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The Importance of Translating Research Skillfully to Benefit the Public—Reply

The Importance of Translating Research Skillfully to Benefit the Public—Reply In reply It is interesting that the Iowa Women's Health Study (IWHS) data, suggesting that many commonly used dietary supplements do not decrease or might even increase mortality,1 were supported by the Kuopio Ischaemic Heart Disease Risk Factor Study as described by Tuomainen et al. However, the authors were concerned about potential reverse causality. Some of the IWHS women may have started the use of supplements because of health issues, and thus disease would be a cause for the increased mortality and supplement use, just a marker. However, sensitivity analyses excluding those women who self-reported cardiovascular disease, diabetes, or cancer at baseline yielded results similar to our main findings. Furthermore, supplement users tended to have healthier lifestyle compared with nonusers. Except in the case of iron, where the relatively high dosages indirectly argue that they were used to combat anemic conditions, these findings argue against reverse causality bias. However, we cannot fully exclude the possibility because the IWHS did not assess the motives for the supplement use and incidence of disease was not exhaustively assessed. We agree with Vogt that detailed data about the supplements used or nutritional status would have improved our study. We provide additional information herein that does not support the contention that those with worst nutritional status would benefit from supplementation. Comparing multivitamin users with nonusers, the multivariable-adjusted hazard ratios for total mortality varied little across the descending quartiles of an a priori diet quality score,2 the lowest quartile corresponding to worst nutritional status: 1.06 (95% CI, 0.98-1.15), 1.10 (95% CI, 1.01-1.20), 1.06 (95% CI, 0.98-1.14), and 1.07 (95% CI, 0.99-1.17). Also, we do not share the view that in Western countries nutritional deficiencies are common, perhaps excepting vitamin D, especially in the northern hemisphere. Even for vitamin D, clinical trials are needed to verify that supplementation improves health. Last, we do not believe that comparing money spent for dietary supplements with that spent on all of health care is a good argument. Supplements should not be considered part of health care unless prescribed by a physician. Justification for use of supplemental isolated compounds should be based on studies that provide evidence for their benefits in the prevention of chronic diseases. We thank Lucock for raising potential mechanisms for how several supplements might be deleterious and, in contrast, how calcium could be beneficial. In the IWHS these mechanisms were not measured and thus other studies should explore these mechanisms. Finally, we have received inquiries from the Council for Responsible Nutrition, the dietary supplement trade organization, concerning the reference group for supplement users. Their letter to us states, [W]e believe that including many supplement users in each of your various “nonuser” groups may make the nonuser groups look better than they should and could potentially obscure actual differences relating to supplement use. We agree that to the extent that some supplements have adverse effects, including them in the reference group would bias the analysis. We report this analysis for multivitamin use. In the multiadjusted model (see Table 2 of our article1), including 14 596 deaths among 36 510 followed from 1986 through 2008, hazard ratio (95% CI) relative to the “purified” reference group (no supplement use) was 0.93 (0.89-0.97) for the users of only other supplements (n = 11 145, driven by calcium supplements), 1.10 (1.03-1.17) for users of only multivitamins (n = 2688), and 1.00 (0.96-1.05) for users of both (n = 10 081). Thus, no inverse association of multivitamins with total mortality emerged from this analysis. A Council for Responsible Nutrition press release3 questioned the wisdom of adjusting for other health behaviors in our analyses, stating: “dietary supplements are commonly taken to help prevent chronic disease,” the operative term being “help.” We studied this issue by using a propensity score created by regressing total mortality on the variables in our Table 2, multivariable-adjusted model version 1, omitting multivitamin use. Risk of total mortality was 1.11 (1.04-1.18) for 18 288 women (6262 multivitamin users) below the median of this propensity score, vs 1.02 (0.98-1.06) for 18 222 women (5911 multivitamin users) above the median. Thus, no inverse association of multivitamin use was seen in those with a worse or better behavioral profile, apart from multivitamin use. “Purifying” the reference group did not substantially alter this conclusion. Nevertheless, we emphasize that ours is an observational study and therefore has only a cautionary message; definitive conclusions would be based on clinical trials. Back to top Article Information Correspondence: Dr Mursu, Department of Public Health, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, Kuopio, FI 70211, Finland (jaakko.mursu@uef.fi). Financial Disclosure: None reported. References 1. Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr. Dietary supplements and mortality rate in older women: the Iowa Women's Health Study. Arch Intern Med. 2011;171(18):1625-163321987192PubMedGoogle ScholarCrossref 2. Nettleton JA, Schulze MB, Jiang R, Jenny NS, Burke GL, Jacobs DR Jr. A priori-defined dietary patterns and markers of cardiovascular disease risk in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2008;88(1):185-19418614740PubMedGoogle Scholar 3. Council for Responsible Nutrition. CRN calls new study on supplements and mortality: “a hunt for harm.” October 10, 2011. http://www.crnusa.org/CRNPR11AIM101011.html. Accessed January 13, 2012 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

The Importance of Translating Research Skillfully to Benefit the Public—Reply

Archives of Internal Medicine , Volume 172 (5) – Mar 12, 2012

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Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2012.39
Publisher site
See Article on Publisher Site

Abstract

In reply It is interesting that the Iowa Women's Health Study (IWHS) data, suggesting that many commonly used dietary supplements do not decrease or might even increase mortality,1 were supported by the Kuopio Ischaemic Heart Disease Risk Factor Study as described by Tuomainen et al. However, the authors were concerned about potential reverse causality. Some of the IWHS women may have started the use of supplements because of health issues, and thus disease would be a cause for the increased mortality and supplement use, just a marker. However, sensitivity analyses excluding those women who self-reported cardiovascular disease, diabetes, or cancer at baseline yielded results similar to our main findings. Furthermore, supplement users tended to have healthier lifestyle compared with nonusers. Except in the case of iron, where the relatively high dosages indirectly argue that they were used to combat anemic conditions, these findings argue against reverse causality bias. However, we cannot fully exclude the possibility because the IWHS did not assess the motives for the supplement use and incidence of disease was not exhaustively assessed. We agree with Vogt that detailed data about the supplements used or nutritional status would have improved our study. We provide additional information herein that does not support the contention that those with worst nutritional status would benefit from supplementation. Comparing multivitamin users with nonusers, the multivariable-adjusted hazard ratios for total mortality varied little across the descending quartiles of an a priori diet quality score,2 the lowest quartile corresponding to worst nutritional status: 1.06 (95% CI, 0.98-1.15), 1.10 (95% CI, 1.01-1.20), 1.06 (95% CI, 0.98-1.14), and 1.07 (95% CI, 0.99-1.17). Also, we do not share the view that in Western countries nutritional deficiencies are common, perhaps excepting vitamin D, especially in the northern hemisphere. Even for vitamin D, clinical trials are needed to verify that supplementation improves health. Last, we do not believe that comparing money spent for dietary supplements with that spent on all of health care is a good argument. Supplements should not be considered part of health care unless prescribed by a physician. Justification for use of supplemental isolated compounds should be based on studies that provide evidence for their benefits in the prevention of chronic diseases. We thank Lucock for raising potential mechanisms for how several supplements might be deleterious and, in contrast, how calcium could be beneficial. In the IWHS these mechanisms were not measured and thus other studies should explore these mechanisms. Finally, we have received inquiries from the Council for Responsible Nutrition, the dietary supplement trade organization, concerning the reference group for supplement users. Their letter to us states, [W]e believe that including many supplement users in each of your various “nonuser” groups may make the nonuser groups look better than they should and could potentially obscure actual differences relating to supplement use. We agree that to the extent that some supplements have adverse effects, including them in the reference group would bias the analysis. We report this analysis for multivitamin use. In the multiadjusted model (see Table 2 of our article1), including 14 596 deaths among 36 510 followed from 1986 through 2008, hazard ratio (95% CI) relative to the “purified” reference group (no supplement use) was 0.93 (0.89-0.97) for the users of only other supplements (n = 11 145, driven by calcium supplements), 1.10 (1.03-1.17) for users of only multivitamins (n = 2688), and 1.00 (0.96-1.05) for users of both (n = 10 081). Thus, no inverse association of multivitamins with total mortality emerged from this analysis. A Council for Responsible Nutrition press release3 questioned the wisdom of adjusting for other health behaviors in our analyses, stating: “dietary supplements are commonly taken to help prevent chronic disease,” the operative term being “help.” We studied this issue by using a propensity score created by regressing total mortality on the variables in our Table 2, multivariable-adjusted model version 1, omitting multivitamin use. Risk of total mortality was 1.11 (1.04-1.18) for 18 288 women (6262 multivitamin users) below the median of this propensity score, vs 1.02 (0.98-1.06) for 18 222 women (5911 multivitamin users) above the median. Thus, no inverse association of multivitamin use was seen in those with a worse or better behavioral profile, apart from multivitamin use. “Purifying” the reference group did not substantially alter this conclusion. Nevertheless, we emphasize that ours is an observational study and therefore has only a cautionary message; definitive conclusions would be based on clinical trials. Back to top Article Information Correspondence: Dr Mursu, Department of Public Health, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, Kuopio, FI 70211, Finland (jaakko.mursu@uef.fi). Financial Disclosure: None reported. References 1. Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr. Dietary supplements and mortality rate in older women: the Iowa Women's Health Study. Arch Intern Med. 2011;171(18):1625-163321987192PubMedGoogle ScholarCrossref 2. Nettleton JA, Schulze MB, Jiang R, Jenny NS, Burke GL, Jacobs DR Jr. A priori-defined dietary patterns and markers of cardiovascular disease risk in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2008;88(1):185-19418614740PubMedGoogle Scholar 3. Council for Responsible Nutrition. CRN calls new study on supplements and mortality: “a hunt for harm.” October 10, 2011. http://www.crnusa.org/CRNPR11AIM101011.html. Accessed January 13, 2012

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Mar 12, 2012

Keywords: translating

References