Are Vitamins Killing us Softly?

Dr Paul Offit, chief of the Division of Infectious Diseases and Director of the Vaccine Education Center at Children’s Hospital in Philadelphia, recently published a book called: “Killing Us Softly: The sense and nonsense of alternative medicine.” It also goes under the title: “Do You Believe in Magic?: The Sense and Nonsense of Alternative Medicine” The book presents some evidence on alternative medicines like homeopathy, Chinese herbs, chiropractic adjustments and, of greatest interest to us, the evidence for and against nutrient supplements for the treatment of illness.

We are strong supporters of evidence-based treatments and have written a lot about the science behind using nutrients and nutrition to prevent and/or treat mental illness. The evidence does need to be critically evaluated and so a book that explores the evidence of alternative medicine has the potential to be an important part of this journey. The problem with this book, however, is that Dr Offit doesn’t always provide a balanced perspective.

Dr. Offit seems to have an agenda – to ensure that the public are well informed of negative results so they stop ‘wasting’ their money on alternative therapies. However, to achieve this goal, Dr Offit engages in far too much cherry picking. Cherry picking is where only selected data (that support an argument) are presented and any data that present an opposing view are ignored. Suppose we want to convince you that vitamins don’t help with memory: then we might present all the studies that have been conducted using vitamins to treat memory problems that have failed to show an effect or even that show they worsen memory. If we are cherry picking, we wouldn’t tell you about all the studies that actually show that vitamins improve memory. Cherry picking is one fundamental problem with Dr. Offit’s approach and why the book could do more harm than good.

Dr Offit seems very keen to showcase all the studies on alternative products that haven’t worked for the treatment of all kinds of ailments, to make statements about the overall lack of rigorous research and also, to argue that these products are generally inert or can even be harmful. He neglects to tell us the other side of the story.

Let’s take the chapter on the supplement industry. By all means, the supplement industry deserves a lot of criticism. There are numerous unfounded claims that do need to be exposed. However, Dr Offit discusses at great length the potential serious side effects of vitamins as well as the studies that have shown that vitamins increase mortality and morbidity. The problem is, Dr Offit was selective in his reporting. What about the study by Zhang et al published in JAMA that showed there was no evidence that vitamins increased risk of cancer in women: “Combined folic acid, vitamin B6, and vitamin B12 treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era.” Or Roswall et al.’s study showing an inverse association between folic acid and prostate cancer? Wouldn’t the public be interested in these findings?

Perhaps the studies he mentioned about the risks of vitamins were so compelling that indeed we do need to pay attention to them. However, in such case, we strongly encourage anyone to first go to the original source before drawing such a conclusion. Don’t trust someone else’s interpretation of a trial nor the media’s interpretation. A few years ago, there was a massive amount of media attention on a meta-analysis of antioxidant supplements for prevention of mortality published in JAMA by Bjelakovic and colleagues. The authors concluded that “vitamin A, beta-carotene, and vitamin E may increase mortality”.  The media headlines reflected these conclusions: “Your Vitamins Are Killing You!”, “The Dark Side of Antioxidants!” and “Can a Vitamin Kill You?”

There has been tons of criticism on how Bjelakovic and colleagues analysed their data. But even taking all of these criticisms into account (including length of the trials compared to how long it takes for cancers to develop, how many trials actually looked at mortality as an outcome, inclusion of people who died in car accidents as part of the mortality numbers, combining single nutrient studies with broader based nutrient studies, combining doses, etc), the difference between the groups of people taking antioxidants versus those not taking them in terms of mortality was 2.6%.

Some people might be alarmed by this number; however, it doesn’t actually tell us how much longer one lives without supplements and it also doesn’t tell us if those people died because of the supplements. Maybe people who take supplements take them because of illness. We certainly don’t say that doctors kill us when we go to the doctor more often when we are sick. There are lots of other reasons why we should be careful about how we interpret that statistic.

Also, the public may be interested in whether any other health benefits or risks were found based on these studies. They happen to be in luck. A few years later, Biesalski and colleagues published a study on the health benefits of supplements using the same studies as used in the meta-analysis on mortality. They came to a rather different conclusion than the Bjelakovic group. They documented that there were far more health benefits for those who took the supplements. Of the 66 studies included in the Bjelakovic meta-analysis, 24 (36%) showed that antioxidant supplementation resulted in a positive health outcome, 39 (60%) showed no effect, and only 4% gave negative results. Antioxidant supplementation was found to be especially effective for people who tended to be malnourished. We don’t recall as much media attention to these findings.

The point is, there is always a risk/benefit ratio and consumers need all the information in order to make a truly informed decision about their health. People make decisions based on the quality of their life versus quantity of life (which we can rarely know in advance).

But to return to the topic of micronutrients and mental health, nowhere in Offit’s book does he mention the controlled trials that have shown benefit of micronutrients to treat psychiatric symptoms, like stress, autism, mood, or substance abuse. Nothing. Perhaps, he just chose to ignore them. Or perhaps more worryingly, he is unaware of them.

This book, alongside the recent editorial from the Annals of Internal Medicine (“Enough is Enough: Stop Wasting Money on Vitamin and Mineral Supplements”), do a disservice to the rigorous and well conducted body of literature that shows benefits of additional nutrients for some people. Not all nutrient supplements are created equally. To conclude this blog, we want to point out two of the many areas in which supplements vary:

1. They vary in dose. A student of Julia’s looked at supermarket vitamins marketed for children and compared the dose of all the nutrients with the formulas used in research for childhood disorders (Rucklidge et al. in press). The contrast was like night and day. The doses of those formulas used in research were much larger than the doses of the everyday supermarket brands. There is no wonder that purchased brands don’t always produce an effect. We need to look at the dose. This point is well acknowledged by the group who studied the effects of a daily multivitamin on cognitive decline that was one of the studies commented on in the Annals of Internal Medicine editorial. Grodstein et al stated: “Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin.” After all, when doses are much higher, positive results have been demonstrated; for example, reduction in brain atrophy related to Alzheimer’s (Douaud et al., 2013).
2. They vary in breadth of the nutrients used within a formula. The fewer the ingredients, the less effective the formula is likely to be (see our blog on single bullet madness). Again, another one of the studies published in the Annals of Internal Medicine reviewing the literature on the use of vitamins and minerals in the primary prevention of cardiovascular disease and cancer raised this issue. While remarking on the limited and overall disappointing evidence, the authors also said that “the physiological systems affected by vitamins and minerals 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 . . .” They go on to say that “the best support for benefit of supplementation came from 2 multivitamin trials that used physiological doses of a wider variety of agents.” Indeed, both of these trials using a greater breadth of nutrients showed lower cancer incidence in men. So really the editorial commenting on these articles might have done better to say – Enough is Enough: Stop Wasting Money on Magic Bullet Research of Single Nutrients!

Ultimately, the problem is that one size doesn’t fit all. We can’t take these studies that show no benefit to mortality or heart disease and extrapolate this lack of an association or benefit to the entire population. Obviously there are segments of the population who probably don’t benefit from supplements. But the vulnerable portion of our population, the mentally ill, the poor, and those who do not have good access to nutritious food, are very likely to benefit and indeed, we have presented some of the extensive research support in previous blogs. Let’s not see the exercise as one to take down one industry (often in support of another). Let’s take the really challenging approach and figure out what works and for whom.

References:

Biesalski HK, Grune T et al. Reexamination of a Meta-Analysis of the Effect of Antioxidant Supplementation on Mortality and Health in Randomized Trials. Nutrients 2010; 2(9):929-949.

Bjelakovic G, Nikolova D et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention. Systematic review and meta-analysis JAMA 2007; 297:842-857.

Douaud, G., Refsum, H., de Jager, C. A., Jacoby, R., Nichols, T. E., Smith, S. M., & Smith, A. D. (2013). Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A, 110(23), 9523-9528. doi: 10.1073/pnas.1301816110

Fortmann, S. P., Burda, B. U., Senger, C. A., Lin, J. S., & Whitlock, E. P. (2013). 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. Annals of Internal Medicine, 159(12), 824-834. doi: 10.7326/0003-4819-159-12-201312170-00729

Guallar, E., Stranges, S., Mulrow, C., Appel, L. J., & Miller, I. I. I. E. R. (2013). Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements. Annals of Internal Medicine, 159(12), 850-851. doi: 10.7326/0003-4819-159-12-201312170-00011

Grodstein, F., O’Brien, J., Kang, J. H., Dushkes, R., Cook, N. R., Okereke, O., Manson, J. E., Glynn, R. J., Buring, J. E., Gaziano, J. M., & Sesso, H. D. (2013). Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial. Annals of Internal Medicine, 159(12), 806-814. doi: 10.7326/0003-4819-159-12-201312170-00006

Lamas, G. A., Boineau, R., Goertz, C., Mark, D. B., Rosenberg, Y., Stylianou, M., Rozema, T., Nahin, R. L., Lindblad, L., Lewis, E. F., Drisko, J., & Lee, K. L. (2013). Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial. Annals of Internal Medicine, 159(12), 797-805. doi: 10.7326/0003-4819-159-12-201312170-00004

Roswall, N., Larsen, S., Friis, S., Outzen, M., Olsen, A., Christensen, J., Dragsted, L., & Tjønneland, A. (2013). Micronutrient intake and risk of prostate cancer in a cohort of middle-aged, Danish men. Cancer Causes and Control, 1-7. doi: 10.1007/s10552-013-0190-4

Rucklidge, J. J., Harris, A., & Shaw, I. (in press). Are the amounts of vitamins in commercially available dietary supplement formulations relevant for the management of psychiatric disorders in children? New Zealand Journal of Medicine.

Zhang, S. M., Cook, N. R., Albert, C. M., Gaziano, J., Buring, J. E., & Manson, J. E. (2008). Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: A randomized trial. JAMA, 300(17), 2012-2021.