Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer

TO THE EDITOR:

Fortmann and colleagues’ meta-analysis (1) showed that vitamin and mineral supplementation provides little benefit and does not aid cognition (2) or prevent cardiovascular events (3). The authors concluded that supplements have no value. However, data constraints limit interpretation to a narrower conclusion: Supplementation in well-nourished persons does not affect the end points studied but may have other benefits or abolish signs and symptoms of unrecognized deficiencies, which are surprisingly common.

Many studies of vitamin supplements are flawed, including Fortmann and colleagues’ review, because vitamin concentrations at enrollment are usually not measured. It is predictable that study populations include those with low concentrations of vitamins, subclinical deficiencies, or both and others who are vitamin replete. These groups are distinguishable only if baseline, and preferably postsupplementation, vitamin concentrations are measured.

Without measurement, assuming that all participants are vitamin and mineral replete is unsafe. Benefits in one group may be hidden by no effect in the other. Measurement of vitamin concentrations before and after supplementation will allow distinct effects to be recognized.

For example, 22% and 7% of U.S. adults are considered vitamin C insufficient (serum vitamin C concentrations <28 μmol/L) or deficient (<11 μmol/L), respectively (4). Only those with concentrations less than 5 μmol/L may exhibit scurvy. In contrast, vitamin C concentrations of approximately 50 to 60 μmol/L are predictable in persons consuming the recommended dietary allowance of vitamin C; additional vitamin C intake increases concentrations only modestly at best among these persons.

To put the problem in perspective, studies to test antihypertensive therapy would not be done without measuring blood pressure at enrollment. To treat everyone regardless of blood pressure would be illogical. However, this strategy has been persistently pursued in evaluating vitamin supplements.

Vitamin and mineral supplements may benefit persons with marginal deficiencies. For example, patients with plasma vitamin C concentrations less than 20 μmol/L report lassitude, a symptom that precedes scurvy (5). However, lassitude is common and nonspecific, and marginal vitamin C deficiency is difficult to recognize.

Marginal vitamin and mineral deficiencies, even without obvious clinical disease, may decrease quality of life or have long-term adverse effects. This factor may be an adequate reason for supplement use, even if it does not prevent diseases other than deficiency states. Meticulous attention to the design and conduct of clinical trials, many study participants, and meta-analyses cannot compensate for fundamental physiologic oversights about vitamin doses and concentrations. Perhaps vitamin and mineral supplementation has little value in the general population, but these studies are inadequate to show it.