Vitamin A
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Many studies for third world countries find benefits for vitamin A supplements for children, encouraging growth and reducing infections.  However, in the U.S. fewer such findings are reported, perhaps because children in developed countries eat more vegetables and fruits high in natural precursors to vitamin A.

Vitamin A and beta-carotene are two supplements you don't want to take if you are middle-age or older.  Unfortunately, it is contained in almost all multivitamin supplements.  I recommend no multivitamin pills with vitamin A or beta-carotene for men and non-pregnant women.  Multivitamins are probably still OK for children and pregnant women.  All of the necessary vitamins can be obtained with little added cost at the right amounts by following my Recommendations for Healthy Living.   

Vitamin A supplements have been found to increase lung and GI cancers, fractures, heart disease, HIV virus shedding, and stroke in middle-aged adults.  Anyone eating even a half of the recommended amount of vegetables in his or her diet probably get enough carotenes, which the body converts into natural vitamin A.  In a meta-analysis of the 68 best studies, taking antioxidant vitamin A, C, E, and selenium supplements neither increased, nor reduced, the risk of early death.  However, when the researchers eliminated the 21 trials which had a slightly higher possibility of producing a skewed result, the picture changed considerably.  While the risk of death was unchanged among selenium and vitamin C users, a statistically significant increase in risk emerged for the other three supplements.  Beta-carotene produced an approximate 7% increased risk, vitamin E a 4% increase and vitamin A, a 16% increase (Copenhagen, JAMA 2/28/07).

Processed Carrots and Spinach Better Than Raw: Blood levels A-carotene three times higher with processed i.e. heated. Eight women consumed identical amounts each way for four weeks. Rock, UCSD, J Nutr ’98;128:913. Similar benefit in another study with tomatoes with heat releasing more lycopene for absorption.

The Studies

Cancers: Vitamin A, Beta-Carotene Increase GI Cancers: The Cochrane Hepato-Biliary Group reviewed all randomized trials that compared antioxidant supplements with placebo for the prevention of gastrointestinal cancers. These 14 randomized trials covered 170,525 participants. Vitamins A, C, and E; beta-carotene; and selenium (alone or in combination) had no protective effects compared with placebo against esophageal, gastric, colorectal, pancreatic, and liver cancers. Antioxidant supplements were associated with increased mortality in some trials. Seven studies showed a small but significant increase in mortality with antioxidant supplements (relative risk 1.06). And a combination of beta-carotene and vitamin A was associated with a 30% increased risk of death while combined beta-carotene and vitamin E was associated with a 10% increased risk. Selenium had a beneficial effect on the incidence of gastrointestinal cancer in four trials, although three of these were considered to have inadequate methodology. Except for vitamin C and selenium, regular use of these antioxidant supplements does not prevent gastrointestinal cancer. Lancet 2004;364: 1219-28.

Cancer: Carotenoids in diet and Serum is associated with lower Coronary Heart Disease and Cancer especially Lung But Supplements Kill: A 12-year DB study of 50 mg beta carotene every other day had no impact. Hennedens NEJM 334:1145 ’96. Another DB study of Finnish smokers receiving 20 mg/day increased lung cancer 18% NEJM 330:1029, ’94. A large DB study of smokers and asbestos workers was stopped early since 30 mg of beta carotene and 25000 IU of Vitamin A was associated with an increased rate of lung cancer, cardiovascular death and death overall. Omenn NEJM 334:1150 ’96, J Natl Cancer Inst 88:1550 ’96. Med Letter 7/31/98 opinioned that no one should take vitamin A.

Fractures: Too Much Vitamin A Causes Hip Fractures: Women consuming 6660 IU/d had nearly double the hip fractures compared to the lowest intake of less than 1600 IU/d. Vitamin A is high in animal foods like milk and liver and supplements. JAMA 287:47, 2002

Fractures: Too Much Vitamin A Causes Male Hip Fractures: 20 per cent of men with highest levels of blood vitamin A were 1.6 times more likely to break a bone and 2.5 times more likely to have a hip fracture than men with average levels. Another way of boosting vitamin A levels is to take beta-carotene, which the body then converts. But there was no link between blood levels of beta-carotene and fracture risk. Sweden. Analysed vitamin A levels in blood taken 30 years ago from more than 2300 men, who were then between 49 and 51 years old. NEJM 1/24/03.

Fractures: Increased in Hip Fractures Due to Retinol: 18 year follow-up of 72,000 nurses found retinol 3000 units/day was associated with increases in fractures whether in food or pills. Beta-carotene was associated with a non-significant increase.

HIV Pregnancy: Vitamin A Increases Shedding: In a Harvard DB PC study of vitamins A, B, C, and E, significantly more women who received vitamin A had detectable levels of HIV-1 in CVL (74.8%), compared with those who did not receive vitamin A (65.1%) (P=.04). Multivitamin B-complex, C, and E had no effect on the risk of viral shedding. This raises concern about the use of vitamin A supplements by HIV-1-infected women. Effect of prenatal vitamin supplementation on lower-genital levels of HIV type 1 and interleukin type 1 beta at 36 weeks of gestation. Fawzi W, Msamanga G, et al. Clin Infect Dis. 2004 Mar 1;38(5):716-22

HIV Pregnancy: Vitamin A No Help: 312 HIV-seropositive pregnant South African women between 28 and 32 weeks' gestation were randomized to placebo or 5,000 IU retinyl palmitate and 30 mg beta-carotene daily. Vitamin A did not confer any significant beneficial effect on the report of either HIV or pregnancy-related symptoms during the pre- or postnatal period. Randomized controlled trial assessing the effect of vitamin A supplementation on maternal morbidity during pregnancy and postpartum among HIV-infected women. Kennedy CM, Coutsoudis A, et al. Columbia University. J Acquir Immune Defic Syndr. 2000 May 1;24(1):37-44

Immune Response in Elderly: Vitamin A Bad, Zinc Good: In a 118 adult DB PC study of vitamin A 800 mcg, zinc 25 mg/day, or both, zinc supplementation improved cell-mediated immune response, whereas vitamin A had a deleterious effect in this older population. The effect of zinc and vitamin A supplementation on immune response in an older population. Fortes C, Forastiere F, et al. National Institute of Health, Rome, Italy. J Am Geriatr Soc. 1998 Jan;46(1):19-26

Lung Cancer and Heart Death: Vitamin A Caused Big Increase: The 18,314 adult Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended 21 months early because those being given 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET). Redlich CA, Chung JS, et al. Yale University. Atherosclerosis. 1999 Aug;145(2):425-32

Lung Cancer Prevention: Vitamin A, Beta-Carotene Bad; Apples, Cabbage, Broccoli Good: In a 12-year follow-up of 14,120 beta-Carotene and Retinol Efficacy Trial (CARET) participants the RR for highest versus lowest fifth in total fruit consumption in the placebo arm was 0.56 (P = 0.003). Two specific groups were associated with reduced risk of lung cancer. Compared with the lowest quintile of rosaceae fruit (apples, peaches, pears) consumption, placebo participants in the top quintile had a RR of 0.63; for cruciferae vegetables (broccoli, cabbage, brussel spouts), the RR was 0.68. However, there was not any benefit from fruits and vegetables on lung cancer risk among for adults taking the supplements (30 mg of beta-carotene and 25,000 IU of retinyl palmitate). Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). Neuhouser ML, Patterson RE, et al. Seattle, Washington. Cancer Epidemiol Biomarkers Prev. 2003 Apr;12(4):350-8

Lung Cancer: Beta-Carotene Killed Smokers; Vitamin E No Benefit: In a 5-8 year DB PC primary prevention study, 29,133 Finnish male smokers ages 50-69 took alpha-tocopherol (vitamin E)(50 mg per day) alone, beta carotene (vitamin A)(20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Among the 876 new cases of lung cancer, no reduction occurred with alpha-tocopherol. Those on beta carotene had an 18% higher rate of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol. Beta carotene had little or no effect on the incidence of other cancers. Alpha-tocopherol had no effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received it. Total mortality was 8% higher among the participants who received beta carotene than among those who did not, primarily from lung cancer and ischemic heart disease. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994 Apr 14;330(15):1029-35.

Lung Infections: Zinc, Not Vitamin A, Helped Infant Boys with Lower Respiratory Infection: In a DB PC study of 153 infants in India with severe acute lower respiratory infection (ALRI) is a leading cause of childhood death, zinc 5 mg twice a day caused recovery rates from very ill status and from fever in zinc-treated boys were 2.6 times (P = 0.004) and 3 times (P = 0.003) faster than boys without zinc, but vitamin A had no positive effects. Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A in infants and young children with severe acute lower respiratory infection. Mahalanabis D, Lahiri M, et al. Kolkata, India. Am J Clin Nutr. 2004 Mar;79(3):430-6

Dermatologists Still Using High-Dose Vitamin A: In one DB PC study of 2,297 adults with moderately severe actinic keratoses, 25,000 IU/day vitamin A caused a 32% risk reduction in squamous cell skin cancers. In a 2nd study of 129 with severely sun-damaged skin on their lateral forearms receiving placebo or 25,000, 50,000, or 75,000 IU/day vitamin A for 12 months, authors report no differences between groups in toxicity. Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin. Alberts D, Ranger-Moore J, et al. University of Arizona. Clin Cancer Res. 2004 Mar 15;10(6):1875-80. Ed: I think that the above practice is very likely to increase deaths from other causes far more than any benefit for skin cancer.

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