Functional Foods as a New Therapeutic Strategy 2.0

Non-communicable diseases (NCDs), including obesity, cardiovascular conditions, cancer, and type II diabetes, are the primary causes of mortality worldwide, accounting for over 41 million deaths annually. NCDs are often associated with a dietary pattern that is considered a risk factor due to its relatively high content of fat, refined sugar, salt, and cholesterol [1]. For this reason, dietary approaches are cost-effective and safe interventions that can provide short- and long-term benefits for the management of these NCDs. In this sense, the use of ‘functional foods’ could be considered a useful strategy to prevent or improve these medical outcomes, and it has gained significant research attention in the fields of food health and technological innovations [2,3].

This Special Issue, entitled “Functional Foods as a New Therapeutic Strategy 2.0”, provides an overview of some potential ingredients and foods that could be used in future therapeutic functional foods and nutraceuticals. Among the foods/ingredients studied in the five original articles and six reviews that make up this Special Issue are (1) vegetables such as quinoa (contribution 1), avocado (contribution 2), and some edible plants (Momordica balsamina, Trifolium pratense, Achillea millefolium, etc.) (contributions 3–5); (2) plant-derived compounds like ursolic acid (contribution 6); (3) commercially available supplements such as Dekosilhue^® (contribution 7), melatonin (contribution 8), and Phoenix caffeine-free (Legion^®) (contribution 9); and (4) marine products such as marine organisms, edible seaweeds (contribution 10), and marine macroalgae (contribution 11).

Taco et al. highlight the potential of quinoa leaves, which consistently show high levels of polyphenols and α-amylase inhibition after 80 days of cultivation, regardless of variety, time, or production site. These leaves exhibit strong free radical scavenging activity and α-amylase inhibition, suggesting potential benefits for managing diabetes and oxidative stress-related diseases. Compared to quinoa seeds, quinoa leaves offer valuable health-promoting properties. The authors noted that further research could unlock the potential of quinoa leaves as a dietary vegetable, functional food, or source of bioactive compounds for the food and pharmaceutical industries.

The avocado (Persea americana) seed contains 64% of the phenolic compounds found in the entire fruit, indicating its potential for use in managing obesity, a significant risk factor for metabolic disorders. Research conducted by Mokhele et al. explored the impact of avocado seed powder on obesity caused by a high-fat diet in rats. After 6 weeks, rats consuming a high-fat diet with avocado seed powder gained less weight than those in the control group. Furthermore, triglyceride levels were lower in the treatment group. Due to its phytochemicals and trace elements, avocado seed powder shows promise as a natural solution for reducing obesity. Nonetheless, more extensive studies are necessary to understand its long-term effects, mechanisms, and safety for human use before it can be recommended as a regular supplement.

On the other hand, three narrative reviews in this Special Issue deal with the bioactive chemical components of edible and wild plants and their potential use in folk medicine. Red clover (Trifolium pratense), native to Southeast Europe and Anatolia, has traditionally been used to treat upper respiratory conditions. Zukić et al. highlight the bioactive compounds in red clover, with a focus on its commercially available isoflavone extracts, which have proven effective in managing menopausal symptoms. These symptoms include hot flashes, mood changes, sleep disturbances, and long-term risks such as osteoporosis, cardiovascular disease, and cognitive decline. The review analyzed eight randomized controlled trials involving 8769 menopausal women. The results showed that isoflavones which are structurally similar to 17β-estradiol activate estrogen receptors, alleviating common menopausal symptoms. Compounds like biochanin A and formononetin reduce hot flashes, improve lipid profiles, maintain bone density, and exhibit anticancer and cognitive benefits. Polyphenols such as daidzein and genistein also address hot flashes, lipid metabolism, and atherosclerosis. The authors concluded that red clover isoflavones hold promise for managing menopause-related health concerns.

The review from Thiaw et al. explores the therapeutic and nutritional potential of Momordica balsamina, commonly known as balsam apple. Widely used in traditional medicine, its various parts—leaves, fruits, roots, and stems—contain bioactive compounds such as polyphenols, flavonoids, terpenes, and carotenoids. These molecules demonstrate diverse biological activities, including antioxidant, anti-inflammatory, anti-diabetic, anticancer, and antimalarial properties. The leaves of this plant are particularly rich in micronutrients, proteins, and amino acids, making them a valuable nutritional resource. The review highlights the chemical composition of this plant, as well as its biological functions and nutritional benefits, while emphasizing the need for conservation strategies, further exploration of its cosmetic applications, and innovative methods for synthesizing its bioactive compounds.

Finally, and continuing in the field of wild edible plants, Fantasma et al. carried out a narrative review that summarizes the phytochemical, nutritional, and pharmacological properties of wild plants commonly found in the central Italian Apennines and the Mediterranean region, such as Achillea millefolium, Borago officinalis, and Foeniculum vulgare. These plants are commonly used to treat ailments like digestive issues, colds, and circulatory problems, as well as more specific conditions such as hypertension and hyperglycemia. Their effects, which are discussed in the review, are attributed to phytochemicals like phenols, polyphenols, flavonoids, and carotenoids, which are gaining attention for their diverse biological effects and health benefits.

In addition to plants, fruits, and seeds, there are compounds that are extracted from plant sources for their health-promoting properties. This is the case with ursolic acid, a triterpenoid found in plants like cranberries, which has strong anticancer potential. Kornel et al. conducted a review of recent evidence on the effect of this acid on colorectal cancer. Research over the past decade suggests that it inhibits the proliferation of colon cancer cells and induces apoptosis. Furthermore, limited animal studies also indicate reduced tumor volumes and angiogenesis.

On the other hand, there are also products on the market that have been shown to have therapeutic effects. Dekosilhue^® (DKS), for example, is a phytocomplex composed of a mix of thirteen plant extracts that is used as a dietary supplement to promote carbohydrate and lipid metabolism and has recently been reported to possess anti-neuroinflammatory activity. The study conducted by Borgonetti et al. evaluated DKS for its potential to reduce microglial senescence, produced by chronic low-grade systemic inflammation, a key factor in obesity.

Senescence was induced in a microglial cell line (BV2 cells) using intermittent lipopolysaccharide stimulation, and treatment with DKS (100 g/mL) decreased β-galactosidase activity, restored senescence-associated heterochromatin foci, and improved cell viability. DKS also reduced transcription factor (NF-κB) expression by 20%, a key regulator of the senescence-associated secretory phenotype. Additionally, DKS increased the viability of neuronal cells (SH-SY5Y cells) exposed to a senescent BV2-conditioned medium. These findings suggest that DKS exhibits senotherapeutic properties, with the potential to serve as an adjunctive intervention for obesity and related neurological disorders.

The effectiveness of caffeine-free fat loss supplements in enhancing thermogenesis remains unclear. The study conducted by Lafontant et al. compared the effects of a caffeinated (CAF) and non-caffeinated (NCAF) fat loss supplement on resting energy expenditure (REE), hunger, and hemodynamic variables in 25 healthy adults. CAF significantly increased participants’ REE compared to the placebo at all time points, while NCAF reduced hunger more effectively than CAF and the placebo at 120 min post ingestion. CAF raised systolic and diastolic blood pressure, but neither supplement affected participants’ heart rate. NCAF showed its potential to work as a fat loss aid through appetite suppression.

The study from Santos-Sánchez et al. explored the effects of melatonin (MLT) on lipid metabolism and cardiovascular risk in ApoE-deficient mice fed a Western diet. Mice were treated intragastrically with 2 or 9 mg/kg of MLT for 12 weeks. Although their body weight remained unchanged, the higher MLT dose significantly reduce low-density lipoprotein (LDL) cholesterol (LDL-C) levels and improved cardiovascular risk indexes. Additionally, MLT lowered hepatic total cholesterol and LDL-C levels, decreased leukocyte and lymphocyte populations, and enhanced antioxidant status. These findings suggest that MLT could be considered a functional ingredient that prevents or treats the development of cardiovascular diseases derived from a high cholesterol intake.

Seaweed is emerging as a sustainable and nutrient-rich food source, offering high levels of the vitamins, minerals, and proteins essential for human health. Seaweeds could serve as an alternative protein source, addressing global food security concerns and dietary needs, particularly within plant-based diets [4]. The review by Cotas et al. explores the growing interest in seaweed as a food source and nutraceutical. Seaweeds are recognized for their sustainability and potential to combat climate change, but their tendency to contain both beneficial and harmful components necessitate regulations to ensure consumer safety. Variations in composition among seaweed species influence their suitability as food or nutraceuticals, emphasizing the need for careful species selection and monitoring. The review underscores the importance of developing safe, innovative, and sustainable seaweed-based food products while addressing regulatory and safety challenges to improve human health.

Taking a more specific approach, the review by Yamaguchi highlights the potential of the marine alga Sargassum horneri to be a functional food factor with therapeutic and preventive effects against various metabolic disorders, including osteoporosis, diabetes, inflammation, and cancer. S. horneri water extracts promote bone health by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption, preventing bone loss from aging and diabetic conditions. They also reduce serum glucose and lipid levels, suppress adipogenesis, and alleviate inflammation. Additionally, S. horneri extract inhibits the growth of bone-metastatic breast cancer cells (MDA-MB-231) and suppresses NF-κB signaling, which is linked to inflammation, in osteoblastic and macrophage cells. This multifunctional bioactive component shows promise for developing health supplements to prevent and manage metabolic disorders.

The research presented in this Special Issue underscores the growing potential of functional foods and nutraceuticals to become viable strategies for preventing and managing NCDs. These diverse studies highlight the expanding scope of dietary interventions in improving metabolic, cardiovascular, and inflammatory conditions. While these findings reinforce the promise of bioactive compounds in addressing key health challenges, further clinical studies are necessary to translate these findings into safe and effective dietary solutions. As functional food science continues to evolve, interdisciplinary collaboration between nutrition, medicine, and food technology will be crucial in developing innovative approaches to enhancing global health.