Applied Evidence

Vitamin supplementation in healthy patients: What does the evidence support?

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In addition to their individual roles, vitamins A, E, and C are antioxidants, functioning to protect cells from oxidative damage by free radical species.2 Due to this shared role, these vitamins are commonly studied together. Antioxidants are hypothesized to protect from various diseases, including cancer, cardiovascular disease, dementia, autoimmune disorders, depression, cataracts, and age-related vision decline.2,37,107-112

Though observational studies have found a correlation of increased risk for disease with lower antioxidant serum levels, RCTs have not demonstrated a reduction in disease risk with supplementation and, in some cases, have found an increased risk of mortality. While several studies have found potential benefit of antioxidant use in reducing colon and breast cancer risk,38,113-115 vitamins A and E have been associated with increased risk of lung and prostate cancer, respectively.47,110 Cardiovascular disease and antioxidant vitamin supplementation has similar inconsistent data, ranging from slight benefit to harm.2,116 After a large Cochrane review in 2012 found a significant increase in all-cause mortality associated with vitamin E and ­beta-carotene,117 the USPSTF made a specific recommendation against supplementation of these vitamins for the prevention of cardiovascular disease or cancer (grade D).118 Given its limited risk for harm, vitamin C was excluded from this recommendation.

Vitamin A

Vitamers: Retinol; retinal; retinyl esters; provitamin A carotenoids (beta-carotene, alpha-carotene, beta-cryptoxanthin)

Physiologic role: Essential for vision and corneal development. Also involved in general cell differentiation and immune function

Dietary sources: Liver, fish oil, dairy, and fortified cereals. Provitamin A sources: leafy green vegetables, orange/yellow vegetables, tomato products, fruits, and vegetable oils

Retinoids and their precursors, carotenoids, serve a critical function in vision, as well as regulating cell differentiation and proliferation throughout the body.2 While evidence suggests mortality benefit of supplementation in populations at risk of deficiency,45 wide-ranging studies have found either inconsistent benefit or outright harms in the developed world.

The takeaway: Given the USPSTF grade “D” recommendation and concern for potential harms, supplementation is not recommended in healthy patients without risk factors for deficiency.2

Vitamin E

Vitamers: Tocopherols (alpha-, beta-, ­gamma-, delta-); tocotrienol (alpha-, beta-, gamma-, delta-)

Physiologic role: Antioxidant; protects polyunsaturated fats from free radical oxidative damage. Involved in immune function, cell signaling, and regulation of gene expression

Dietary sources: Nuts, seeds, vegetable oil, green leafy vegetables, and fortified cereals

Vitamin E is the collective name of 8 compounds; alpha-tocopherol is the physiologically active form. Vitamin E is involved with cell proliferation as well as endothelial and platelet function.2

The takeaway: Vitamin E supplementation’s effects on cancer, cardiovascular disease, ophthalmologic disorders, and cognition have been investigated; data is either lacking to support a benefit or demonstrates harms as outlined above. Given this and the USPSTF grade “D” recommendation, supplementation is not recommended in healthy patients.2

Vitamin C

Vitamers: Ascorbic acid

Physiologic role: Required for synthesis of collagen, L-carnitine, and some neurotransmitters. Also involved in protein metabolism

Dietary sources: Primarily in fruits and vegetables: citrus, tomato, potatoes, red/green peppers, kiwi fruit, broccoli, strawberries, brussels sprouts, cantaloupe, and fortified cereals

Vitamin C supplementation at the onset of illness does not seem to have benefit.

Ascorbic acid is a required cofactor for biosynthesis of collagen, neurotransmitters, and protein metabolism.2 In addition to the shared hypothesized benefits of antioxidants, vitamin C supplementation has undergone extensive research into its potential role in augmenting the immune system and preventing the common cold. Systematic reviews have found daily vitamin C supplementation of at least 200 mg did not affect the incidence of the common cold in healthy adults but may shorten duration and could be of benefit in those exposed to extreme physical exercise or cold.48 Vitamin C supplementation at the onset of illness does not seem to have benefit.48 Data is insufficient to draw conclusions about a potential effect on pneumonia incidence or severity.119,120

The takeaway: Overall, data remain inconclusive as to potential benefits of vitamin C supplementation, although risks of potential harms are likely low.

Continue to: Vitamin D


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