multivitamins: not helpful

3 articles on vitamin supplementation in dec 17th issue of annals of internal medicine. (all with same conclusions).

1. high dose vitamins and minerals post-MI (see cad mvi not help post MI annals 2013 in dropbox, or doi:10.7326/0003-4819-159-12-201312170-00004). 1700 pts >50yo with MI at least 6 weeks earlier and serum creat <2.  Randomized to high dose vitamins/minerals, with composition designed by alternative med practitioners (vitamins significantly above "daily value" include: vitamins A, C, E, B6, niacin, pantothenic acid, manganese, selenium). results:

                --mostly white males (82% male, 94% white) from Brigham and Duke hospitals

 --unusually terrible adherence (which involved 3 pills bid), with 46% discontinuation rates in both the placebo and treatment arms

                --nonsignificant difference in outcomes: 5-year event rates (total death, recurrent MI, stroke, coronary revasc, hosp for angina) in 34.2% on vitamins and 37% on placebo

2. vitamins and cognitive function (see cognitive function and vitamins annals 2013, or doi:10.7326/0003-4819-159-12-201312170-00006). 12 year study of 6000 men >65 yo in the Physicians' Health Study II, randomized to multivitamins (Centrum Silver or placebo), with 4 repeated cognitive assessments. concept is that several vitamins may prevent oxidative damage to the brain (eg, vits C, E, b-carotene), are involved in development of neurotransmitters, DNA, and neuronal membranes (B vitamins), and are involved in neuronal survival and plasticity (vitamin A). overall  this study was of a pretty healthy group (96% nonsmokers, 60% with vigorous exercise at least 1/wk, 8% with diabetes, 53% with htn and 40% with hyperlipidemia). results:

                --no diff in telephone assessment of cognitive function or in secondary outcome of verbal memory

but, this is a pretty select group of highly educated and baseline healthy people (and cognitive testing is less sensitive in those with more education), who likely ate well during their lives, and, if they didn't, are receiving vitamin supplementation only late in their lives (negating a potential benefit since there is already a significant age-related decline by their age of >65yo at the start of the study).

3. a systematic review of the literature on vitamin and mineral supplementation in primary prevention of cardiovasc dz and cancer, reviewed for the US Preventive Service Task Force (see cad cancer primary prev vitamins annals 2013, or  doi:10.7326/0003-4819-159-12-201312170-00729).  findings:

                --1/2 of Americans use vitamin/mineral supplements, spending $11.8B/yr

                --26 studies reviewed (5 assessed use of multivitamins, rest looked at individual vitamins or small combinations)

                --for multivitamins: 2 very large studies predominated the analysis. no effect found for fatal or nonfatal cardiovasc events. one study (PHS-II, same study group as in the second article above) did find a protective effect in men (31% decreased risk), but not women. some studies with adverse events in vitamin group (melanomas in women, hip fracture rate in women). the investigators are hesitant to overgeneralize the cancer benefit in men, since it was only marginally significant and applied only to men (and there was no significant benefit on any specific subgroup of cancers, such as prostate cancer).

                --single and  paired vits/minerals: no consistent protective effect for cardiovasc dz or cancer risk, inconsistent or contradictory results for calcium/vitamin D. other than b-carotene (assoc with higher incidence of lung cancer in smokers or those with asbestos exposure), there were differing adverse events in the different trials, without a consistent pattern.

major issue here is that the preponderance of evidence suggests that in people eating a "healthy" diet without evident micronutrient deficiency, there really is no indication at this time for vitamin supplementation (the data are still equivocal and awaiting large RCTs with regard to vitamin D, especially beyond bone and muscle development, decreasing falls in the elderly). the case of homocysteine provides an interesting case-in-point. hyperhomocysteinemia is associated with a variety of vitamin deficiencies (B12, folate, pyridoxine), hyperhomocysteinemia was pretty consistently found to be associated with adverse vascular events, those vitamins are really important ones for life, there are no known significant toxicities to them, and surrogate markers improved (not just decreasing the homocysteine levels, but studies also showing improved endothelial function, for example), BUT many different studies looking at real clinical outcomes surprisingly (at least to me) found no efficacy with vitamin supplementation.  the other issue was elaborated by walt willett at harv school of pub  health after the b-carotene supplementation study found the surprising increase in lung cancer in smokers (surprising in that b-carotene is also an important anti-oxidant which one would think might at least somewhat counter the toxicity of cigarettes, felt in part to be associated with their oxidant action). His position (with me taking significant liberties) was that there are dozens of naturally occurring carotenoids, and that it is fundamentally reductionist to try to purify a single ingredient of foods and then market it as beneficial: the reality is that there is a complex interplay of different vitamins, minerals, etc in naturally occurring healthy foods, and that we should eat these foods (eg fruits and vegetables) instead of looking for the magic pill...  although i must admit i do test and treat for vitamin b12 deficiency, persisting with the flawed logic i mentioned above:  B12 deficiency occurs relatively frequently in those over 50 years old (which is typically above the age that evolution acts...), is easily treated (in most cases orally), seems to be nontoxic in high doses, and is associated with significant clinical problems (esp anemia and neuropathy).....   unfortunately, there are no long-term studies, starting with early finding of B12 deficiency through routine screening, and following cognitive decline (or neuropathy) over many years.

so, what is the bottom line? hard to be certain. at this point it makes sense not to suggest multivitamins for someone without a compelling medical or social reason which would predispose them to vitamin deficiency. but.... would they be useful if started at age 30 (before most people have significant atherosclerotic disease or cognitive decline)? are there subgroups of people who might benefit (should i give vitamin supplements to my kid who assiduously avoids eating anything green, like most vegetables)? these studies have not been done.