Vitamin A

Overview

Vitamin A is fat-soluble vitamin that is part of a family of compounds including retinol, retinal and beta-carotene. Beta-carotene is also known as “pro-vitamin A” because it can be converted into vitamin A when additional levels are required. Food sources of vitamin A include organ meats such as liver and kidney, egg yolks, butter, cod liver oil, fortified dairy products such as milk and some margarines. For comparitive purposes, one serving (3 ounces) of beef liver contains approximately 30,000IU of vitamin A, while one cup of fortified milk contains 500IU and an egg contains 250-300IU. For beta-carotene, an average carrot provides about 20,000IU of vitamin A, while a half-cup of spinach or sweet potatoes provides approximately 7,000IU

Vitamin A is involved in myriad metabolic reactions in the body, but as a dietary supplement, the most prevalent claims are for promoting skin health, eyesight, and general immune function, with occasional claims made in the areas of “anti-aging” and “anti-cancer” effects.

Comments

Retinol, is the most usable form of vitamin A, and is often referred to as “preformed” vitamin A and found in dietary supplement in various stabilized forms. Beta-carotene is a provitamin A carotenoid that is more efficiently converted into retinol than other carotenoids, but the most prudent approach to vitamin A and carotenoids supplementation may be a combined approach that delivers small supplemental amounts of preformed vitamin A along with mixed carotenoids (versus purely beta-carotene at high doses).

Scientific Support

Vitamin A is needed by all of the body’s tissues for general growth and repair processes and is especially important for bone formation, healthy skin/hair, night vision and function of the immune system. Because of these myriad functions, the health claims associated with vitamin A are numerous.

Vitamin A may help boost immune system function and resistance to infection and the clinical and laboratory evidence to support such supplement claims is quite extensive. Vitamin A supplements have been suggested for treatment and prevention of HIV infection – even though some in vitro data suggest that vitamin A may actually activate HIV (Humphrey et al. 1999, Nduati et al. 1995). Studies of vitamin A supplementation in HIV+ patients (up to a single oral dose of 300,000IU) showed no differences in any lymphocyte subset or activation marker or any change in viral load at any time during an 8-week follow up period – suggesting no benefit nor adverse effect of vitamin A supplements on immune parameters in HIV+ patients (Humphrey et al. 1999).

In elderly Italian subjects, vitamin A supplementation (800mcg/d retinol palmitate) has been shown to reduce T-cell numbers, suggesting a comprised cell-mediated immune function, (Fortes et al. 1998) while in populations of healthy men (van Poppel et al. 1993), vitamin A deficient children (Semba et al. 1992), lung cancer patients (Micksche et al. 1977), and elderly English patients (Penn at el. 1991), vitamin A (or beta-carotene) supplementation resulted in a significant increase in cell-mediated immunity, including absolute number of T cells, T4 subsets, T4 to T8 ratio, and lymphocyte proliferation responses.

Low plasma retinol concentrations indicate depleted levels of vitamin A – and occurrence that can result from an inadequate intake of vitamin A, but also from a deficiency in protein, calories, and zinc (all needed for the synthesis of retinol binding protein, which is needed for the mobilization of vitamin A from liver stores to the general circulation).

The “immune” angle for vitamin A and its derivatives follows from its role in cell differentiation and maintenance of the surface linings of eyes and respiratory, urinary, and intestinal tracts as well as skin and mucous membranes throughout the body (thwarting bacterial infection). Vitamin A is also known to have wide-ranging effects on general functioning of the immune system cells, including lymphocytes.

Safety / Dosage

Be aware that as a fat-soluble vitamin, vitamin A can be stored in the body and levels can build up over time. Possible toxicity can result with high dose supplementation (50,000 IU/day) leading to vomiting, headaches, joint pain, skin irritation, gastrointestinal distress and hair loss. Extreme caution should be exercised during pregnancy, as high dose vitamin A has been associated with teratogenic effects (birth defects). Maximum intake of 5000 IU of vitamin A is suggested during pregnancy.

Vegetarians, who do not consume eggs and dairy foods, often need greater amounts of provitamin A carotenoids to meet their need for vitamin A. Vegans may especially benefit from a daily supplement containing a blend of provitamin A carotenoids and preformed vitamin A.

The Recommended Dietary Allowance (RDA) for vitamin A is listed in units referred to as Retinol Activity Equivalanets (RAEs) to account for differences in the activities of retinol and provitamin carotenoids such as beta-carotene. On dietary supplement labels, however, the Daily Value is used for all nutrients – with the value for vitamin A set at 5,000 IU for adults – even while the RAE for vitamin A is lower – at 2330IU (700mcg RAE) for adult women and 3000IU (900mcg RAE) for adult men. Based on the most recent evidence for the long-term effects of high vitamin A intake on bone health (see below), it is prudent to keep total vitamin A intake from foods, fortification, and supplements to less than 300IU of preformed vitamin A daily. Although there is no established DV for beta carotene, a daily intake of 5-20mg would roughly approach those levels achieved by a diet high in fruits and vegetables and the Institute of medicine suggests that a daily consumption of 3-6mg of beta-carotene will maintain plasma beta-carotene levels in the range associated with a lower risk of chronic diseases.

Much has been made in the general media about the “osteoporosis risk” associated with higher than average vitamin A intakes. These stories are based on research studies that note the highest incidence of osteoporosis occurs in northern Europe – a population with a high vitamin A intake. What the researchers also note, and many of the media reports fail to also note, is that this northern European population also has a reduced biosynthesis of vitamin D associated with lower levels of sun exposure. More recent studies of the effect of vitamin A intake on vitamin D metabolism and bone health have suggested that a high vitamin A intake may impair the ability of vitamin D to promote intestinal calcium absorption. At very high levels of intake (retinol intake at more than 1500-3000mcg/day (2-3 times the recommended amount for adults), studies have shown a reduced bone mineral density and an increased risk of hip fracture compared to lower intakes of vitamin A (500-1250mcg/day). There does not seem to be any evidence of an association between beta-carotene intake and increased risk of osteoporosis – or between recommended intakes of preformed vitamin A and osteoporosis. The Tolerable Upper Intake Level (UL) for vitamin A is the same for men, women, and pregnant women (3000mcg RAEs, or 10,000IU).

Beta-carotene is covered in more detail as an antioxidant in the Eye Health section. Although some large clinical trials have associated beta-carotene supplements with a greater incidence of lung cancer and death in current/heavy smokers, other large studies have found no adverse effects of up to 25-50mg/day of beta-carotene in otherwise healthy subjects.

References

1.Allende LM, Corell A, Madrono A, Gongora R, Rodriguez-Gallego C, Lopez-Goyanes A, Rosal M, Arnaiz-Villena A. Retinol (vitamin A) is a cofactor in CD3-induced human T-lymphocyte activation. Immunology. 1997 Mar;90(3):388-96.

2.Daudu PA, Kelley DS, Taylor PC, Burri BJ, Wu MM. Effect of a low beta-carotene diet on the immune functions of adult women. Am J Clin Nutr. 1994 Dec;60(6):969-72.

3.Fortes C, Forastiere F, Agabiti N, Fano V, Pacifici R, Virgili F, Piras G, Guidi L, Bartoloni C, Tricerri A, Zuccaro P, Ebrahim S, Perucci CA. The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc. 1998 Jan;46(1):19-26.

4.Humphrey JH, Quinn T, Fine D, Lederman H, Yamini-Roodsari S, Wu LS, Moeller S, Ruff AJ. Short-term effects of large-dose vitamin A supplementation on viral load and immune response in HIV-infected women. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Jan 1;20(1):44-51.

5.Kutukculer N, Akil T, Egemen A, Kurugol Z, Aksit S, Ozmen D, Turgan N, Bayindir O, Caglayan S. Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children. Vaccine. 2000 Jul 1;18(26):2979-84.

6.Micksche M, Cerni C, Kokron O, Titscher R, Wrba H. Stimulation of immune response in lung cancer patients by vitamin A therapy. Oncology. 1977;34(5):234-8.

7.Molina EL, Patel JA. A to Z: vitamin A and zinc, the miracle duo. Indian J Pediatr. 1996 Jul-Aug;63(4):427-31.

8.Nduati RW, John GC, Richardson BA, Overbaugh J, Welch M, Ndinya-Achola J, Moses S, Holmes K, Onyango F, Kreiss JK. Human immunodeficiency virus type 1-infected cells in breast milk: association with immunosuppression and vitamin A deficiency. J Infect Dis. 1995 Dec;172(6):1461-8.

9.Penn ND, Purkins L, Kelleher J, Heatley RV, Mascie-Taylor BH, Belfield PW. The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial. Age Ageing. 1991 May;20(3):169-74.

10.Quadro L, Gamble MV, Vogel S, Lima AA, Piantedosi R, Moore SR, Colantuoni V, Gottesman ME, Guerrant RL, Blaner WS. Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins. J Infect Dis. 2000 Sep;182 Suppl 1:S97-S102.

11.Ravaglia G, Forti P, Maioli F, Bastagli L, Facchini A, Mariani E, Savarino L, Sassi S, Cucinotta D, Lenaz G. Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y. Am J Clin Nutr. 2000 Feb;71(2):590-8.

12.Rosales FJ, Kjolhede C. A single 210-mumol oral dose of retinol does not enhance the immune response in children with measles. J Nutr. 1994 Sep;124(9):1604-14.

13.Rumore MM. Vitamin A as an immunomodulating agent. Clin Pharm. 1993 Jul;12(7):506-14.

14.Schmidt K. Antioxidant vitamins and beta-carotene: effects on immunocompetence. Am J Clin Nutr. 1991 Jan;53(1 Suppl):383S-385S.

15.Semba RD, Muhilal, Scott AL, Natadisastra G, Wirasasmita S, Mele L, Ridwan E, West KP Jr, Sommer A. Depressed immune response to tetanus in children with vitamin A deficiency. J Nutr. 1992 Jan;122(1):101-7.

16.Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev. 1998 Jan;56(1 Pt 2):S38-48.

17.Semba RD. Vitamin A and immunity to viral, bacterial and protozoan infections. Proc Nutr Soc. 1999 Aug;58(3):719-27.

18.Semba RD. Vitamin A, immunity, and infection. Clin Infect Dis. 1994 Sep;19(3):489-99.

19.van Poppel G, Spanhaak S, Ockhuizen T. Effect of beta-carotene on immunological indexes in healthy male smokers. Am J Clin Nutr. 1993 Mar;57(3):402-7.

20.West CE, Rombout JH, van der Zijpp AJ, Sijtsma SR. Vitamin A and immune function. Proc Nutr Soc. 1991 Aug;50(2):251-62.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.