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Mar. Drugs 2011, 9(3), 319-333; doi:10.3390/md9030319
Abstract: Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological functions of carotenoids relevant for life on earth. Biological properties of carotenoids allow for a wide range of commercial applications. Indeed, recent interest in the carotenoids has been mainly for their nutraceutical properties. A large number of scientific studies have confirmed the benefits of carotenoids to health and their use for this purpose is growing rapidly. In addition, carotenoids have traditionally been used in food and animal feed for their color properties. Carotenoids are also known to improve consumer perception of quality; an example is the addition of carotenoids to fish feed to impart color to farmed salmon.
1. Marine Carotenoids: Biological Functions and Benefits to Human Health
In photosynthetic organisms including plants and microalgae, carotenoids play various roles. Essentially, carotenoids may act as accessory pigments in light harvesting functions during the light phase of photosynthesis and are also able to photoprotect the photosynthetic machinery from excess light by scavenging reactive oxygen species (ROS) like singlet oxygen and other free radicals .
In humans, the most relevant biological functions of carotenoids are linked to their antioxidant properties, which directly emerge from their molecular structure. In recent years, the understanding of ROS-induced oxidative stress mechanisms and the search for suitable strategies to fight oxidative stress has become one the major goals of medical research efforts. A number of studies have been reported which implicate oxidative stress involvement in degenerative pathogenesis, e.g., Alzheimer and Parkinson [1,2]. In parallel, a carotenoid-enriched diet has been found to diminish the risk of suffering from degenerative diseases .
Moreover, far from being just a speculative hypothesis, the benefits of carotenoids (lutein, β-carotene, lycopene) to human health have been shown based on the positive impacts of the antioxidant bioactivity of carotenoids in inmunoresponse modulation, in signaling transduction between cells and in anti-inflammatory response mechanisms [3–5]. These positive consequences are the result of either the direct chemical action of carotenoids on biological molecules and structures or through expression of different genes involved in antioxidant responses . The main biological functions of carotenoids and benefits to health are listed in Table 1.
1.1. Provitamin A Activity
One of the most important functions of carotenoids in the human body is their ability to convert into retinol (provitamin A function), a faculty that about 10% of carotenoids identified in nature possess . Vitamin A is well recognized as a factor of great importance for child health and survival, its deficiency causes disturbances in vision and various related lung, trachea and oral cavity pathologies . Animals and humans cannot synthesize carotenoids de novo, although they are able to convert them into vitamin A. Diet is the only source for these precursors for retinol synthesis, fruits, vegetables and microalgae being the major suppliers of provitamin A active carotenoids. As a reference value, a recommended daily intake of 6 mg of carotenoids has been proposed. This value is based on the contribution of compounds with provitamin A activity, specially β-carotene, which has been assigned a provitamin A activity of 100% .
1.2. Carotenoids and Cancer
In recent years, epidemiological evidence supporting a protective effect of carotenoids to the development of chronic and degenerative diseases has grown considerably. We must not forget that cancer and cardiovascular diseases are the leading causes of death in the world and that approximately 50% of all tumors are attributed to the diet .
From a nutritional point of view, an antioxidant can be defined as any substance present in foods that significantly reduces the adverse effects of reactive oxygen species in normal physiological conditions in humans . Antioxidants, in particular carotenoids, are essential for cell health due to their protective action on cellular components against oxidative damage . These activities have generated two lines of research related to the physiological functionality of carotenoids: on one hand, their activity as membrane antioxidants, therefore involved in the oxidative cell cycle  and, on the other hand, their involvement in control processes of cell differentiation and proliferation . As an example of the first, a recent study showed that antioxidant enzymes including catalase, superoxide dismutase and peroxidase levels in plasma and liver of mice increased significantly when the animals were fed with microalgae biomass (Haematococcus pluvialis, Scenedesmus platensis or Botryococcus braunii), which reveals an increased antioxidant protection against free radicals .
It is well known that cellular proliferation is controlled by the communication established between the cells in a tissue. Cell communications reset or stimulation becomes essential if abnormal cell proliferation occurs. In that respect, it has been mentioned that carotenoids might stimulate expression of genes directly involved in regulation of cell communication processes. In more detail, carotenoids would directly act on DNA in order to regulate the production of RNA that is responsible for gap-junctions communications, which could successfully explain some anti-tumor activities of carotenoids [2,12]. Immune system cells also require intercellular communication to conduct their activity efficiently, so the previous action mechanism of carotenoids could also apply for supporting the immune system activity. As an example, high doses of β-carotene increase the CD4 to CD8 lymphocyte ratio, which is very low in patients suffering from HIV disease .
In the last decades, many laboratory and epidemiological studies have been conducted which suggest that intake of carotenoids and cancer prevalence are inversely related [4,15–17]. Among the carotenoids, lycopene has been one of the most extensively studied [4,18–20] probably due to the greater anticancer capacity shown with respect to other carotenoids . Within the wide frame of research carried out by Giovannucci et al. , lycopene intake and prostate cancer were found to be inversely related. The inverse relation was based on in vivo and in vitro studies on the effect of lycopene in tumor cell lines that showed tumor cells growth inhibition by the action of lycopene [19,20]. Although the functional meaning of the lycopene distribution in the organism has not been fully elucidated, it is particularly interesting that this carotenoid predominates in testes and adrenal glands, with an abundance of about 60 to 80% of the total carotenoids . It has also been inferred that astaxanthin could be effective against benign prostatic hyperplasia and against prostatic cancer through inhibition of the enzyme 5-a-reductase which is involved in abnormal prostate growth [2,23].
Antitumoral activity of carotenoids toward other type of cancer has also been observed. In particular, β-carotene, astaxanthin, cantaxanthin and zeaxanthin have been shown to promote reduction in size and number of liver neoplasias in vivo [21,24]. Other studies have shown that inclusion of carotenoids in the diet and reduced risk of colon cancer might be directly related [25–27]. The antitumoral effect of b-carotene has also been associated to the nutritional situation of the studied population. As an example, β-carotene implementation studies carried out at Linxian (China) in population that suffered from a diet deficient in vitamins and mineral salts, led to reduced incidence of total mortality from gastrointestinal cancer . Interestingly, in population not affected by nutritional deficiency but included in cancer risk groups (e.g., smokers or asbestos-exposed groups) it has been shown that β-carotene supplements even might increase cancer risk, probably due to generation of metabolites that increase the cell oxidative state and led to reduced control of cell differentiation and cell proliferation processes [29–32].
Although carotenoids including zeaxanthin, criptoxanthin and lutein antitumoral activities have still been scarcely studied, the strategy of using carotenoids as chemoprotecting agents is not yet endorsed by clinical trials. More on the contrary, in spite of using β-carotene as pure drug for producing an intense punctual effect after any dosage intake, the derived positive action of carotenoids should be produced through continuous intake of usual quantities. This idea is in line with current dietary recommendations that suggest consumption of five fruit and vegetables portions a day, which will provide water, vitamins, fiber and phytochemical compounds including carotenoids in sufficient quantities to meet our body needs [10,16].
1.3. Carotenoids and Cardiovascular Diseases
Cardiovascular diseases are the leading cause of death in developed countries, and have become the main health problem also in developing countries . These include acute myocardial infarction and disorder of high morbidity and mortality . Oxidative stress and inflammation are the main factors contributing to the pathophysiology of these disorders [35,36]. In particular, the oxidative stress induced by ROS can cause low density lipoproteins oxidation (LDL), an aspect that plays a key role in the pathogenesis of atherosclerosis [37,38].
Another major feature of carotenoids is protection of LDL against oxidation [39,40], which confers carotenoids antiatherogenic properties [2,36,41]. In addition, carotenoids have been shown to inhibit in vivo lipid peroxidation processes , by which the presence of carotenoids in cell membranes is essential to act as stabilizing elements of these structures [8,43]. In this sense, the antioxidant activity of some carotenoids during radical peroxide-induced cholesterol oxidation was investigated by Palozza et al. , showing that carotenoids exerted a significant antioxidant activity, in the decreasing activity order indicated: astaxanthin, cantaxanthin, lutein and β–carotene. Several authors have published that daily dietary β-carotene supplementation in mammals led to decreased plasma levels of total lipids, cholesterol and triglycerides [45,46].
Numerous epidemiological studies suggest that diets rich in carotenoids could protect the human body from certain cardiovascular diseases due to the involvement of oxidizing substances and oxidative stress in the development and clinical expression of coronary heart disease . In fact, high lycopene levels in plasma and tissues have been inversely linked to coronary heart disease , myocardial infarction  and risk to suffer from arteriosclerosis . Low lutein levels in plasma have also been associated with an increased tendency to suffer from myocardial infarction , while a high intake of lutein has been inversely related with the risk of stroke .
Likewise, low α-carotene levels in serum have been shown to inversely correlate prevalence of coronary artery disease and formation of arterial plaque, by which α-carotene has been proposed as a potential marker for human atherosclerosis. In addition, carotenoids displaying high levels of provitamin A activity, including α-carotene, β-carotene and β-cryptoxanthin, have been associated with reduced risk of angina pectoris disease [53,54]. Other epidemiological studies have also found low levels of oxygenated carotenoids (namely xanthophylls: lutein, zeaxanthin, lycopene, β-cryptoxanthin, β-carotene and α-carotene) in plasma of patients with acute and chronic coronary syndromes [55,56]. Particularly, in the recent study by , high levels of β-cryptoxanthin and lutein in plasma have been shown to decrease risk for suffering from myocardial infarction, but no statistically significant associations with other carotenoids were found.
1.4. Carotenoids and Eye Health
Many research studies showed that lutein and zeaxanthin are the main responsible pigments for both the yellowing and the maintenance of normal visual function of the human eye macula [57,58], while other major carotenoids in serum (α-carotene, β-carotene, lycopene and β-cryptoxanthin), are absent or are found in trace amounts in the human macula . In the eye macula, lutein and zeaxanthin absorb blue light and also attenuate pernicious photooxidative effects caused by the excess blue light, while reducing eye chromatic aberration. Due to their antioxidant properties, carotenoids protect the eye macula from adverse photochemical reactions . In people over the age of 64, visual sensitivity directly depends on lutein and zeaxanthin concentrations in retina .
Major prevalency of cataracts has also been linked to people with low levels of lutein and zeaxanthin . Also macular degeneration, the main cause of irreversible loss of vision in people above 65 years in industrialized countries, has been associated with very low levels of lutein and zeaxanthin [63,64].
The spectra of lutein and zeaxanthin show a wide absorption band with a peak at 450 nm, which is thought to be involved in absorbing excess blue light before it comes to photoreceptors, therefore preventing the eye macula from being damaged by blue light . Moreover, due to lutein’s and zeaxanthin’s biophysical and biochemical properties for ROS scavenging, these carotenoids might also preserve the membrane structure in the eye photoreceptors from lipid peroxidation processes , in contrast to non-polar carotenoids as lycopene and β-carotene . Concentration of lutein and zeaxanthin in the retina can be increased on diet bases (spinach and maize) and on supplements of both pigments [60,68].
1.5. Other Physiological Functions of Carotenoids
Carotenoids provide skin photoprotection against UV light [69–71]. Due to their scavenging action on ROS, carotenoids also possess anti-inflammatory properties [72–74]. In this sense, it has been recently described that astaxanthin raises anti-inflammatory effects while preserving essential lipids and proteins of human lymphocytes . Astaxanthin would act by inducing superoxide dismutase and catalase enzyme activities . Other studies have shown astaxanthin to protect from CCl4-induced hepatic damage by inhibiting lipid peroxidation, stimulating the cellular antioxidant system and modulating the inflammatory process . Table 1 resumes biological functions, benefits to health and applications of the main carotenoids, including their role in prevention of cataracts [75,76], macular degeneration [77–80], retinitis [81–83] and gastric infection .
Carotenoids have been used as preservatives in cosmetics and, combined with other antioxidants or algal bioactive substances, also in creams and lotions for sun protection . The beneficial effect of carotenoids has also been shown in patients with psoriasis, skin inflammatory pathology. Lima and Kimball  found low levels of carotenoids in the skin correlate well with psoriasis prevalence.
Finally, it is interesting to note that, in recent years, carotenoids are being considered as important protective molecules in gastric disorders. It has been published that a high intake of carotenoids prevents the development of disorders caused by Helicobacter pylori [84,87,88], a Gram negative bacteria genus that colonizes the gastric mucosa of at least half of the human population .
2. Marine Carotenoids: Applications
Carotenoids have been traditionally used in food and animal feed due to their color properties. The natural carotenoids are used to reinforce fish color, which increases consumers’ perception of quality. An example is the addition of carotenoids to fish feed to impart color to farmed salmon. The nutraceutical properties of carotenoids also attracted attention of the food industry. Large numbers of scientific studies have confirmed the benefits of carotenoids to health and use for this purpose is growing rapidly. Besides, carotenoids have been proposed as added-value compounds that could contribute to make microalgal biofuel production economically feasible [90,91].
Among all existing natural carotenoids, five can be considered to be the most relevant ones in economical terms (Table 2). The main applications of carotenoids are currently as dietary supplements, fortified foods, food color, animal feed and pharmaceuticals and cosmetics.
β-carotene, the most widely known of the carotenoids, is known to be a vitamin A precursor, likely several other carotenoids. Carotenoids have antioxidant properties and a large number of studies have confirmed their benefits to health. In particular, carotenoids are thought to reduce the risk of degenerative diseases and cancer especially in elderly people, as explained above [29,32,41].
The health industry uses carotenoids in over-the-counter (OTC) dietary supplements and fortified foods. This is one of the fastest growing segments of the industry but is still relatively small compared to the color segment. The pharmaceutical and cosmetics industries also use carotenoids mainly for their coloring properties, though their use by the pharmaceutical and cosmetics companies is growing rapidly due to their nutraceutical properties. An example of a new product from this segment is a ‘beauty pill’ containing the carotenoid lycopene. This product belongs to a new market segment known as ‘cosmeceuticals’, which aims to combine cosmetics and nutraceutical food ingredients to create products to improve skin and hair.
Chemically synthesized nature identical carotenoids dominate the market but naturally extracted carotenoids are growing in popularity due to increasing demand for natural products from consumers. Natural carotenoids can be extracted from plant material such as tomatoes, algae and fungi. Individual carotenoids are available in a variety of forms. The most common forms are cold water soluble powder, oil emulsion and beadlets. Concentrations range from 0.2 to 100%. The most common concentration is 10%. Blends or mixed carotenoids are also available containing two or more different carotenoids. Like the individual carotenoids, blends are available in a variety of forms including, water dispersible powder, oil suspension and beadlet forms. The concentration of blends ranges from 1 to 30%, with the most common concentration being 10% [91–93].
2.1. Dietary Supplements and Food Color
Carotenoids are widely used as color enhancers in natural foods including egg yolk, chicken meat or fish . However, among more than 400 known carotenoids just few of them have been commercially used, including β-carotene, lycopene, asthaxanthin and lutein . One of the main advantages in the use of microalgae as a carotenoid carrier in the food industry is that many other antioxidant compounds present in the microalgal biomass have positive impact on human health, sometimes acting with carotenoids synergistically .
In addition, if carotenoids are disposed within the microalgal matrix (carotenoid enriched dry biomass) also a number of minerals whose presence is inherent to the algal biomass are provided in the formula. These mineral have positive effects to human health, especially in enhancing anabolic activities. Carotenoids have also been used as preservatives in cosmetics and solar protection products .
Because of the content of carotenoids, the commercial value of microalgae increased and their use extended widely into many applications of the food market. That includes the use of Arthrospira, Chlorella, Dunaliella, Spirulina and Aphanizomenon as functional foods which can be found in the market in the form of pills, tablets and capsules. These microalgae have also been integrated in nutritional formula of pasta, snacks, sweets, drinks and bubble gum [91,93].
Microalgae are also used in fish color quality improvement in aquaculture. Salmonids are supplied with astaxanthin-enriched microalgae species, in particular Haematococcus pluvialis .
2.2. Environmental Applications: Carotenoids in Biorefining
Microalgae have gained interest as promising feedstocks for biofuels. The productivity of these photosynthetic microorganisms in converting carbon dioxide into carbon-rich lipids greatly exceeds that of agricultural oleaginous crops, without competing for arable land. However, large scale production of lipid-enriched algal biomass is not yet economically feasible and still requires major efforts in developing suitable technology which allows for reducing biomass production costs at large scale by at least an order of magnitude. Recent advances in systems biology, genetic engineering and methods to profit from the fractions of the biomass residue open new scenarios to make biofuel production from microalgae economically suitable within a period of about 15 years. Production of biodiesel and other bio-products from microalgae can be more cost-effective and profitable if combined with processes such as wastewater and flue gas treatments [94,95]. Carotenoids are, indeed, one of the main bio-products whose production is required to make biofuel production economically feasible. The paradox, therefore, is that production of high-added value compounds as carotenoids should so far be the only way to approach economical production of a low value energy source as biofuel from microalgae.
2.3. Commercial Value for Carotenoids
In recent years, production of carotenoids has become one of the most successful activities in microalgal biotechnology. The demand for carotenoids obtained from natural sources is increasing. This has promoted major efforts to improve carotenoid production from biological sources instead of chemical synthesis . According to the report published by Business Communications in March, 2008, the global market for all commercial carotenoids accounted for 766 million dollars, with expectations of rising to 919 million dollars in 2015. In particular, beta-carotene market volume in 2007 was 247 million dollars, with expectations of reaching 285 million dollars in 2015. Besides lycopene and β-carotene, xanthophylls lutein, astaxanthin and cantaxanthin appear as the most demanded and valuable carotenoids. Astaxanthin market volume in aquaculture in 2009 was 260 million dollars and about 2500 $ kg−1. In addition, lutein market volume in 2010 accounted for about 190 million dollars, the carotenoid experiencing the most rapid growth in sales . Therefore, carotenoid-containing microalgae find many applications in a wide range of commercial activities, the reason for which carotenoid-enriched microalgae production is steeply becoming an attractive business (Table 3).
This work has been supported by grant AGR-4337 (Proyecto de Excelencia, Junta de Andalucía) and grant Bioándalus (Junta de Andalucía, Estrategia de Impulso a la Biotecnología).
- Samples Availability: Available from the authors.
- Murthy, K; Vanitha, A; Rajesha, J; Swamy, M; Sowmya, P; Ravishankar, GA. In vivo antioxidant activity of carotenoids from Dunaliella salina, a green microalga. Life Sci 2005, 76, 1381–1390. [Google Scholar]
- Guerin, M; Huntley, ME; Olaizola, M. Haematococcus astaxanthin: Applications for human health and nutrition. Trends Biotech 2003, 21, 210–216. [Google Scholar]
- Le Marchand, L; Hankin, JH; Kolonel, LN; Beecher, GR; Wilkens, LR; Zhao, LP. Intake of specific carotenoids and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1993, 2, 183–187. [Google Scholar]
- Giovannucci, E; Ascherio, A; Rimm, EB; Stampfer, MJ; Colditz, GA; Willett, WC. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Nat Cancer Inst 1995, 87, 1767–1776. [Google Scholar]
- Biesalski, H. Evidence from Intervention Studies. In Functions of Vitamins beyond Recommended Dietary Allowances; Walter, P, Hornig, D, Moser, U, Eds.; Woodhead Publishing Limited: Cambridge, UK, 2001; pp. 92–134. [Google Scholar]
- García-González, M; Moreno, J; Manzano, JC; Florencio, FJ; Guerrero, MG. Production of Dunaliella salina biomass rich in 9-cis-β-carotene and lutein in a closed tubular photobioreactor. J Biotechnol 2005, 115, 81–90. [Google Scholar]
- Indicators for assessing vitamin A deficiency and their implications in monitoring and evaluating intervention programmes. WHO/NUT/9610; World Health Organization: Geneva, Switzerland, 1998.
- Graham, RD; Rosser, JM. Carotenoids in staple foods: Their potential to improve human nutrition. Food Nutr Bull 2000, 21, 405–409. [Google Scholar]
- Williams, GM; Williams, CL; Weisburger, JH. Diet and cancer prevention: The fiber first diet. Toxicol Sci 1999, 52, 72–86. [Google Scholar]
- Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids; Institute of Medicine, National Academy Press: Washington, DC, USA, 2000. [Google Scholar]
- McNulty, HP; Byun, J; Lockwood, SF; Jacob, RF; Mason, RP. Differential effects of carotenoids on lipid peroxidation due to membrane interactions: X-ray diffraction analysis. Biochim Biophys Acta 2007, 1768, 167–174. [Google Scholar]
- Bertram, JS. Carotenoids and gene regulation. Nutr Rev 1999, 57, 182–191. [Google Scholar]
- Ranga Rao, A; Raghunath, RL; Baskaran, V; Sarada, R; Ravishankar, GA. Characterization of microalgal carotenoids by mass spectrometry and their bioavailability and antioxidant properties elucidated in rat model. J Agric Food Chem 2010, 58, 8553–8559. [Google Scholar]
- Olson, JA. Carotenoids and human health. Arch Latinoamer Nutr 1999, 49(1-S), 7–11. [Google Scholar]
- Garewall, H. Antioxidants in oral cancer prevention. Am J Clin Nutr 1995, 62(Suppl), 1403S–1417S. [Google Scholar]
- Mayne, ST. β-Carotene, carotenoids, and disease prevention in humans. FASEB J 1996, 10, 690–701. [Google Scholar]
- Rock, CL. Carotenoids: Biology and treatment. Pharmacol Ther 1997, 75, 185–197. [Google Scholar]
- Narisawa, T; Fukaura, Y; Hasebe, M; Ito, M; Aizawa, R; Murakoshi, M; Uemura, S; Khachik, F; Nishino, H. Inhibitory effects of natural carotenoids, alpha-carotene, beta-carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rats. Cancer Lett 1996, 107, 137–142. [Google Scholar]
- Graydon, R; Gilchrist, S; Young, I; Obermüller-Jevic, U; Hasselwander, U; Woodside, J. Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: A double-blind, placebo-controlled trial. Eur J Clin Nutr 2007, 61, 1196–1200. [Google Scholar]
- Schwarz, S; Obermüller-Jevic, U; Hellmis, E; Koch, W; Jacobi, G; Biesalski, H-K. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr 2008, 138, 49–53. [Google Scholar]
- Nishino, H; Murakoshi, M; Li, T; Takemura, M; Kuchide, M; Kanazawa, M; Mou, X; Wada, S; Masuda, M; Ohsaka, Y; Yogosawa, S; Satomi, Y; Jinno, K. Carotenoids in cancer chemoprevention. Cancer Metast Rev 2002, 21, 257–264. [Google Scholar]
- Stahl, W; Sundquist, AR; Hanusch, M; Schwarz, W; Sies, H. Separation of β-carotene and lycopene geometrical isomers in biological samples. Clin Chem 1993, 39, 810–814. [Google Scholar]
- Anderson, M. Method of inhibiting 5α-reductase with astaxanthin to prevent and treat benign prostate hyperplasia (BPH) and prostate cancer in human males. US Patent No 6277417 2001. [Google Scholar]
- Gradelet, S; Le Bon, AM; Berges, R; Suschetet, M; Astorg, P. Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: Role of the modulation of aflatoxin B1 metabolism. Carcinogenesis 1998, 19, 403–411. [Google Scholar]
- Erhardt, JG; Meisner, C; Bode, JC; Bode, C. Lycopene, β-carotene and colorectal adenomas. Am J Clin Nutr 2003, 78, 1219–1224. [Google Scholar]
- Senesse, P; Touvie, M; Kesse, E; Faivre, J; Boutron-Ruault, M-C. Tobacco use and associations of β-carotene and vitamin intakes with colorectal adenoma risk. J Nutr 2005, 135, 2468–2472. [Google Scholar]
- Ramadas, A; Kandiah, M; Jabbar, F; Zarida, H. Dietary risk factors for colorectal adenomatous polyps: a mini review. J Sci Technol 2010, 18(2), 321–349. [Google Scholar]
- Blot, WL; Li, J-Y; Taylor, PR; Guo, W; Dawsey, S; Wang, G; Yang, C; Zheng, S; Gail, M; Li, G; et al. Nutrition intervention trials in Linxian, China: Supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Nat Cancer Inst 1993, 85, 1483–1492. [Google Scholar]
- Albanes, D; Heinonen, OP; Taylor, PR; Virtamo, J; Edwards, BK; Rautalahti, M; Hartman, AM; Palmgren, J; Freedman, LS; Haapakoski, J; et al. α-Tocopherol and β-carotene supplements and lung cancer incidence in the α-tocopherol, β-carotene cancer prevention study: Effects of base-line characteristics and study compliance. J Nat Cancer Inst 1996, 88, 1560–1570. [Google Scholar]
- Hennekens, C; Buring, J; Manson, J; Stampfer, J; Rosner, B; Cook, N; Belanger, C; LaMotte, F; Gaziano, J; Ridker, P; Willet, W; Peto, R. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasm and cardiovascular disease. N Engl J Med 1996, 334, 1145–1149. [Google Scholar]
- Rowe, PM. β-Carotene takes a collective beating. Lancet 1996, 347, 249. [Google Scholar]
- Lee, IM; Cook, NR; Manson, JE; Buring, JE; Hennekens, CH. β-carotene supplementation and incidence of cancer and cardiovascular disease: the Women’s Health Study. J Nat Cancer Inst 1999, 91, 2102–2106. [Google Scholar]
- American Heart Association. Heart Disease and Stroke Statistics—2008 Update; American Heart Association: Dallas, TX, USA, 2008. [Google Scholar]
- Lloyd-Jones, D; Adams, R; Carnethon, M; De Simone, G; Ferguson, TB; Flegal, K; Ford, E; Furie, K; Go, A; Greenlund, K; et al. Heart disease and stroke statistics—2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009, 119, 480–486. [Google Scholar]
- Heller, FR; Descamps, O; Hondekijn, JC. LDL oxidation: Therapeutic perspectives. Atherosclerosis 1998, 137(Suppl), S25–S31. [Google Scholar]
- Riccioni, G. Carotenoids and cardiovascular disease. Curr Atheroscl Rep 2009, 11, 434–439. [Google Scholar]
- Yla-Herttuala, S. Macrophages and oxidized low density lipoproteins in the pathogenesis of atherosclerosis. Ann Med 1991, 23, 561–567. [Google Scholar]
- Koh, W-P; Yuan, J; Wang, R; Lee, Y-P; Lee, B-L; Yu, MC; Ong, CN. Plasma carotenoids and risk of acute myocardial infarction in the Singapore Chinese Health Study. Nutr Metab Cardiovasc Dis 2011, 21, 1–6. [Google Scholar]
- Dugas, TR; Morel, DW; Harrison, EH. Dietary supplementation with β-carotene, but not with lycopene, inhibits endothelial cell-mediated oxidation of low-density lipoprotein. Free Radic Biol Med 1999, 26, 1238–1244. [Google Scholar]
- Bub, A; Watzl, B; Abrahamse, L; Delincée, H; Adam, S; Wever, J; Müller, H; Rechkemmer, G. Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men. J Nutr 2000, 130, 2200–2206. [Google Scholar]
- Sies, H; Stahl, W. Vitamins E and C, β-carotene and other carotenoids as antioxidants. Amer J Clin Nutr 1995, 62, 1315S–1321S. [Google Scholar]
- Seppanen, SM; Csallany, AS. The effect of paprika carotenoids on in vivo lipid peroxidation measured by urinary excrection of secondary oxidation products. Nutr Res 2002, 22, 1055–1065. [Google Scholar]
- Wieslaw, I. Carotenoid orientation: Role in membrane stabilization. In Carotenoids in Health and Disease; Krinsky, NI, Mayne, ST, Sies, H, Eds.; CRC Press Inc: Boca Raton, FL, USA, 2004; pp. 151–163. [Google Scholar]
- Palozza, P; Barone, E; Mancuso, C; Picci, N. The protective role of carotenoids against 7-keto-cholesterol formation in solution. Mol Cell Biochem 2008, 309, 61–68. [Google Scholar]
- Ben-Amotz, A; Yatziv, S; Sela, M; Greenberg, S; Rachmilevich, B; Shawarzman, M; Weshler, Z. Effect of natural beta-carotene supplementation in children exposed to radiation from the Chernobyl accident. Rad Environ Biophys 1998, 37, 187–193. [Google Scholar]
- El-Baky, H; El-Baz, F; El-Baroty, GS. Production of carotenoids from marine microalgae and its evaluation as safe food colorante and lowering cholesterol agents. Amer-Eur J Agric Environ Sci 2007, 2(6), 792–800. [Google Scholar]
- Kohlmeier, L; Hastings, SB. Epidemiologic evidence of a role of carotenoids in cardiovascular disease prevention. Amer J Clin Nutr 1995, 62(Suppl), 1370S–1377S. [Google Scholar]
- Kristenson, M; Zieden, B; Kucinskiene, Z; Elinder, LS; Bergdahl, B; Elwing, B; Abaravicius, A; Razinkoviene, L; Calkauskas, H; Olsson, AG. Antioxidant state and mortality from coronary heart diases in Lithuanian and Swedish men: Concomitant cross sectional study on men aged 50. BMJ 1997, 314, 629–633. [Google Scholar]
- Kohlmeier, L; Kark, JD; Gomez-Gracia, E; Martin, BC; Steck, SE; Kardinaal, A; Ringstad, J; Thamm, M; Masaev, V; Riemersma, R; Martin-Moreno, JM; Huttunen, JK; Kok, FJ. Lycopene and myocardial infarction risk in the EURAMIC study. Amer J Epidemiol 1997, 146, 618–626. [Google Scholar]
- Klipstein-Grobush, K; Launer, L; Geleijnse, JM; Boeing, H; Hofman, A; Witteman, JC. Serum antioxidant and atherosclerosis. The rotterdam study. Atherosclerosis 2000, 148, 49–56. [Google Scholar]
- Street, DA; Comstock, GW; Salkeld, RM; Schuep, W; Klag, M. Serum antioxidants and myocardial infarction: Are low levels of carotenoids and α-tocopherol risk factors for myocardial infarction? Circulation 1994, 90, 1154–1161. [Google Scholar]
- Ascherio, A; Rimm, EB; Hernán, M; Giovannucci, E; Kawachi, I; Stampfer, M; Willet, W. Relation of consumption of vitamin E, vitamin C and carotenoids to risk for stroke among men in the United States. Ann Intern Med 1999, 130, 963–970. [Google Scholar]
- Kritchewsky, SB. β-carotene, carotenoids and the prevention of coronary heart disease. J Nutr 1999, 129, 5–8. [Google Scholar]
- Ford, ES; Giles, WH. Serum vitamins, carotenoids and angina pectoris: Findings from the National Health and Nutrition Examination Survey III. Ann Epidemiol 2000, 10, 106–116. [Google Scholar]
- Sesso, HD; Buring, JE; Norkus, EP; Gaziano, JM. Plasma lycopene, other carotenoids, retinol and the risk of cardiovascular disease in men. Amer J Clin Nutr 2005, 81, 990–997. [Google Scholar]
- Lidebjer, C; Leanderson, P; Ernerudh, J; Jonasson, L. Low plasma levels of oxygenated carotenoids in patients with coronary artery disease. Nutr Metab Cardiovasc Dis 2007, 17, 448–456. [Google Scholar]
- Khachik, F; De Moura, FF; Zhao, DY; Aebischer, CP; Bernstein, PS. Transformations of selected carotenoids in plasma, liver, and ocular tissues of humans and in nonprimate animalmodels. Invest Ophthalmol Vis Sci 2002, 43, 3383–3392. [Google Scholar]
- Le, M; Xiao-Ming, L. Effects of lutein and zeaxanthin on aspects of eye health. J Sci Food Agr 2010, 90, 2–12. [Google Scholar]
- Bates, CJ; Chen, S-J; MacDonald, A; Holden, R. Quantitation of vitamin E and a carotenoid pigment in cataractous human lenses and the effect of a dietary supplement. Internat J Vit Nutr Res 1996, 66, 316–321. [Google Scholar]
- Landrum, JT; Bohne, R. Luteín, zeaxanthin and the macular pigment. Arch Biochem Biophys 2001, 385, 28–40. [Google Scholar]
- Hammond, BR; Wooten, B; Snodderly, DM. Preservation of visual sensitivity of older individuals: Association with macular pigment density. Invest Ophthalmol Vis Sci 1998, 39, 397–406. [Google Scholar]
- Olmedilla, B; Granado, F; Blanco, I; Vaquero, M; Cajigal, C. Lutein in patients with cataracts and age-related macular degeneration: A longterm supplementation study. J Sci Food Agr 2001, 81, 904–909. [Google Scholar]
- Snodderly, MD. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Amer J Clin Nutr 1995, 62, 1448–1461. [Google Scholar]
- Friedman, DS; O’Colmain, BJ; Munoz, B; Tomany, SC; McCarty, C; De Jong, PT; Nemesure, B; Mitchell, P; Kempen, J; Congdon, N. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004, 122, 564–572. [Google Scholar]
- Greenstein, VC; Chiosi, F; Baker, P; Seiple, W; Holopigian, K; Braunstein, RE; Sparrow, JR. Scotopic sensitivity and color vision with a blue-lightabsorbing intraocular lens. J Cataract Refract Surg 2007, 33, 667–672. [Google Scholar]
- Sujak, A; Gabrielska, J; Grudzinski, W; Borc, R; Mazurek, P; Gruszecki, WI. Lutein and zeaxanthin as protectors of lipid membranes against oxidative damage: The structural aspects. Arch Biochem Biophys 1999, 371, 301–307. [Google Scholar]
- Woodall, AA; Britton, G; Jackson, MJ. Carotenoids and protection of phospholipids in solution or in liposomes against oxidation by peroxyl radicals: Relationship between carotenoid structure and protective ability. Biochim Biophys Acta 1997, 1336, 575–586. [Google Scholar]
- Jonhson, E; Hammond, BR; Yeum, K-J; Wang, XD; Castaneda, C; Snodderly, DM; Russell, RM. Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. Amer J Clin Nutr 2000, 71, 1555–1562. [Google Scholar]
- Sies, H; Stahl, W. Nutritional protection against skin damage from sunlight. Annu Rev Nutr 2004, 24, 173–200. [Google Scholar]
- Aust, O; Stahl, W; Sies, H; Tronnier, H; Heinrich, U. Supplementation with tomato-based products increases lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema. Int J Vitam Nutr Res 2005, 75, 54–60. [Google Scholar]
- Wertz, K; Hunziker-Buchwald, P; Seifert, N; Riss, G; Neeb, M; Steiner, G; Goralczyk, R. β-carotene interferes with ultraviolet light A-induced gene expression by multiple pathways. J Invest Dermatol 2005, 124, 428–434. [Google Scholar]
- Akyon, Y. Effect of antioxidants on the immune response of Helicobacter pylori. Clin Microbiol Infect 2002, 8, 438–441. [Google Scholar]
- Kim, SH; Jean, D; Lim, YP; Lim, C; An, G. Weight gain limitation and liver protection by long-term feeding of astaxanthin in murines. J K Soc Appl Biol Chem 2009, 52, 180–185. [Google Scholar]
- Bolin, AP; Macedo, RC; Marin, DP; Barros, MP; Otton, R. Astaxanthin prevents in vitro auto-oxidative injury in human lymphocytes. Cell Biol Toxicol 2010, 26, 457–467. [Google Scholar]
- Gale, CR; Hall, NF; Phillips, D; Martyn, CN. Plasma antioxidant vitamins and carotenoids and age-related cataract. Ophthalmology 2001, 108, 1992–1998. [Google Scholar]
- Vu, HT; Robman, L; Hodge, A; McCarty, CA; Taylor, HR. Lutein and zeaxanthin and the risk of cataract: The melbourne visual impairment project. Invest Ophthalmol Vis Sci 2006, 47, 3783–3786. [Google Scholar]
- Neelam, K; O’Gorman, N; Nolan, J; O’Donovan, O; Wong, HB; Eong, KG; Beatty, S. Measurement of macular pigment: Raman spectroscopy versus heterochromatic flicker photometry. Invest Opthalmol Vis Sci 2005, 46, 1023–1032. [Google Scholar]
- Moeller, SM; Parekh, N; Tinker, L; Ritenbaugh, C; Blodi, B; Wallace, RB; Mares, JA. Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Agerelated Eye Disease Study (CAREDS): Ancillary study of the Women’s Health Initiative. Arch Ophthalmol 2006, 124, 1151–1162. [Google Scholar]
- Christen, WG; Liu, S; Glynn, RJ; Gaziano, JM; Buring, JE. Dietary carotenoids, vitamins C and E, and risk of cataract in women: A prospective study. Arch Ophthalmol 2008, 126, 1606–1607. [Google Scholar]
- Tan, JS; Wang, JJ; Flood, V; Rochtchina, E; Smith, W; Mitchell, P. Dietary antioxidants and the long-term incidence of agerelated macular degeneration: The Blue Mountains Eye Study. Ophthalmology 2008, 115, 334–341. [Google Scholar]
- Dagnelie, G; Zorge, IS; McDonald, TM. Lutein improves visual function in some patients with retinal degeneration: A pilot study via the Internet. Optometry 2000, 71, 147–164. [Google Scholar]
- Aleman, TS; Duncan, JL; Bieber, ML; De Castro, E; Marks, DA; Gardner, LM; Steinberg, JD; Cideciyan, AV; Maguire, MG; Jacobson, SG. Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome. Invest Ophthalmol Vis Sci 2001, 42, 1873–1881. [Google Scholar]
- Bahrami, H; Melia, M; Dagnelie, G. Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial. BMC Ophthalmol 2006, 6. [Google Scholar]
- Molnár, P; Deli, J; Tanaka, T; Kann, Y; Tani, S; Gyémánt, N; Molnár, J; Kawases, M. Carotenoids with anti-Helicobacter pylori activity from Golden Delicious apple. Phytother Res 2010, 24, 644–648. [Google Scholar]
- Del Campo, JA; Moreno, J; Rodríguez, H; Vargas, MA; Rivas, J; Guerrero, MG. Carotenoid content of chlorophycean microalgae: Factors determining lutein accumulation in Muriellopsis sp. (Chlorophyta). J Biotechnol 2000, 76, 51–59. [Google Scholar]
- Lima, XT; Kimball, AB. Skin carotenoid levels in adult patients with psoriasis. J Eur Acad Derm Vener 2010. [Google Scholar]
- Zhang, ZW; Patchett, SE; Perrett, D; Domizio, P; Farthing, M. Gastric α-tocopherol and β-carotene concentrations in association with Helicobacter pylori infection. Eur J Gastr Hep 2000, 12, 497–503. [Google Scholar]
- Kupcinskas, L; Lafolie, P; Lignell, A; Kiudelis, G; Jonaitis, L; Adamonis, K; Andersen, LP; Wadstrom, T. Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: A prospective, randomized, double blind, and placebo-controlled study. Phytomedicine 2008, 15, 391–399. [Google Scholar]
- Kusters, JG; Van Vliet, AH; Kuipers, EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 2006, 19, 449–490. [Google Scholar]
- Becker, EW. Microalgae in human and animal nutrition. In Handbook of Microalgal Culture; Richmond, A, Ed.; Blackwell: Oxford, UK, 2004; pp. 312–351. [Google Scholar]
- Pulz, O; Gross, W. Valuable products from biotechnology of microalgae. Appl Microbiol Biotechnol 2004, 65, 635–648. [Google Scholar]
- Belay, A. Current knowledge on potential health benefits of Spirulina platensis. J Appl Phycol 1993, 5, 235–240. [Google Scholar]
- Liang, S; Wueming, L; Chen, F; Chen, Z. Current microalgal health food R&D activities in China. Hydrobiologia 2004, 512, 45–48. [Google Scholar]
- Wijffels, R; Barbosa, M. An outlook on microalgal biofuels. Science 2010, 329, 796–799. [Google Scholar]
- Mata, T; Martins, A; Caetano, N. Microalgae for biodiesel production and other applications: A review. Renew Sustain Energ Rev 2011, 14, 217–232. [Google Scholar]
- Del Campo, JA; García-González, M; Guerrero, MG. Outdoor cultivation on microalgae for carotenoid production: Current state and perspectives. Appl Microbiol Biotechnol 2007, 74, 1163–1174. [Google Scholar]
- Fernandez-Sevilla, JM; Acien Fernandez, FG; Molina Grima, E. Biotechnological production of lutein and its applications. Appl Microbiol Biotechnol 2010, 86, 27–40. [Google Scholar]
|Carotenoid||Functions and benefits to health||References|
|Lycopene||In prostatic hyperplasia and prostate cancer||[19–21]|
|In the prevention of atherosclerosis and acute and chronic coronary syndromes||[48–50,55,56]|
|β–carotene||Provitamin A function||[6,8]|
|In colorectal cancer||[25–27]|
|In the prevention of acute and chronic coronary syndromes||[53–56]|
|Photoprotection of skin against UV light||[69–71]|
|Astaxanthin||In benign prostatic hyperplasia and prostate and liver tumors||[2,21–24]|
|Zeaxanthin||Active against liver neoplasms||[21,24]|
|In the prevention of acute and chronic coronary syndromes||[55,56]|
|Helps to maintain a normal visual function||[57,58]|
|In the prevention of cataracts||[62,75,76]|
|To prevent macular degeneration associated with age||[65,77–80]|
|Lutein||In the prevention of acute and chronic coronary syndromes and stroke||[38,55,56,66]|
|Helps to maintain a normal visual function||[57,58]|
|In the prevention of cataracts||[62,75,76]|
|To prevent macular degeneration associated with age||[65,77–80]|
|In the prevention of retinitis||[58,81–83]|
|To avoid gastric infection by H. Pylori|||
|β-carotene||Synthetic and naturally extracted forms [6,22].|
|Astaxanthin||Synthetic nature identical and naturally extracted forms [2,13]|
|Canthaxanthin||Comes in synthetic nature identical form .|
|Lycopen||Only currently available in natural form |
|Lutein||Only comes in natural form [6,13,85].|
|Chorella vulgaris||Aquaculture, cosmetics, nutraceuticals, food ingredient||Dry powder, tablets||$30–100 kg−1|
|Isochrysis galbana||Aquaculture, cosmetics, nutraceutical||Paste, dry powder||$100–400 kg−1|
|Nannochloropsis gaditana||Aquaculture, cosmetics||Paste, dry powder||$300 kg−1|
|Pavlova lutheri||Aquaculture||Paste, dry powder||>$300 kg−1|
|Phaeodactylum tricornutum||Aquaculture, nutraceuticals||Paste, dry powder||>$200 kg−1|
|Tetraselmis||Aquaculture||Paste, dry powder||$600–800 kg−1|
|Thalassiosira weissflogii||Aquaculture||Paste, dry powder||>$300 kg−1|
|Arthrospira||Cosmetics, nutraceuticals||Paste, dry powder||>$200 kg−1|
|Haematococcus pluvialis||Aquaculture, nutraceuticals||Dry powder||>$600 kg−1|
|Dunaliella salina||Nutraceuticals, food ingredients||Dry powder, tablets||$100–400 kg−1|
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