Reference: Alzheimers Dement. 2022 Sep 14 early online
Practice Point: Multivitamins are still not proven to reduce cognitive decline.
EBM Pearl: The bar is higher for multivariate analyses: do not accept results as valid unless the statistical analysis is adjusted to account for multiple outcomes.
The antioxidant vitamin supplement hypothesis should work. However, a few months ago the USPSTF threw cold water onto the vitamin industry’s claims by concluding that not only are vitamin supplements generally ineffective, but the preponderance of evidence suggests two of the antioxidants, vitamin E and beta carotene (a precursor of vitamin A), caused more harm than good when given in supplemental form for prevention of disease. In September, a group of researchers gave a lifeline to the vitamin industry when they published a paper in the journal Alzheimer's & Dementia claiming that multivitamins (MVIs) improved memory.
The researchers enrolled a well-educated (89% with college degree or higher) and White (also 89%) group of people in their mid-70s to take annual telephone interviews assessing health characteristics along with a fairly comprehensive assessment of memory, executive function and overall cognitive abilities. Then, in a four-group factorial study, they compared the benefits of a cocoa extract and a commercially available MVI tablet daily to placebos over an up-to-three-year follow up. Notably, almost half the participants were taking vitamins before the study began. About a quarter of the participants did not complete the full three year follow up.
After three years, the cocoa didn’t seem to do much, but the people who received a multivitamin tablet performed better in terms of memory, executive function and overall cognition. The researchers concluded that the MVI “improved” cognition and the MVI company is now touting this on their website.
Hold your horses, please. Although there are several wonderful things about this trial, such as the length of follow-up and the relatively large number of participants, we have a lot of concerns about its validity. The results are not generalizable given the population studied. The clinical significance of the reported z-scores is hard to judge, and the 25% dropout rate is another red flag. Notably, the participants who dropped out of the trial were more likely to have diabetes or be smokers and had lower cognitive scores and daily physical activity to begin with. If antioxidants caused harm, these dropouts may have been the group more likely to be harmed by the antioxidants in the multivitamin tablets. In addition, there was no adjustment of the statistical analysis to address the multiple outcomes assessed. Finally, given that the vitamins were “donated” by a multivitamin manufacturer (as were the cocoa tablets), we should view conclusions from the authors touting the benefits of MVIs with some skepticism.
This study and its conclusions remind us of the old maxim to throw some things up against the wall to see what sticks. It’s fair to say that the outcome might suggest a potential benefit of vitamins, but it is not accurate to conclude that the vitamins caused this improvement, as the authors state in their highlights. More research is needed. These results aren’t enough to support a change in advice for patients concerned about cognitive decline.
For more information, see the topic Mild Cognitive Impairment (MCI) in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed; and Sarah Hill, MSc, Associate Editor at DynaMed.