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    6 Comments for this article
    Supplement-related Mortality?
    Marcia K Roark, BSN | retired nurse
    My question is: what other health issues were going on with these subjects(not mentioned in the abstract) that may have contributed to the mortality rates, and how does it differ from the general death rate of this population? This assumption of relationship is quite a leap, when nothing is mentioned about environment, genetic predisposition, obesity,smoking, etc. Also, self-reporting of supplements is often unreliable. Thanks for any light you can shed on this issue. Sincerely,
    Marcia Roark

    Conflict of Interest: None declared
    Dietary Supplements and Mortality Rate in Older Women
    Pamela B. Baines, MD | Pamela B. Baines, MD, PA
    One suspects, from reading the conclusions of this study, that the authors have a bias against nutritional supplements, particularly vitamins. Observational studies typically cannot demonstrate causality, so attributing a risk to vitamin supplements is a stretch, plus the degree of risk presented does not appear to be significant. If you look at the situation with iron supplements, most women (other than those hooked on Geritol), do not normally take supplemental iron without a perceived need, such as a diagnosis of anemia. An underlying medical condition such as anemia might be expected to increase relative mortality risk over the 16- year period examined, and would be a significant confounding factor. I am concerned that the media and many physicians will now scare patients who should be taking supplemental vitamins or minerals into stopping them.
    Conflict of Interest: None declared
    What does the highly publicized recent study tell us about supplement use?
    Douglas MacKay, ND | Council for Responsible Nutrition
    The methodology used to identify “users” and “non-users” (Table 2) and used throughout the data analysis is flawed. Given that the cohort of supplement users demonstrated improved biomarkers of good health and healthy lifestyle habits, an overall comparison of “users” to “non-users” of dietary supplements is an important omission in the manuscript. If such a comparison demonstrated decreased or no change in risk of total mortality, this finding would significantly weaken the relevance of individual findings for multivitamins, vitamin B6, copper, and iron. A finding of reduced or decreased risk for all “users” combined would challenge the authors’ conclusions about risks associated with vitamin and mineral use. The manuscript excluded a full discussion of recent studies on the same topic, such as the “Multivitamin use and the risk of mortality and cancer incidence: the multiethnic cohort study” by Park et al (8). This study included 182,099 participants, both men and women, from multiple ethnic backgrounds. Park et al found no associations between multivitamin use and mortality from all causes, cardiovascular diseases, or cancer in “users” vs. “non-users.” The findings did not vary across subgroups by ethnicity, age, body mass index, pre-existing illness, single vitamin/mineral supplement use, hormone replacement therapy use, or smoking status. There also was no evidence indicating that multivitamin use was associated with risk of cancer, overall or at major sites such as lung, colon/rectum, prostate, and breast. In conclusion, there was no clear decrease or increase in mortality from all causes, cardiovascular disease, or cancer, nor in morbidity from overall or major cancers among multivitamin supplement users (8).
    The inherent limitations of observational studies, confounded by the classification of “users” and “non-users” adopted by Mursu et al, makes the findings of the current study questionable at best. The manuscript lacks discussions of similar recent studies and includes statements of the authors’ opinions, such as, “We recommend that [dietary supplements] be used with strong medically based cause, such as symptomatic nutrient deficiency….” In my opinion, waiting until a diagnosis of scurvy before taking action is irresponsible. Therefore, the findings reported by Mursu et al. should be interpreted with caution and do not justify changes to integrative clinicians’ recommendations regarding multivitamins or other nutrients.

    Conflict of Interest: Douglas MacKay is the Vice President, Scientific & Regulatory Affairs at the Council for Responsible Nutrition
    Dietary Supplements and Mortality Rate in Older Women: A “Supplement” to the Story.
    Ayaz Virji, MD | Take Care Health
    The publication by Mursu et al. demonstrates that multivitamin use in a carte blanche style does not reduce all-cause mortality in women, but to the contrary, may slightly increase it. The Mursu study, though well executed, exhibits a number of methodological limitations. The study utilizes the Harvard Service Food Frequency Questionnaire (HSFFQ), originally designed to assess the diets of low-income women in order to gather information on dietary supplement utilization. The dietary supplement portion of the questionnaire has not been independently validated. In addition, there exist a certain subset of patients who inappropriately substitute dietary supplements in place of medications to manage chronic disease. This concerning, yet uncaptured, trend could potentially confound the results. The study does not report on the specific doses, excluding calcium and iron, or the source of the supplements. Both qualities play an important role. For example, Recent studies show that supplemental doses > 400 IU of vitamin E may increase one’s risk of developing congestive heart failure and prostate cancer – though in aggregate the data are inconclusive (2,3). However, the Nurses’ Health Study found that women consuming 100 IU daily had a 44% reduction in developing major coronary disease (4).
    Various isomers of the same vitamin have different effects. Considering vitamin E again, á tocopherol and ã tocopherol have different anti-inflammatory properties and bioavailability. It is likely that a healthy ratio of the two is more important to preventing coronary artery disease than is taking one isomer in excess, which may deplete the other (5). In addition, unlike pharmaceutical agents, the source of vitamin supplements plays an important role as well. Synthetic vitamin E (dl) is thought to be much less potent than its natural vitamin E (d) counterpart and may have a varying clinical effect.
    It would be imprudent to make broad, imprecise statements about the “ineffectivity” of dietary supplements as a whole, though it may be tempting to do so. A targeted, rational strategy for supplement use developed in partnership with a medical provider is likely to lead to a different outcome than that reported in the current study. The authors themselves concede “It is not advisable to make a causal statement of excess risk based on these observational data (1).”
    1. Mursu J, Robien K, Harmack LJ, et al. Dietary supplements and mortality rate in older women. Arch Intern Med. 2011;171:1625-33.
    2. Klein EA, Thompson IM, Tangen CM, et al. JAMA 2011;306:1549-56.
    3. The HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. JAMA 2005;293:1328-47.
    4. Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328:1444-49.
    5. Jiang Q, Christen S, Shigenaga MK, et al. ã-Tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr 2001;74:714-22.

    Conflict of Interest: None declared
    Dear Authors,
    Kathleen Welch, MD | pvt practice
    Why (and how) do Finnish authors in Finland report on the Iowa Women's Health study? And recent studies seem to indicate that calcium supplements increase the risk of heart disease. Any comments?
    Kathleen Welch MD

    Conflict of Interest: None declared
    Dietary supplements -- more consideration
    Jeffrey B. Blumberg, PhD | Tufts University
    As also mentioned in the Readers Reply by Douglas MacKay, the report relating to mortality among users and nonusers of nutrient supplements in the Iowa Women's Health Study (1) is puzzling because the authors’ definition of "nonusers" of dietary supplements actually includes many “users” of these products. At baseline, there were 24,329 women who used supplements and 14,443 women who used no supplements (Table 1). The number of multivitamin users is listed as 12,769 and the other 25,474 women are classified as nonusers (Table 2); thus, nonusers group include 11,031 women who are users of supplements other than multivitamins. As another example of this curious definition of users and nonusers, 4,082 women reported using vitamin D supplements with 33,105 others being listed as nonusers; thus, 18,662 women in the nonusers group were actually taking supplements, including supplements like multivitamins and calcium that are typically formulated with vitamin D. Table 1 indicates that 67% (16,278) of the baseline supplement users were alive and responding to a subsequent survey in 2004, compared to only 20% (2,846) of the nonusers, though the authors make no mention of this apparent difference in survival. More importantly, it is surprising that Mursu and his colleagues appear not to have addressed the fundamental question that they raise in their study, i.e., is there a difference in overall difference in mortality between older women who actually take dietary supplements and those who take none? Indeed, if there is a significant increase in mortality among older women taking multivitamins and other dietary supplements who, compared to nonusers, also have a lower prevalence of energy and saturated fat intake, diabetes, hypertension, overweight, and smoking and also a greater amount of fruit, vegetable, and whole grain consumption, higher education, and physical activity, it would be interesting to know the cause of their deaths.
    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):1625-1633.

    Conflict of Interest: None declared
    Original Investigation
    Health Care Reform
    Oct 10, 2011

    Dietary Supplements and Mortality Rate in Older Women: The Iowa Women's Health Study

    Author Affiliations

    Author Affiliations: Department of Health Sciences, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland (Dr Mursu); Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (Drs Mursu, Robien, Harnack, and Jacobs); Department of Food and Nutrition, Yeungnam University, Gyeongbuk, Republic of Korea (Dr Park); and Department of Nutrition, School of Medicine, University of Oslo, Oslo, Norway (Dr Jacobs).

    Arch Intern Med. 2011;171(18):1625-1633. doi:10.1001/archinternmed.2011.445

    Background Although dietary supplements are commonly taken to prevent chronic disease, the long-term health consequences of many compounds are unknown.

    Methods We assessed the use of vitamin and mineral supplements in relation to total mortality in 38 772 older women in the Iowa Women's Health Study; mean age was 61.6 years at baseline in 1986. Supplement use was self-reported in 1986, 1997, and 2004. Through December 31, 2008, a total of 15 594 deaths (40.2%) were identified through the State Health Registry of Iowa and the National Death Index.

    Results In multivariable adjusted proportional hazards regression models, the use of multivitamins (hazard ratio, 1.06; 95% CI, 1.02-1.10; absolute risk increase, 2.4%), vitamin B6 (1.10; 1.01-1.21; 4.1%), folic acid (1.15; 1.00-1.32; 5.9%), iron (1.10; 1.03-1.17; 3.9%), magnesium (1.08; 1.01-1.15; 3.6%), zinc (1.08; 1.01-1.15; 3.0%), and copper (1.45; 1.20-1.75; 18.0%) were associated with increased risk of total mortality when compared with corresponding nonuse. Use of calcium was inversely related (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94; absolute risk reduction, 3.8%). Findings for iron and calcium were replicated in separate, shorter-term analyses (10-year, 6-year, and 4-year follow-up), each with approximately 15% of the original participants having died, starting in 1986, 1997, and 2004.

    Conclusions In older women, several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality risk; this association is strongest with supplemental iron. In contrast to the findings of many studies, calcium is associated with decreased risk.