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Cancer — Folate deficiency may contribute to aberrant DNA synthesis and carcinogenesis by decreasing methionine availability and interfering with normal DNA methylation. Biologic and observational evidence suggests that sufficient folate intake might prevent cancers in certain populations at risk.

Cardiovascular disease — High levels of homocysteine are associated with an increased risk of cardiovascular disease. Supplementation with folic acid, vitamin B6, and vitamin B12 can lower homocysteine levels.

• High folate intake may reduce the risk of hypertension. In multivariate analyses from the large prospective Nurses' Health Study, compared with women who consumed diets with less than 200 mcg folate per day, the risk of hypertension was reduced in young women age 27 to 44 years consuming diets with more than 1000 mcg per day (RR 0.54, 95% CI 0.45-0.66) and to a lesser extent in older women age 43 to 70 years (RR 0.82, 0.69-0.97). There is insufficient evidence to recommend folic acid supplementation to reduce the risk of hypertension.

VITAMIN D — The intake of vitamin D in older adults should be the equivalent of at least 800 to 1000 units daily, provided in the diet or as a vitamin D3 supplement (cholecalciferol) dosed daily, weekly, or monthly. Dietary vitamin D intake is often low in older adults. Thus, for most older adults, we suggest supplementation with 1000 units of vitamin D daily; there can be a downward adjustment in this dose for dietary intake.

 

Subclinical vitamin D deficiency or insufficiency is extremely common and may contribute to the development of osteoporosis, falls, and fractures. We do not routinely measure serum 25-hydroxyvitamin D levels in most individuals. However, serum 25-hydroxyvitamin D should be measured in patients who are at risk for inadequate serum vitamin D concentrations, including institutionalized individuals, patients being evaluated for osteoporosis, and patients with malabsorption (for example Crohn disease and celiac disease).

 

ANTIOXIDANT VITAMINS — The antioxidant vitamins include total vitamin A, consisting of preformed vitamin A (retinol) and the carotenoids such as beta-carotene, as well as vitamins C and E. Many other compounds found in food, especially vegetables and fruits, also have antioxidant properties. A number of studies have examined the hypothesis that antioxidants can prevent cancer and cardiovascular disease by augmenting the body's ability to dispose of toxic free radicals, thereby retarding oxidative damage.

 

Vitamin A and the carotenoids — Total vitamin A consists of preformed vitamin A (retinol) and the carotenoids such as beta-carotene. Retinol is only found in animal products and supplements, while carotenoids that can be converted into vitamin A (provitamin A carotenoids) are found in fruits and vegetables. In addition to antioxidant properties, retinol may also decrease cancer risk via other mechanisms such as inducing cellular differentiation.

 

Vitamin C — Vitamin C is commonly found in citric fruits and many types of vegetables. Vitamin C may have a minor role in preventing the common cold, specifically for persons involved in high-intensity physical activity in extreme cold climates.

VITAMIN B2 (RIBOFLAVIN) — Vitamin B2 is found in many commonly consumed foods, including milk, meat, eggs, cereal, and green leafy vegetables. This may explain why overt riboflavin deficiency is rare.

There is no strong evidence that supplemental vitamin B2 is helpful in healthy people eating a balanced diet.

VITAMIN B6 (PYRIDOXINE) — Vitamin B6 is found in bananas, nuts, and many common vegetables such as potatoes, green beans, cauliflower, and carrots. Vitamin B6 is thought to reduce the risk of cardiovascular disease and cancer.

 

VITAMIN B12 (COBALAMIN) — Suboptimal vitamin B12 level is most commonly caused by poor absorption and inadequate intake of vitamin B12-containing food sources (for example, liver, milk, fish, meat). Malabsorption of cobalamin is primarily the result of inability to release cobalamin from dietary proteins, especially in the presence of autoimmune antibodies against intrinsic factor or reduced gastric acid secretion. In older adults, gastric atrophy and hypochlorhydria result in reduced gastric acid and inefficient vitamin B12 absorption. Vitamin B12 deficiency can also be seen among people following a vegan diet.

• Severe vitamin B12deficiency causes neurologic disease and megaloblastic anemia. Subtle B12 deficiency, even without anemia, is associated with dementia and low cognitive function. However, there is no solid evidence that taking vitamin B12 supplements prevents dementia. In addition, B12 deficiency may lead to deteriorating balance in some older adults, but this has not been well-studied.
• Vitamin B12deficiency may also be an important cause of hyperhomocysteinemia, particularly in older adults. High levels of homocysteine are associated with an increased risk of cardiovascular disease. Supplementation with folic acid, vitamin B6, and vitamin B12 can lower homocysteine levels.
• Hyperhomocysteinemia is also associated with osteoporosis. It is not known whether this association is causal or whether lowering homocysteine levels would affect risk. Similarly, it is unknown whether supplementation with folate and vitamin B12in high-risk groups would reduce the risk of fractures.

Measuring vitamin B12 levels may be indicated in individuals at increased risk for poor vitamin B12 intake, including vegans, alcoholics, and people with little dietary variation (such as some older adults). Vitamin B12 supplementation in healthy adults and in those with vitamin B12 deficiency is well-tolerated without significant adverse effects.

Safety — In the United States, the federal government does not regulate food supplements (vitamins, minerals, and herbs) to assure safety and efficacy. Multivitamins are sold in a variety of combinations and doses. However, manufacturers are required to list contents in a standard way, making it easier for consumers to compare brands.

Individual vitamin doses in multivitamins are apparently safe for most adults. The dose of vitamin E is well below the levels reported to cause an increase in overall mortality, and the dose of beta-carotene, usually a part of the total vitamin A activity, is well below levels associated with lung cancer. The dose of folic acid is also lower than that found to potentially increase cancer risk. Some formulations of vitamins sold over-the-counter may contain several times the RDA of vitamin B12, which is harmless even at much higher doses.

Some individuals may be harmed by even ordinary doses of vitamin A. Vitamin A has been shown in observational studies to be a risk factor for osteopenia and fractures in the range ingested by a substantial proportion of the adult population in the United States. People at increased risk of osteopenia, or with relatively high dietary intake of vitamin A, should not take additional supplements containing vitamin A until further research clarifies whether the association between vitamin A and osteopenia is causal. Additionally, vitamin A is teratogenic starting at doses of only 10,000 units/day of supplementation. Manufacturers have been reducing the amount of vitamin A in multivitamins, but supplementation, even at less than 100 percent of the RDA, does not seem prudent in people who are otherwise at increased risk.

TOXICITY AT HIGH DOSES — Potentially toxic levels of individual vitamins can be achieved easily in people who take very high-potency vitamins, which can be obtained in specialty stores, over the internet, and even in pharmacies. High doses can also be achieved by taking a large number of pills even if the dose per pill is not high. The Institute of Medicine (IOM) and the Office of Dietary Supplements has suggested Tolerable Upper Intake Levels for specific vitamins, which is the highest daily dose that is unlikely to cause adverse health effects in the general population.

Water soluble vitamins (folate, vitamin C, B vitamins) can generally be tolerated at high doses, with toxicity occurring only at doses thousands of times the Recommended Dietary Allowance (RDA). A possible exception is the risk of kidney stones, which may be increased after doses of vitamin C that are 10 to 25 times the RDA.

Fat soluble vitamins (vitamins A, D, E, K) are generally more toxic than water soluble vitamins. Vitamin D may cause hypercalcemia at doses as low as 4000 units/day (recommended upper limit) in some people. Vitamin A in pregnancy is teratogenic at doses as low as several times the RDA (with an apparent threshold at 10,000 units/day of supplemental vitamin A). Beta-carotene appears to increase the risk of lung cancer in adults who are otherwise at high risk because of smoking or exposure to asbestos. As discussed above, there are concerns that vitamin E supplementation above 400 units per day may be associated with increased all-cause mortality.