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PART III: CAROTENOIDS 211 CAROTENOIDS C arotenoids are natural pigments found in plants, and are abundant in deeply colored fruits and vegetables. The most prevalent carotenoids in North American diets are a-carotene, b-carotene, lycopene, lutein, zeaxanthin, and b-cryptoxanthin. Of these, a-carotene, b-carotene, and b- cryptoxanthin can be converted into retinol (vitamin A) in the body and are called provitamin A carotenoids. Lycopene, lutein, and zeaxanthin have no vi- tamin A activity and are called nonprovitamin A carotenoids. The only known function of carotenoids in humans is to act as a source of vitamin A in the diet (provitamin A carotenoids only). There are no DRIs specifically for carotenoids (see Part III, “Vitamin A” for vitamin A DRIs and the contribution of carotenoids to vitamin A intake). Al- though epidemiological evidence suggests that higher blood concentrations of b-carotene and other carotenoids obtained from foods are associated with a lower risk of several chronic diseases, other evidence suggests possible harm arising from very large doses in population subgroups, such as smokers and asbestos workers. Currently, there is insufficient evidence to recommend that a certain percentage of dietary vitamin A should come from provitamin A carot- enoids. However, existing recommendations calling for the increased consump- tion of carotenoid-rich fruits and vegetables for their health-promoting benefits are strongly supported. Based on evidence that b-carotene supplements have not been shown to aid in the prevention or cure of major chronic diseases, and may cause harm in certain population subgroups, b-carotene supplements are not advisable other than as a provitamin A source and for the prevention and control of vitamin A deficiency in at-risk populations. Foods rich in carotenoids include deep yellow-, red-, and orange-colored fruits and vegetables and green leafy vegetables. Carotenoids found in ripe fruits and cooked yellow tubers are more efficiently converted into vitamin A than are carotenoids from equal amounts of dark green, leafy vegetables. If adequate retinol (vitamin A) is provided in the diet, there are no known clinical effects of consuming diets low in carotenes over the short term; carotenodermia or lycopenodermia (skin discoloration) are the only proven adverse effects associ- ated with excess consumption of carotenoids.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 212 CAROTENOIDS AND THE BODY Function In plants, carotenoids function as pigments. In humans, the only known func- tion of carotenoids is their provitamin A activity. Carotenoids may have addi- tional functions, such as enhancing immune function and decreasing the risk of macular degeneration, cataracts, some cardiovascular events, and some types of cancer (particularly lung, oral cavity, pharyngeal, and cervical cancers), but the evidence is inconclusive. The risks for some diseases appear to be increased in certain population subgroups when large doses of b-carotene are taken. Absorption, Metabolism, Storage, and Excretion Dietary carotenoids are fat-soluble and are absorbed in the intestine via bile acid micelles. The uptake of b-carotene by intestinal mucosal cells is believed to occur by passive diffusion. Once inside the mucosal cells, carotenoids or their metabolic products (e.g., vitamin A) are incorporated into chylomicrons and released into the lymphatic system. Carotenoids are either absorbed intact or, in the case of provitamin A carotenoids, cleaved to form vitamin A prior to secretion into the lymph. Carotenoids are transported in the blood by lipoproteins and stored in various body tissues, including the adipose tissue, liver, kidneys, and adrenal glands. (The adipose tissue and liver appear to be the main storage sites.) Ex- cretion occurs via the bile and urine. DETERMINING DRIS Determining Requirements Data were inadequate to estimate the requirements for b-carotene and other carotenoids. Although epidemiological evidence suggests that higher blood con- centrations of b-carotene and other carotenoids obtained from foods are associ- ated with a lower risk of several chronic diseases, this evidence could not be used to establish a requirement for b-carotene or other carotenoid intake be- cause the observed effects may be due to other substances found in carotenoid- rich food, or other behavioral correlates of increased fruit and vegetable con- sumption. Other evidence suggests possible harm arising from very large doses in population subgroups, such as smokers and asbestos workers. Currently, there is insufficient evidence to recommend that a certain per- centage of dietary vitamin A should come from provitamin A carotenoids. Al- though no DRI values are proposed for carotenoids, existing recommendations calling for the increased consumption of carotenoid-rich fruits and vegetables

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PART III: CAROTENOIDS 213 for their health-promoting benefits are strongly supported. The existing recom- mendation to consume 5 or more servings of fruits and vegetables per day would provide 3–6 mg/day of b-carotene. (For vitamin A DRIs, the contribution of carotenoids to vitamin A intake, and conversion factors of the various carotenoids to retinol activity equivalents [RAEs], see Part III, “Vitamin A,” and Appendix F .) The UL There were insufficient data available on the potential adverse effects of excess carotenoid intake to derive a Tolerable Upper Intake Level (UL). However, in light of research indicating an association between high-dose b-carotene supple- ments and lung cancer in smokers (see “Excess Intake”), b-carotene sup- plements are not advisable for the general population. No adverse effects other than carotenodermia (skin discoloration) have been reported from the con- sumption of carotenoids in food. DIETARY SOURCES Foods Foods rich in carotenoids include deep yellow-, red-, and orange-colored fruits and vegetables and green leafy vegetables. Major contributors of b-carotene to the diets of U.S. women of childbearing age include carrots (the major con- tributor), cantaloupe, broccoli, vegetable-beef or chicken soup, spinach, and collard greens. Major contributors of a-carotene, b-cryptoxanthin, lycopene, and lutein and zeaxanthin, respectively, are carrots, orange juice and orange juice blends, tomatoes and tomato products, and spinach and collard greens. Carotenoids are not added to most infant formulas (milk- or soy-based), and the carotenoid content of human milk highly varies depending on the ca- rotenoid content of the mother’s diet. Dietary Supplements b-Carotene, a-carotene, b-cryptoxanthin, lutein and zeaxanthin, and lycopene are available as dietary supplements. However, there are no reliable estimates of the amount being consumed by people in the United States or Canada. Bioavailability The extent of conversion of a highly bioavailable source of dietary b-carotene to vitamin A in humans has been shown to be between 60 and 75 percent, with an

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 214 additional 15 percent of the b-carotene absorbed intact. However, absorption of most carotenoids from foods is considerably lower and can be as low as 2 per- cent. Several other factors affect the bioavailability and absorption of carotenoids, including: Food matrix: The food matrix in which ingested carotenoids are found affects bioavailability the most. For example, the absorption of b-carotene supplements that are solubilized with emulsifiers and protected by antioxidants can be 70 percent or more; absorption from fruits exceeds tubers, and the absorption from raw carrots can be as low as 5 percent. Cooking techniques: Cooking appears to improve the bioavailability of some carotenoids. For example, the bioavailability of lycopene from tomatoes is vastly improved when tomatoes are cooked with oil. Steaming also improves carot- enoid bioavailability in carrots and spinach. However, prolonged exposure to high temperatures, through boiling, for example, may reduce the bioavailability of carotenoids from vegetables. Dietary fat: Studies have shown that to optimize carotenoid absorption, dietary fat must be consumed during the same meal as the carotenoid. Other factors: Lipid-lowering drugs, olestra, plant sterol–enriched margarines, and dietary pectin supplements have all been shown to reduce carotenoid absorption. Dietary Interactions Different carotenoids may compete with each other for absorption. This is more likely to occur in people who take supplements of a particular carotenoid than in people who consume a variety of carotenoid rich fruits and vegetables. For example, b-carotene supplements reduce lutein absorption from food; and when carotene and lutein are given as supplements, b-carotene absorption increases. INADEQUATE INTAKE AND DEFICIENCY If adequate retinol (vitamin A) is provided in the diet, there are no known clinical effects of consuming diets low in carotenes over the short term. Special Considerations Smoking: Smokers tend to have lower plasma concentrations of carotenoids compared to nonsmokers. It is unknown whether this is attributable solely to

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PART III: CAROTENOIDS 215 poor intake or if tobacco smoke somehow reduces the circulating levels of ca- rotenoids. The greater the intensity of smoking (the number of cigarettes per day), the greater the decrease in serum carotenoid concentrations. Although smoking may result in a need for higher intakes of dietary carotenoids to achieve optimal plasma concentrations, caution is warranted because studies have shown an increased risk of lung cancer in smokers who took b-carotene supplements (see “Excess Intake”). Recommendations made to smokers to increase carot- enoid intake should emphasize foods, not supplements, as the source. Alcohol consumption: As with tobacco, alcohol intake is inversely associated with serum carotenoid concentrations. Those who chronically consume large quantities of alcohol are often deficient in many nutrients, but it is unknown whether the deficiency is the result of poor diet or of the metabolic conse- quences of chronic alcoholism or the synergistic effect of both. EXCESS INTAKE Harmless skin discoloration in the form of carotenodermia (yellow discolora- tion) or lycopenodermia (orange discoloration) is the only proven adverse ef- fect associated with the excess consumption of carotenoids from food and supple- ments. This condition has been reported in adults who took supplements containing 30 mg/day or more of b-carotene for long periods of time or who consumed high levels of carotenoid-rich foods, such as carrots. Skin discolora- tion is also the primary effect of excess carotenoid intake noted in infants, tod- dlers, and young children. The condition is reversible when carotene ingestion is discontinued. Special Considerations Increased risk of lung cancer in smokers: In the Alpha-Tocopherol, Beta- Carotene Cancer Prevention (ATBC) Trial, an increase in lung cancer was asso- ciated with supplemental b-carotene in doses of 20 mg/day or greater (for 5 to 8 years) in current smokers. Another multicenter lung cancer prevention trial, the Carotene and Retinol Efficacy Trial (CARET), which involved smokers and asbestos-exposed workers, reported more lung cancer cases in a group supple- mented with a nutrient combination that contained both b-carotene and retinol than in a group that received placebos. In contrast, the Physicians’ Health Study, conducted in the United States, reported no significant effect of 12 years of supplementation with b-carotene (50 mg every other day) on cancer or total mortality, even among smokers who took the supplements for up to 12 years. Supplemental forms of b-carotene have markedly greater bioavailability than b-carotene from foods, and the concentrations associated with possible adverse

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 216 effects are well beyond the concentrations achieved through foods. So, although 20 mg/day of supplemental b-carotene is enough to raise blood concentrations to a range associated with increased lung cancer risk, the same amount of b-carotene in foods is not. Individuals with increased needs: Supplemental b-carotene can be used as a provitamin A source or for the prevention of vitamin A deficiency in popula- tions with inadequate vitamin A nutriture. Long-term supplementation with b-carotene in people with adequate vitamin A status does not increase the concentration of serum retinol. For vitamin A-deficient individuals and for people suffering from erythropoietic protoporphyria (a photosensitivity disor- der), treatment using higher doses may be called for, but only under a physician’s direction.

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PART III: CAROTENOIDS 217 KEY POINTS FOR CAROTENOIDS Carotenoids are natural pigments found in plants, and are 3 abundant in deeply colored fruits and vegetables. Certain carotenoids function as a source of vitamin A in humans. There are no DRIs specifically for carotenoids. 3 Currently, there is insufficient evidence to recommend that a 3 certain percentage of dietary vitamin A should come from provitamin A carotenoids. Carotenoids may enhance immune function and decrease the 3 risk of macular degeneration, cataracts, some vascular events, and some types of cancer. But carotenoids have also been linked to an increased incidence of cancer in certain population subgroups, such as smokers and asbestos workers. Foods rich in carotenoids include deep yellow-, red-, and 3 orange-colored fruits and vegetables and green leafy vegetables. Carotenoids found in ripe fruits and cooked yellow tubers are more efficiently converted into vitamin A than are carotenoids from equal amounts of dark green, leafy vegetables. Several factors influence the bioavailability and absorption of 3 carotenoids, including the food matrix, cooking techniques, the presence of dietary fat, and lipid-lowering drugs and dietary constituents. If adequate retinol (vitamin A) is provided in the diet, there are 3 no known clinical effects of consuming diets low in carotenes over the short term. Harmless skin discoloration can result from excess 3 consumption of carotenoids from food or supplements. Based on evidence that b-carotene supplements have not been 3 shown to aid in the prevention of major chronic diseases, and may cause harm in certain population subgroups, b-carotene supplements are not advisable other than as a provitamin A source and for the prevention and control of vitamin A deficiency in at-risk populations.