Multivitamins, minerals linked to higher risk of mortality, but calcium may boost survival

By Stephen Daniells

- Last updated on GMT

Related tags Dietary supplements Dietary supplement Dietary mineral

Multivitamins, minerals linked to higher risk of mortality, but calcium may boost survival
Consuming multivitamins, and iron and copper dietary supplements may increase the risk of death in older women, says a new study published in the Archives of Internal Medicine.

On the other hand, calcium supplements were associated with better survival, report researchers from the University of Minnesota.

“Most of the supplements studied were not associated with a reduced total mortality rate in older women,”​ wrote the researchers, led by Jaakko Mursu, PhD.

“In contrast, we found that several commonly used dietary vitamin and mineral supplements, including multivitamins, vitamins B6, and folic acid, as well as minerals iron, magnesium, zinc, and copper, were associated with a higher risk of total mortality.

“Of particular concern, supplemental iron was strongly and dose dependently associated with increased total mortality risk.

“Supplemental calcium was consistently inversely related to total mortality rate; however, no clear dose-response relationship was observed.”

Shift in use

In an accompanying editorial, Dr Goran Bjelakovic, MD, and Christian Gluud, MD from Copenhagen University Hospital described the study as “well designed and well conducted”,​ while noting that it is an observation study and therefore some confounding by other factors “cannot be excluded”​.

The Copenhagen-based scientists added that the apparent link between calcium and better survival is “interesting.”​ Indeed, this result challenges the findings of a meta-analysis published in the British Medical Journal​.

Dr Bjelakovic is no stranger to the link between supplements and mortality, having authored a controversial meta-analysis published in the Journal of American Medical Association (JAMA)​ in 2007, which concluded that antioxidant supplements would increase mortality risk.

“Dietary supplementation has shifted from preventing deficiency to trying to promote wellness and prevent diseases,”​ wrote Drs Bjelakovic and Gluud. “Consumers believe that vitamin and mineral supplements are safe and use them without the supervision of their physicians.

“Until recently, the available data regarding the adverse effects of dietary supplements has been limited and grossly underreported. We think the paradigm ‘the more the better’ is wrong. One should consider the likely U-shaped relationship between micronutrient status and health.

“We believe that for all micronutrients, risks are associated with insufficient and too-large intake. Low levels of intake increase the risk of deficiency. High levels of intake increase the risk of toxic effects and disease.

“Therefore, we believe that politicians and regulatory authorities should wake up to their responsibility to allow only safe products on the market,” ​added Bjelakovic and Gluud.


The study, it's conclusions, and the comments of Bjelakovic and Gluud in the editorial have come in for criticism by members of the dietary supplements industry.

Cara Welch, PhD, VP of scientific & regulatory affairs for the Natural Products Association (NPA), told NutraIngredients-USA that the majority of vitamin and mineral supplements are taken to address or prevent deficiencies.

"While we would prefer Americans get these nutrients from their diet, studies have consistently shown they do not take in the compounds essential for their health and supplementation can help.

"I’m always pleased to see research done on the long-term effects of supplementation but this study is limited in that it is observational and self-reported so contributing factors are not addressed. There are plenty of studies published that demonstrate the benefit of supplementation and fortification, this specific study should not dissuade the general population from the benefit of addressing a vitamin/mineral deficiency with dietary supplements,"​ added Dr Welch.

Nutrients vs drugs

Duffy MacKay, ND, VP of scientific and regulatory affairs for the Council for Responsible Nutrition (CRN) said that nutrients may be robbed of their beneficial effects when viewed as if they were pharmaceutical agents, with scientists looking to isolate those effects, good or bad.

Steve Mister, president and CEO of CRN added that he was concerned over the "recent drive to combine political agendas with what should be pure science. The supplement industry regularly gets accused of this practice - in some cases rightly so - yet medical journals seem to be given a pass, as if somehow they held no bias whatsoever.

"It’s time scientific journals acknowledge they have some biases, just like industry.”

Study details

Dr Mursu and his co-workers analyzed data from 38,772 women with an average age of 62 enrolled in the Iowa Women's Health Study. The use of 15 supplements was assessed three times over a 19 year period.

The researchers documented 15,594 deaths during the study period. Their statistical analysis of the data revealed that the so-called absolute mortality risk increase associated with multivitamins was 2.4%, folic acid was 5.9%, copper was 18%, and iron was 3.9%.

On the other hand, the absolute mortality risk reduction for calcium was 3.5%.

"Based on existing evidence, we see little justification for the general and widespread use of dietary supplements,"​ the authors conclude. "We recommend that they be used with strong medically based cause, such as symptomatic nutrient deficiency disease."

The statistics were challenged by Harry Rice, PhD, VP of regulatory and scientific affairs for the United Natural Products Alliance (UNPA). Dr Rice told NutraIngredients-USA that, from a statistical perspective, "it doesn't appear that the association between dietary vitamin and mineral supplements with increased total mortality risk was statistically significant".

"The standard P value of 0.05 must be dropped for every covariate adjustment. In the current study, there were 15 separate tests which means that the P value for significance should have gone from 0.05 to 0.003 (0.05/15).

"The Iowa Women's Health Study is an important study to determine the degree to which diet and other lifestyle factors influence risk of chronic disease. To the best of my knowledge, it was never meant to serve as a basis for public health recommendations in the absence of further research."

CRN's Dr MacKay added: "It’s important to keep in mind that this is an associative—not a cause and effect—study. Further, the authors themselves have noted additional limitations​.

"In fact, when the authors did their initial [minimum adjusted] analysis, it appears they actually found benefit for many of the supplements, not just calcium; yet instead of stopping there, they went on to “further adjust” the data, possibly until they found statistics worthy of this publication’s acceptance. The study may make for interesting scientific water cooler discussion, but certainly does not warrant sweeping, overstated concerns for elderly women​."

Source: Archive of Internal Medicine
2011, Volume 171, Issue 18, Pages 1625-1633
“Dietary Supplements and Mortality Rate in Older Women: The Iowa Women's Health Study”
Authors: J. Mursu, K. Robien, L.J. Harnack, K. Park, D.R. Jacobs Jr

Editorial: Archive of Internal Medicine
2011, Volume 171, Issue 18, Pages 1633-1634
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"
Authors: G. Bjelakovic, C. Gluud

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