Applied Evidence

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

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This review, with handy tables, summarizes which vitamins offer proven benefits—and which don’t.


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Since their discovery in the early 1900s as the treatment for life-threatening deficiency syndromes, vitamins have been touted as panaceas for numerous ailments. While observational data have suggested potential correlations between vitamin status and every imaginable disease, randomized controlled trials (RCTs) have generally failed to find benefits from supplementation. Despite this lack of proven efficacy, more than half of older adults reported taking vitamins regularly.1

Vitamin overview: RDA and toxicity risk

While most clinicians consider vitamins to be, at worst, expensive placebos, the potential for harm and dangerous interactions exists. Unlike pharmaceuticals, vitamins are generally unregulated, and the true content of many dietary supplements is often difficult to elucidate. Understanding the physiologic role, foundational evidence, and specific indications for the various vitamins is key to providing the best recommendations to patients.

Vitamin overview: RDA and toxicity risk

Vitamins are essential organic nutrients, required in small quantities for normal metabolism. Since they are not synthesized endogenously, they must be ingested via food intake. In the developed world, vitamin deficiency syndromes are rare, thanks to sufficiently balanced diets and availability of fortified foods. The focus of this article will be on vitamin supplementation in healthy patients with well-balanced diets. TABLE W12 (available at lists the 13 recognized vitamins, their recommended dietary allowances, and any known toxicity risks. TABLE 22 outlines elements of the history to consider when evaluating for deficiency. A summary of the most clinically significant evidence for vitamin supplementation follows; a more comprehensive review can be found in TABLE 3.3-96

Relevant history in the evaluation of potential vitamin deficiency


Vitamin B1

Vitamers: Thiamine (thiamin)

Physiologic role: Critical in carbohydrate and amino-acid catabolism and energy metabolism

Dietary sources: Whole grains, meat, fish, fortified cereals, and breads

Thiamine serves as an essential cofactor in energy metabolism.2 Thiamine deficiency is responsible for beriberi syndrome (rare in the developed world) and Wernicke-Korsakoff syndrome, the latter of which is a relatively common complication of chronic alcohol dependence. Although thiamine’s administration in these conditions can be curative, evidence is lacking to support its use preventively in patients with alcoholism.3 Thiamine has additionally been theorized to play a role in cardiac and cognitive function, but RCT data has not shown consistent patient-oriented benefits.4,5

The takeaway: Given the lack of evidence, supplementation in the general population is not recommended.

Vitamin supplementation: The evidence at a glance

Vitamin B2

Vitamers: Riboflavin

Physiologic role: Essential component of cellular function and growth, energy production, and metabolism of fats and drugs

Dietary sources: Eggs, organ meats, lean meats, milk, green vegetables, fortified cereals and grains

Riboflavin is essential to energy production, cellular growth, and metabolism.2

The takeaway: Its use as migraine prophylaxis has limited data,97 but there is otherwise no evidence to support health benefits of riboflavin supplementation.

Vitamin supplementation: The evidence at a glance

Vitamin B3

Vitamers: Nicotinic acid (niacin); nicotinamide (niacinamide); nicotinamide riboside

Physiologic role: Converted to nicotinamide adenine dinucleotide (NAD), which is widely required in most cellular metabolic redox processes. Crucial to the synthesis and metabolism of carbohydrates, fatty acids, and proteins

Dietary sources: Poultry, beef, fish, nuts, legumes, grains. (Tryptophan can also be converted to NAD.)

Niacin is readily converted to NAD, an essential coenzyme for multiple catalytic processes in the body. While niacin at doses more than 100 times the recommended dietary allowance (RDA; 1-3 g/d) has been extensively studied for its role in dyslipidemias,2 pharmacologic dosing is beyond the scope of this article.

The takeaway: There is no evidence supporting a clinical benefit from niacin supplementation.

Vitamin supplementation: The evidence at a glance

Vitamin B5

Vitamers: Pantothenic acid; pantethine

Physiologic role: Required for synthesis of coenzyme A (CoA) and acyl carrier protein, both essential in fatty acid and other anabolic/catabolic processes

Dietary sources: Almost all plant/animal-based foods. Richest sources include beef, chicken, organ meats, whole grains, and some vegetables

Pantothenic acid is essential to multiple metabolic processes and readily available in sufficient amounts in most foods.2 Although limited RCT data suggest pantethine may improve lipid measures,12,98,99 pantothenic acid itself does not seem to share this effect.

The takeaway: There is no data that supplementation of any form of vitamin B5 has any patient-oriented clinical benefits.

Continue to: Vitamin B6


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