RT Journal
A1 Morris M, Tangney CC
T1 A potential design flaw of randomized trials of vitamin supplements
JF JAMA
JO JAMA
YR 2011
FD April 6
VO 305
IS 13
SP 1348
OP 1349
DO 10.1001/jama.2011.383
UL http://dx.doi.org/10.1001/jama.2011.383
AB 
What are scientists, physicians, and the general public to make of the many null findings from randomized controlled trials (RCTs) of vitamin supplements? These trials are usually conducted on the basis of positive findings from prospective epidemiological studies and laboratory evidence of biological mechanisms. A common view is that the negative findings from the RCTs offer incontrovertible evidence that the nutrient is unrelated to disease and that the epidemiological studies are biased. An alternative explanation is that most RCTs of vitamin supplements are designed to test the hypothesis that supplementation, no matter the nutrient status, is protective. Vitamin treatment may not be effective in these trials because nutrient intake among the participants is already at optimum levels. To specify, examples are provided from the field of dementia and investigations of 3 dietary components: vitamin E, B vitamins, and docosahexaenoic acid.