant profile by ABTS and DPPH Nanoencapsulation of the CE in gelatin was performed	CE antioxidant potential increased by 57–59% after nanoencapsulation After 60 days, a low retention of β-carotene (0–43.6%) in the CE was observed at 25 °C light (0.00) and dark (10.0%) EPG preserved β-carotene in the dark at 25 °C (99.0%), light (83.1%), and dark (99.0%) at 5 °C, as well as by 68.7–48.3% the antioxidant action EPG enhanced and stabilized the antioxidant potential of carotenoids EPG’s β-carotene antioxidant potential was preserved for 60 days	Antioxidant activity enhancement via nanoencapsulation Health-promising activity	2021	[62]
Cereal/ Grains	Gluten-free (GF) bread from pea flour by Chlorella sorokiniana	All-trans-lutein, all-trans-β-carotene, all-trans- zeaxanthin, and 9-cis-β-carotene along with other lutein, β-carotene, violaxanthin, and zeaxanthin	This study’s main investigation was focused on the partial replacement of pea flour by C. sorokiniana biomass powder to increase the nutritional quality of a GF bread (in vitro)	The bread was enriched with 2.5 g (M2.5) or 5.0 g (M5.0) of microalgae powder/100 g of blended rice flour and corn starch (substitute of pea flour) For the evaluation of the carotenoid profile and fatty acid composition, tests at 220 °C/12 min and 180 °C/15 min were performed Determination of total lipids and fatty acid methyl esters (FAMEs), TCC, bread quality, and sensory evaluation was mainly assessed	Comparing control and M5.0 bread: microalgae increased the protein (67 to 85 mg/g) and lutein content (1.6 to 57.5 μg/g) ω-3 content increased from 5.0% to 6.1% Sensory analysis revealed an M2.5 bread acceptance rate greater than 70% No impact on the texture, specific volume, proteins, ashes, moisture, color, bake loss, and lipids was seen by C. sorokiniana The protein content increased 26% for the M5.0 bread Baking process did not affect β-carotene content High temperature and short baking time: lower lutein degradation The M5.0 bread can be classified as a high-lutein functional food	The generally low nutritional value GF bread was nourished by the microalgae addition Potential for high-quality functional food by the GF bread-microalgae combination	2020	[208]
	Cereal product	High amounts of β-carotene (as well as γ-linolenic acid (GLA))	Examination of the influence of the addition of pre-fermented cereal products with high β-carotene and GLA amounts into the feed of broiler chickens on their immune status and the number of lactic acid bacteria and enterobacteria (in vivo)	The 1-day-old chicks were divided into two groups: control and experimental (n = 50, each) Chicks for the first 10 days were fed a starter multi-ingredient diet (BR-1) Feed mixtures BR-2 and BR-3 were nourished with 10% cereals (GLA and β-carotene) Day 38: 15 chicks were randomly selected, and blood samples were collected Real-time PCR and microbiological analysis were also conducted	A notable increase in the oxidative burst of phagocytes, CD4 and CD8 lymphocytes, and the CD4:CD8 ratio Upregulation of gene IgA expression indicated that β-lymphocytes were triggered at the local gut Caecum: increased mRNA expression for mucin-2 (MUC-2) and insulin-like growth factor 2 (IGF-2) was observed Protection of intestinal mucosa and alterations in microbial composition Vast enterobacteria reduction after receiving GLA and β-carotene	Pre-fermented cereals containing GLA/β-carotene represent a low-cost supplement for broiler diet Beneficial health effect Positive influence on the gut microbiota and immunity of broilers	2018	[209]
Herbs and Spices	Paprika oleoresin (Capsicum annuum)	Mostly capsanthin and capsorubin	Investigation on the protective role of emulsions loaded with paprika oleoresin carotenoids on the liver and serum of healthy rats and the effects of non-ionic surfactants on mice liver (in vivo and in vitro)	Twenty Wistar male rats, 21 weeks old, b.w. 400–600 were used Conventional and nanoemulsion (CE and NE) preparation (5 rats/4 groups) Group I: physiological saline solution (PISA, oral) (control) Group II: surfactant in an aqueous solution (47.4 μg/kg/day, oral) Groups III and IV: oral administration (3 mg/kg/day carotenoids in CE and NE) All groups: twice/day, every 12 h, 5 days Body weight was recorded Antioxidant action was measured by the FRAP assay	CE and NE had particle sizes of 157.9 and 39.2 nm Carotenoid levels: EC50 of 347 for CE and 359 μg/mL for NE CE positive liver effect: increased antioxidant activity—no modifying of transaminases activity Antioxidant activity: inversely proportional to the particle size Transaminase activity was affected by interface and surfactant When the surfactant was administered alone: liver damage and potent mitochondrial injury that causes necrosis	Antioxidant capacity and radical scavenging ability	2020	[210]
	Paprika oleoresin (Capsicum annuum) (zeaxanthin) and marigold flower oleoresin (lutein)	Zeaxanthin and lutein	Assessment of the efficacy and safety of Bend Skincare anti-aging formula on MED in skin (in vivo)	28 subjects with Fitzpatrick skin types I, II, or III took four capsules/day/8 weeks: 1400 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), 120 mg GLA, 5 mg lutein, 2.5 mg zeaxanthin, and 1000 IU of vitamin D3 Back skin of each subject was exposed to UV radiation at baseline, after 4- and 8-week treatment to find the MED Compared results before and after treatment: three t-tests and three linear mixed models	The treatment notably improved UV exposure tolerance: increased MED at 4 and 8 weeks Protection increased with prolonged use of Bend Skincare anti-aging formula: progressively increased MED between 0 and 4 weeks and 4 and 8 weeks Nearly 86% of patients responded to treatment within 4 weeks, and 100% of patients responded by the end of the study 39% mean MED increase at 4 weeks and 84% mean increase in MED at 8 weeks No product-related adverse effects and a few mild side ones appeared	Skin photo-protection and anti-aging potential	2017	[211]
	Coriander (Coriandrum sativum L.)	Total carotenoids and β-carotene	Ten commercial varieties of coriander, grown under similar conditions, were evaluated for their specific carotenoid content, their bio-efficacy, and their stability during drying (in vitro)	β-carotene HPLC–MS analysis on ten commercially cultivated coriander species Pigment stability microwave drying, antioxidant activity of carotenoid extracts (DPPH), DNA degradation, and gel electrophoresis were held	Β-carotene was higher in foliage at mature stage than in seedlings and seeds GS4 Multicut: highest biomass (6.18 ± 0.73 g/plant), TCC (217.50 ± 5.6 mg/100 g d.w.), and β-carotene (73.64 ± 0.3 mg/100 g d.w.) at pre-flowering stage Carotenoids extract: high antioxidant capacity, IC50 of 14.29 ± 1.68 μg/mL Great radical scavenging potential and high DNA protection than standard GA (IC50 = 357.21 ± 4.29) Microwave drying: rapid pigment retention, high β-carotene extractability, compared with oven drying	Antioxidant, radical scavenging (anti-radical), and cytotoxic effects of these carotenoid extracts Potential in the direct use in processed foods and in culinary preparations	2012	[212]
	Parsley (Petroselinum crispum)	Capsanthone (the only carotenoid) and other acids, furanocoumarins, and flavonoids	Investigation on the improvement of nutraceutical value of parsley leaves on field applications of beneficial microorganisms (in vitro)	Streptomyces fulvissimus strain AtB-42 and Trichoderma harzianum strain T22 were utilized as a single or combined (microbial consortium) at transplanting and 2 weeks later After harvesting was conducted, the plants were subjected to metabolomic analysis by GC–MS and LC–MS	Identification of seven polar metabolites AbT-42 alone or combined with T22 induced the collection of xanthotoxol/bergaptol-xanthotoxin/bergapten Microbial consortium: accumulation of capsanthone compared with single treatment No important/relative differences were found for the volatile fraction S. fulvissimus and T. harzianum initiated a metabolic profile change and metabolites with nutraceutical value accumulation	Potent antioxidant, anti-microbial, and anti-cancer chemo-protective activity Potent applications as a nutraceutical	2021	[45]

Table 3. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids of plant and herb origin in nutricosmetics, cosmeceuticals, and cosmetics applications.

Plant Source	Type of Plant/Herb	Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results–Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year of Study	References
Fruits and Vegetables	Tomato powder	Phytoene and phytofluene	In vivo study in 22 healthy women for 12 weeks	The female volunteers were given an oral supplement equivalent to phytoene and phytofluene a day for 12 weeks	MED was measured after 6 and 12 weeks, and it was increased by 10% in all panelists; 2/3% of them had an increase of 20% after 12 weeks No increase in skin color was observed Skin quality was improved to 55–95% of women	Anti-inflammatory, antioxidant activity of phytoene, phytofluene Skin photo-protection	2015	[188]
	Tomato-derived lycopene nanostructured lipid carriers (NLC)	Lycopene	In vitro physicochemical and overall characterization of lycopene-loaded NLCs for topical administration	Lycopene was loaded into NLCs with Eumulgrin® SG-orange wax-rice bran oil by high-pressure homogenization. Physicochemical estimation of lycopene’s properties, particle size, ζ potential, entrapment efficiency, X-ray diffractometry, in vitro release study, occlusion test, antioxidant capacity by ABTS and DPPH assays, and stability study were held	The lycopene-loaded NLC had a size of 150–160 nm with a relatively small size distribution A relatively fast release (first 6 h) followed by sustained release (18 h) was observed Occlusive properties of lycopene NLCs increased by increased lycopene 50% lycopene loading had a Trolox equivalent antioxidant capacity value of 36.6 ± 0.4 μM Trolox/mg NLC, higher than that of the NLC base alone (26.6 ± 0.1 μM Trolox/mg) The IC50 antioxidant activity of the 50% lycopene-loaded NLC was 14.1 ± 0.6 mg/mL and lower than that of the formulation without it (17.7 ± 0.4 mg/mL) Particle size and ζ potential of lycopene NLC stored at different temperatures of 4, 30, and 40 °C for 120 days did not change in time	Antioxidant, radical scavenging, and increased stability of lycopene-loaded NLCs	2015	[189]
	Lycopene-rich tomato nutrient complex (TNC)	Lycopene	Investigation on the protection from UVA1-induced (340–400 nm) and UVA-induced (320–400 nm)/UVB-induced (280–320 nm) upregulation of molecular markers by the carotenoid-rich TNC against UVB-induced threshold erythema formation	149 healthy volunteers were divided into two groups and subjected to a 5-week washout phase followed by a 12-week treatment, receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, and 5.6 mg tocopherols from a tomato extract and 4 mg carnosic acid from rosemary extract per day, or placebo from medium-chain triglycerides At the end of each phase, MED, UVB, chromametry biopsies, and blood samples were assessed	No difference was shown in the MED of treated and placebo groups Carotenoid-containing supplement remarkably protected against UVB-induced threshold erythema formation (Δa* after the intervention minus the Δa* after the washout phase) compared with the placebo The intake of the active supplement protected with great efficacy against the UVB-induced upregulation of pro-inflammatory markers IL-6 and TNF-α Carotenoid plasma levels notably increased	Anti-erythema formation and anti-inflammatory-related activity	2019	[190]
	Lycopene capsule and tomato paste	Lycopene	Investigation on the report that orally lycopene reduces immediate, UVB-induced threshold erythema (in vivo)	A comparative 10-week study in 20 subjects, divided into two groups: 10 for capsule—10 for tomato paste intake Blood samples were collected for serum lycopene by HPLC Chromatometer was used to measure the MED dose at 24 h after exposure of the subjects to UVB radiation Evaluations were made at baseline, 4, 8, and 10 weeks Three subjects dropped out after 4 weeks	Serum lycopene demonstrated variability, while notably higher levels for tomato paste after 4 weeks as compared with capsules and significant increases were detected No visual alteration in the MED was observed for both groups Chromatometer measures displayed no difference in the mean of MED at baseline between groups Slight color variation after 10 weeks was observed, with a tendency to be greater for capsule use and no adverse effects Lycopene regular intake was safe for systemic UVB photo-protection No correlation with serum lycopene was detected	Skin photo-protection against UVB-induced erythema	2015	[191]
	Tomato extract, lutein, and lycopene	Lycopene and lutein	Investigation on tomato extract, lutein, and lycopene’s potential in improving endothelial function and attenuating inflammatory NF-κΒ signaling in endothelial cells (in vitro)	A wide number of functional and inflammatory markers were investigated in two different cultured endothelial cell models (EA.hy926 and human umbilical vein endothelial cells (HUVECs), exposed to oleoresin, lutein, and lycopene carotenoids	All carotenoids improved endothelial function, revealed by reduced NO and endothelin release Effective attenuation of the NF-κΒ, decrease in TNF-α-mediated leukocyte adhesion, expression of ICAM-1, vascular cell adhesion molecule 1 (VCAM-1), and nuclear translocation of NF-κΒ and IκΒ ubiquitination All carotenoids were able to inhibit NF-κΒ activation in endothelial cells The oleoresin-lutein combination exerted synergistic effects on preclusion of leukocyte adhesion	Anti-inflammatory and anti-cancer potential	2013	[192]
	Tomato waste extracts	Lycopene and β-carotene	In vitro study to examine the antioxidant ability of five different tomato genotypes in cell growth activity (telomerase positive: HeLa and MCF7 and normal human embryonic lung: MRC-5 cell lines)	Pre-incubation of cells for 24 h at 37 °C in an atmosphere of 5% CO2 Extracts were added to the cells and then incubated for another 48 h	Different carotenoid content depending on the genotype Antioxidant, anti-cancer, and anti-proliferative abilities were observed Low-cost alternative of tomato waste extracts	Antioxidant and anti-cancer ingredient in health-oriented food products Application in nutraceuticals and nutricosmetics Use of agro-industrial waste into bioactive resources	2014	[193]
	Tomato capsules	Lutein and lycopene	In vivo, randomized, double-blinded, placebo-controlled study of 65 healthy people (52 men, 13 women) for a 12-week period, separated by a 2-week washout period Soft-gel lycopene capsules enriched with other TNC derivatives (phytoene, phytofluene, tocopherols) or lutein-containing capsules	Group 1 (n = 15): lycopene-rich soft gel capsules with phytoene, phytofluene, and tocopherols per day Group 2 (n = 14): lutein softgel capsules stabilized by carnosic acid, per day Group 3 (n = 14): placebo softgel capsules contained soybean oil (lycopene arm) Group 4 (n = 14): placebo softgel capsules contained (lutein arm)	Inhibition of UVA1-UVA/B induced expression of HO-1, ICAM-1, and MMP-1 genes that trigger oxidative stress	Antioxidant and radical scavenging capacity	2016	[140]
	Tomato and marine algae-derived products	Phytoene and phytofluene	Presentation of several topical in vivo and in vitro results from human toxicological studies with additional phytoene- and phytofluene-rich liquid extracts from tomato and marine algal sources	A tomato extract in squalene oil (0.75 mg/mL phytoene and phytofluene) and an extract of Dunaliella salina in hydrogenated polydecene oil (1 mg/mL phytoene and phytofluene) were utilized Culture in Dulbecco’s modified eagle medium (DMEM), treatment with fetal calf serum and penicillin/streptomycin, at 37 °C under 5% CO2, 24 h In vitro toxicology and in vivo topical toxicology in humans with a 48 h patch testing and repeat insult patch testing (HRIPT) were held	Lack of irritancy or sensitization reactions The tested sample had no genotoxic potential up to a 1/10 dilution Phytoene and phytofluene-rich extracts are classified as non-irritant, with very good skin compatibility No sensitization or allergic reactions were observed Very good toleration on human skin such products was also demonstrated	All results suggested: Antioxidant, anti-inflammatory, and anti-cancer effect Photo-protective ability Skin compatibility with no irritation, allergic, or sensitization reaction in cosmetic products	2018	[194]
	Carrots (Daucus carota L., cv. Flacoro and Nantejska)	β-carotene, phenolic acids, and flavonoids	Organic certified carrots are richer in health-promoting phenolics (including carotenoids) (in vitro) than the conventionally grown ones	Carrot roots gained from seven conventional and thirteen organic farms, characterized by similar agricultural environments (≥1 kg each root), were cut into cubes and freeze-dried at −40 °C under 10 Pa pressure, then ground in a laboratory mill and stored at −80 °C Phenolic compounds and carotenoid determination were further conducted	The samples contained 4.29 ± 0.83 mg/100 g fresh weight (f.w.) β-carotene and 9.09 ± 2.97 mg/100 g f.w. polyphenols with 4.44 ± 1.42 mg/100 g f.w. phenolic acids and 4.65 ± 1.96 mg/100 g f.w. flavonoids (on average) Slightly higher carotenoid levels were shown in conventionally cultivated roots (4.67 ± 0.88 mg/100 g f.w.) versus the organic (4.08 ± 0.74 mg/100 g f.w.) cultivars A higher polyphenol concentration in organically grown roots (9.33 ± 3.17 mg/100 g f.w.) versus the conventionally grown ones (8.64 ± 2.58 mg/100 g f.w.) and Nantejska (9.60 ± 2.87 mg/100 g f.w.) versus Flacoro ones (8.46 ± 3.03 mg/100 g f.w.) was found	Promising antioxidant potential of these carotenoids	2022	[41]
	Palmyra (Borassus flabellifer) and (soapberry (Sapindus mukorossi) and aloe vera and extraction by virgin coconut oil)	β-carotene and its isomers	Evaluation of the antioxidant capacity of a facial cream, solid soap, and liquid soap made with the carotenoid extract of the palmyra fruit pulp (in vitro)	Carotenoids in the palmyra fruit were extracted in virgin coconut oil and used for facial cream and solid and liquid soap creation Similar cosmetics were made with coconut oil (no carotenoid content), and a commercial cream and soap were used Palmyra fruit pulp was extracted by squeezing fruits with 50 mL distilled water Characterization of the pigment oil by UV/Vis, determination of β-carotene, and evaluation of the DPPH antioxidant activity were performed	UV/Vis characterization of the pigment oil extract revealed the presence of β-carotenoids by green UV fluorescence (365 nm) Cosmetic products made with the palmyra fruit pulp extract had a notably higher antioxidant activity than the control or commercial ones 1 mL of 1 mg/mL of pigment cream, solid soap, and liquid soap showed 41.58% (±2.40), 66.37% (±2.70), and 60.52% (±0.09) inhibitory activity, respectively However, as compared with the antioxidant activity of standard ascorbic acid, pigment activity was low	Great antioxidant and radical scavenging activity Potent utilization as natural antioxidant, non-toxic and healthy products	2023	[47]
	Red guava (Psidium guajava L.)	All-trans-β-carotene, all-trans-lycopene, and their isomers	Evaluation of a lycopene-rich extract from red guava for its antioxidant and anti-inflammatory profile by its activity in reducing suggestive hallmarks of acute inflammatory response in mice (in vivo)	Lycopene extract (LEG) and lycopene purified from guava (LPG) were assessed for their anti-inflammatory action in paw edema induced by carrageenan/dextran (48/80), histamine, and PGE2 A peritonitis model was used The effect on the expression of iNOS, COX-2, and NF-κB was evaluated Leukocyte migration, MPO action, and GSH levels were also assessed	Oral and i.p. administration of LEG and LPG inhibited inflammation caused by carrageenean LPG of 12.5 mg/kg p.o. notably inhibited edema formation, which was induced by several phlogistic agents and immunostaining for iNOS, COX-2, and NF-κΒ Leukocytes migration in paw tissue and peritoneal cavity decreased MPO concentration decreased, and GSH in turn increased Beneficial effect on acute inflammation and oxidative stress protection Inhibition of genes involved in thrombo-inflammatory responses was observed	Anti-inflammatory and antioxidant potential	2017	[195]
	Pink guava (Psidium guajava L. Cv. ‘Criolla’)	All-trans-β-carotene, all-trans-lycopene, and 15-cis-lycopene	Assessment of the carotenoid profile, antioxidant potential, and chromoplasts of pink guava during fruit ripening (in vitro)	Two days after being harvested, the fruits were prepared for microscopy and physicochemical analysis of fruit at ripening stages RG1, RG2, RG3, and RG4 Total soluble solids and moisture content assessment, extraction and identification of carotenoids by HPLC-DAD and LC–MS, antioxidant capacity evaluation, light, and TEM usage were also performed	Seventeen carotenoids were identified, and alterations in their profile during fruit ripening were observed All-trans-β-carotene, all-trans-lycopene, and 15-cis-lycopene were present in all RG stages All-trans-lycopene was the main carotenoid traced from 63 to 92% of the total carotenoids All-trans-lycopene was responsible for the lipophilic antioxidant capacity as exhibited by spectrophotometry used All-trans-β-carotene and all-trans-lycopene were detected by the formation of large crystalline chromoplasts	Potential of pink guava being considered as a functional food High antioxidant value	2017	[43]
	Sweet Orange	β-carotene	In vivo study in β-carotene-modified orange fed to Caenorhabditis elegans to improve the antioxidant ability of the fruit	Group 1: Caenorhabditis elegans fed to the carotenoid alone Group 2: Worm fed with the unmodified orange Group 3: Worm fed with enriched orange	Modified orange had 26 times more β-carotene Group 3 had 71.67% survival rate under oxidative stress compared with 52% of the other two groups Enriched pulp had a better antioxidant action because of the synergistic effect of β-carotene with the other antioxidants	Antioxidant and anti-inflammatory capacity	2014	[196]
	Red bell pepper extract (RBPE) (Capsicum annum L.)	β-carotene, β-cryptoxanthin, and capsanthin	Investigation in the nanoencapsulation efficiency of red bell pepper carotenoids and their application as natural food pigments or colors (in vitro)	RBPE was encapsulated by four different agents: calcium caseinate (ECC), bovine gelatin (EBG), and whey proteins isolate (EWPI) and concentrate (EWPC) to find the most effective coating and water dispersibility enabling material Formulations were obtained by O/W emulsification, followed by freeze-drying Samples were characterized for their encapsulation efficacy, HPLC, FT-IR, DLS, atomic force microscopy (AFM), thermogravimetric analysis (TGA), dispersion stability, and CIElab color	Nanoemulsions presented carotenoid encapsulation efficacy of 54.0% (ECC), 57.6% (EWPI), 56.6% (EWPC), and 64.0% (EBG) Recovered carotenoids from nanoformulations had a similarity to the RBPE, indicating the efficacy of encapsulation Average particle sizes~109 nm (ECC), 71 nm (EWPI), 64 nm (EWC), and 173 nm (EBG) were found AFM revealed that all samples were dispersed in water (8 mg/mL) and presented an intense color and sedimentation stability for 48 h In TGA analysis, all samples had a similar thermal behavior and lower decomposition speed than RBPE, implying an improved thermal stability All formulations effectively increased the carotenoid dispersibility in water, presenting their potential application as natural food pigments	Potential application as natural food pigments or colors Potential increase of shelf-life in their application in food matrices	2022	[197]
	Avocado (Persea americana)	Mostly the xanthophyll lutein and then zeaxanthin	Examination on the effect of systemic avocado consumption on cognitive function among adults with overweight complications and obesity and retinal lutein accumulation (in vivo)	A total of 84 adults (25–45 years, 31 males/53 females) were divided into a treatment group (n = 47) receiving a 12-week daily meal with fresh Hass avocado and a control (n = 37) receiving an isocaloric meal Serum lutein and macular pigment optical density (MPOD) were utilized Attention and inhibition were assessed via the Flanker, Oddball, and Nogo tasks with accompanying electroencephalographic (EEG) assessments	The treatment group exhibited notable improvement in serum lutein and accuracy There were no associations, however, between performance and changes in the lutein status or neuroelectric variables No significant alterations in the MPOD were observed, but notable ones were presented during the attentional inhibition task Cognitive benefits were independent of changes in lutein concentration Diet improvements have the potential to improve cognitive function	Improved performance in attentional inhibition Increase in serum lutein levels associated with improved cognitive control	2020	[198,199]
	Avocado (Persea americana) cv ‘Hass’	β-carotene, all-trans-lutein, all-trans-lutein-5,6-Epoxide, all-trans- violaxanthin, all-trans-Neochrome, and Chrysanthemaxanthin	Evaluation on the effect of the ripeness stage of Hass avocado on the profile and content of lipophilic and hydrophilic phytochemicals and their in vitro cytotoxic activity	Quantitative and qualitative analysis of phytochemicals was conducted in four ripeness stages by GC- and LC–MS Avocados were obtained, sanitized with chlorinated water (200 ppm) for 2 min, and dried at 25 °C for 1 h A-60 fruit lot was chosen and ripened for 14 days at 15 °C, RS1, 2, 3, and 4 (15-fruit lot each), at days 0, 4, 8, and 12 Analysis of phenolics, carotenoids, tocopherols, and phytosterols was conducted The cytotoxic activity of the methanolic avocado extracts was measured against RAW264.7 and HeLa cells	Phenolics, carotenoids, tocopherols, and phytosterols increased during the ripening stage Decrease of individual phytochemicals β-carotene was found at 0.9 to 0.4 mg/100 g d.w., while a decrease in the protocatechuic acid (0.36 to 0.03 mg/100 g d.w.), δ-tocopherol, and quercetin was traced At the end of the ripening stage, lutein at 0.5 mg/100 g was recorded The ripening stage had a dose-dependent effect, hence, it influenced the concentration of specific compounds in each group of phytochemicals, as well as the in vitro cytotoxic activity Extracts from RS1 and RS2 were the most effective against HeLa and RAW264.7 cells	Mexican ‘Hass’ avocados have similar phytochemical profiles during ripening Cytotoxic, anti-proliferative, and antioxidant potential of the avocado extracts	2020	[198,200]
	Avocado (Persea americana)	Lutein, α-carotene, β-carotene, and retinol	Evaluation of a moderate-fat diet with one avocado/day on whether it increased plasma antioxidants and decreased small and dense LDLs (sdLDLs), susceptible to in vivo oxidation and linked to increased risk of CVDs in adults with overweight and obesity	This trial was conducted with 45 male and female subjects, aged 21–70 years, overweight or obese and with high LDL 3 cholesterol-lowering diets were provided for 5 weeks, randomly: a lower-fat (LF) diet (24% calories from fat-7% saturated fatty acids (SFAs), 11% MUFAs, and 6% poly-unsaturated fatty acids (PUFAs)) and two moderate-fat (MF) diets (34% calories from fat-6% SFAs, 17% MUFAs, and 9% PUFAs): the avocado diet (AV) included one Hass avocado (~136 g/day), and the MF diet utilized oleic acid (OA) oils to match the fatty acid profile of 1 avocado	Compared with the baseline, the AV diet notably decreased circulating oxidized LDLs (−7.0 U/L, −8.8%), and both changes differentiated remarkably after the MF and LF diets The alteration in the oxidized LDLs caused by AV was correlated with number changes in sdLDLs (decreasing) but not large, buoyant LDLs The high-carbohydrate LF diet did not increase oxidized LDLs, although increasing sdLDLs An increase in fruit, vegetables, and whole grains in the diet may protect one from atherogenic lipoprotein oxidation	Antioxidant and anti-atherogenic impact against oxidized LDLs Potential inhibitory effect towards CVDs	2020	[198,201]
	Field Pumpkin (Cucurbita pepo L. (CpL)	Lycopene, b-carotene, and lutein	In vitro study in human keratinocyte cell line (HaCaT) affected by ROS In vivo, randomized, double-blind, placebo-controlled study on healthy women (n = 40, age 35–55) with visible wrinkles and skin dryness for 4 weeks	In vitro: ROS production by H2O2 and UVB radiation measurement CpL was administered in several doses to examine its bioactivity In vivo: Group 1’s skin explants were treated with CpL emulgel twice/day for 4 weeks to evaluate its effect on epidermal hydration, collagen production, and wrinkle reduction Group 2 was administered placebo as control	In vitro: CpL reduced ROS in the cells and protected against UVB; hydration factor and ceramide synthases were increased In vivo: CpL increased hydration on the skin, TEWL and wrinkles were minimized, and collagen production was enhanced	Photo-protective and Anti-aging Anti-wrinkle and hydrating ability of CpL on its use in cosmetics	2024	[42]
	Sweet Potato (Ipomoea batatas (L.) Lam) TNG66	β-carotene, violaxanthin, lutein, zeaxanthin, α-carotene, and β-cryptoxanthin and their isomers	Investigation on the inhibition of breast cancer cells and tumors in mice by a prepared carotenoid extract from sweet potato peel integrated in an ideal nanoemulsion (in vitro)	The sweet potato peel was freeze-dried, powdered, and stored at −20 °C Cell culture and animal studies, HPLC, quantification of carotenoids, stability test, in vitro release test, MTT assay, and determination of caspases 3, 8, and 9 were held The nanoemulsion was prepared by mixing a carotenoid extract, Tween 80, polyethylene glucol (PEG) 400, soybean oil, and deionized water	A total of 10 carotenoids were separated β-carotene was mainly present (638.8 μg/g) 97% nanoemulsion encapsulation efficacy High stability was recorded after 90 days of storage (25 °C) and heating (100 °C, 2 h) The release percentage of TCC under intestinal or gastric conditions: 49.1 and 18.3%, respectively The carotenoid nanoemulsion was more effective than the extract in inhibiting the growth of MCF-7 breast cells Paclitaxel (10 μg/mL), carotenoid nanoemulsion (20 and 10 μg/mL), and extract (20 and 10 μg/mL) reduced tumor volume by 75.4, 65.0, 49.7, 46.7, and 36.5% and weight by 77.4, 56.2, 40.3, 36.1, and 18.7%, respectively Both the carotenoid nanoemulsion (better) and extract decreased the epidermal growth factor (EGF) and vascular EGF (VEGF) serum levels	Anti-cancer and anti-proliferative potential	2022	[202]
	Spinach (Spinachia oleracea)	Lutein	Evaluation of the inhibitory activity of lutein against breast cancer cell growth by suppressing antioxidant and cell survival signals and induction of apoptosis (in vitro)	A molecular mechanism of growth inhibitory potential of lutein in MDA-MB-231 and MCF-7 was depicted Spinach lutein was identified by HPLC and LC–MS Cell viability measured by tetrazolium-1 assay 2′,7′-dichloro-fluorescein assay, measured ROS levels Western blot analysis of protein expression of antioxidant defense markers Lutein-induced apoptosis was measured by 4′,6-diamidino-2-phenylindole staining and caspase 3 activity assays	Purified lutein inhibited the viability of MCF-7 and MDA-MB-231 cells Lutein suppressed protein expression of SOX-2 and HO-1 and its transcription factor Nrf2 Lutein blocked cell survival proteins, NF-κΒ, phosphorylated protein kinase B (PKB), and phosphorylated extracellular-regulated kinase ½ (ERK1/2) Lutein induced apoptosis by elevating caspase-3 and downregulating the expression of B-cell lymphoma protein 2 (Bcl-2) and poly-adenosine diphosphate (ADP) ribose polymerase	Inhibition of human breast cancer cell growth, anti-cancer activity Antioxidant ability	2020	[203]
	Broccoli (Brassica oleracea)	β-carotene and other carotenoid phenolics	Investigation concerning the revalorization of broccoli by-products for cosmetic uses via supercritical fluid extraction (SFE) (in vitro)	By-products were cut, crushed, and dried at 55 °C for 24 h (moisture content 4%) A quantification of the bioactive compounds in the extracts: chlorophylls, carotenoids, phytosterols, TPC, and α-tocopherol The antioxidant ability, cytotoxic evaluation, and cell viability assay were held	SFE extracts were rich in phenolics, chlorophylls, β-carotene, and phytosterols In the bioactivity assays, the SFE extracts had high antioxidant activity and cytoprotective effects SFE extracts were far richer in total bioactive compounds than the conventional ones Antioxidant activity and attenuation of the adverse effect of UVB light on HaCaT cells	Antioxidant and cytoprotective activity Potent cosmeceutical ingredients	2020	[204]
	Waste apricot flesh (WAF)	Phytoene at the highest content of total carotenoids	Investigation on the recovery of carotenoids from WAF for determining their types, content, and potential applications (in vitro)	WAF was washed, freeze-dried, crushed, and refrigerated at 4 °C Extraction of carotenoids by ultrasound-assisted corn oil method, TCC, color assay, UPLC-atmospheric pressure chemical ionization (APCI)-MS/MS analysis, GC–MS for fatty acids analysis, and antioxidant assay were also conducted	The TCC was 42.75 mg/100 g d.w. (60 min time, 41.53 °C, 200 W power, liquid to solid (LS) ratio of 0.10 g/mL) Phytoene had the highest content of in the corn oil extracts (COE), and COE carotenoids degraded at high temperatures The green-red chromaticity axis (a*) of COE fries was 7.31 times higher than corn oil ones The natural carotenoids in the extract notably improved the a* of French fries in frying	Guidance for green recovery of carotenoids and WAF valorization The extract can be used at high temperatures and may have potent applications to reduce the use of industrial colors in food, nutraceuticals, and nutricosmetics	2023	[44]
	Pineapple (Ananas comosus L. Merr.)	α-carotene, β-carotene, lutein, β-cryptoxanthin, lycopene, neoxanthin, violaxanthin, zeaxanthin, and retinol, as well as other constituents like tocopherol and vitamins C and E	Evaluation on the impact of UV-C radiation on the bioactives of pineapple and potent antioxidant valued action (in vitro)	The amounts of vitamins C and E, as well as the aforementioned carotenoids, were analyzed before and after treatment with UVC radiation Moisture content estimation and extraction of carotenoids was also performed	All treated and un-treated pineapple by-products contained β-carotene as the main carotenoid (rind, 2537–3225 μg, and core, 960–994 μg/100 g d.w. Pineapple rind also contained lutein (288–297 μg/100 g d.w.) and α-carotene (89–126 μg/100 g d.w.)	Potent antioxidant and photo-protective activity Potential valorization as pharmaceuticals, cosmetics, and food industries	2015	[205]
	Kernel oils from sour cherry (Prunus cerasus L.)	All-trans-β-carotene (mainly) and total carotenoids, along with fatty acids, total tocochromanols, tocopherols, sterols, and squalene	Investigation on the composition of bioactives in kernel oils recovered from sour cherry by-products and the impact of the cultivar on potential applications (in vitro)	Sour cherries of six cultivars were grown in three independent batches for each cultivar Kernels were frozen (−18 °C) and freeze-dried at −51 ± 1 °C (0.055–0.065 mBar, 48 h), Undamaged kernels were milled and powdered Oil extraction, fatty acid composition by GC or GC–MS, tocopherol, TCC, tocotrienol, sterols, and squalene by UV/Vis or MS were also examined	Emphasis on carotenoids and fatty acids results: Oil yields ranged between 17.5 and 37.1%, with an average of 31.8% The main fatty acids were linoleic (35.59–46.06%), oleic (25.25–45.30%), α-eleostearic (7.43–15.76%), and palmitic (5.06–7.38%), with 94–96% of total traced fatty acids (TFAs) in the oil TCC was between 0.51 and 1.75 mg/100 g oil, with the main carotenoid traced being β-carotene The cultivar has a significant impact on the amount of the bioactive compounds in kernel oil α-Eleostearic acid was found for the first time in sour cherry kernel oils (7–16% of TFAs)	Potent antioxidant and anti-cancer potential	2016	[206]
	Mango (Ataulfo)	β-carotene	Evaluation of mango fruit intake on facial wrinkles and erythema in postmenopausal women (in vivo)	16 weeks of either 85 g or 250 g mango intake in healthy postmenopausal women with Fitzpatrick skin type II or III were evaluated Participants were given frozen mangoes prepackaged into 85 g (0.5 cup) or 250 g (1.5 cups) and consumed one cup four times/week (without heat) Facial photographs (weeks 0, 8, and 16), wrinkles at the lateral canthi, and erythema at the cheeks were qualified by Reflection spectroscopy measured skin carotenoids	Deep wrinkle severity decreased notably in the 85 g group after 16 weeks compared with baseline measures On the contrary, women in the 250 g group had an increase after 16 weeks in average wrinkle severity, average wrinkle length, and fine and emerging wrinkle severity Erythema in the cheeks elevated by 85 g intake 85 g intake reduced wrinkles in fair-skinned postmenopausal women An intake of 250 g had the opposite effect	Skin photo-protection against erythema and facial wrinkle reduction on postmenopausal women with 85 g mango feeding	2020	[207]
	Cantaloupe melon (Cucumis melo L.)	β-carotene, α-carotene, lutein, and zeaxanthin	Evaluation of the vital antioxidant stability enhancement of carotenoid-rich extract (CE) from cantaloupe melon (EPG), nanoencapsulated in gelatin under several storage conditions (in vitro)	In the pulp and melon flour processing, grain flour size was determined, and 50 g of melon flour was utilized CE and EPG stability were evaluated at 25 and 5 °C, with or without light (1600lx) β-carotene–CE concentration was determined by UHPLC and UV-Vis and antioxidant profile by ABTS and DPPH Nanoencapsulation of the CE in gelatin was performed	CE antioxidant potential increased by 57–59% after nanoencapsulation After 60 days, a low retention of β-carotene (0–43.6%) in the CE was observed at 25 °C light (0.00) and dark (10.0%) EPG preserved β-carotene in the dark at 25 °C (99.0%), light (83.1%), and dark (99.0%) at 5 °C, as well as by 68.7–48.3% the antioxidant action EPG enhanced and stabilized the antioxidant potential of carotenoids EPG’s β-carotene antioxidant potential was preserved for 60 days	Antioxidant activity enhancement via nanoencapsulation Health-promising activity	2021	[62]
Cereal/ Grains	Gluten-free (GF) bread from pea flour by Chlorella sorokiniana	All-trans-lutein, all-trans-β-carotene, all-trans- zeaxanthin, and 9-cis-β-carotene along with other lutein, β-carotene, violaxanthin, and zeaxanthin	This study’s main investigation was focused on the partial replacement of pea flour by C. sorokiniana biomass powder to increase the nutritional quality of a GF bread (in vitro)	The bread was enriched with 2.5 g (M2.5) or 5.0 g (M5.0) of microalgae powder/100 g of blended rice flour and corn starch (substitute of pea flour) For the evaluation of the carotenoid profile and fatty acid composition, tests at 220 °C/12 min and 180 °C/15 min were performed Determination of total lipids and fatty acid methyl esters (FAMEs), TCC, bread quality, and sensory evaluation was mainly assessed	Comparing control and M5.0 bread: microalgae increased the protein (67 to 85 mg/g) and lutein content (1.6 to 57.5 μg/g) ω-3 content increased from 5.0% to 6.1% Sensory analysis revealed an M2.5 bread acceptance rate greater than 70% No impact on the texture, specific volume, proteins, ashes, moisture, color, bake loss, and lipids was seen by C. sorokiniana The protein content increased 26% for the M5.0 bread Baking process did not affect β-carotene content High temperature and short baking time: lower lutein degradation The M5.0 bread can be classified as a high-lutein functional food	The generally low nutritional value GF bread was nourished by the microalgae addition Potential for high-quality functional food by the GF bread-microalgae combination	2020	[208]
	Cereal product	High amounts of β-carotene (as well as γ-linolenic acid (GLA))	Examination of the influence of the addition of pre-fermented cereal products with high β-carotene and GLA amounts into the feed of broiler chickens on their immune status and the number of lactic acid bacteria and enterobacteria (in vivo)	The 1-day-old chicks were divided into two groups: control and experimental (n = 50, each) Chicks for the first 10 days were fed a starter multi-ingredient diet (BR-1) Feed mixtures BR-2 and BR-3 were nourished with 10% cereals (GLA and β-carotene) Day 38: 15 chicks were randomly selected, and blood samples were collected Real-time PCR and microbiological analysis were also conducted	A notable increase in the oxidative burst of phagocytes, CD4 and CD8 lymphocytes, and the CD4:CD8 ratio Upregulation of gene IgA expression indicated that β-lymphocytes were triggered at the local gut Caecum: increased mRNA expression for mucin-2 (MUC-2) and insulin-like growth factor 2 (IGF-2) was observed Protection of intestinal mucosa and alterations in microbial composition Vast enterobacteria reduction after receiving GLA and β-carotene	Pre-fermented cereals containing GLA/β-carotene represent a low-cost supplement for broiler diet Beneficial health effect Positive influence on the gut microbiota and immunity of broilers	2018	[209]
Herbs and Spices	Paprika oleoresin (Capsicum annuum)	Mostly capsanthin and capsorubin	Investigation on the protective role of emulsions loaded with paprika oleoresin carotenoids on the liver and serum of healthy rats and the effects of non-ionic surfactants on mice liver (in vivo and in vitro)	Twenty Wistar male rats, 21 weeks old, b.w. 400–600 were used Conventional and nanoemulsion (CE and NE) preparation (5 rats/4 groups) Group I: physiological saline solution (PISA, oral) (control) Group II: surfactant in an aqueous solution (47.4 μg/kg/day, oral) Groups III and IV: oral administration (3 mg/kg/day carotenoids in CE and NE) All groups: twice/day, every 12 h, 5 days Body weight was recorded Antioxidant action was measured by the FRAP assay	CE and NE had particle sizes of 157.9 and 39.2 nm Carotenoid levels: EC50 of 347 for CE and 359 μg/mL for NE CE positive liver effect: increased antioxidant activity—no modifying of transaminases activity Antioxidant activity: inversely proportional to the particle size Transaminase activity was affected by interface and surfactant When the surfactant was administered alone: liver damage and potent mitochondrial injury that causes necrosis	Antioxidant capacity and radical scavenging ability	2020	[210]
	Paprika oleoresin (Capsicum annuum) (zeaxanthin) and marigold flower oleoresin (lutein)	Zeaxanthin and lutein	Assessment of the efficacy and safety of Bend Skincare anti-aging formula on MED in skin (in vivo)	28 subjects with Fitzpatrick skin types I, II, or III took four capsules/day/8 weeks: 1400 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), 120 mg GLA, 5 mg lutein, 2.5 mg zeaxanthin, and 1000 IU of vitamin D3 Back skin of each subject was exposed to UV radiation at baseline, after 4- and 8-week treatment to find the MED Compared results before and after treatment: three t-tests and three linear mixed models	The treatment notably improved UV exposure tolerance: increased MED at 4 and 8 weeks Protection increased with prolonged use of Bend Skincare anti-aging formula: progressively increased MED between 0 and 4 weeks and 4 and 8 weeks Nearly 86% of patients responded to treatment within 4 weeks, and 100% of patients responded by the end of the study 39% mean MED increase at 4 weeks and 84% mean increase in MED at 8 weeks No product-related adverse effects and a few mild side ones appeared	Skin photo-protection and anti-aging potential	2017	[211]
	Coriander (Coriandrum sativum L.)	Total carotenoids and β-carotene	Ten commercial varieties of coriander, grown under similar conditions, were evaluated for their specific carotenoid content, their bio-efficacy, and their stability during drying (in vitro)	β-carotene HPLC–MS analysis on ten commercially cultivated coriander species Pigment stability microwave drying, antioxidant activity of carotenoid extracts (DPPH), DNA degradation, and gel electrophoresis were held	Β-carotene was higher in foliage at mature stage than in seedlings and seeds GS4 Multicut: highest biomass (6.18 ± 0.73 g/plant), TCC (217.50 ± 5.6 mg/100 g d.w.), and β-carotene (73.64 ± 0.3 mg/100 g d.w.) at pre-flowering stage Carotenoids extract: high antioxidant capacity, IC50 of 14.29 ± 1.68 μg/mL Great radical scavenging potential and high DNA protection than standard GA (IC50 = 357.21 ± 4.29) Microwave drying: rapid pigment retention, high β-carotene extractability, compared with oven drying	Antioxidant, radical scavenging (anti-radical), and cytotoxic effects of these carotenoid extracts Potential in the direct use in processed foods and in culinary preparations	2012	[212]
	Parsley (Petroselinum crispum)	Capsanthone (the only carotenoid) and other acids, furanocoumarins, and flavonoids	Investigation on the improvement of nutraceutical value of parsley leaves on field applications of beneficial microorganisms (in vitro)	Streptomyces fulvissimus strain AtB-42 and Trichoderma harzianum strain T22 were utilized as a single or combined (microbial consortium) at transplanting and 2 weeks later After harvesting was conducted, the plants were subjected to metabolomic analysis by GC–MS and LC–MS	Identification of seven polar metabolites AbT-42 alone or combined with T22 induced the collection of xanthotoxol/bergaptol-xanthotoxin/bergapten Microbial consortium: accumulation of capsanthone compared with single treatment No important/relative differences were found for the volatile fraction S. fulvissimus and T. harzianum initiated a metabolic profile change and metabolites with nutraceutical value accumulation	Potent antioxidant, anti-microbial, and anti-cancer chemo-protective activity Potent applications as a nutraceutical	2021	[45]

6.4. Vitamin A, Vitaminoids, and Carotenoids from Microorganism Sources

Microbial-derived sources provide a sustainable, scalable platform for producing carotenoids and retinoids without relying on animal, plant, herb, or marine sources. More specifically, except for microorganisms of animal, plant, or marine origin that have been included in the previous sections, other microbial-associated sources can be cultivated in controlled bioreactors with optimized conditions, yielding high-purity carotenoids and retinoid derivatives for nutricosmetics, cosmeceuticals, and cosmetics applications. Microorganisms, including bacteria, fungi, yeast, and microalgae, represent a cutting-edge solution for meeting increasing demands in the cosmetic industry, particularly for products targeting skin photo-protection and anti-aging [18,149].

Filamentous fungi, especially ascomycetes, generate secondary vitamin A metabolites such as β-carotene, while a heterothallic zygomycetes fungus formulates lycopene with significant coloring, antimicrobial, anti-cancer, antioxidant, anti-proliferative, antiradical, and cytotoxic activity. In Blakeslea trispora fungus, the biosynthesized β-carotene and is utilized widely in biotechnological processes for microbial stimulation and oxidative stress prevention, while other Mucor circinelloides strains and Fusarium sporotrichioides species yield lycopene and β-carotene, have the potential to produce mycotoxins, enhance health, and lower cardiovascular/circulatory disease risk [18,106,213,214]. Moreover, yeast-derived microorganisms like Rhodotorula spp. (e.g., Rhodotorula glutinis) are prolific producers of carotenoids like β-carotene, torulene, and torularhodin, with several antioxidant and photo-protective properties in nutraceuticals and nutricosmetics, while others like Phaffia rhodozyma generate β-carotene and astaxanthin, with vital skin photo-protection and anti-aging properties [48,106,215].

Bacteria producing microorganisms, such as Paracoccus spp., Dietzia natronolimnaea, Croceibacterium aestuarii, Micrococcus luteus, and Gordonia jacobaea, are capable of producing astaxanthin, canthaxanthin, and zeaxanthin and also own antioxidant, anti-inflammatory, and anti-aging properties. Additionally, non-marine microalgae (cultured in controlled systems), including Chlorella zofingiensis and Coelastrella spp., produce β-carotene, astaxanthin, and canthaxanthin under stress conditions and exhibit beneficial skin photo-protection, anti-aging, and antioxidant protection [106]. Finally, retinoid-producing microorganisms like engineered bacteria (e.g., Escherichia coli) that produce retinol and yeast (e.g., Saccharomyces cerevisiae) that convert carotenoids such as β-carotene to retinoids like retinol and retinoic acid in controlled fermentation systems also possess several benefits [106,216,217]. Clinical data regarding the significance of vitamin A, vitaminoids, and carotenoids from microorganisms in nutricosmetics, cosmeceuticals, and cosmetics products are included in Table 4.

Table 4. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids from microorganism sources in nutricosmetics, cosmeceuticals, and cosmetics applications.

Type of Microorganism	Microorganism	Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results—Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year Study	References
Fungi	Blakeslea trispora and Mucor circinelloides	β-carotene	Three photoreceptor genes in B. trispora were cloned, expressed, and characterized via bioinformatics and photoreception in vitro analyses, while their analysis in vivo was conducted in M. circinelloides	Btwc-1a, btwc-1b, and btwc-1c from B. trispora were cloned and expressed Wort medium was prepared by saccharification of 200 g of wheat flour, added to 80 mL water, stirred, and heated at 50, 72, and 76 °C for 1 h each Photo-responsive analysis of btwc-1 was held in vitro UV-visible light, fluorescence scanning, and analysis of the genes in vivo were also held	Btwc-1: photoreceptor protein that acts as a light sensor to regulate carotenoidogenesis in B. trispora Light-oxygen voltage domains (LOV) of these proteins undergo a photochemical reaction that indicates photoreception ability through cysteine residues B. trispora genes were expressed in M. circinelloides ones Such genes are photosensitive B. trispora genes were implicated in different light transduction cascades regulating both carotenogenesis and phototropism	Carotenogenesis modulation Phototropism regulation	2020	[218]
	Blakeslea trispora	Phytoene-rich β-carotene and lycopene	Evaluation of the efficacy of the carotenoid biosynthesis inhibitors diphenylamine (DPA) and 2-methyl imidazole and sterol biosynthesis inhibitor, terbinafine hydrochloride (TH) (in vitro and in vivo)	The microorganisms for fermentation were Β. Trispora ATCC 14271, of mating types (+) and (−), grown separately at 26 °C for 5 days The yeast strain for the in vivo experiment was Saccharomyces cerevisiae EGY48 (stored at 4 °C) In vivo antioxidant activity assay was held	An increase in phytoene production was made according to TH and DPA addition, while concurrently lycopene decreased Yeast cells with no phytoene treatment were sensitive to the oxidizing agent (20% survival), in contrast to those treated with phytoene-rich carotenoid extract, which showed 93% survival rates	Strong antioxidant activity of the phytoene-rich extract Cytoprotective effect	2024	[219]
	Mucor circinelloides	β-carotene	Optimization of β-carotene production in M. circinelloides strain 277.49 by response surface methodology (RSM) (in vitro)	Cerulenin and ketoconazole were used for inhibiting fatty acids and sterol biosynthesis pathways, respectively Fungal fermentation was conducted, with seed culture prepared by inoculating 100 μL spore suspension into 150 mL Screening of carbon sources for optimal C/N ratios, effect of inhibitors on β-carotene formation, and optimization by RSM were also held	Carbon/nitrogen (C/N) ratio, cerulenin, and ketoconazole were synergistic combinations for β-carotene formation 4.26 mg/L (0.43 mg/g) of β-carotene was produced as compared with the control sample RSM has a beneficial effect on recognizing medium components	Ideal model strain for carotenogenesis and lipid production for biotechnological applications Cytoprotective effect of the product	2020	[220]
	Neurospora crassa and Fusarium fujikuroi	Neurosporaxanthin	The investigation of neurosporaxanthin’s antioxidant activity in vitro by the aid of several assays and liposomes, which was produced by carS gene mutant of F. fujikuroi (in vitro)	Fusarium fujikuroi wild strains IMI58289 and FKMC1995 and carS mutants were used (low-N medium, 10% ICI medium (80 g/L D(+)-glucose)) All samples were stored (−80 °C) and freeze-dried (24 h) Carotenoids were extracted and dissolved in acetone Spectrophotometry, HPLC, antioxidant DPPH and FRAP assay, quenching and scavenging activity in liposomes, was also held	Carotenoid overproduction by microorganisms was observed F. fujikuroi SG39 extracts had substantially higher antioxidant activity than SG256 High antioxidant capacity and scavenging ability against several free radicals in aqueous solutions and liposome environments The quenching ability correlated well with the one found in fruits and vegetables Significant quenching ability of neurosporaxanthin-rich extracts against [O2(1Δg)] in organic solvent at least as efficient as β-carotene High scavenging activity against HO radicals in liposomal systems	Antioxidant activity, high scavenging ability, and high quenching ability Promising for future use as a feed or food additive	2020	[39]
Yeast	Rhodotorula mucilaginosa (Pinaceae forest ecosystems)	β-carotene (mainly), torulene, and torularhodin	Four-pigment-producing yeasts isolated from park soils were examined for their potential to produce carotenoids (in vitro)	Samples were obtained with scraping of soil surface that provided about 10 g of soil (incubated at 28 °C for 48–72 h, maintained in agar) All yeast isolates were characterized by PCR and HPLC, Fourier transformed infrared spectroscopy (FT-IR), and gene submission	The main potential candidate produced was β-carotene Maximized carotenoid formation was observed by applying yeast extract peptone glycerol medium (120 h incubation, at 28 °C, pH 6.0, and white light exposure) The average maximum carotenoid content was 223.5 μg/g (d.w.) Apart from carotenoids, significant enzyme and lipid generation was observed	R. mucilaginosa could be a potent bio-source of natural antioxidant carotenoids Anti-cancer, antioxidant, and health-promoting properties	2021	[221,222]
	Rhodotorula glutinis (P4M422)	Preformed Vitamin A	Intracellular microbial production and examination of the most appropriate method for cell disruption (in vitro)	Rhodotorula glutinis (P4M422) was grown in yeast malt broth Cyclization inhibitors: imidazole, ketoconazole, and 2-isopropylimidazole aided in avoiding β-carotene-accumulating lycopene SEM and HPLC techniques Antimicrobial and antifungal activity of the capsules against several fungi was examined (petri dishes with agar, 30 °C) Antioxidant activity by ABTS, DPPH, and FRAP assays	Higher carotenoid extraction was obtained under bead mill-assisted treatment that does not require toxic solvents like DMSO, with thus less associated health risk Highest lycopene concentration of 18.61 mg/L was obtained with 2-isopropylimidazole’s addition Lycopene capsules did not show significant antifungal activity but exhibited notable antioxidant action	Antioxidant and radical scavenging activity	2017	[223]
	Sporidiobolus pararoseus	Torularhodin	Oxidative activity and induced liver injury amelioration and confrontation by torularhodin	The antioxidant effects of torularhodin were investigated by DPPH and ABTS Moreover, this study also used a cell oxidative damage model in vitro and a d-galactose-induced liver-injured mouse model in vivo	Torularhodin affected oxidative damage by H2O2 to AML12 cells Torularhodin significantly reduced inflammatory cytokines It increased antioxidant enzyme action in mouse serum and liver D-Galactose oxidative damage, liver-induced, was mediated by torularhodin improving Nrf2/HO-1 activity B-cell lymphoma protein 2-associated X (Bax) and NF-κΒ expression were reduced Torularhodin upregulated mRNA expression of liver Nrf2, NAD(P)H dehydrogenase quinone 1 (NQO1), and HO-1	Free radical scavenging activity Oxidative damage prevention Strong antioxidant activity	2019	[224]
	Sporidiobolus pararoseus	Torulene and torularhodin	Cytoprotective effect and mechanisms of action examination concerning torulene and torularhodin on human prostate stromal cells (in vitro)	Torulene and torularhodin antioxidant action was traced in H2O2-induced oxidative damage in human prostate stromal cells (WPMY-1) Torulene and torularhodin were isolated from the extract S. pararoseus by HPLC method Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay Measurement of ROS levels, apoptosis, RNA extraction, RT-PCR, and western blot	After cells were treated with H2O2, a notable decrease in cell viability was observed The decrease attenuated after pre-treatment with torulene and torularhodin (0.5–10 μM) in WST-1 These carotenoids also attenuated H2O2-induced apoptosis in WPMY-1 cells via inhibiting ROS species and MDA overproduction, as well as the activation of CAT, SOD, and GSH-Px action This pre-treatment also led to regulation of mRNA and protein expression in Bcl-2 and Bax	Antioxidant and cytoprotective activity Human prostate cells’ protection from oxidative stress damage via Bcl-2/Bax-mediated apoptosis	2017	[225]
	Phaffia Rhodozyma (NRRL-Y 17268)	β-carotene, astaxanthin, and lutein	Establishment of the stability and antioxidant activity of the extracts obtained via different methods for recovering carotenoids (in vitro)	Yeast was preserved on YM agar, and stock cultures were incubated (48 h, 25 °C) Cell disruption was observed via DMSO and enzymatic disruption techniques TCC estimation, HPLC with variable wavelength detectors (HPLC-VWD), and antioxidant activity assay were also held	β-carotene was obtained at 81% among the carotenoids extracted Freezing favored the extraction, but carotenoids did not always have higher antioxidant activity By enzymatic extraction, the highest antioxidant activity values were received by ABTS and FRAP assays (4.00 and 3.66 mM trolox/μg, respectively)	Antioxidant and cytoprotective effect	2015	[226]
	Saccharomyces cerevisiae	β-carotene	Examination of the dual regulation of lipid droplet triacylglycerol metabolism and ERG9 expression for the improved production of β-carotene in this yeast (in vitro)	OA and cheap unsaturated fatty acids (UFAs) were used Quantitation of neutral lipid droplets (LDs) as the main storage location of β-carotene in this yeast was conducted Optimization of OA-promoting LDs formation and a series of OA-repressible promoters to replace ERG9 (transcriptional assay) were also held	LDs were the major storage locations of β-carotene in this yeast The competition for precursors between β-carotene and LDs, triacylglycerol biosynthesis, and enlarging storage space by engineering LDs genes, led to minor β-carotene accumulation Adding 2 mM of OA notably improved LDs triacylglycerol metabolism and resulted in 36.4% increase in β-carotene IZH1 promoter was utilized for replacing native ERG9 promoter The metabolic flux was diverted to β-carotene synthesis pathway and achieved 31.7% content increase No negative effects on cell growth	Gene transcription and antioxidant activity enhancement	2022	[227]
Bacteria	Paracoccus aurantius (MBLB3053T)	Mostly astaxanthin	Establishment of the production and identification of this bacteria species (in vitro)	The strain weighed 1.0 g was suspended in 10 mL of 0.85 % (w/v) NaCl, diluted in Reasoner’s 2A broth (aliquots: incubation at 30 °C, 1 week) Chemotaxonomic, physiological, biochemical, etc. studies, whole-genome sequencing, pigment extraction, and antioxidant potential of the carotenoid extract were held	All studies pointed out that the genus of P. aurantius, MBLB3053T strain, was utilized Genus’s authenticity and expected chemotaxonomic properties Astaxanthin (all-trans form) was mainly obtained Other astaxanthin isomers were as well generated High in vitro antioxidant activity of the cis astaxanthin isomers compared with the all-trans astaxanthin ones	High DPPH-scavenging activity Antioxidant ability	2024	[228]
	Paracoccus carotinifaciens	Astaxanthin-rich extract from P. carotinifaciens (supplement)	Examination of the effect of this supplement on cognitive function of middle-aged subjects (45–64 years) (in vivo)	Group 1: Cognitive functions of 28 subjects, orally given 8 mg astaxanthin/day of this supplement for 8 weeks Group 2: 26 subjects were given a placebo All subjects were compared by word memory test, verbal fluency, and Stroop test Then, subjects were divided into over/equal (≥) and under (<) 55 years old groups	The astaxanthin group experienced remarkably larger increase in the blood astaxanthin levels than the placebo group, with no notable intergroup differences Results for the “words recalled after 5 min” assay in the word memory test in the under 55 years old group revealed that the subjects showed notable improvement in the astaxanthin group than the placebo one, which was not found in the ≥55 years old group subjects No safety-related problems were demonstrated	Cognitive function improvement for individuals aged 45–54 years old after ingesting astaxanthin supplements for 8 weeks	2018	[229]
	Arthrobacter agilis DSM 20550T and Arthrobacter bussei DSM 109896T	Bacterioruberin	Investigation on the membrane fluidity regulation by C50 bacterioruberin in pink-pigmented Arthrobacter species (in vitro and in vivo)	All bacterial strains were appropriately cultured and cultivated and statistically evaluated Total carotenoid content was estimated by HPLC, and freeze–thaw stress test was conducted	Strains showed increased bacterioruberin content by the time the growth temperature was reduced from 30 to 10 °C In vivo anisotropy with trimethylammonium-diphenylhexatriene had increased membrane fluidity and a broadening phase transition with increased bacterioruberin membrane content at low-temperature growth Suppression of bacterioruberin synthesis at 10 °C with sodium chloride: bacterioruberin highly modulates membrane fluidity Increased bacterioruberin content correlated with increased cell resistance to freeze–thaw stress Adaptive function of bacterioruberin strains at low °C	Membrane fluidity modulation	2022	[230]
	Citricoccus parietis AUCs	β-carotene	Investigation on the production of bioactive β-carotene by the endophytic bacterium Citricoccus parietis AUCs and the in vitro biological potential (in vitro)	Production of pigment by C. parietis strain AUCS by cultivation, nutrient broth inoculation, incubation for 72 h at 35 °C and 150 rpm, and extraction of the pigment Purification and identification by TLC, UV/Vis, and HPLC Evaluation of the antibacterial, antioxidant (DPPH), and anti-diabetic potential	The extracted yellow pigment obtained by this strain was extracted by methanol and identified as β-carotene by TLC The pigment displayed great antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Streptococcus agalactiae The pigment extract had considerable TAC (3097.5± 5.4 μg AAE/mg pigment extract) and DPPH scavenging activity (87%) Notable anti-diabetic inhibition of pancreatic α-amylase (73.8%) and increased glucose uptake by yeast cells (55.32 and 71.7% at 5 mM and 10 mM glucose), respectively	Antibacterial, antioxidant, and anti-diabetic	2023	[231]
	Exiquobacterium acetilicum S01	Lycopene (Car-I), Diapolycopene-dioic-acid-diglucosyl-ester (Car-II), β-carotene (Car-III), zeaxanthin (Car-IV), astaxanthin (Car-V), and Keto-Myxocoxanthin (Car-VI)	Evaluation of the anti-cancer, antioxidant, and anti-inflammatory potential of this bacterium	The six carotenoids were isolated and identified from the methanolic extract HPLC, cell viability by the MTT assay in HT-29 cells, anti-inflammatory activity by triggering PBMCs with LPS (1 h) and 100 μM carotenoids (24 h), and DPPH activity estimation were utilized	Two structurally novel and four known carotenoids were identified All six carotenoids exhibited notable inhibition of the HT-29 cell viability, dose-dependently, with no cytotoxicity for PBMCs They also inhibited LPS-induced iNOS generation, TNF-α activity, and lipid peroxidation in PBMCs Four carotenoids had a potent anti-proliferative effect against colorectal cancer Car-II and Car-VI displayed a promising anti-inflammatory activity in LPS-induced PBMCs Car-II and Car-VI had a notably higher antioxidant potential than ascorbic acid (DPPH)	Potential therapeutic agents for inflammation-associated cancer Antioxidant, radical scavenging, anti-inflammatory, and also anti-proliferative activity	2020	[232]
	Dietzia natronolimnaea (waste molasses and its hydrolysate)	Canthaxanthin	Examination of the carotenoid production from hydrolyzed molasses by this bacterium HS-1 with different cultivation methods (in vitro)	Three cultivation strategies: batch, fed batch, continuous culture for biomass and carotenoids synthesis Enzymatic, acidic, and acidic at high temperature pre-treatment was conducted to find the best hydrolysate by sucrose conversion rate Pigment extraction, dry biomass, TCC, and carotenoid pigment analysis were held	Canthaxanthin and enzymatic hydrolysis were the most abundant pigment biosynthesized and the most suitable process for substrate production An increase (double) in reducing sugar levels of enzymatic hydrolase molasses (EHM) (25 to 50 g/L): decrease in biomass formation-substrate use EHM of 25 g/L was a better substrate for cell growth and product formation than waste molasses of EHM 25 g/L Enhanced biomass generation, mostly in fed-batch culture Continuous cultivation had the highest biomass (12.98 g/L), carotenoid (27.33 mg/L), and canthaxanthin (25.04 mg/L) yields	Canthaxanthin may be used as a natural antioxidant for possible formation of healthy, functional foods	2014	[233]
	Escherichia coli	Carotenoid holoprotein and carotenoids in general (mainly β-carotene and violaxanthin)	A method for producing large amount of holo-orange carotenoid protein (holo-OCP) that is suitable for pharmaceutical and cosmetic industry (in vitro and in vivo results)	Six different genes were involved in holo-OCP synthesis and were introduced via three different plasmids in E. coli Amplification and cloning of Crt genes encoding enzymes and an ocp gene, OCP isolation, calculation of holo-OCP levels, OCP fluorescence quenching ability, 1O2 detection, TCC in OCPs by HPLC, and mass spectrometry were used	200 times more holo-OCP in 20% of the time of purifications, involving overexpression in cyanobacterial cells In only 4 days, more than 30 mg of holo-Synechocystis-OCP may be obtained via E. coli Carotenoid genes must be induced with arabinose (37 °C) for high carotenoid cells, then by isopropyl β-D-thiogalactopyranoside (IPTG) addition (20–28 °C) to slow down protein synthesis, allowing protein folding and carotenoid binding	Antioxidants of great interest for pharmaceuticals and cosmetics Antiradical and photo-protective activity	2015	[234,235]
	Escherichia coli	Retinyl palmitate	Evaluation of the microbial production of retinyl palmitate and its benefits in skin physiology (in vitro)	A heterologous biosynthesis pathway (retinyl palmitate) in E. coli by expression agents in Pantoea agglomerans, Salinibacter ruber, and Homo sapiens E. coli cells were grown at 37 °C and cloned at 30 °C Extraction and retinoid analysis, batch and fed-batch, cell viability, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and RT-PCR were conducted	High retinyl palmitate production (69.96 ± 2.64 mg/L) was obtained by fed-batch fermentation Application of purified microbial retinyl palmitate to human foreskin HS68 fibroblasts resulted in cellular retinoic acid-binding protein 2 (CRABP2) mRNA level, acceleration of cell proliferation, and procollagen synthesis Other retinyl fatty acids may be produced by further metabolic engineering of retinyl palmitate producing E. coli	Strong anti-aging impact First evidence for application in cosmetic and cosmeceutical products	2020	[236]
	Spirulinaplatensis	B-carotene	Study and evaluation of skin creams integrated with bioactive S. platensis extract	The bacterium was cultivated, and in vitro cytotoxicity of this extract was evaluated (0.001–1% concentrations for 1, 3, and 7 days on HS2 keratinocytes) Crude extracts were integrated into skin creams at 0.01% (w/w) In vitro wound healing, genotoxicity studies, and immunohistochemical staining for collagen action assessment were performed	0.1% S. platensis extract exhibited higher proliferation activity in contrast to the control group 198% cell viability was observed after 3 days Skin cream with 1.125% S. platensis crude extract displayed an enhanced wound healing effect on the HS2 keratinocyte cell line and the highest HS2 cell viability (5) Micronucleus (MN) assay outcomes pointed out that this cream had no genotoxic effect on human peripheral blood cells Collagen type I immunoreactivity was positively impacted by increased extract concentration (1.125% extract)	S. platensis extract incorporated in a skin cream has potent value in cosmeceutical and biomedical applications Collagen production improvement Wound healing ability	2017	[237]
	Spirulina platensis	β-carotene and zeaxanthin (blue–green) in this microalgae powder	Investigation of the influence of a food supplement powder of this bacterium on the skin (in vivo)	Ten heathy Caucasians (eight females and two males) with skin types II and III (25–54 years old) ingested 0.7 g/dose stirred into peach juice and applied products twice/day for 8 weeks Measurement of the second-harmonic generation to autofluorescence aging index of dermis (SAAID), collagen/elastin index, and cutaneous carotenoid levels	Powder carotenoid content: 461 mg/100 g with mainly β-carotene (214 mg/100 g) and zeaxanthin (191 mg/100 g) Notable average increase from 2.76 ± 0.86 arb. units to 3.25 ± 0.93 in cutaneous carotenoid concentration was detected after the oral powder application Significant improvement of the antioxidant status of the skin Slight but not remarkable increase (p = 0.33) in dermal SAAID mean values (−0.54 ± 0.11 to −0.51 ± 0.11)	Improved antioxidant status of the human skin	2015	[238]
	Micrococcus Luteus (Q24)	Carotenoid pigments probiotics	Determination of the impact of direct skin application of a topical serum formulation containing this probiotic on several key cosmetic skin quality parameters and its beneficial impact on the modulation of the skin’s microbiome (in vivo)	The serum contained two chambers: chamber A with the serum and B with the hydrator 10 healthy females (18–60 years old), with healthy skin but concerns on mild-to-moderate breakout, fine lines, wrinkles, uneven skin tone, dullness, or redness cases, participated Females applied two pumps (>1 × 108 cfu/dose) of the serum on the face twice/day (morning and night) for 25 days Skin parameters and skin swab samples were tested Whole-genome sequencing (WGS) was performed Patients were instructed not to change their skincare routine or try new products	Significant reduction in pores, spots, wrinkles, and impurities scores was exhibited along with a 101% hydration score observation 45–80% of participants had a decrease in pores, spots, wrinkles, and impurities 90% of the females partaking in the experiment showed a hydration increase after 25 days of the probiotic serum application WGS analysis in skin swab samples demonstrated notable increase in the relative abundance of M. luteus Colonization efficacy and hydration level improvement was as well confirmed	Topical application of this serum offers improved skin health quality Potential beneficial effects in cosmetic products Antioxidant, antibacterial, and UV-protective properties of carotenoids isolated from this bacterium were observed in a previous (almost similar research (2013))	2024	[64,239]
Algae	Neochloris oleoabundans	Lutein, carotenoid monoesters, and violaxanthin	Microalgae extracts were obtained by pressurized liquid extraction (PLE) to evaluate differences in the type and number of carotenoids produced (in vitro)	Cultures were established in modified bold’s basal medium (BBM) until optimal density All experiments were carried out in a chamber (24 ± 2 °C, 16 h photoperiod) Nitrogen, light, and CO2 impact Quantification of carotenoids and chlorophylls Anti-proliferative assay	Under appropriate conditions, these microalgae extracts obtained by PLE are able to produce considerable β-carotene, lutein, and carotenoid monoesters Violaxanthin formation	Potent use of carotenoids from N. oleoabundans as a functional food or nutraceutical in preventing colon cancer Cytoprotective and anti-proliferative activity	2016	[240]
	Coelastrella oocystiformis.	β-carotene, astaxanthin, lutein, canthaxanthin and phytofluene	Characterization of this microalgae species’ high carotenoid potential and evaluation of its anti-cancer ability (in vitro)	BG11 media was utilized for the isolation of this microalgae with several ingredients (g/L), (pH = 7.1, at 25 °C, 5000 lux, and 12:12 h light/dark cycle) GC–MS, analysis of pigments by high-performance thin-layer chromatography (HPTLC), and anti-cancer potential estimation	The strain had a doubling time of 12 ± 1.0 h with 3% CO2 and 27 ± 1.0 h without 3% CO2 With 3% CO2 a biomass of 89.6 + 2.0 mg/L/day and without only 42.555 + 2.0 mg/L/day were yielded Carotenoid content: 1.972% d.w. HPTLC revealed carotenoids, β-carotene, lutein (518.64 μg/g), free astaxanthin (120.5 μg/g), canthaxanthin (208.84 μg/g), and phytofluene (232.5 μg/g) (d.w.) Carotenoid extract was capable of inhibiting 5% of the human prostate cancer cell line DU-145	Anti-cancer potential of carotenoids Carotenoids may be used as an adjunct so as to reduce the effective concentration of a cancer drug, causing less harm to normal cells present besides tumor growth Although the anti-cancer activity is minimal, it reflects high potential at even higher concentrations	2015	[241]

Table 4. Clinical data of the beneficial use of carotenoids, vitamin A, and its vitaminoids from microorganism sources in nutricosmetics, cosmeceuticals, and cosmetics applications.

Type of Microorganism	Microorganism	Type of Vitamin A Derivative	Hypothesis—Intervention (Type of Study)	Study Design—Parameters Examined	Results—Observed Benefits	Nutricosmetic, and/or Cosmeceutical, and/or Cosmetic Application	Year Study	References
Fungi	Blakeslea trispora and Mucor circinelloides	β-carotene	Three photoreceptor genes in B. trispora were cloned, expressed, and characterized via bioinformatics and photoreception in vitro analyses, while their analysis in vivo was conducted in M. circinelloides	Btwc-1a, btwc-1b, and btwc-1c from B. trispora were cloned and expressed Wort medium was prepared by saccharification of 200 g of wheat flour, added to 80 mL water, stirred, and heated at 50, 72, and 76 °C for 1 h each Photo-responsive analysis of btwc-1 was held in vitro UV-visible light, fluorescence scanning, and analysis of the genes in vivo were also held	Btwc-1: photoreceptor protein that acts as a light sensor to regulate carotenoidogenesis in B. trispora Light-oxygen voltage domains (LOV) of these proteins undergo a photochemical reaction that indicates photoreception ability through cysteine residues B. trispora genes were expressed in M. circinelloides ones Such genes are photosensitive B. trispora genes were implicated in different light transduction cascades regulating both carotenogenesis and phototropism	Carotenogenesis modulation Phototropism regulation	2020	[218]
	Blakeslea trispora	Phytoene-rich β-carotene and lycopene	Evaluation of the efficacy of the carotenoid biosynthesis inhibitors diphenylamine (DPA) and 2-methyl imidazole and sterol biosynthesis inhibitor, terbinafine hydrochloride (TH) (in vitro and in vivo)	The microorganisms for fermentation were Β. Trispora ATCC 14271, of mating types (+) and (−), grown separately at 26 °C for 5 days The yeast strain for the in vivo experiment was Saccharomyces cerevisiae EGY48 (stored at 4 °C) In vivo antioxidant activity assay was held	An increase in phytoene production was made according to TH and DPA addition, while concurrently lycopene decreased Yeast cells with no phytoene treatment were sensitive to the oxidizing agent (20% survival), in contrast to those treated with phytoene-rich carotenoid extract, which showed 93% survival rates	Strong antioxidant activity of the phytoene-rich extract Cytoprotective effect	2024	[219]
	Mucor circinelloides	β-carotene	Optimization of β-carotene production in M. circinelloides strain 277.49 by response surface methodology (RSM) (in vitro)	Cerulenin and ketoconazole were used for inhibiting fatty acids and sterol biosynthesis pathways, respectively Fungal fermentation was conducted, with seed culture prepared by inoculating 100 μL spore suspension into 150 mL Screening of carbon sources for optimal C/N ratios, effect of inhibitors on β-carotene formation, and optimization by RSM were also held	Carbon/nitrogen (C/N) ratio, cerulenin, and ketoconazole were synergistic combinations for β-carotene formation 4.26 mg/L (0.43 mg/g) of β-carotene was produced as compared with the control sample RSM has a beneficial effect on recognizing medium components	Ideal model strain for carotenogenesis and lipid production for biotechnological applications Cytoprotective effect of the product	2020	[220]
	Neurospora crassa and Fusarium fujikuroi	Neurosporaxanthin	The investigation of neurosporaxanthin’s antioxidant activity in vitro by the aid of several assays and liposomes, which was produced by carS gene mutant of F. fujikuroi (in vitro)	Fusarium fujikuroi wild strains IMI58289 and FKMC1995 and carS mutants were used (low-N medium, 10% ICI medium (80 g/L D(+)-glucose)) All samples were stored (−80 °C) and freeze-dried (24 h) Carotenoids were extracted and dissolved in acetone Spectrophotometry, HPLC, antioxidant DPPH and FRAP assay, quenching and scavenging activity in liposomes, was also held	Carotenoid overproduction by microorganisms was observed F. fujikuroi SG39 extracts had substantially higher antioxidant activity than SG256 High antioxidant capacity and scavenging ability against several free radicals in aqueous solutions and liposome environments The quenching ability correlated well with the one found in fruits and vegetables Significant quenching ability of neurosporaxanthin-rich extracts against [O2(1Δg)] in organic solvent at least as efficient as β-carotene High scavenging activity against HO radicals in liposomal systems	Antioxidant activity, high scavenging ability, and high quenching ability Promising for future use as a feed or food additive	2020	[39]
Yeast	Rhodotorula mucilaginosa (Pinaceae forest ecosystems)	β-carotene (mainly), torulene, and torularhodin	Four-pigment-producing yeasts isolated from park soils were examined for their potential to produce carotenoids (in vitro)	Samples were obtained with scraping of soil surface that provided about 10 g of soil (incubated at 28 °C for 48–72 h, maintained in agar) All yeast isolates were characterized by PCR and HPLC, Fourier transformed infrared spectroscopy (FT-IR), and gene submission	The main potential candidate produced was β-carotene Maximized carotenoid formation was observed by applying yeast extract peptone glycerol medium (120 h incubation, at 28 °C, pH 6.0, and white light exposure) The average maximum carotenoid content was 223.5 μg/g (d.w.) Apart from carotenoids, significant enzyme and lipid generation was observed	R. mucilaginosa could be a potent bio-source of natural antioxidant carotenoids Anti-cancer, antioxidant, and health-promoting properties	2021	[221,222]
	Rhodotorula glutinis (P4M422)	Preformed Vitamin A	Intracellular microbial production and examination of the most appropriate method for cell disruption (in vitro)	Rhodotorula glutinis (P4M422) was grown in yeast malt broth Cyclization inhibitors: imidazole, ketoconazole, and 2-isopropylimidazole aided in avoiding β-carotene-accumulating lycopene SEM and HPLC techniques Antimicrobial and antifungal activity of the capsules against several fungi was examined (petri dishes with agar, 30 °C) Antioxidant activity by ABTS, DPPH, and FRAP assays	Higher carotenoid extraction was obtained under bead mill-assisted treatment that does not require toxic solvents like DMSO, with thus less associated health risk Highest lycopene concentration of 18.61 mg/L was obtained with 2-isopropylimidazole’s addition Lycopene capsules did not show significant antifungal activity but exhibited notable antioxidant action	Antioxidant and radical scavenging activity	2017	[223]
	Sporidiobolus pararoseus	Torularhodin	Oxidative activity and induced liver injury amelioration and confrontation by torularhodin	The antioxidant effects of torularhodin were investigated by DPPH and ABTS Moreover, this study also used a cell oxidative damage model in vitro and a d-galactose-induced liver-injured mouse model in vivo	Torularhodin affected oxidative damage by H2O2 to AML12 cells Torularhodin significantly reduced inflammatory cytokines It increased antioxidant enzyme action in mouse serum and liver D-Galactose oxidative damage, liver-induced, was mediated by torularhodin improving Nrf2/HO-1 activity B-cell lymphoma protein 2-associated X (Bax) and NF-κΒ expression were reduced Torularhodin upregulated mRNA expression of liver Nrf2, NAD(P)H dehydrogenase quinone 1 (NQO1), and HO-1	Free radical scavenging activity Oxidative damage prevention Strong antioxidant activity	2019	[224]
	Sporidiobolus pararoseus	Torulene and torularhodin	Cytoprotective effect and mechanisms of action examination concerning torulene and torularhodin on human prostate stromal cells (in vitro)	Torulene and torularhodin antioxidant action was traced in H2O2-induced oxidative damage in human prostate stromal cells (WPMY-1) Torulene and torularhodin were isolated from the extract S. pararoseus by HPLC method Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay Measurement of ROS levels, apoptosis, RNA extraction, RT-PCR, and western blot	After cells were treated with H2O2, a notable decrease in cell viability was observed The decrease attenuated after pre-treatment with torulene and torularhodin (0.5–10 μM) in WST-1 These carotenoids also attenuated H2O2-induced apoptosis in WPMY-1 cells via inhibiting ROS species and MDA overproduction, as well as the activation of CAT, SOD, and GSH-Px action This pre-treatment also led to regulation of mRNA and protein expression in Bcl-2 and Bax	Antioxidant and cytoprotective activity Human prostate cells’ protection from oxidative stress damage via Bcl-2/Bax-mediated apoptosis	2017	[225]
	Phaffia Rhodozyma (NRRL-Y 17268)	β-carotene, astaxanthin, and lutein	Establishment of the stability and antioxidant activity of the extracts obtained via different methods for recovering carotenoids (in vitro)	Yeast was preserved on YM agar, and stock cultures were incubated (48 h, 25 °C) Cell disruption was observed via DMSO and enzymatic disruption techniques TCC estimation, HPLC with variable wavelength detectors (HPLC-VWD), and antioxidant activity assay were also held	β-carotene was obtained at 81% among the carotenoids extracted Freezing favored the extraction, but carotenoids did not always have higher antioxidant activity By enzymatic extraction, the highest antioxidant activity values were received by ABTS and FRAP assays (4.00 and 3.66 mM trolox/μg, respectively)	Antioxidant and cytoprotective effect	2015	[226]
	Saccharomyces cerevisiae	β-carotene	Examination of the dual regulation of lipid droplet triacylglycerol metabolism and ERG9 expression for the improved production of β-carotene in this yeast (in vitro)	OA and cheap unsaturated fatty acids (UFAs) were used Quantitation of neutral lipid droplets (LDs) as the main storage location of β-carotene in this yeast was conducted Optimization of OA-promoting LDs formation and a series of OA-repressible promoters to replace ERG9 (transcriptional assay) were also held	LDs were the major storage locations of β-carotene in this yeast The competition for precursors between β-carotene and LDs, triacylglycerol biosynthesis, and enlarging storage space by engineering LDs genes, led to minor β-carotene accumulation Adding 2 mM of OA notably improved LDs triacylglycerol metabolism and resulted in 36.4% increase in β-carotene IZH1 promoter was utilized for replacing native ERG9 promoter The metabolic flux was diverted to β-carotene synthesis pathway and achieved 31.7% content increase No negative effects on cell growth	Gene transcription and antioxidant activity enhancement	2022	[227]
Bacteria	Paracoccus aurantius (MBLB3053T)	Mostly astaxanthin	Establishment of the production and identification of this bacteria species (in vitro)	The strain weighed 1.0 g was suspended in 10 mL of 0.85 % (w/v) NaCl, diluted in Reasoner’s 2A broth (aliquots: incubation at 30 °C, 1 week) Chemotaxonomic, physiological, biochemical, etc. studies, whole-genome sequencing, pigment extraction, and antioxidant potential of the carotenoid extract were held	All studies pointed out that the genus of P. aurantius, MBLB3053T strain, was utilized Genus’s authenticity and expected chemotaxonomic properties Astaxanthin (all-trans form) was mainly obtained Other astaxanthin isomers were as well generated High in vitro antioxidant activity of the cis astaxanthin isomers compared with the all-trans astaxanthin ones	High DPPH-scavenging activity Antioxidant ability	2024	[228]
	Paracoccus carotinifaciens	Astaxanthin-rich extract from P. carotinifaciens (supplement)	Examination of the effect of this supplement on cognitive function of middle-aged subjects (45–64 years) (in vivo)	Group 1: Cognitive functions of 28 subjects, orally given 8 mg astaxanthin/day of this supplement for 8 weeks Group 2: 26 subjects were given a placebo All subjects were compared by word memory test, verbal fluency, and Stroop test Then, subjects were divided into over/equal (≥) and under (<) 55 years old groups	The astaxanthin group experienced remarkably larger increase in the blood astaxanthin levels than the placebo group, with no notable intergroup differences Results for the “words recalled after 5 min” assay in the word memory test in the under 55 years old group revealed that the subjects showed notable improvement in the astaxanthin group than the placebo one, which was not found in the ≥55 years old group subjects No safety-related problems were demonstrated	Cognitive function improvement for individuals aged 45–54 years old after ingesting astaxanthin supplements for 8 weeks	2018	[229]
	Arthrobacter agilis DSM 20550T and Arthrobacter bussei DSM 109896T	Bacterioruberin	Investigation on the membrane fluidity regulation by C50 bacterioruberin in pink-pigmented Arthrobacter species (in vitro and in vivo)	All bacterial strains were appropriately cultured and cultivated and statistically evaluated Total carotenoid content was estimated by HPLC, and freeze–thaw stress test was conducted	Strains showed increased bacterioruberin content by the time the growth temperature was reduced from 30 to 10 °C In vivo anisotropy with trimethylammonium-diphenylhexatriene had increased membrane fluidity and a broadening phase transition with increased bacterioruberin membrane content at low-temperature growth Suppression of bacterioruberin synthesis at 10 °C with sodium chloride: bacterioruberin highly modulates membrane fluidity Increased bacterioruberin content correlated with increased cell resistance to freeze–thaw stress Adaptive function of bacterioruberin strains at low °C	Membrane fluidity modulation	2022	[230]
	Citricoccus parietis AUCs	β-carotene	Investigation on the production of bioactive β-carotene by the endophytic bacterium Citricoccus parietis AUCs and the in vitro biological potential (in vitro)	Production of pigment by C. parietis strain AUCS by cultivation, nutrient broth inoculation, incubation for 72 h at 35 °C and 150 rpm, and extraction of the pigment Purification and identification by TLC, UV/Vis, and HPLC Evaluation of the antibacterial, antioxidant (DPPH), and anti-diabetic potential	The extracted yellow pigment obtained by this strain was extracted by methanol and identified as β-carotene by TLC The pigment displayed great antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Streptococcus agalactiae The pigment extract had considerable TAC (3097.5± 5.4 μg AAE/mg pigment extract) and DPPH scavenging activity (87%) Notable anti-diabetic inhibition of pancreatic α-amylase (73.8%) and increased glucose uptake by yeast cells (55.32 and 71.7% at 5 mM and 10 mM glucose), respectively	Antibacterial, antioxidant, and anti-diabetic	2023	[231]
	Exiquobacterium acetilicum S01	Lycopene (Car-I), Diapolycopene-dioic-acid-diglucosyl-ester (Car-II), β-carotene (Car-III), zeaxanthin (Car-IV), astaxanthin (Car-V), and Keto-Myxocoxanthin (Car-VI)	Evaluation of the anti-cancer, antioxidant, and anti-inflammatory potential of this bacterium	The six carotenoids were isolated and identified from the methanolic extract HPLC, cell viability by the MTT assay in HT-29 cells, anti-inflammatory activity by triggering PBMCs with LPS (1 h) and 100 μM carotenoids (24 h), and DPPH activity estimation were utilized	Two structurally novel and four known carotenoids were identified All six carotenoids exhibited notable inhibition of the HT-29 cell viability, dose-dependently, with no cytotoxicity for PBMCs They also inhibited LPS-induced iNOS generation, TNF-α activity, and lipid peroxidation in PBMCs Four carotenoids had a potent anti-proliferative effect against colorectal cancer Car-II and Car-VI displayed a promising anti-inflammatory activity in LPS-induced PBMCs Car-II and Car-VI had a notably higher antioxidant potential than ascorbic acid (DPPH)	Potential therapeutic agents for inflammation-associated cancer Antioxidant, radical scavenging, anti-inflammatory, and also anti-proliferative activity	2020	[232]
	Dietzia natronolimnaea (waste molasses and its hydrolysate)	Canthaxanthin	Examination of the carotenoid production from hydrolyzed molasses by this bacterium HS-1 with different cultivation methods (in vitro)	Three cultivation strategies: batch, fed batch, continuous culture for biomass and carotenoids synthesis Enzymatic, acidic, and acidic at high temperature pre-treatment was conducted to find the best hydrolysate by sucrose conversion rate Pigment extraction, dry biomass, TCC, and carotenoid pigment analysis were held	Canthaxanthin and enzymatic hydrolysis were the most abundant pigment biosynthesized and the most suitable process for substrate production An increase (double) in reducing sugar levels of enzymatic hydrolase molasses (EHM) (25 to 50 g/L): decrease in biomass formation-substrate use EHM of 25 g/L was a better substrate for cell growth and product formation than waste molasses of EHM 25 g/L Enhanced biomass generation, mostly in fed-batch culture Continuous cultivation had the highest biomass (12.98 g/L), carotenoid (27.33 mg/L), and canthaxanthin (25.04 mg/L) yields	Canthaxanthin may be used as a natural antioxidant for possible formation of healthy, functional foods	2014	[233]
	Escherichia coli	Carotenoid holoprotein and carotenoids in general (mainly β-carotene and violaxanthin)	A method for producing large amount of holo-orange carotenoid protein (holo-OCP) that is suitable for pharmaceutical and cosmetic industry (in vitro and in vivo results)	Six different genes were involved in holo-OCP synthesis and were introduced via three different plasmids in E. coli Amplification and cloning of Crt genes encoding enzymes and an ocp gene, OCP isolation, calculation of holo-OCP levels, OCP fluorescence quenching ability, 1O2 detection, TCC in OCPs by HPLC, and mass spectrometry were used	200 times more holo-OCP in 20% of the time of purifications, involving overexpression in cyanobacterial cells In only 4 days, more than 30 mg of holo-Synechocystis-OCP may be obtained via E. coli Carotenoid genes must be induced with arabinose (37 °C) for high carotenoid cells, then by isopropyl β-D-thiogalactopyranoside (IPTG) addition (20–28 °C) to slow down protein synthesis, allowing protein folding and carotenoid binding	Antioxidants of great interest for pharmaceuticals and cosmetics Antiradical and photo-protective activity	2015	[234,235]
	Escherichia coli	Retinyl palmitate	Evaluation of the microbial production of retinyl palmitate and its benefits in skin physiology (in vitro)	A heterologous biosynthesis pathway (retinyl palmitate) in E. coli by expression agents in Pantoea agglomerans, Salinibacter ruber, and Homo sapiens E. coli cells were grown at 37 °C and cloned at 30 °C Extraction and retinoid analysis, batch and fed-batch, cell viability, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and RT-PCR were conducted	High retinyl palmitate production (69.96 ± 2.64 mg/L) was obtained by fed-batch fermentation Application of purified microbial retinyl palmitate to human foreskin HS68 fibroblasts resulted in cellular retinoic acid-binding protein 2 (CRABP2) mRNA level, acceleration of cell proliferation, and procollagen synthesis Other retinyl fatty acids may be produced by further metabolic engineering of retinyl palmitate producing E. coli	Strong anti-aging impact First evidence for application in cosmetic and cosmeceutical products	2020	[236]
	Spirulinaplatensis	B-carotene	Study and evaluation of skin creams integrated with bioactive S. platensis extract	The bacterium was cultivated, and in vitro cytotoxicity of this extract was evaluated (0.001–1% concentrations for 1, 3, and 7 days on HS2 keratinocytes) Crude extracts were integrated into skin creams at 0.01% (w/w) In vitro wound healing, genotoxicity studies, and immunohistochemical staining for collagen action assessment were performed	0.1% S. platensis extract exhibited higher proliferation activity in contrast to the control group 198% cell viability was observed after 3 days Skin cream with 1.125% S. platensis crude extract displayed an enhanced wound healing effect on the HS2 keratinocyte cell line and the highest HS2 cell viability (5) Micronucleus (MN) assay outcomes pointed out that this cream had no genotoxic effect on human peripheral blood cells Collagen type I immunoreactivity was positively impacted by increased extract concentration (1.125% extract)	S. platensis extract incorporated in a skin cream has potent value in cosmeceutical and biomedical applications Collagen production improvement Wound healing ability	2017	[237]
	Spirulina platensis	β-carotene and zeaxanthin (blue–green) in this microalgae powder	Investigation of the influence of a food supplement powder of this bacterium on the skin (in vivo)	Ten heathy Caucasians (eight females and two males) with skin types II and III (25–54 years old) ingested 0.7 g/dose stirred into peach juice and applied products twice/day for 8 weeks Measurement of the second-harmonic generation to autofluorescence aging index of dermis (SAAID), collagen/elastin index, and cutaneous carotenoid levels	Powder carotenoid content: 461 mg/100 g with mainly β-carotene (214 mg/100 g) and zeaxanthin (191 mg/100 g) Notable average increase from 2.76 ± 0.86 arb. units to 3.25 ± 0.93 in cutaneous carotenoid concentration was detected after the oral powder application Significant improvement of the antioxidant status of the skin Slight but not remarkable increase (p = 0.33) in dermal SAAID mean values (−0.54 ± 0.11 to −0.51 ± 0.11)	Improved antioxidant status of the human skin	2015	[238]
	Micrococcus Luteus (Q24)	Carotenoid pigments probiotics	Determination of the impact of direct skin application of a topical serum formulation containing this probiotic on several key cosmetic skin quality parameters and its beneficial impact on the modulation of the skin’s microbiome (in vivo)	The serum contained two chambers: chamber A with the serum and B with the hydrator 10 healthy females (18–60 years old), with healthy skin but concerns on mild-to-moderate breakout, fine lines, wrinkles, uneven skin tone, dullness, or redness cases, participated Females applied two pumps (>1 × 108 cfu/dose) of the serum on the face twice/day (morning and night) for 25 days Skin parameters and skin swab samples were tested Whole-genome sequencing (WGS) was performed Patients were instructed not to change their skincare routine or try new products	Significant reduction in pores, spots, wrinkles, and impurities scores was exhibited along with a 101% hydration score observation 45–80% of participants had a decrease in pores, spots, wrinkles, and impurities 90% of the females partaking in the experiment showed a hydration increase after 25 days of the probiotic serum application WGS analysis in skin swab samples demonstrated notable increase in the relative abundance of M. luteus Colonization efficacy and hydration level improvement was as well confirmed	Topical application of this serum offers improved skin health quality Potential beneficial effects in cosmetic products Antioxidant, antibacterial, and UV-protective properties of carotenoids isolated from this bacterium were observed in a previous (almost similar research (2013))	2024	[64,239]
Algae	Neochloris oleoabundans	Lutein, carotenoid monoesters, and violaxanthin	Microalgae extracts were obtained by pressurized liquid extraction (PLE) to evaluate differences in the type and number of carotenoids produced (in vitro)	Cultures were established in modified bold’s basal medium (BBM) until optimal density All experiments were carried out in a chamber (24 ± 2 °C, 16 h photoperiod) Nitrogen, light, and CO2 impact Quantification of carotenoids and chlorophylls Anti-proliferative assay	Under appropriate conditions, these microalgae extracts obtained by PLE are able to produce considerable β-carotene, lutein, and carotenoid monoesters Violaxanthin formation	Potent use of carotenoids from N. oleoabundans as a functional food or nutraceutical in preventing colon cancer Cytoprotective and anti-proliferative activity	2016	[240]
	Coelastrella oocystiformis.	β-carotene, astaxanthin, lutein, canthaxanthin and phytofluene	Characterization of this microalgae species’ high carotenoid potential and evaluation of its anti-cancer ability (in vitro)	BG11 media was utilized for the isolation of this microalgae with several ingredients (g/L), (pH = 7.1, at 25 °C, 5000 lux, and 12:12 h light/dark cycle) GC–MS, analysis of pigments by high-performance thin-layer chromatography (HPTLC), and anti-cancer potential estimation	The strain had a doubling time of 12 ± 1.0 h with 3% CO2 and 27 ± 1.0 h without 3% CO2 With 3% CO2 a biomass of 89.6 + 2.0 mg/L/day and without only 42.555 + 2.0 mg/L/day were yielded Carotenoid content: 1.972% d.w. HPTLC revealed carotenoids, β-carotene, lutein (518.64 μg/g), free astaxanthin (120.5 μg/g), canthaxanthin (208.84 μg/g), and phytofluene (232.5 μg/g) (d.w.) Carotenoid extract was capable of inhibiting 5% of the human prostate cancer cell line DU-145	Anti-cancer potential of carotenoids Carotenoids may be used as an adjunct so as to reduce the effective concentration of a cancer drug, causing less harm to normal cells present besides tumor growth Although the anti-cancer activity is minimal, it reflects high potential at even higher concentrations	2015	[241]

7. Recent Advances in the Delivery Systems of Vitamin A and Its Derivatives in Nutricosmetics, Cosmeceuticals, and Cosmetics Applications

Vitamin A, retinoids, and carotenoids are incorporated into a variety of formulations for topical, oral, and injectable applications, depending on their intended use in nutricosmetics, cosmeceuticals, and cosmetics. Considering vitamin A and retinoids in topical formulations, creams and serums containing retinol, retinal, and tretinoin are commonly included in anti-aging and acne treatment products as stabilizers against oxidation and as agents for skin penetration enhancement [111,242]. Similarly, carotenoids, including β-carotene, lutein, or lycopene, have been utilized in topical creams and lotions for photo-protection and antioxidant benefits enhancement, which are best achieved when such formulations use liposomes, nanoemulsions, or microencapsulation for stability and better skin delivery [15,243]. Apart from creams and serums, retinol and retinoids have also been utilized in higher concentrations in gels and ointments for conditions like psoriasis and severe acne [244,245], while they have been incorporated in microneedle patches able to deliver them into deeper skin layers [246].

Oral vitamin A and retinoid supplementation is accomplished by the consumption of capsules, soft gels, or tablets that are comprised of retinyl esters or retinol for systemic benefits, including addressing vitamin A deficiency or enhancing skin and eye health [11,247,248]. Furthermore, injectable retinol-based formulations are also preferred during vitamin A deficiency [21,74]. Following vitamin A supplementation, nutraceuticals in the form of capsules or powders contain carotenoids like β-carotene, lutein, zeaxanthin, or lycopene as dietary supplements and nutricosmetics for skin protection, eye health, and antioxidant support [53,249]. Functional foods and beverages infused with carotenoids such as astaxanthin or lycopene for oral consumption have been confirmed as well to be great antioxidants, anti-proliferatives, and anti-aging agents [250,251].

However, the increase in the resilience and complications of several disorders has called for the improvement in the delivery systems of both vitamin A and its derivatives. Advanced delivery systems include formulations tailored to the bioavailability, stability, and specific health benefits of the active compounds, ensuring their efficacy across a range of applications. Retinol, retinoids, and carotenoids have been incorporated in nanocarriers like nanoemulsions and liposomes as nanoscale delivery systems so as to enhance stability, skin absorption, and targeted delivery [15]. Moreover, hydrogels, biodegradable polymers, and emulsions have also been exploited in topical applications for controlled release and sustained effects of retinol, retinoids, and carotenoids [244,245]. Finally, microencapsulation has also been utilized for enclosing and rapidly delivering vitamin A, retinoids, and carotenoids to target cells (Figure 13) [15].

Figure 13. Different formulations, microencapsulation, and nanoencapsulation for systemic delivery of vitamin A, retinoids, and carotenoids.

Microencapsulation and nanoencapsulation are two encapsulation technologies currently utilized for vitamin transportation, and many attempts towards overcoming their chemical instability have been conducted. The procedure of coating or enclosing tiny solid, liquid, or gas particles in a continuous polymeric layer is microencapsulation. The coated substance, also known as the payload, internal phase, fill, core material, or actives, can be encapsulated alone or in conjunction with additional substances, while the coating material is also referred to as an encapsulating agent, wall material, shell, or carrier and frequently takes the form of combined materials. Since vitamin A is a hydrophobic, fat-soluble compound, it can rapidly break down in the presence of water-based solutions, while it is poorly soluble in aqueous solutions due to its low polarity. Furthermore, it is an extremely sensitive substance that reacts with a variety of other substances, including oxidants, temperature, trace metals, light, heat, and moisture [15,252,253,254]. By selecting the correct encapsulation method, vitamin A can be added to carriers with favorable chemical and physical characteristics to boost its remedial ability, bioavailability, dispersity, controlled release, accurate delivery at the intended spot, and maximum absorbance. Importantly, with a view to achieving the desired encapsulation efficiency, microparticle stability, and essential final product qualities in accordance with its applicability, the right encapsulating agent must be selected, which should not react with the core material, be eco-friendly, and be non-toxic. Spray-cooling, spray-drying, cochleates, coacervation (phase separation), emulsion systems, liposomes, and solid lipid nanoparticles are widely appealing microencapsulation techniques, while the most utilized microencapsulation method for carotenoids is spray-drying technology, with multiple studies globally documenting using a variety of biopolymers as encapsulating materials [244,245,255,256,257]. For instance, Arabic gum has been pointed out as a promising encapsulating agent due to its capacity to generate stable microemulsions of sufficient solubility and low viscosity for carotenoids’ delivery (Figure 13) [257,258].

Nanoencapsulation has also been proven as a highly efficacious approach for improving carotenoid’s chemical stability, thereby safeguarding their bioactivity and stability against potential external influences throughout diverse processing and storage conditions. This method refers to the entrapment of active compounds like vitamin A, its vitaminoids, and carotenoids within nanoscale carriers including liposomes, polymeric nanoparticles, micelles, and solid-lipid nanoparticles for targeted and controlled delivery of bioactives, improved skin penetration, protection from degradation and sun exposure, reduced toxicity and irritation, enhanced stability, antioxidant activity, and bioavailability, as well as effective treatment of retinol deficiency, wound healing, and skin disorders (i.e., acne in topical, oral, or systemic delivery) [15,197,252,259,260]. The most frequently used nanoencapsulation methods are nanoemulsions of vitamin A and carotenoids, namely colloidal dispersions with nanometer-sized droplets (20–200 nm) in a continuous phase, stabilized with surfactants. Nanoemulsions improve the solubility of lipophilic compounds like retinol, enhance their stability, amplify their bioavailability, and promote rapid penetration, while being created via ultrasonication, high-pressure homogenization, and/or micro-fluidization (Figure 13) [15,197,252,259,260].

8. Limitations and Future Perspectives of Vitamin A, Vitaminoids, and Carotenoids in Nutricosmetics, Cosmeceuticals, and Cosmetics Applications

Despite the recognized potential of vitamin A, its vitaminoids, and carotenoids in several scientific fields, certain limitations hinder their widespread application in nutricosmetic, cosmeceutical, and cosmetic formulations. Vitamin A, vitaminoids, and carotenoids are highly sensitive to light, heat, and oxygen; thus, they are prone to oxidative degradation and loss of potency during formulation, storage, and use (photodegradation) [3,136,261]. Due to their chemical instability [262], vitamin A and its derivatives also demonstrate chemical instability that requires the use of advanced encapsulation and stabilizers, which may subsequently increase production costs and manufacturing complexity. Moreover, such compounds are lipophilic, resulting in poor solubility in aqueous systems and limited absorption in the GI, while their low skin penetration is also an important disadvantage [105,127]. Additionally, several adverse effects follow systemic retinoids and carotenoids excessive usage in some cases, counting skin irritation, oxidative stress, elevated cancer risk, hypervitaminosis, carotenemia [123], build-up of tolerance, dermatological issues (e.g., erythema) [100], and concurrently, inconsistent clinical efficacy, questionable bioavailability, safety aspects, and environmental sustainability play a significant role in boundless utilization [53,125,127].

Concerns regarding the lack of robust and recent clinical evidence to support the anti-aging, photo-protective, and antioxidant claims of many retinoids and carotenoids pose another significant limitation. Many strategies have been put out to slow down the aging process and rejuvenate older skin, but as of right now, there are no 100% safe and effective treatment solutions to prevent skin atrophy in older people [242,263]. More specifically, the cellular and molecular processes ATRA uses to prevent aging are currently unknown exactly, while there is a significant lack of studies examining the molecular basis of topical retinol anti-aging benefits in aged human skin, in contrast to ATRA. As a consequence, it has been proven challenging to comprehend the molecular pathways by which retinoids exacerbate aging in human skin, due to an absence of suitable in vivo and in vitro models [111]. Numerous studies evaluating retinoids and carotenoids suffer from methodological limitations like small sample sizes, inappropriate control groups, little to no rigorous scientific backing, and a lack of standardization, which create uncertainty regarding the true efficacy of retinoids currently used in cosmetics [242,263].

The future of vitamin A and its derivatives in cosmetics lies in addressing these limitations and exploring new frontiers. With a view to overcoming all limitations and bettering the clinical experience for patients, many advances, primarily in the delivery systems of vitamin A and vitaminoids, are necessary. More specifically, nanotechnology improvements, including nanoemulsions, liposomes, solid lipid nanoparticles, and micelles, offer promising solutions for developing more stable, bioavailable systems capable of controlled release of such compounds [15,125,127,197,242,253,254]. For instance, retinyl retinoate, retinyl N-formyl aspartamate, and other chemically stable ester derivatives are being thoroughly investigated to enhance resistance to degradation [242]. Biopolymeric encapsulation, antioxidants encapsulation, light-protective packaging, and hybrid delivery systems utilizing hydrogels for encapsulating such bioactives may further optimize targeted delivery and enhance stability for topical and oral applications [244,245]. Furthermore, advances in bioengineered sources, microbial fermentation, genetic engineering of microorganisms, and synthetic biology may enable the production of carotenoids and retinoid-like compounds from non-animal, plant, herb, or marine sources. Hence, sustainable plant-based and microbial-derived agents can offer more sustainable, scalable, and ethical alternatives [1,18,142]. Additionally, combination therapies of vitamin A derivatives with other bioactive compounds, such as antioxidants (e.g., vitamin E, coenzyme Q10 (CoQ10)) or peptides, may enhance synergistic effects in anti-aging and photo-protection formulations [14,26,80,123,243].

Personalized/customized formulations capable of targeting specific skin concerns based on an individual’s profile, more in vivo and in vitro clinical trials, and exploration of other novel applications of vitamin A and its derivatives such as epigenetics [264,265], anti-inflammatory treatment [73,84], and skin microbiome modulation [11,266] are only a few scientific approaches needed to be made prior to these bioactives’ systemic use.

9. Conclusions

Vitamin A and its derivatives, including retinoids and carotenoids, represent a cornerstone in skin health, offering many benefits in nutricosmetic, cosmeceutical, and cosmetic applications. Such bioactives have an unparalleled efficacy in skin rejuvenation, photo-protection, and anti-aging. Retinoids like retinol and mainly retinoic acid enhance collagen synthesis, accelerate epidermal turnover, and repair UV-induced damage by upregulating repair enzymes and inhibiting MMPs. Meanwhile, carotenoids like β-carotene and lycopene exhibit antioxidant properties, scavenge ROS, and mitigate oxidative stress, crucial for preventing photo-aging and inflammation. Topical formulations, including creams, serums, and nanocarrier-based systems, ensure targeted delivery, addressing diverse skin concerns such as hyperpigmentation, acne, and elasticity loss. Moreover, nutraceutical supplementation with β-carotene or astaxanthin during several topical applications offers promising skin-health-related benefits by integrating carotenoids into human skin tissues, boosting systemic antioxidant defenses, and enhancing the skin’s resilience and tolerance against environmental aggressors.

Despite their remarkable benefits for skin health, aging, and other health aspects, vitamin A, vitaminoids, and carotenoids face limitations primarily related to stability, bioavailability, and adverse effects. Advances in nanotechnology, synthetic biology, and personalized approaches offer promising solutions for overcoming these challenges. By focusing on sustainable production, robust clinical validation, enhancing delivery systems, and developing encapsulation technologies, these bioactives hold immense potential to effectively drive the future of the cosmetic field. With ongoing research into novel delivery systems and synergistic formulations, vitamin A derivatives remain pivotal towards advancing skin health and solidifying their role as indispensable agents in nutricosmetics, cosmeceuticals, and cosmetics.