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Carotenoids are a class of more than 600 naturally occurring pigments synthesized by plants, algae, and photosynthetic bacteria. These richly colored molecules are the sources of the yellow, orange, and red colors of many plants (1). Fruits and vegetables provide most of the carotenoids in the human diet. Alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, and zeaxanthin are the most common dietary carotenoids. Alpha-carotene, beta-carotene and beta-cryptoxanthin are provitamin A carotenoids, meaning they can be converted by the body to retinol (Figure 1). Lutein, lycopene, and zeaxanthin cannot be converted to retinol, so they have no vitamin A activity (Figure 2). Carotenoids can be broadly classified into two classes, carotenes (alpha-carotene, beta-carotene, and lycopene) and xanthophylls (beta-cryptoxanthin, lutein, and zeaxanthin).
For dietary carotenoids to be absorbed intestinally, they must be released from the food matrix and incorporated into mixed micelles (mixtures of bile salts and several types of lipids) (2). Therefore, carotenoid absorption requires the presence of fat in a meal. As little as 3-5 g of fat in a meal appears sufficient to ensure carotenoid absorption (3, 4). Because they do not need to be released from the plant matrix, carotenoids supplements (in oil) are more efficiently absorbed than carotenoids in foods (4). Within the cells that line the intestine (enterocytes), carotenoids are incorporated into triglyceride-rich lipoproteins called chylomicrons and released into the circulation (2). Triglycerides are depleted from circulating chylomicrons through the activity of an enzyme called lipoprotein lipase, resulting in the formation of chylomicron remnants. Chylomicron remnants are taken up by the liver, where carotenoids are incorporated into lipoproteins and secreted back into the circulation. In the intestine and the liver, provitamin A carotenoids may be cleaved to produce retinal, a form of vitamin A. The conversion of provitamin A carotenoids to vitamin A is influenced by the vitamin A status of the individual (5). Although the regulatory mechanism is not yet clear in humans, cleavage of provitamin A carotenoids appears to be inhibited when vitamin A stores are high.
Vitamin A Activity
Vitamin A is essential for normal growth and development, immune system function, and vision. Currently, the only essential function of carotenoids recognized in humans is that of provitamin A carotenoids (alpha-carotene, beta-carotene and beta-cryptoxanthin) to serve as a source of vitamin A (6). The vitamin A activity of beta-carotene in foods is 1/12 that of retinol (preformed vitamin A), while the vitamin A activities of alpha-carotene and beta-cryptoxanthin are both 1/24 that of retinol (6).
In plants, carotenoids have the important antioxidant function of quenching (deactivating) singlet oxygen, an oxidant formed during photosynthesis (7). Test tube studies indicate that lycopene is one of the most effective quenchers of singlet oxygen among carotenoids (8). Although important for plants, the relevance of singlet oxygen quenching to human health is less clear. Test tube studies indicate that carotenoids can also inhibit the oxidation of fats (i.e., lipid peroxidation) under certain conditions, but their actions in humans appear to be more complex (9). At present, it is unclear whether the biological effects of carotenoids in humans are a result of their antioxidant activity or other non-antioxidant mechanisms.
The long system of alternating double and single bonds common to all carotenoids allows them to absorb light in the visible range of the spectrum (7). This feature has particular relevance to the eye, where lutein and zeaxanthin efficiently absorb blue light. Reducing the amount of blue light that reaches the critical visual structures of the eye may protect them from light-induced oxidative damage (10).
Carotenoids can facilitate communication between neighboring cells grown in culture by stimulating the synthesis of connexin proteins (11). Connexins form pores (gap junctions) in cell membranes, allowing cells to communicate through the exchange of small molecules. This type of intercellular communication is important for maintaining cells in a differentiated state and is often lost in cancer cells. Carotenoids facilitate intercellular communication by increasing the expression of the gene encoding a connexin protein, an effect that appears unrelated to the vitamin A or antioxidant activities of various carotenoids (12).
Immune System Activity
Because vitamin A is essential for normal immune system function, it is difficult to determine whether the effects of provitamin A carotenoids are related to their vitamin A activity or other activities of carotenoids. Although some clinical trials have found that beta-carotene supplementation improves several biomarkers of immune function (13-15), increasing intakes of lycopene and lutein—carotenoids without vitamin A activity—have not resulted in similar improvements in biomarkers of immune function (16-18).
Although consumption of provitamin A carotenoids (alpha-carotene, beta-carotene, and beta-cryptoxanthin) can prevent vitamin A deficiency (see vitamin A), no overt deficiency symptoms have been identified in people consuming low-carotenoid diets if they consume adequate vitamin A (6). After reviewing the published scientific research in 2000, the Food and Nutrition Board of the Institute of Medicine concluded that the existing evidence was insufficient to establish a recommended dietary allowance (RDA) or adequate intake (AI) for carotenoids. The Board has set a RDA for vitamin A. Recommendations by the National Cancer Institute, American Cancer Society and American Heart Association to consume a variety of fruits and vegetables daily are aimed, in part, at increasing intakes of carotenoids.
Beta-carotene was the first carotenoid to be measured in foods and human blood. The results of early observational studies suggested an inverse relationship between lung cancer risk and beta-carotene intake, often assessed by measuring blood levels of beta-carotene (19, 20). More recently, the development of databases for other carotenoids in foods has allowed scientists to estimate dietary intakes of total and individual dietary carotenoids more accurately. In contrast to early retrospective studies, more recent prospective cohort studies have not consistently found inverse associations between beta-carotene intake and lung cancer risk. Analysis of dietary carotenoid intake and lung cancer risk in two large prospective cohort studies in the U.S. that followed more than 120,000 men and women for at least ten years revealed no significant association between dietary beta-carotene intake and lung cancer risk (21). However, men and women with the highest intakes of total carotenoids, alpha-carotene, and lycopene were at significantly lower risk of developing lung cancer than those with the lowest intakes. Dietary intakes of total carotenoids, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin, but not beta-carotene, were associated with significant reductions in risk of lung cancer in a 14-year study of more than 27,000 Finnish male smokers (22), while only dietary intakes of beta-cryptoxanthin and lutein and zeaxanthin were inversely associated with lung cancer risk in a 6-year study of more than 58,000 Dutch men (23). An analysis of the pooled results of six prospective cohort studies in North America and Europe also found no relationship between dietary beta-carotene intake and lung cancer risk, although those with the highest beta-cryptoxanthin intakes had a risk of lung cancer that was 24% lower than those with the lowest intakes (24). While smoking remains the strongest risk factor for lung cancer, results of recent prospective studies using accurate estimates of dietary carotenoid intake suggest that diets rich in a number of carotenoids—not only beta-carotene—may be associated with reduced lung cancer risk. However, a recent systematic review of prospective cohort studies concluded that any protective effect of dietary carotenoids against the development of lung cancer is likely small and not statistically significant (25).
The effect of beta-carotene supplementation on the risk of developing lung cancer has been examined in three large randomized, placebo-controlled trials. In Finland, the Alpha-Tocopherol Beta-Carotene (ATBC) cancer prevention trial evaluated the effects of 20 mg/day of beta-carotene and/or 50 mg/day of alpha-tocopherol on more than 29,000 male smokers (26), and in the United States, the Beta-Carotene And Retinol Efficacy Trial (CARET) evaluated the effects of a combination of 30 mg/day of beta-carotene and 25,000 IU/day of retinol (vitamin A) in more than 18,000 men and women who were smokers, former smokers, or had a history of occupational asbestos exposure (27). Unexpectedly, the risk of lung cancer in the groups taking beta-carotene supplements was increased by 16% after six years in the ATBC participants and increased by 28% after four years in the CARET participants. The Physicians’ Health Study examined the effect of beta-carotene supplementation (50 mg every other day) on cancer risk in more than 22,000 male physicians in the United States, of whom only 11% were current smokers (28). In that lower risk population, beta-carotene supplementation for more than 12 years was not associated with an increased risk of lung cancer. Although the reasons for the increase in lung cancer risk are not yet clear several mechanisms have been proposed (29), many experts feel that the risks of high-dose beta-carotene supplementation outweigh any potential benefits for cancer prevention, especially in smokers or other high-risk populations (30, 31). Beta-carotene is sold as individual supplements and also found in supplements marketed to promote visual health (32).
The results of several prospective cohort studies suggest that lycopene-rich diets are associated with significant reductions in the risk of prostate cancer, particularly more aggressive forms (33). In a prospective study of more than 47,000 health professionals followed for eight years, those with the highest lycopene intake had a risk of prostate cancer that was 21% lower than those with the lowest lycopene intake (34). Those with the highest intakes of tomatoes and tomato products (accounting for 82% of total lycopene intake) had a risk of prostate cancer that was 35% lower and a risk of aggressive prostate cancer that was 53% lower than those with the lowest intakes. Similarly, a prospective study of Seventh Day Adventist men found those who reported the highest tomato intakes were at significantly lower risk of prostate cancer (35), and a prospective study of U.S. physicians found those with the highest plasma lycopene levels were at significantly lower risk of developing aggressive prostate cancer (36). However, dietary lycopene intake was not related to prostate cancer risk in a prospective study of more than 58,000 Dutch men (37). A meta-analysis that combined the results of 11 case-control and ten prospective studies found men with the highest intakes of dietary lycopene or tomatoes had modest, 11-19% reductions in prostate cancer risk (38). Most recently, a prospective study in a cohort of 29,361 men followed for 4.2 years found no association between dietary lycopene intake and prostate cancer risk (39). Additionally, a recent large prospective study found no association between plasma concentrations of lycopene, or plasma concentrations of total carotenoids, and overall risk of prostate cancer (40). While there is considerable scientific interest in the potential for lycopene to help prevent prostate cancer, it is not yet clear whether the prostate cancer risk reduction observed in some epidemiological studies is related to lycopene itself, other compounds in tomatoes or other factors associated with lycopene-rich diets. To date, results of short-term, dietary intervention studies using lycopene in prostate cancer patients have been promising (41). Yet, the safety and efficacy of long-term use of lycopene supplements for prostate cancer prevention or treatment is not known (41). Large-scale, controlled clinical trials would be needed to address these issues.
Because they are very soluble in fat and very insoluble in water, carotenoids circulate in lipoproteins along with cholesterol and other fats. Evidence that low-density lipoprotein (LDL) oxidation plays a role in the development of atherosclerosis led scientists to investigate the role of antioxidant compounds like carotenoids in the prevention of cardiovascular disease (42). The thickness of the inner layers of the carotid arteries can be measured noninvasively using ultrasound technology. This measurement of carotid intima-media thickness is considered a reliable marker of atherosclerosis (43). A number of case-control and cross-sectional studies have found higher blood levels of carotenoids to be associated with significantly lower measures of carotid artery intima-media thickness (44-49). Higher plasma carotenoids at baseline have been associated with significant reductions in risk of cardiovascular disease in some prospective studies (50-54) but not in others (55-58). While the results of several prospective studies indicate that people with higher intakes of carotenoid-rich fruits and vegetables are at lower risk of cardiovascular disease (58-61), it is not yet clear whether this effect is a result of carotenoids or other factors associated with diets high in carotenoid-rich fruits and vegetables.
In contrast to the results of epidemiological studies suggesting that high dietary intakes of carotenoid-rich fruits and vegetables may decrease cardiovascular disease risk, four randomized controlled trials found no evidence that beta-carotene supplements in doses ranging from 20-50 mg/day were effective in preventing cardiovascular diseases (26, 28, 62, 63). Based on the results of these randomized controlled trials, the U.S. Preventive Health Services Task Force concluded that there was good evidence that beta-carotene supplements provided no benefit in the prevention of cardiovascular disease in middle-aged and older adults (31, 64). Thus, although diets rich in beta-carotene have generally been associated with reduced cardiovascular disease risk in observational studies, there is no evidence that beta-carotene supplementation reduces cardiovascular disease risk (65).
In Western countries, degeneration of the macula, the center of the eye’s retina, is the leading cause of blindness in older adults. Unlike cataracts, in which the diseased lens can be replaced, there is no cure for age-related degeneration (AMD). Therefore, efforts are aimed at disease prevention or delaying the progression of AMD.
Dietary Lutein and Zeaxanthin
The only carotenoids found in the retina are lutein and zeaxanthin. Lutein and zeaxanthin are present in high concentrations in the macula, where they are efficient absorbers of blue light. By preventing a substantial amount of the blue light entering the eye from reaching the underlying structures involved in vision, lutein and zeaxanthin may protect against light-induced oxidative damage, which is thought to play a role in the pathology of age-related macular degeneration (10). It is also possible, though not proven, that lutein and zeaxanthin act directly to neutralize oxidants formed in the retina. Epidemiological studies provide some evidence that higher intakes of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD) (66). However, the relationship is by no means clear-cut. While cross-sectional and retrospective case-control studies found that higher levels of lutein and zeaxanthin in the diet (67-69), blood (70, 71), and retina (72, 73) were associated with a lower incidence of AMD, several prospective cohort studies found no relationship between baseline dietary intakes or serum levels of lutein and zeaxanthin and the risk of developing AMD over time (74-77). Although scientists are very interested in the potential for increased lutein and zeaxanthin intakes to reduce the risk of macular degeneration, it is premature to recommend supplements without more data from randomized controlled trials (78). A clinical trial, the Age-related Eye Disease Study 2 (AREDS2), is currently under way to evaluate the effect of supplemental lutein and zeaxanthin on the progression of advanced AMD (79). To date, the available scientific evidence suggests that consuming at least 6 mg/day of dietary lutein and zeaxanthin from fruits and vegetables may decrease the risk of age-related macular degeneration (67-69).
A randomized controlled trial in patients with atrophic AMD found that supplementation with 10 mg/day of lutein slightly improved visual acuity after one year compared to a placebo (80). However, the investigators concluded that further research was needed to assess the effects of long-term lutein supplementation on atrophic AMD.
The first randomized controlled trial (AREDS1) designed to examine the effect of a carotenoid supplement on AMD used beta-carotene in combination with vitamin C, vitamin E, and zinc because lutein and zeaxanthin were not commercially available as supplements at the time the trial began (81). Although the combination of antioxidants and zinc lowered the risk of developing advanced macular degeneration in individuals with signs of moderate to severe macular degeneration in at least one eye, it is unlikely that the benefit was related to beta-carotene since it is not present in the retina. Supplementation of male smokers in Finland with 20 mg/day of beta-carotene for six years did not decrease the risk of AMD compared to placebo (82) A placebo-controlled trial in a cohort of 22,071 healthy U.S. men found that beta-carotene supplementation (50 mg every other day) had no effect on the incidence of age-related maculopathy-an early stage of AMD (83). Recent systematic reviews of randomized controlled trials have concluded that there is no evidence that beta-carotene supplementation prevents or delays the onset of AMD (84, 85).
Ultraviolet light and oxidants can damage proteins in the eye’s lens, causing structural changes that result in the formation of opacities known as cataracts. As people age, cumulative damage to lens proteins often results in cataracts that are large enough to interfere with vision (7).
Dietary Lutein and Zeaxanthin
The observation that lutein and zeaxanthin are the only carotenoids in the human lens has stimulated interest in the potential for increased intakes of lutein and zeaxanthin to prevent or slow the progression of cataracts (10). Four large prospective studies found that men and women with the highest intakes of foods rich in lutein and zeaxanthin, particularly spinach, kale, and broccoli, were 18-50% less likely to require cataract extraction (86, 87) or develop cataracts (88-90). Additional research is required to determine whether these findings are related specifically to lutein and zeaxanthin intake or to other factors associated with diets high in carotenoid-rich foods (66).
Evidence from epidemiological studies that cataracts were less prevalent in people with high dietary intakes and blood levels of carotenoids led to the inclusion of beta-carotene supplements in several large randomized controlled trials of antioxidants. The results of those trials have been somewhat conflicting. Beta-carotene supplementation (20 mg/day) for more than six years did not affect the prevalence of cataracts or the frequency of cataract surgery in male smokers living in Finland (82). In contrast, a 12-year study of male physicians in the U.S. found that beta-carotene supplementation (50 mg every other day) decreased the risk of cataracts in smokers but not in nonsmokers (91). Note that use of beta-carotene supplements have been shown to increase the risk of lung cancer in smokers (see above). Three randomized controlled trials examined the effect of an antioxidant combination that included beta-carotene, vitamin C, and vitamin E on the progression of cataracts. Two trials found no benefit after supplementation for five years (92) or more than six years (93), but one trial found a small decrease in the progression of cataracts after three years of supplementation (94). Overall, the results of randomized controlled trials suggest that the benefit of beta-carotene supplementation in slowing the progression of age-related cataracts does not outweigh the potential risks.
The most prevalent carotenoids in North American diets are alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin (6). Carotenoids in foods are mainly in the all-trans form (Figure 1 and Figure 2), although cooking may result in the formation of other isomers. The relatively low bioavailability of carotenoids from most foods compared to supplements is partly due to the fact that they are associated with proteins in the plant matrix (2). Chopping, homogenizing, and cooking disrupt the plant matrix, increasing the bioavailability of carotenoids (4). The bioavailability of lycopene from tomatoes is substantially improved by heating tomatoes in oil (95, 96).
Alpha-Carotene and Beta-Carotene
Alpha-carotene and beta-carotene are provitamin A carotenoids, meaning they can be converted in the body to vitamin A. The vitamin A activity of beta-carotene in foods is 1/12 that of retinol (preformed vitamin A). Thus, it would take 12 mcg of beta-carotene from foods to provide the equivalent of 1 mcg (0.001 mg) of retinol. The vitamin A activity of alpha-carotene from foods is 1/24 that of retinol, so it would take 24 mcg of alpha-carotene from foods to provide the equivalent of 1 mcg of retinol. Orange and yellow vegetables like carrots and winter squash are rich sources of alpha- and beta-carotene. Spinach is also a rich source of beta-carotene, although the chlorophyll in spinach leaves hides the yellow-orange pigment. Some foods that are good sources of alpha-carotene and beta-carotene are listed in the tables below (97).
|Alpha-Carotene Content of Selected Foods|
|Pumpkin, canned||1 cup||11.7|
|Carrot juice, canned||1 cup (8 fl oz)||10.2|
|Carrots, cooked||1 cup||5.9|
|Carrots, raw||1 medium||2.1|
|Mixed vegetables, frozen, cooked||1 cup||1.8|
|Winter squash, baked||1 cup||1.4|
|Plantains, raw||1 medium||0.8|
|Collards, frozen, cooked||1 cup||0.2|
|Tomatoes, raw||1 medium||0.1|
|Tangerines, raw||1 medium||0.09|
|Peas, edible-podded, frozen, cooked||1 cup||0.09|
|Beta-Carotene Content of Selected Foods|
|Carrot juice, canned||1 cup (8 fl oz)||22.0|
|Pumpkin, canned||1 cup||17.0|
|Spinach, frozen, cooked||1 cup||13.8|
|Sweet potato, baked||1 medium||13.1|
|Carrots, cooked||1 cup||13.0|
|Collards, frozen, cooked||1 cup||11.6|
|Kale, frozen, cooked||1 cup||11.5|
|Turnip greens, frozen, cooked||1 cup||10.6|
|Pumpkin pie||1 piece||7.4|
|Winter squash, cooked||1 cup||5.7|
|Carrots, raw||1 medium||5.1|
|Dandelion greens, cooked||1 cup||4.1|
|Cantaloupe, raw||1 cup||3.2|
Like alpha-and beta-carotene, beta-cryptoxanthin is a provitamin A carotenoid. The vitamin A activity of beta-cryptoxanthin from foods is 1/24 that of retinol, so it would take 24 mcg of beta-cryptoxanthin from food to provide the equivalent of 1 mcg (0.001 mg) of retinol. Orange and red fruits and vegetables like sweet red peppers and oranges are particularly rich sources of beta-cryptoxanthin. Some foods that are good sources of beta-cryptoxanthin are listed in the table below (97).
|Beta-Cryptoxanthin Content of Selected Foods|
|Pumpkin, cooked||1 cup||3.6|
|Papayas, raw||1 medium||2.3|
|Sweet red peppers, cooked||1 cup||0.6|
|Sweet red peppers, raw||1 medium||0.6|
|Orange juice, fresh||1 cup (8 fl oz)||0.4|
|Tangerines, raw||1 medium||0.4|
|Carrots, frozen, cooked||1 cup||0.3|
|Yellow corn, frozen, cooked||1 cup||0.2|
|Watermelon, raw||1 wedge (1/16 of a melon that is 15 inches long x 7.5 inches in diameter)||0.2|
|Paprika, dried||1 tsp||0.2|
|Oranges, raw||1 medium||0.2|
|Nectarines, raw||1 medium||0.1|
Lycopene gives tomatoes, pink grapefruit, watermelon, and guava their red color. It has been estimated that 80% of the lycopene in the U.S. diet comes from tomatoes and tomato products like tomato sauce, tomato paste, and catsup (ketchup) (98). Lycopene is not a provitamin A carotenoid, meaning the body cannot convert lycopene to vitamin A. Some foods that are good sources of lycopene are listed in the table below (97).
|Lycopene Content of Selected Foods|
|Tomato paste, canned||1 cup||75.4|
|Tomato purée, canned||1 cup||54.4|
|Tomato soup, canned, condensed||1 cup||26.4|
|Vegetable juice cocktail, canned||1 cup||23.3|
|Tomato juice, canned||1 cup||22.0|
|Watermelon, raw||1 wedge (1/16 of a melon that is 15 inches long x 7.5 inches in diameter)||13.0|
|Tomatoes, raw||1 cup||4.6|
|Catsup (ketchup)||1 tablespoon||2.5|
|Pink grapefruit, raw||½ grapefruit||1.7|
|Baked beans, canned||1 cup||1.3|
Lutein and Zeaxanthin
Although lutein and zeaxanthin are different compounds, they are both from the class of carotenoids known as xanthophylls. They are not provitamin A carotenoids. Some methods used to quantify lutein and zeaxanthin in foods do not separate the two compounds, so they are typically reported as lutein and zeaxanthin or lutein + zeaxanthin. Lutein and zeaxanthin are present in a variety of fruits and vegetables. Dark green leafy vegetables like spinach and kale are particularly rich sources of lutein and zeaxanthin. One study found that the bioavailability of lutein from lutein-enriched eggs (from chickens fed a lutein-enriched diet) was significantly higher than from spinach or lutein supplements (99). Some foods that are good sources lutein and zeaxanthin are listed in the table below (97).
|Lutein + Zeaxanthin Content of Selected Foods|
|Food||Serving||Lutein + Zeaxanthin (mg)|
|Spinach, frozen, cooked||1 cup||29.8|
|Kale, frozen, cooked||1 cup||25.6|
|Turnip greens, frozen, cooked||1 cup||19.5|
|Collards, frozen, cooked||1 cup||18.5|
|Dandelion greens, cooked||1 cup||9.6|
|Mustard greens, cooked||1 cup||8.3|
|Summer squash, cooked||1 cup||4.0|
|Peas, frozen, cooked||1 cup||3.8|
|Winter squash, baked||1 cup||2.9|
|Pumpkin, cooked||1 cup||2.5|
|Brussel sprouts, frozen, cooked||1 cup||2.4|
|Broccoli, frozen, cooked||1 cup||2.0|
|Sweet yellow corn, boiled||1 cup||1.5|
For more information on the carotenoid content of the foods, search the USDA National Nutrient Database.
Dietary supplements providing purified carotenoids and combinations of carotenoids are commercially available in the U.S. without a prescription. Carotenoids are best absorbed when taken with a meal containing fat.
Because it is has vitamin A activity, beta-carotene may be used to provide all or part of the vitamin A in multivitamin supplements. The vitamin A activity of beta-carotene from supplements is much higher than that of beta-carotene from foods. It takes only 2 mcg (0.002 mg) of beta-carotene from supplements to provide 1 mcg of retinol (preformed vitamin A). The beta-carotene content of supplements is often listed in international units (IU) rather than mcg; 3,000 mcg (3 mg) of beta-carotene provides 5,000 IU of vitamin A. Most commercial supplements contain 5,000-25,000 IU of beta-carotene (100).
Lycopene has no vitamin A activity. Synthetic lycopene and lycopene from natural sources, mainly tomatoes, are available as nutritional supplements. Many commercial supplements provide 5-20 mg of lycopene (100).
Lutein and Zeaxanthin
Lutein and zeaxanthin have no vitamin A activity. Lutein and zeaxanthin supplements are available as free carotenoids or as esters (esterified to fatty acids). One study found that free luteine and lutein esters had comparable bioavailability (99), while another found that lutein esters were more bioavailable than free lutein (101). Many commercially available lutein and zeaxanthin supplements have much higher amounts of lutein than zeaxanthin (102). Such supplements typically contain 4-20 mg of lutein and 0.2-1 mg of zeaxanthin, although other dosages are available (100). Supplements containing only lutein or only zeaxanthin are also available.
Although beta-carotene can be converted to vitamin A, the conversion of beta-carotene to vitamin A decreases when body stores of vitamin A are high. This may explain why high doses of beta-carotene have never been found to cause vitamin A toxicity (103). High doses of beta-carotene (up to 180 mg/day) have been used to treat erythropoietic protoporphyria, a photosensitivity disorder, without toxic side effects (6).
Lycopene, Lutein, and Zeaxanthin
No toxicities have been reported (104).
Increased lung cancer risk: Two randomized controlled trials in smokers and former asbestos workers found that supplementation with 20-30 mg/day of beta-carotene for 4-6 years was associated with significant 16-28% increases in the risk of lung cancer compared to placebo (see section on Lung Cancer). Although the reasons for these findings are not yet clear, many experts feel that the risks of high-dose beta-carotene supplementation outweigh any potential benefits for chronic disease prevention, especially in smokers or other high-risk populations (30, 31).
Carotenodermia: High doses of beta-carotene supplements (30 mg/day or more) and the consumption of large amounts of carotene-rich foods have resulted in a yellow discoloration of the skin known as carotenodermia. Carotenodermia is not associated with any underlying health problems and resolves when beta-carotene supplements are discontinued or dietary carotene intake is reduced.
Lycopenodermia: High intakes of lycopene-rich foods or supplements may result in a deep orange discoloration of the skin known as lycopenodermia. Because lycopene is more intensely colored than the carotenes, lycopenodermia may occur at lower doses than carotenodermia (6).
Lutein and Zeaxanthin
Adverse effects of lutein and zeaxanthin have not been reported (102).
Safety in Pregnancy and Lactation
Unlike vitamin A, high doses of beta-carotene taken by pregnant women have not been associated with increased risk of birth defects (6). However, the safety of high-dose beta-carotene supplements in pregnancy and lactation has not been well-studied. Although there is no reason to limit dietary beta-carotene intake, pregnant and breast-feeding women should avoid consuming more than 3 mg/day (5,000 IU/day) of beta-carotene from supplements unless they prescribed under medical supervision (102, 103).
The safety of carotenoid supplements other than beta-carotene in pregnancy and lactation has not been established, so pregnant and breastfeeding women should obtain carotenoids from foods rather than supplements. There is no reason to limit the consumption of carotenoid-rich fruits and vegetables during pregnancy (102, 105).
The cholesterol-lowering agents, cholestyramine (Questran) and colestipol (Colestid), can reduce absorption of fat-soluble vitamins and carotenoids, as can mineral oil and Orlistat (Xenical), a drug used to treat obesity (102). Colchicine, a drug used to treat gout, can cause intestinal malabsorption. However, long-term use of 1-2 mg/day of colchicine did not affect serum beta-carotene levels in one study (106). Increasing gastric pH through the use of proton pump inhibitors, such as Omeprazole (Prilosec, Losec), Lansoprazole (Prevacid), Rabeprazole (Aciphex), and Pantoprazole (Protonix, Pantoloc), decreased the absorption of a single dose of a beta-carotene supplement, but it is not known if the absorption of dietary carotenoids is affected (107).
Antioxidant Supplements and HMG-CoA Reductase Inhibitors (Statins)
A 3-year randomized controlled trial in 160 patients with documented coronary heart disease and low serum high density lipoprotein (HDL) concentrations found that a combination of simvastatin (Zocor) and niacin increased HDL2 levels, inhibited the progression of coronary artery stenosis, and decreased the frequency of cardiovascular events, including MI and stroke (108). Surprisingly, when an antioxidant combination (1,000 mg of vitamin C, 800 IU of alpha-tocopherol, 100 mcg of selenium, and 25 mg of beta-carotene daily) was taken with the simvastatin-niacin combination, these protective effects were diminished. Since the antioxidants were taken together in this trial, the individual contribution of beta-carotene cannot be determined. In contrast, a much larger randomized controlled trial of simvastatin and an antioxidant combination (600 mg of vitamin E, 250 mg of vitamin C, and 20 mg of beta-carotene daily) in more than 20,000 men and women with coronary artery disease or diabetes found that the antioxidant combination did not diminish the cardioprotective effects of simvastatin therapy over a 5-year period (109), suggesting that the antioxidant combination may have interfered with the HDL-raising effect of niacin in the former trial. Further research is needed to determine potential interactions between antioxidant supplements and cholesterol-lowering agents, such as niacin and HMG-CoA reductase inhibitors (statins).
Interactions with Foods
In a controlled feeding study, consumption of 18 g/day of the fat substitute Olestra™ (sucrose polyester) resulted in a 27% decrease in serum carotenoid concentrations after three weeks (110). Studies in people before and after the introduction of Olestra-containing snacks to the marketplace found that total serum carotenoid concentrations decreased by 15% in those who reported consuming at least 2 g/day of Olestra (111). One study in adults found that those who consumed more than 4.4 g or Olestra weekly experienced a 9.7% decline in total serum carotenoids compared to those not consuming Olestra (112).
Plant Sterol- or Stanol-Containing Foods
Some studies found that the regular use of plant sterol-containing spreads resulted in modest, 10-20% decreases in the plasma concentrations of some carotenoids, particularly alpha-carotene, beta-carotene, and lycopene (113, 114) (see Phytosterols). However, advising people who use plant sterol- or stanol-containing margarines to consume an extra serving of carotenoid-rich fruits or vegetables daily prevented decreases in plasma carotenoid concentrations (115, 116).
The relationships between alcohol consumption and carotenoid metabolism are not well understood. There is some evidence that regular alcohol consumption inhibits the conversion of beta-carotene to retinol (117). Increases in lung cancer risk associated with high-dose beta-carotene supplementation in two randomized controlled trials were enhanced in those with higher alcohol intakes (27, 118).
Interactions Among Carotenoids
The results of metabolic studies suggest that high doses of beta-carotene compete with lutein and lycopene for absorption when consumed at the same time (119-121). However, the consumption of high-dose beta-carotene supplements did not adversely affect serum carotenoid concentrations in long-term clinical trials (122-125).
Written in December 2005 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in June 2009 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University
Reviewed in June 2009 by:
Elizabeth J. Johnson, Ph.D., Research Scientist
Carotenoids & Health Laboratory
Jean Mayer USDA Human Nutrition Research Center on Aging
Assistant Professor, Friedman School of Nutrition Science
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