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Are dietary supplements a dangerous waste of money?

"The truth is rarely pure and never simple"   Oscar Wilde 

Being a doctor, I tend to get occasional health queries from family members.  Recently my brother emailed me saying "I have been taking multivitamin supplements for a while (also fish oil).  Does the (linked) article mean that I am wasting my $$$$. at least on the vitamins?  If so, then I shall make a donation to charity instead... ".   The article he's referring to is an editorial in the "Annals of Internal Medicine" entitled "Enough is enough: stop wasting money on vitamin and mineral supplements".  The editorial itself is triggered by three research papers published in December's "Annals" "Oral high-dose multivitamins and minerals after myocardial infarction: a randomized controlled trial", "Long-term multivitamin supplementation and cognitive function in men: a randomized controlled trial" and, probably most importantly, "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force" (this latter paper is available in free full text).

As you can probably guess from the editorial's title, the three research papers largely failed to show any benefit from taking multivitamin & mineral supplements.  This finding seems particularly strong for cardiovascular disease when taken alongside other recent publications like the BMJ paper "Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: Systematic review and meta-analysis of randomised controlled trials" and JAMA's "Multivitamins in the prevention of cardiovascular disease in men: The physicians' health study II randomized controlled trial".  The data is a bit less clear for primary prevention of cancer, so last year's companion study "Multivitamins in the prevention of cancer in men: The physicians' health study II randomized controlled trial" concluded that "daily multivitamin supplementation modestly but significantly reduced the risk of total cancer."  As the accompanying commentary - "Multiplicities in the assessment of multiple vitamins: Is it too soon to tell men that vitamins prevent cancer?" - pointed out, these cancer findings were pretty tentative & should probably be treated cautiously.  But this caution about possible positive effects of multivitamin & mineral supplements on cancer mortality extends to the negative findings as well.  As this month's already mentioned "Annals of Internal Medicine" "systematic evidence review" acknowledges "The results of vitamin supplementation trials have been disappointing at best, despite having a solid mechanistic basis. One explanation for this result could be that the physiologic systems affected by vitamins and other antioxidant supplements are so complex that the effects of supplementing with only 1 or 2 components is generally ineffective or actually does harm. This hypothesis is compatible with our finding that the best support for benefit of supplementation came from 2 multivitamin trials that used physiologic doses of a wider variety of agents.  Two good-quality trials of multivitamin supplementation found lower cancer incidence in men. The SU.VI.MAX trial included women and did not find an effect in this subgroup." Interestingly, the SU.VI.MAX study studied the effect of a 5 only ingredient multivitamin on 13,017 French men & women, while the PHS-II trial looked at the effect of a much more extensive 30 ingredient multivitamin on 14,641 US male physicians.

Overall though, the promise of reduced mortality through taking vitamin & mineral supplements has been weakened very considerably through a sequence of recent research papers.  Happily the same can largely be said for the fear that such preparations generally increase mortality - see this year's review "Multivitamin-multimineral supplementation and mortality: A meta-analysis of randomized controlled trials".  It's intriguing to consider though whether a broad multi-ingredient supplement given to a representative sample of the population might result in reduced cancer deaths.  The PHS-II study only involved male US doctors and it produced somewhat hopeful results - and this was in a population which presumably was well nourished, unlike many of the poor and elderly.  What's crashingly obvious though is that studies on the benefits of a good, healthy diet far outweigh studies on dietary supplements when it comes to showing a whole raft of health benefits.  And worryingly it seems as though taking supplements may sometimes actually interfere with focusing on a healthy diet - see the 2011 paper "Ironic effects of dietary supplementation" with its abstract reading "The use of dietary supplements and the health status of individuals have an asymmetrical relationship: The growing market for dietary supplements appears not to be associated with an improvement in public health.  Building on the notion of licensing, or the tendency for positive choices to license subsequent self-indulgent choices, we argue that because dietary supplements are perceived as conferring health advantages, use of such supplements may create an illusory sense of invulnerability that disinhibits unhealthy behaviors.  In two experiments, participants who took placebo pills that they believed were dietary supplements exhibited the licensing effect across multiple forms of health-related behavior: They expressed less desire to engage in exercise and more desire to engage in hedonic activities (Experiment 1), expressed greater preference for a buffet over an organic meal (Experiment 1), and walked less to benefit their health (Experiment 2) compared with participants who were told the pills were a placebo.  A mediational analysis indicated that perceived invulnerability was an underlying mechanism for these effects."  And while commenting on diet & supplements it's also worth noting the greater benefits that appear to accrue from eating "the whole thing" rather than just relying on a component - see "Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: Systematic review and meta-analysis" and "Fruit consumption and risk of type 2 diabetes: Results from three prospective longitudinal cohort studies."  

So for possible physical health benefits (especially reduced mortality rates) from dietary supplements, my reading of the current data is that generally single/few item supplements seem to be largely ineffective (with the possible exception of some individual substances such as vitamin D). Reassuringly the evidence suggests no increased mortality from supplements.  Multi-item supplements may be more beneficial, for example in cancer prevention especially in representative general population groups.  More research is needed to clarify this issue.  

My own professional interest is however more in the psychological & quality of life fields rather than just in the rather blunter (although crucial!) area of simple mortality risk. Here the research findings are currently more supportive of supplementation.  So the 2013 paper by Long & Benton - "Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: A meta-analysis" - comments "Biochemical processes in the brain affect mood. Minor dietary inadequacies, which are responsible for a small decline in an enzyme’s efficiency, could cumulatively influence mood states. When diet does not provide an optimal intake of micronutrients, supplementation is expected to benefit mood. This meta-analysis evaluated the influence of diet supplementation on mood in nonclinical samples.  Methods: Databases were evaluated and studies were included if they considered aspects of stress, mild psychiatric symptoms, or mood in the general population; were randomized and placebo-controlled; evaluated the influence of multivitamin/mineral supplements for at least 28 days. Eight studies that met the inclusion criteria were integrated using meta-analysis.  Results: Supplementation reduced the levels of perceived stress (p < .001), mild psychiatric symptoms (p = .001), and anxiety (p < .001), but not depression (p < .089). Fatigue (p < .001) and confusion (p < .003) were also reduced.  Conclusions: Micronutrient supplementation has a beneficial effect on perceived stress, mild psychiatric symptoms, and aspects of everyday mood in apparently healthy individuals. Supplements containing high doses of B vitamins may be more effective in improving mood states."

Don't get me wrong ... in the psychological field too, it seems extremely likely that the overall quality of one's diet is typically going to be considerably more important than any supplements that one takes - see, for example, my earlier post "Emerging research on diet suggests it's startlingly important in the prevention of anxiety & depression".  However Long & Benton's meta-analysis (see above) highlights potential mental benefits from general multivitamin/mineral supplements, and it's interesting too to note their comment about the potential value of B vitamins to improve mood states - see, for example, the papers "Association between vitamin B12 levels and melancholic depressive symptoms: A Finnish population-based study" and "Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time."  There is even reason to consider possible benefits of some B vitamins in psychotic disorders - see last year's publication "Randomized multicenter investigation of folate plus vitamin b12 supplementation in schizophrenia".  Folic acid has intriguing potential for psychological disorders - see the 2012 American Journal of Psychiatry editorial "The evolving story of folate in depression and the therapeutic potential of l-methylfolate" - and clearly there are a raft of folate benefits for pregnant women including potential reduction of neural tube defects, autistic disorderssevere language delay and emotional & behavioural problems in offspring.  Other dietary supplements too may be important for psychological wellbeing around childbirth - selenium, for example, looks a possible candidate in last year's "Prenatal micronutrient supplementation and postpartum depressive symptoms in a pregnancy cohort".   

And for the general population, studies suggest potential value for other substances like s-adenosyl methionine (SAMe), zinc - "Zinc in depression: A meta-analysis" -  and fish oil.  This latter area is complex with, for example, some research suggesting that the DHA component of fish oil is particularly helpful for anxiety - "Dietary intake of fish and PUFA, and clinical depressive and anxiety disorders in women" and "Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial" - while high EPA levels may be more significant for depression - "Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression".  Fish oils may also have value in boosting antidepressant response - "Omega-3 fatty acid augmentation of citalopram treatment for patients with major depressive disorder" - as too may newer options like creatine - see the intriguing Lyoo et al paper "A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder".  So for psychological & general wellbeing benefits from taking dietary supplements, the evidence looks stronger than for straightforward mortality improvement.  It's interesting territory.  

Well ... are dietary supplements a dangerous waste of money?  No I don't think they are.  My position on the research at the moment is that supplements certainly don't look particularly dangerous.  For reduction in some physical outcomes like cancer risk, a broad-ranging multi-ingredient supplement is of potential benefit.  And psychologically there are a series of options that have enough research backing to make them well worth considering.  And ... as always ... the next edition of the journals may move all this further forward.  As has been remarked often "When the facts change, I change my mind.  What do you do, sir?"      

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