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Fat-Soluble Vitamins & Micronutrients: Vitamins A and E and Carotenoids

In This Section

Vitamin A, Vitamin E, gamma-Tocopherol, alpha-Carotene, trans-beta-Carotene, beta-Cryptoxanthin, Lutein/zeaxanthin, trans-Lycopene

Background

Vitamins A (retinol) and E (tocopherol) and the carotenoids are fat-soluble micronutrients that are found in many foods, including some vegetables, fruits, meats, and animal products. Fish-liver oils, liver, egg yolks, butter, and cream are known for their higher content of vitamin A. Nuts and seeds are particularly rich sources of vitamin E (Thomas 2006). At least 700 carotenoids—fat-soluble red and yellow pigments—are found in nature (Britton 2004). Americans consume 40–50 of these carotenoids, primarily in fruits and vegetables (Khachik 1992), and smaller amounts in poultry products, including egg yolks, and in seafoods (Boylston 2007). Six major carotenoids are found in human serum: alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, trans-lycopene, and zeaxanthin. Major carotene sources are orange-colored fruits and vegetables such as carrots, pumpkins, and mangos. Lutein and zeaxanthin are also found in dark green leafy vegetables, where any orange coloring is overshadowed by chlorophyll. Trans-Lycopene is obtained primarily from tomato and tomato products. For information on the carotenoid content of U.S. foods, see the 1998 carotenoid database created by the U.S. Department of Agriculture and the Nutrition Coordinating Center at the University of Minnesota.

Vitamin A, found in foods that come from animal sources, is called preformed vitamin A. Some carotenoids found in colorful fruits and vegetables are called provitamin A; they are metabolized in the body to vitamin A. Among the carotenoids, beta-carotene, a retinol dimer, has the most significant provitamin A activity. Because of limitations in the body’s ability to absorb and metabolize vitamin A, approximately 12 micrograms (µg) of dietary beta-carotene are needed to equal 1 µg of retinol. Other provitamin A carotenoids, such as alpha-carotene and beta-cryptoxanthin, are half as active as beta-carotene (Institute of Medicine 2000). The bioconversion of carotenoids to vitamin A is highly variable from person to person (Krinsky 2005). Vitamin E activity is derived from at least eight naturally occurring tocopherols, the most potent of which is alpha-tocopherol. Other less active forms of vitamin E are plentiful in the U.S. diet, with gamma-tocopherol being the predominant form.

The absorption of fat-soluble micronutrients from the gastrointestinal tract depends on processes responsible for fat absorption or metabolism. Thus, people with conditions resulting in fat malabsorption (e.g., celiac disease, Crohn’s disease, pancreatic disorders) can develop vitamin A deficiency over time. Vitamin A also has interactions with other nutrients. Iron and zinc deficiency can affect vitamin A metabolism and transport of vitamin A stores from the liver to body tissues (Institute of Medicine 2001). The absorption of carotenoids from foods is highly dependent on cooking techniques that break down plant cell walls and release carotenoids and also on the availability of dietary fat to enhance carotenoid uptake (Krinsky 2005). The liver regulates the concentration of vitamin A in the circulation by releasing stored retinyl esters as needed; only when liver reserves are nearly exhausted does serum vitamin A fall into the deficient range (Napoli 2006). The variation in serum carotenoid concentrations among people in the United States is relatively large, primarily reflecting wide-ranging differences in dietary intake (Lacher 2005). Plasma concentrations of tocopherols vary widely among healthy individuals and are highly correlated with plasma lipid concentrations (Ford 1999; Ford 2006).

Inadequate or excessive intake of vitamins A or E can lead to various disorders. For example, vitamin A deficiency is considered to be the main cause of childhood blindness (Roodhooft 2002), a rare condition in the United States. Prominent signs of vitamin A deficiency include night blindness, corneal thinning, and conjunctival metaplasia. Vitamin A is also essential for proper immune function, epithelial growth and repair, bone growth, reproduction, and normal embryonic and fetal development (West 2006). Acute toxicity, resulting from single or short-term large doses of preformed vitamin A, is characterized by nausea, vomiting, headache, vertigo, blurred vision, increased cerebrospinal fluid pressure, and lack of muscular coordination. Central nervous system effects, liver abnormalities, bone and skin changes, and other nonspecific adverse effects can be indicative of chronic hypervitaminosis A. Consuming excess amounts of vitamin A during early pregnancy may lead to serious birth defects (Institute of Medicine 2001). The U.S. Food and Drug Administration (FDA) currently recommends that pregnant women obtain vitamin A from foods containing beta-carotene (U.S. Food and Drug Administration 1995).

Carotenoids are considered among the best biological markers for fruit and vegetable intake. The strongest dietary predictors of serum carotenoid concentrations are fruits (for sources of beta-cryptoxanthin), carrots and root vegetables (for sources of carotenes), and tomato products (for sources of trans-lycopene) (Al-Delaimy 2005). Research studies have shown inconsistencies in the relation between carotenoid intake and protection from cancer. Carotenoids in foods, even when consumed over long periods and in large amounts, are not known to produce adverse health effects. However, results of intervention studies of smokers who used 20-30 milligrams (mg) of beta-carotene per day showed that this group had more lung cancers than placebo-treated groups (Redlich 1998; Albanes 1996).

Vitamin E deficiency occurs only rarely in people, and overt deficiency symptoms in people consuming low-vitamin E diets have never been described (Institute of Medicine 2000). The main manifestation of vitamin E deficiency is peripheral neuropathy characterized by the degeneration of the large-caliber axons of sensory neurons (Institute of Medicine 2000). The upper limit (UL) for vitamin E intake (1000 mg/day) was based on hemorrhagic effects; however, a causal association between excess alpha-tocopherol intake in apparently healthy individuals and adverse health outcomes has not consistently been shown (Institute of Medicine 2000). Studies evaluating tocopherols to reduce the risk for cardiovascular disease demonstrated inconsistent findings (Agency for Healthcare Research and Quality 2003). The American Heart Association currently advises that antioxidant supplements (such as vitamins E and C and beta-carotene) should not be used for primary or secondary prevention of cardiovascular disease (Lichtenstein 2006). Nevertheless, the American Heart Association recommends consuming food sources of antioxidant nutrients, principally from a variety of plant-derived foods such as fruits, vegetables, whole grains, and vegetable oils.

The National Academy of Sciences has established dietary-requirement intake values for vitamins A and E by determining the adequate intake (AI) for infants and the recommended dietary allowance (RDA) for older age groups (Institute of Medicine 2000 and 2001). The RDA for vitamin A for adults is 900 µg/day of retinol equivalents; for children, the RDA ranges from 300–700 µg/day. For infants (aged 0–12 months), the AI is set at 400–500 µg/day of retinol equivalents. For adults, the RDA for vitamin E is 15 mg/day of alpha-tocopherol; for children (1–18 years), the RDA ranges from 6 mg to 15 mg/day. There is no RDA for other forms of vitamin E such as gamma-tocopherol. Although no quantitative recommendations are available for the intake of carotenoids, existing recommendations support increased consumption of carotenoid-rich fruits and vegetables. Current public health guidelines advise that people consume 5 to 13 servings of fruits and vegetables a day, depending on caloric need, to ensure adequate nutrient intake (U.S. Department of Health and Human Services and U.S. Department of Agriculture 2005).

Chemists perform extraction of fat-soluble vitamins from serum.

Clinical laboratories typically use conventional units for serum concentrations of these fat-soluble micronutrients (µg per deciliter [dL]). Conversion factors to international system (SI) units are 1 µg/dL = 0.0349 micromole per liter (µmol/L) for vitamin A and 1 µg/dL = 0.02322 µmol/L for vitamin E. Depending on its molecular weight, each carotenoid has a specific conversion factor.

The diagnosis of vitamin A or E deficiency is supported by measuring these concentrations in the body. Vitamin A deficiency can be diagnosed in a number of ways. People with serum concentrations of retinol of less than 20 µg/dL are considered vitamin A deficient, and those with serum concentrations of less than 10 µg/dL are considered severely deficient (West 2006). Carotenoid deficiency has no defined serum concentrations. The laboratory diagnosis of vitamin E deficiency is based on serum concentrations of alpha-tocopherol (less than 500 µg/dL or less than 0.8 mg of alpha-tocopherol per gram of total lipids) (Beers 2006). Such concentrations are associated with in vitro hydrogen peroxide-induced red blood cell lysis, not with clinical deficiency symptoms (Institute of Medicine 2000). Among most laboratories participating in an external quality assurance program, standardized high performance liquid chromatography (HPLC) methods for measuring fat-soluble micronutrients show consistent agreement of values (Duewer 2000).

More information on vitamins A and E and carotenoids is available online:

American Society for Nutrition fact sheets*
Institute of Medicine Dietary Reference Intake reports:
- Vitamin A*
- Vitamin E and Carotenoids*
National Institutes of Health fact sheets:
- Vitamin A and Carotenoids
- Vitamin E

Since 1971, various fat-soluble micronutrients have been measured in the serum of NHANES participants. In NHANES III (1988–1994), clinically low concentrations of serum retinol were uncommon in U.S. residents aged 4 years and older, although racial/ethnic and socioeconomic differences existed (Ballew 2001). Variations in serum carotenoid concentrations by ethnicity and sex were found for adults, children, and adolescents (Ford 2000; Ford 2002). Ford et al. also found sociodemographic variations in serum concentrations of alpha-tocopherol among U.S. adults in NHANES III (1999) and alpha- and gamma-tocopherol in NHANES 1999–2000 (2006). Application of the most common cut-off value for serum alpha-tocopherol concentrations in NHANES 1999–2000 (500 µg/dL), resulted in a low prevalence of vitamin E deficiency, despite the fact that the U.S. Department of Agriculture (USDA) estimated dietary intakes of vitamin E were low and that most of the U.S. population (> 90 percent) did not meet dietary recommendations either in 1999–2000 (Ahuja 2004) or in 2001–2002 (Moshfegh 2005). However, the USDA report is based on intakes from food only and does not include dietary supplements. Furthermore, in NHANES only alpha-tocopherol is estimated for assessing dietary vitamin E intake. In NHANES 2001–2002, 44 percent of survey participants had an estimated dietary intake (from food only) of vitamin A (including carotenoids) that was less than the vitamin A estimated average requirement (EAR) (Moshfegh 2005). Low dietary intakes of certain micronutrients without widespread manifestation of deficiency suggest the need for further evaluations to determine whether improved estimates are necessary, either in the nutrient tables or in dietary intake.

Selected Observations and Highlights

The following sample observations are taken from the tables of 1999–2002 (for vitamins A and E) or 2001–2002 data (for all carotenoids) contained in this report. Statements about categorical differences between demographic groups noted below are based on non-overlapping confidence limits from univariate analysis without adjusting for demographic variables (e.g., age, sex, race/ethnicity) or other determinants of these blood concentrations (e.g., dietary intake, supplement usage, smoking, BMI). A multivariate analysis may alter the size and statistical significance of these categorical differences. Furthermore, additional significant differences of smaller magnitude may be present despite their lack of mention here (e.g., if confidence limits slightly overlap or if differences are unobservable before covariate adjustment has occurred). For a selection of citations of descriptive NHANES papers related to these biochemical indicators of diet and nutrition, see Appendix E.

General Observations

Females have lower concentrations of serum vitamin A and trans-lycopene than do males. Females have higher concentrations of serum vitamin E and beta-carotene than do males.
Non-Hispanic blacks and Mexican Americans have lower serum concentrations of vitamin A than do non-Hispanic whites.
Non-Hispanic blacks have higher serum concentrations of gamma-tocopherol than do Mexican Americans and non-Hispanic whites.
Non-Hispanic blacks have higher serum concentrations of trans-lycopene than do Mexican Americans.
Non-Hispanic blacks have lower serum concentrations of alpha-carotene than do non-Hispanic whites or Mexican Americans.
Non-Hispanic blacks have lower serum concentrations of vitamin E than do Mexican Americans, who have lower serum concentrations of vitamin E than do non-Hispanic whites.
Non-Hispanic whites have lower serum concentrations of beta-cryptoxanthin than do non-Hispanic blacks, who have lower serum concentrations of beta-cryptoxanthin than do Mexican Americans.
Serum alpha-carotene and lutein/zeaxanthin concentrations are lower in adolescents, whereas serum beta-carotene concentrations are lower in adolescents and in adults 20–39 years old than in people in other age groups.
Serum beta-carotene concentrations are higher in older people (≥ 60 years), whereas serum alpha-carotene and lutein/zeaxanthin concentrations are higher in middle-aged and older people compared with people in younger age groups.
Serum beta-cryptoxanthin concentrations are higher in children than in adolescents or adults.
Serum trans-lycopene and gamma-tocopherol concentrations are lower in young children and older people than in people in other age groups.
Serum vitamin A and E concentrations are lower in children and adolescents than in adults.

Highlights

The majority of the U.S. population (> 95 percent) has adequate serum concentrations of vitamin A (≥ 20 µg/dL) and vitamin E (≥ 500 µg/dL).

Tables

Serum vitamin A

Serum vitamin E

Serum gamma-tocopherol

Serum alpha-carotene

Serum trans-beta-carotene

Serum beta-cryptoxanthin

Serum lutein/zeaxanthin

Serum trans-lycopene

References

Agency for Healthcare Research and Quality. Effect of supplemental antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cardiovascular disease. Evidence Report/Technology Assessment Number 83, 2003.

Ahuja JK, Goldman JD, Moshfegh AJ. Current status of vitamin E nutriture. Ann N Y Acad Sci. 2004;1031:387-90.

Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, et al. Alpha-tocopherol and beta-carotene supplement and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer
Inst .1996;88:1560-70.

Al-Delaimy WK, Ferrari P, Slimani N, Pala V, Johansson I, Nilsson S, et al. Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Clin Nutr. 2005;59:1387-96.

Ballew C, Bowman BA, Sowell AL, Gillespie C. Serum retinol distributions in residents of the United States: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr. 2001;73:586-93.

Beers MH, editor. Vitamin deficiency, dependency, and toxicity. In: Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, (NJ): Merck & Co., Inc.; 2006 [cited 2008]. Available from: http://www.merck.com/mmpe/sec01/ch004/ch004l.html.

Boylston T, Nollet LML. Chemical and biochemical aspects of color in muscle foods. In: Perez-Alvarez JA and Fernandez-Lopez J, editors. Handbook of meat, poultry and seafood quality. Ames (IA): Blackwell Publishing; 2007. p. 25–44.

Britton G, Liaaen-Jensen S, Pfander H., editors. Carotenoids handbook. Basel (Switzerland): Birkhäuser; 2004.

Duewer DL, Kline MC, Sharpless KE, Thomas JB. NIST micronutrients measurement quality assurance program: Characterizing the measurement community‘s performance over time. Anal Chem. 2000;72:4163-70.

Ford ES, Sowell A. Serum α-tocopherol status in the United States population: findings from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 1999;150:290-300.

Ford ES. Variations in serum carotenoid concentrations among United States adults by ethnicity and sex. Ethn Dis. 2000;10:208-17.

Ford ES, Gillespie C, Ballew C, Sowell A, Mannino DM. Serum carotenoid concentrations in U.S. children and adolescents. Am J Clin Nutr. 2002;76:818-27.

Ford ES, Schleicher RL, Mokdad AH, Ajani UA, Liu S. Distribution of serum concentrations of alpha-tocopherol and gamma-tocopherol in the U.S. population. Am J Clin Nutr. 2006;84:375-83.

Institute of Medicine, Food and Nutrition Board. Dietary reference intakes: vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C.: National Academy Press; 2000.

Institute of Medicine, Food and Nutrition Board. Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, D.C.: National Academy Press; 2001.

Khachik F, Beecher GR, Goli MB, Lusby WR. Separation and quantitation of carotenoids in foods. Methods Enzymol. 1992;213:347–59.

Krinsky NI, Johnson EJ. Carotenoid actions and their relation to health and disease. Mol Aspects Med. 2005;26:459–516.

Lacher DA, Hughes JP, Carroll MD. Estimate of biological variation of laboratory analytes based on the Third National Health and Nutrition Examination Survey. Clin Chem. 2005;51:450–2.

Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, Franch HA, et al. Summary of American Heart Association diet and lifestyle recommendations revision. Arterioscler Thromb Vasc Biol. 2006;26:2186–91.

Moshfegh A, Goldman J, Cleveland L. What we eat in America, NHANES 2001-02: usual nutrient intakes from food compared to dietary reference intakes. Beltsville (MD): U.S. Department of Agriculture, Agricultural Research Service; 2005 [cited 2008]. Available from: http://www.ars.usda.gov/SP2UserFiles/Place/12355000/pdf/usualintaketables2001-02.pdf.

Napoli JL. Vitamin A: biochemistry and physiological role. In: Caballero B, Allen L, Prentice A, editors. Encyclopedia of human nutrition. 2nd ed. Amsterdam: Elsevier Ltd.; 2006. p. 339–47.

Redlich CA, Blaner WS, Van Bennekum AM, Chung JS, Clever SL, Holm CT, Cullen MR. Effect of supplementation with beta-carotene and vitamin A on lung nutrient levels. Cancer Epidemiol Biomarkers Prev. 1998;7:211–14.

Roodhooft JM. Leading causes of blindness worldwide. Bull Soc Belge Ophthalmol. 2002;283:19–25.

Thomas, RG, Gebhardt, SE. Nuts and seeds as sources of alpha and gamma tocopherols. ICR/WCRF International Research Conference, 2006 Jul 13-14; Washington, D.C. [cited 2008]. Available from:
http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Articles/AICR06_NutSeed.pdf.

U.S. Department of Health and Human Services and U.S. Department of Agriculture. Dietary guidelines for Americans, 2005. 6th ed. Washington, D.C.: U.S. Government Printing Office; January 2005.

U.S. Food and Drug Administration. FDA recommendation for pregnant women, T95-56. Washington, D.C.: Food and Drug Administration; October 6, 1995 [cited 2008]. Available from: http://www.fda.gov/bbs/topics/ANSWERS/ANS00689.html.

West Jr, KP. Vitamin A: deficiency and interventions. In: Caballero B, Allen L, Prentice A, editors. Encyclopedia of human nutrition. 2nd ed. Amsterdam: Elsevier Ltd.; 2006. p. 348–59.

National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population 1999–2002