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, zeaxanthin, and lycopene 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, zeaxanthin, and lycopene cannot be converted to retinol, so they have no vitamin A activity (Figure 2).
Metabolism and Bioavailability
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 reminants. 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).
Antioxidant Activity
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 (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 nonantioxidant mechanisms.
Light Filtering
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 structures of the eye that are critical to vision may protect them from light-induced oxidative damage (10).
Intercellular Communication
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—did not result in similar improvements in immune function biomarkers (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. 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 carotenoid-rich vegetables.
Dietary 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, 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 US that followed more than 120,000 men and women for at least 10 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 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.
Beta-Carotene Supplements
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/d of beta-carotene and/or 50 mg/d of alpha-tocopherol on more than 29,000 male smokers (25), and in the US, the beta-Carotene And Retinol Efficacy Trial (CARET) evaluated the effects of a combination of 30 mg/d of beta-carotene and 25,000 IU/d 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 (26). Unexpectedly, the risk of lung cancer in the groups taking beta-carotene supplements was increased by 16% after 6 years in the ATBC participants and increased by 28% after 4 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 US, of whom only 11% were current smokers (27). 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, 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 (28, 29).
Dietary Lycopene
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 (30). 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 (31). 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 that those who reported the highest tomato intakes were at significantly lower risk of prostate cancer (32), and a prospective study of US physicians found that those with the highest plasma lycopene levels were at significantly lower risk of developing aggressive prostate cancer (33). However, dietary lycopene intake was not related to prostate cancer risk in a prospective study of more than 58,000 Dutch men (34). A meta-analysis that combined the results of 11 case-control and 10 prospective studies found that those with the highest intakes of dietary lycopene or tomatoes had modest 11-19% reductions in prostate cancer risk (35). 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.
Dietary Carotenoids
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 an role in the development of atherosclerosis led scientists to investigate the role of antioxidant compounds like carotenoids in the prevention of cardiovascular disease (36). 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 (37). 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 (38-43). Higher plasma carotenoids at baseline have been associated with significant reductions in cardiovascular disease risk in some prospective studies (44-46) but not in others (47-50). 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 (50-53), 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.
Beta-Carotene Supplements
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/d were effective in preventing cardiovascular
diseases (25, 27,
54, 55).
Based on the results of these randomized controlled trials, the US 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 (29,
56).
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.
Age-Related Macular Degeneration
In Western countries, degeneration of the macula, the center of the eye’s retina, is the leading cause of blindness in older adults.
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 underlying structures involved in vision, lutein and zeaxanthin may protect them from 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) (57). 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 (58-60), blood (61, 62), and retina (63, 64) 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 (65-68). 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 (69). The available scientific evidence suggests that consuming at least 6 mg/d of lutein and zeaxanthin from fruits and vegetables may decrease the risk of age-related macular degeneration (58-60).
Lutein Supplements
In a randomized controlled trial, supplementation of patients who had atrophic AMD with 10 mg/d of lutein resulted in slight improvement in visual acuity after one year compared to a placebo (70). However, the investigators concluded that further research was needed to assess the effects of long-term lutein supplementation on atrophic AMD.
Beta-Carotene Supplements
The first randomized controlled trial 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 (71). 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/d of beta-carotene for 6 years did not decrease the risk of AMD compared to placebo (72).
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). Three large prospective studies found that men and women with the highest intakes of foods that are rich in lutein and zeaxanthin, particularly spinach, kale, and broccoli, were 20-50% less likely to require cataract extraction (73, 74) or develop cataracts (75). 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 lutein-rich foods (57).
Beta-Carotene Supplements
Evidence from epidemiological studies that cataracts were less prevalent in people with the 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/d) for more than 6 years did not affect the prevalence of cataracts or the frequency of cataract surgery in male smokers living in Finland (72). In contrast, a 12-year study of male physicians in the US found that beta-carotene supplementation (50 mg every other day) decreased the risk of cataracts in smokers but not in nonsmokers (76). Two randomized controlled trials examined the effect of an antioxidant combination that included beta-carotene, vitamin C, and vitamin E on the progression of cataracts. While one study found no benefit after more than 6 years of supplementation (77), the other study found a small decrease in the progression of cataracts after 3 years of supplementation (78). 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.
Food Sources
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 (79, 80).
Alpha-Carotene and Beta-Carotene
Alpha-carotene and beta-carotene are provitamin A carotenoids, meaning they can be converted by 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 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.
| Alpha-Carotene Content of Selected Foods | ||
| Food | Serving | Alpha-Carotene (mcg) |
| Pumpkin, canned | 1 cup | 11,748 |
| Carrot juice, canned | 1 cup (8 fl oz) | 10,247 |
| Carrots, cooked | 1 cup | 5,891 |
| Carrots, raw | 1 medium | 2,028 |
| Mixed vegetables, frozen, cooked | 1 cup | 1,762 |
| Winter squash, baked | 1 cup | 1,398 |
| Plantains, raw | 1 medium | 784 |
| Pumpkin pie | 1 piece | 748 |
| Collards, frozen, cooked | 1 cup | 216 |
| Tomatoes, raw | 1 medium | 124 |
| Tangerines, raw | 1 medium | 85 |
| Peas, frozen, cooked | 1 cup | 85 |
| Beta-Carotene Content of Selected Foods | ||
| Food | Serving | Beta-Carotene (mcg) |
| Carrot juice, canned | 1 cup (8 fl oz) | 21,955 |
| Pumpkin, canned | 1 cup | 17,003 |
| Sweet potato, baked | 1 medium | 16,803 |
| Spinach, frozen, cooked | 1 cup | 13,750 |
| Carrots, cooked | 1 cup | 12,998 |
| Collards, frozen, cooked | 1 cup | 11,591 |
| Kale, frozen, cooked | 1 cup | 11,470 |
| Turnip greens, frozen, cooked | 1 cup | 10,593 |
| Pumpkin pie | 1 piece | 7,366 |
| Dandelion greens, cooked | 1 cup | 6,248 |
| Winter squash, cooked | 1 cup | 5,726 |
| Cantaloupe, raw | 1 cup | 3,232 |
Beta-Cryptoxanthin
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 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.
| Beta-Cryptoxanthin Content of Selected Foods | ||
| Food |
Serving | Beta-Cryptoxanthin (mcg) |
| Pumpkin, cooked | 1 cup | 3,553 |
| Sweet red peppers, cooked | 1 cup | 2,817 |
| Papayas, raw | 1 medium | 2,313 |
| Sweet red peppers, raw | 1 medium | 583 |
| Orange juice, fresh | 1 cup (8 fl oz) | 419 |
| Tangerines, raw | 1 medium | 342 |
| Carrots, cooked | 1 cup | 315 |
| Watermelon, raw | 1 wedge | 223 |
| Yellow corn, frozen, cooked | 1 cup | 200 |
| Paprika, dried | 1 tsp | 166 |
| Oranges, raw | 1 medium | 152 |
| Nectarines, raw | 1 medium | 133 |
Lycopene
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) (81). 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.
| Lycopene Content of Selected Foods | ||
| Food | Serving | Lycopene (mcg) |
| Tomato paste, canned | 1 cup | 75,362 |
| Tomato puree, canned | 1 cup | 54,385 |
| Marinara sauce | 1 cup | 39,975 |
| Tomato soup, canned | 1 cup | 25,615 |
| Vegetable juice cocktail, canned | 1 cup | 23,337 |
| Tomato juice, canned | 1 cup | 21,960 |
| Watermelon, raw | 1 wedge | 12,962 |
| Tomatoes, raw | 1 cup | 4,631 |
| Catsup (ketchup) | 1 tablespoon | 2,551 |
| Pink grapefruit, raw | ½ grapefruit | 1,745 |
| Baked beans, canned | 1 cup | 1,298 |
| Sweet red peppers, raw | 1 cup | 459 |
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. Some foods that are good sources lutein and zeaxanthin are listed in the table below.
| Lutein + Zeaxanthin Content of Selected Foods | ||
| Food | Serving | Lutein + Zeaxanthin (mcg) |
| Spinach, frozen, cooked | 1 cup | 29,811 |
| Kale, frozen, cooked | 1 cup | 25,606 |
| Turnip greens, frozen, cooked | 1 cup | 19,541 |
| Collards, frozen, cooked | 1 cup | 18,527 |
| Mustard greens, cooked | 1 cup | 8,347 |
| Dandelion greens, cooked | 1 cup | 4,944 |
| Summer squash, cooked | 1 cup | 4,048 |
| Peas, frozen, cooked | 1 cup | 3,840 |
| Winter squash, baked | 1 cup | 2,901 |
| Broccoli, frozen, cooked | 1 cup | 2,756 |
| Pumpkin, cooked | 1 cup | 2,484 |
| Brussel sprouts, frozen, cooked | 1 cup | 2,389 |
| Sweet yellow corn, boiled | 1 cup | 1,586 |
For more information on the carotenoid content of the foods you eat, search the USDA National Nutrient Database.
Supplements
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.
Beta-Carotene
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 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.
Lycopene
Lycopene has no vitamin A activity. Synthetic lycopene and lycopene from natural sources, mainly tomatoes, are available as nutritional supplements.
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). Both forms appear to have comparable bioavailability (82). Many commercially available lutein and zeaxanthin supplements have much higher amounts of lutein than zeaxanthin (83). Supplements containing only lutein or only zeaxanthin are also available.
Toxicity
Beta-Carotene
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 (84). 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 (84).
Adverse Effects
Beta-Carotene
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 (28, 29).
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.
Lycopene
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 (83).
Safety in Pregnancy and Lactation
Beta-Carotene
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 breastfeeding women should avoid consuming more than 3 mg/day (5,000 IU/day) of beta-carotene from supplements unless they prescribed under medical supervision (83, 85).
Other Carotenoids
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 (83, 86).
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 (83). Colchicine, a drug used to treat gout, can cause intestinal malabsorption. However, long-term use of 1-2 mg/d did not affect serum beta-carotene levels (87). 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 (88).
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 (89). 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, the 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 (90), 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
Olestra™
In a controlled feeding study, consumption of 18 g/d of the fat substitute Olestra™ (sucrose polyester) resulted in a 27% decrease in serum carotenoid concentrations after 3 weeks (91). Studies in free-living 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/d of Olestra (92).
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 (93, 94) (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 (95, 96).
Alcohol
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 (97). 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 (26, 98).
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 (99-101). However, the consumption of high-dose beta-carotene supplements did not adversely affect serum carotenoid concentrations in long-term clinical trials (102-105).
Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Reviewed by:
Norman I. Krinsky, Ph.D., Professor, Emeritus
Department of Biochemistry
Tufts University School of Medicine
USDA Human Nutrition Research Center on Aging
Last updated 12/21/2005 Copyright 2004-2008 Linus Pauling Institute
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