Archive for December 26th, 2011

Who Should Take Vitamin Supplements?

Monday, December 26, 2011 // Uncategorized

The following is the latest recommendation from The Medical Letter, a publication from a nonprofit, that analyzes new medications and advises on the use of older medication.  When they last published recommendations on this subject, they concluded that there was no evidence that taking vitamin supplements was of benefit.  Now their recommendations are a little different.

Who Should Take Vitamin Supplements?


The Medical Letter on Drugs and Therapeutics • December 12, 2011 (Issue 1379) p. 101
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Many patients ask their healthcare providers whether they should take vitamins. Since the last Medical Letter article on this subject,1 more data have become available on the benefits and risks of taking vitamins.

VITAMIN E — Vitamin E in food, which is mostly gamma-tocopherol, acts as an antioxidant. Vitamin E in supplements is mostly alpha-tocopherol, which may block the antioxidant activity of gamma-tocopherol and may have a pro-oxidant effect in vivo.2 High doses of vitamin E may interfere with vitamin K metabolism and platelet function.

Effect on Mortality – A meta-analysis of 26 clinical trials including 105,065 subjects found that supplementation with vitamin E alone or in combination with beta-carotene and vitamin A was associated with an increased risk of death.3

Pregnancy – A meta-analysis of 9 trials involving 19,810 pregnant women found that vitamin E and C supplementation was associated with an increased risk of gestational hypertension and premature rupture of membranes.4 A randomized, double-blind trial in 10,154 pregnant women found that 400 IU of vitamin E and 1000 mg of vitamin C started at any time between weeks 9-16 of gestation did not decrease the risk of preeclampsia.5

Stroke – A meta-analysis of 13 randomized, controlled trials in 166,282 patients found that supplementation with vitamin E at any dose was not beneficial in preventing any type of stroke.6 Another meta-analysis of 9 trials in 118,765 patients found that vitamin E increased the risk of hemorrhagic stroke by 22% and reduced the risk of ischemic stroke by 10%.7

Cardiovascular Events and Cancer – Three randomized trials, one in 14,641 men and two in 39,876 and 8171 women found that supplementation with vitamin E did not reduce the risk of major cardiovascular events or cancer.8-10 A randomized, controlled trial in 35,533 men found that after 7 years (5.5 years on supplements and 1.5 off supplements), men taking vitamin E alone (400 IU/day) had a statistically significant 17% increase in the risk of prostate cancer, compared to those taking a placebo.11

VITAMIN A AND BETA-CAROTENE — Vitamin A and beta-carotene, a potent source of vitamin A, are antioxidants, but may also have pro-oxidant effects in vivo. Multivitamin preparations usually contain 1000 to 10,000 IU (0.6 to 6 mg) of beta-carotene; betacarotene supplements usually contain 12-15 mg.

Cancer – A double-blind, randomized, placebo-controlled trial in 18,314 smokers, former smokers and workers exposed to asbestos found that 30 mg/day of a beta-carotene supplement plus 25,000 IU/day of vitamin A for an average of 4 years increased the incidence of lung cancer.12 A placebo-controlled trial in Finnish smokers found that 20 mg/day of a beta-carotene supplement significantly increased the risk of lung cancer.13 A prospective study that analyzed serum vitamin A levels in 29,104 men found that higher serum vitamin A concentrations were associated with an increased risk of prostate cancer.14

VITAMIN D — Many elderly people, especially those with dark skin, have inadequate amounts of vitamin D because of limited exposure to sunlight, decreased synthesis of vitamin D in the skin, and decreased absorption and activation of the vitamin. The latest US recommendations for the minimum daily requirement of vitamin D (vitamin D3 is preferred), based on amounts that have slowed the rate of bone loss, are 600 IU for males and females 1-70 years old, and 800 IU for men and women over 70. Persons infrequently exposed to the sun may need 800-1000 IU of vitamin D daily, and many experts now recommend 800 IU or more for all postmenopausal women.15 Elderly people who do not expose themselves to sunlight will need to take supplements to achieve adequate serum levels of vitamin D.

Fractures – Some experts have suggested that serum levels of 25-OH vitamin D ≥30 ng/mL may be desirable in older adults to help prevent fractures and falls.16 A meta-analysis of 7 randomized, controlled trials in men and women ≥60 years old indicated that a minimum of 700 IU/d of vitamin D3 , with or without calcium supplementation, could decrease the risk of nonvertebral fractures.17 Another meta-analysis in men and women ≥50 years old reported that use of calcium alone or calcium plus vitamin D reduced fractures of all types, especially with calcium doses ≥1200 mg/d and vitamin D doses ≥800 IU/d.18

A double-blind trial in 2256 women ≥70 years old at high risk for fracture found that a single 500,000-IU dose of vitamin D3 taken once a year for 3-5 years increased the risk of fractures and falls, compared to placebo.19

VITAMIN C — Dietary levels of about 300-400 mg/day of vitamin C maintain body pools of the vitamin. One 8-oz glass of orange juice contains about 100 mg of vitamin C.

Cancer – Vitamin C 500 mg/day plus 400 IU of vitamin E every other day for a mean follow-up period of 8 years in men ≥ 50 years old failed to reduce the risk of cancer, compared to placebo.20 Similar findings have been reported in women.10

Cardiovascular Disease – The Physicians’ Health Study II found no beneficial effect of vitamin C supplementation (in combination with vitamin E) on the primary or secondary prevention of cardiovascular disease.8

Upper Respiratory Infection – A meta-analysis of 30 trials involving 11,350 subjects showed that prophylactic use of ≥200 mg/day of vitamin C did not significantly reduce the risk of developing a cold or the severity of cold symptoms.21

Toxicity – High doses of vitamin C (more than 1 gram) are poorly absorbed, cause diarrhea, and could increase urinary oxalate excretion to a level that might cause kidney stones in people with pre-existing hyperoxaluria.

VITAMIN B12 — Vitamin B12 deficiency, diagnosed by elevated serum concentrations of methylmalonic acid with or without elevated serum homocysteine and low serum B12 concentrations, is common in older patients. Atrophic gastritis, which affects 10-30% of older people, results in inability to absorb vitamin B12 from food, with absorption of crystalline vitamin B12 usually left intact. Vitamin B12 can be taken orally or sublingually, injected IM once monthly, or sprayed intranasally.22

FOLATE — The standard US diet provides 50-500 mcg of absorbable folate per day, but the bioavailability of folate in mixed diets varies. Folic acid in supplements is about twice as bioavailable as folate in food. All enriched cereal grains sold in the US contain 140 mcg of folic acid per 100 g of grain; estimates suggest that this fortification increases folic intake by about 215-240 mcg/day. Even this amount, however, may be inadequate for prevention of neural tube defects, which occur early in pregnancy before most women know that they are pregnant.

Neural Tube Defects – Supplementing the diet of women of child-bearing age with 400 mcg of folic acid per day, the amount contained in most multivitamin preparations, has decreased the incidence of neural tube defects in their offspring.23

Toxicity – High doses of folic acid can mask vitamin B12 deficiency, permitting progression of neurologic disease.

VITAMIN B6 – Cardiovascular Disease – A randomized, double-blind, placebo-controlled trial in 5422 women with, or at risk for, cardiovascular disease found that a combination of 2.5 mg of folic acid, 50 mg of vitamin B6 (pyridoxine) and 1 mg of vitamin B12 for 5 years reduced homocysteine levels, but did not reduce the risk of stroke.24 Other trials have also failed to demonstrate that vitamin B6 supplementation, in addition to folate and vitamin B12, reduces the risk of stroke or any other cardiovascular event.25,26

Cancer — A meta-analysis of 12 studies found that vitamin B6 supplementation reduced the risk of colorectal cancer,27 but 2 randomized, double-blind trials found no association between vitamin B6 supplementation alone and a reduction in the risk of any cancer.28

MULTIVITAMINS — A study in 38,772 women (mean age 61.6 years) found that self-reported use of at least one supplement containing either multivitamins, vitamin B6, folic acid, iron, magnesium, zinc or copper was associated with an increased mortality rate.29

BARIATRIC SURGERY — A study in 58 patients who underwent bariatric surgery found that serum levels of vitamin B12, vitamin C and beta-carotene remained low even with supplementation.30 Bariatric surgery patients are also at risk for deficiencies in folate and vitamins B1, A, D and K.31

CONCLUSION — In healthy people living in developed countries and eating a normal diet, the benefit of taking vitamin supplements is well established only to ensure an adequate intake of folic acid in young women and of vitamins D and B12 in the elderly. There is no good reason to take vitamins A, C or E routinely. No one should take high-dose beta-carotene supplements. Long-term consumption of any biologically active substance should not be assumed to be free from risk.

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