Last week during my usual work commute traffic/weather check-in with WTOP radio, I repeatedly heard a soundbyte about how a freshly published study demonstrated that many vitamin supplements were found to be associated with increased death in elderly people who take them. Calcium alone, they reported, was shown to increase lifespan in the elderly. The segment was only 30 seconds long, and offered no further comment or critique.
CC BY image from bradley j via Flickr
A sterling example of excellent medical reporting? Somehow, I suspect not. Let’s take a look.
Bookends – The article in question today is Dietary Supplements and Mortality Rate in Older Women (abstract here for free access, full article here imprisoned behind a paywall), which was published in the October 10, 2011, issue of the Archives of Internal Medicine. Archives is a peer-reviewed journal published by the American Medical Association, which also publishes the better known JAMA, the Journal of the American Medical Association; while JAMA covers many broad aspects of medicine, Archives focuses more on clinical aspects of internal medicine practice. Archives is number 8 on the list of general medical journals rated by impact factor, meaning that articles published therein tend to be cited rather frequently compared to most other journals in the field.
In terms of the article in question, the authors all have non-medical graduate degrees and are primarily affiliated with the University of Minnesota, without any major conflicts of interest. The funding for the study came from unbiased sources, as grants from National Cancer Institute and the Academy of Finland. As such, there is no obvious financial agenda behind the study.
Background – Vitamins are biologically active, organic compounds that humans cannot synthesize enough of ourselves to remain healthy, and so we need to consume in our diet. For the vast majority of people, a normal balanced diet of different foodstuffs will give us all of the vitamins we require to stay healthy without needing to take additional supplements. Having a deficiency of a particular vitamin can cause specific diseases – scurvy is the classic example in those consuming too little vitamin C, for instance – and those with a poor diet or certain medical conditions may require a vitamin supplement to make sure they have normal levels in the body to prevent these diseases.
There has long been an idea that taking a general multivitamin or specific vitamins in high doses on top of an already balanced diet can somehow do any one of a number of amazing things, including preventing certain diseases, boosting one’s energy level, or even extending lifespan. Despite the claims of the multi-billion dollar vitamin and supplement industry, scientific studies have repeatedly shown no benefit and some possible harm in giving supplemental vitamins to healthy, well-nourished people. This study sought to look at the question of whether women taking any one of a number of vitamins would have a lower death rate than those who did not:
“The aim of the present study was to assess the relationship between supplement use and total mortality rate in older women in the Iowa Women’s Health Study. Our hypothesis, based on the findings of a previous study by some of us, was that the use of dietary supplements would not be associated with a reduced rate of total mortality.”
Methods — This paper was an analysis of data from the Iowa Women’s Health Study, which was a prospective observational cohort study designed to look at how various diet and lifestyle factors affected the incidence of new cancers and death in women after menopause. The study design involved enrolling 41,836 women between the ages of 55 and 69 in 1986, and having them complete questionnaires about their health every few years. Since it was observational, there were no interventions carried out on the patients and no attempt was made to influence their health habits. This particular paper focused on 38,772 of the women who gave adequate information about their dietary habits and vitamin use in 1986, and look at the same information when 29,230 of them completed a followup survey in 1997, and 19,142 who did so in 1984. Notably, 99.2% of these women were of Caucasian descent.
Questions were asked on each survey about whether a general multivitamin or any of 14 specific vitamin supplements were used, as well as general questions about medical problems such as diabetes or high blood pressure, physical activity, and details about their diet. Any participants who died were classified as their death being due to cardiovascular disease, cancer, or other causes. General demographic data was also gathered. Several standard and appropriate statistical tests were used to analyze the data, and control for different variables involved.
Results – As is want to happen in studies of this type, large amounts of data were generated, with several interesting results. At baseline in 1986, 62.7% of participants reported using at least 1 supplement, which increased up to 85.1% in 2004. Those who used supplements tended to have less problems with diabetes and high blood pressure, be more physically active, and have better diets. Statistically, 7 of the 15 supplements studied – multivitamins, vitamin B6, folic acid, iron, magnesium, zinc, and copper – were associated with slight but significant increased risk of total mortality when compared with those not using them. Taking calcium supplements showed a statistically significant decreased risk of mortality. In running different statistical tests over shorter time periods, the association of less death with calcium and more death with iron use remained, and seemed to be more profound with higher doses, especially for iron.
Discussion – The article’s discussion noted that for many of the vitamins associated with an increased risk of death when taking them, there aren’t any obvious plausible reasons why that would be the case. Furthermore, they note that previous studies have shown concerns about long-term calcium use increasing death from heart disease, which they did not see here. With regards to the increased association of mortality seen with iron, they note that other studies haven’t shown this to be a strong issue. They noted the interesting fact that those who took vitamins seemed to have healthier habits than those who did not, but still had an increase in mortality; the authors speculate this might be due to that fact that those patients had other illnesses to begin with, causing them to actively take supplements and do healthier things, but still have a greater mortality rate.
They note that the strengths of their study include the large number of participants, and the multi-survey design over a period of years. There were many identified weaknesses, however. Nearly all the participants were women of Caucasian descent, making it hard to generalize the results to the general population. While doses of some vitamins were recorded in general ranges on the patient surveys, the specific formulations and exact doses were not reported or analyzed in detail. No questions were asked about concurrent medication use along with vitamins or about most other medical problems beyond cancer, heart disease, high blood pressure, and diabetes, all of which could have played a role in the results.
The investigators put their findings in context thusly:
Among the elderly population, the use of dietary supplements is widespread, and supplements often are used with the intention of attaining health benefits by preventing chronic diseases. Although we cannot rule out benefits of supplements, such as improved quality of life, our study raises a concern regarding their long-term safety. Also, cumulative effects of widespread supplement use, together with food fortification, have raised concern regarding exceeding upper recommended levels and, thus, regarding long-term safety. It is not advisable to make a causal statement of excess risk based on these observational data; however, it is noteworthy that dietary supplements, unlike drugs, do not require rigorous RCT testing, and observational studies are often the best-available method for assessing the safety of long-term use. Based on existing evidence, we see little justification for the general and widespread use of dietary supplements. We recommend that they be used with strong medically based cause, such as symptomatic nutrient deficiency disease.
My Critique – Many people want vitamins to be magic things that give energy and prevent disease. Not only does the medical evidence and basic biology show this to be untrue, but there may be risks involved from taking unneeded vitamin supplements, especially at high doses. That said, it’s worth noting that there is little in the way of conclusions that can be drawn from this particular study. Large, observational cohort studies are excellent at looking for strong positive or negative associations of certain exposures or interventions with health outcomes, such as with vaccines and autism, mobile phone use and brain cancer, or vitamin supplementation with mortality. Results of a single study of that type, be they positive or negative, are certainly interesting… but given the missed variables and lack of controls involved, making any guess about correlation of taking vitamins with one’s chances of dying isn’t a valid thing to do. Nonetheless, further studies will undoubtedly be done that will hopefully shed a bit more light on the idea that in post-menopausal women, taking some vitamins might somehow increase the chance that they would die.
Studies such as these are the grist for many popular media medical stories, and they really shouldn’t be. Given the variables involved, and the fact that the conclusions aren’t anything solid that doctors would rely on to change how they advise their patients at this point, having a very brief, nuance-free news story that implies that giving vitamins to the elderly is a “death panel-ish” thing to do is irresponsible reporting. Interestingly, the original story I heard on WTOP mentioned only that elderly patients were involved, not specifying further that they were post-menopausal Caucasian women, which was clearly a huge error.
The most important message of this paper is to remind both patients and physicians that vitamins are essential substances that our bodies need to function that we can’t make ourselves, but that for the vast majority of them, there is no evidence that taking higher doses than required for our essential biological functions gives any added benefit, and may carry some risk. It is possible to take too much of a vitamin such that you experience a toxic disease state, such as with the increasing cases of hypervitaminosis D being seen with the increased popularity of high-dose vitamin D supplementation in recent years. Whether or not getting just “little bit extra” is truly correlated with increased mortality for some reason remains to be seen, and certainly isn’t proved here.
Reference: Bjelakovic G, & Gluud C (2011). Vitamin and Mineral Supplement Use in Relation to All-Cause Mortality in the Iowa Women’s Health Study: Comment on “Dietary Supplements and Mortality Rate in Older Women”. Archives of Internal Medicine, 171 (18), 1633-4 PMID: 21987193
Episode 0048: The Great Old Pumpkin