Trash the Vitamins Medscape article

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Lyndon McGill, D.C.

Salem, Oregon

www.SalemSpineClinic.com

www.LimitlessRelief.com

Trash the Vitamins: Convince Your Patients

A Best Evidence Review

P. Vega, MD; Veena Kulchaiyawat, DO

Posted: 01/05/2012

Best Evidence Review of Dietary Supplements and Mortality

Rates in Older Women

Mursu J, Robien K, Harnack LJ, Park K, s Jr DR.

Dietary supplements and mortality rate in older women. Arch

Intern Med. 2011;171:1625-1633.

Dietary supplements are widely used by older adults, even

though the effectiveness of these supplements in preventing

illness is questionable. But can dietary supplements

actually promote a higher risk for death? A new study

suggests that the answer is yes for some of the most common

supplements. This Best Evidence Review describes the

findings of this study and puts these results in context.

Background

Vitamins and dietary supplements play an important role in

the health and healthcare of many adults, and the business

of supplements constitutes a multibillion-dollar industry

worldwide. Based on the Third National Health and Nutrition

Examination Survey, 40% of men and 50% of women older than

60 years of age consume at least 1 vitamin or mineral

supplement.[1] A national survey by the US Food

and Drug Administration found that 73% of US adults were

found to use dietary supplements in 2002, providing annual

sale costs in 2005 of over $20 billion.[2,3]

The widespread use of dietary supplements is not supported

by practice guidelines. The US Preventive Services Task

Force (USPSTF) states that there is insufficient evidence to

recommend for or against the use of vitamins A, C, E, or

multivitamins with folic acid or antioxidants.[4]

Specifically, the USPSTF cites concerns regarding the

balance of benefits vs harms of these supplements. The

American Medical Association recommends supplements

specifically for seniors who have generalized decreased food

intake, while the American Dietetic Association advises

low-dose multivitamin and mineral supplements depending on

individualized dietary assessment.[5] The

American Heart Association emphasizes healthy eating

patterns rather than supplementation with specific

nutrients.[6]

These recommendations against the routine use of

supplements are grounded in good evidence. A Cochrane

intervention review of 77 randomized controlled trials with

232,550 participants found no evidence to recommend

antioxidant supplementation for primary or secondary

prevention of mortality.[7] Moreover, there is

the possibility of harm related to the use of some

supplements. For example, the Alpha-Tocopherol Beta-Carotene

Cancer Prevention Trial demonstrated that beta-carotene

supplements increased the risk for lung cancer among male

smokers.[8]

The Study

The study under discussion by Mursu and colleagues raises

even more concerns regarding the safety of dietary

supplements. The study enrolled 41,836 women between the

ages of 55 and 69 years in 1986. Women completed validated

food frequency questionnaires at baseline and in 2004, and

the use of any of 15 different dietary supplements was

queried in 1986, 1997, and 2004.

The main study outcome was the relationship between

supplement use and all-cause mortality, which was assessed

from state and national registries. Researchers adjusted

this result to account for the following factors: age,

energy intake, educational level, place of residence,

smoking status, body mass index (BMI), waist-to-hip ratio,

physical activity, diet composition, alcohol consumption,

the use of estrogen therapy, and the presence of diabetes

mellitus and hypertension. Serum lipids or blood pressure

were not measured as part of the study.

A total of 38,772 women provided study data. The mean age

of participants at enrollment was 61.6 years, and over 99%

of women were white. The average BMI was 27 kg/m2

at baseline and follow-up in 2004, and the majority of women

were physically active. The average consumption of fruits

and vegetables exceeded 6 servings per day during the study

period. Out of this population, 36.8% of women reported

hypertension, and 6.8% had diabetes.

The use of dietary supplements increased with time; 62.7%

of women reported use of at least 1 supplement in 1986, and

this figure rose to 85.1% by 2004. The most commonly used

supplements were calcium, multivitamins, vitamin C, and

vitamin E.

Women who used supplements generally had better health

characteristics compared with nonusers. They had higher

educational status, lower BMI and waist-to-hip ratio, and

lower rates of diabetes and hypertension compared with

nonusers, and they were also less likely to smoke and had a

healthier dietary profile. Supplement users were also more

likely to use estrogen therapy compared with nonusers.

There were 15,594 deaths (40.2% of the study cohort) during

a mean follow-up period of 19 years. In fully adjusted

models, the use of multiple supplements was associated with

a higher risk for mortality, including multivitamins (hazard

ratio

---

, 1.06; 95% confidence interval [CI], 1.02-1.10),

vitamin B6 (1.10; 1.01-1.21), folic acid (1.15; 1.00-1.32),

iron (1.10; 1.03-1.17), magnesium (1.08; 1.01-1.15), zinc

(1.08; 1.01-1.15), and copper (1.45; 1.20-1.75). The use of

vitamin A, beta-carotene, and selenium were associated with

nonsignificant trends toward a higher risk for mortality,

and the use of vitamins C, D, and E had nearly no effect on

mortality. In contrast, taking calcium supplements

significantly reduced the risk for mortality (HR, 0.91, 95%

CI, 0.88-0.94).

Researchers performed a number of additional analyses of

the data to evaluate the validity of their outcomes. The

main study results were not significantly changed after

excluding women with a known history of cardiovascular

disease or diabetes at baseline. An analysis using shorter

follow-up intervals also confirmed the findings of higher

risks for mortality with the use of iron. Moreover, there

was evidence of a positive dose-response relationship

between iron supplements and the risk for mortality.

However, no dose-response effect was found for vitamins A,

C, D, and E as well as the minerals selenium and zinc.

Commentary

The principal limitation of the current study was its

observational nature, which leaves open the possibility of

confounding by indication. Specifically, there is the

possibility that women with higher risks for mortality or

who developed serious chronic illnesses as they grew older

had a wider use of supplements.

Nonetheless, it is worth remembering that women who used

supplements had superior health characteristics compared

with nonusers. Therefore, supplement users should have

experienced a lower risk for death overall. While it is

plausible that some women started taking multiple

supplements when confronted with news of a severe illness,

such as cancer, it is hard to imagine that this practice

alone was common enough to tip the scales toward a higher

overall risk for mortality associated with the use of

supplements.

One of the more fascinating findings in this very

interesting study is the higher risk for mortality

associated with the use of iron supplements. Higher levels

of serum iron and transferrin saturation have been

associated with a lower risk for mortality.[9,10]

However, another study found that men with a serum ferritin

level of 200 mcg/L or more experienced more than a twofold

increased risk for myocardial infarction.[11]

Finally, both increased serum iron levels and higher

transferrin saturation have been associated with an

increased risk for death due to cancer.[12] Of

course, in this study, women with existing anemia due to any

number of chronic serious medical conditions, such as cancer

or chronic kidney disease, could have been told to take iron

supplements by their physician, and these illnesses might

account for their higher mortality. In any case, it appears

that the role of iron among adults without iron deficiency

is controversial, and there is little data from clinical

trials to suggest a benefit to the routine use of iron

supplementation among adults.

An additional interesting finding in the current study is

the effect of calcium, but not vitamin D, supplements in

reducing the risk for mortality. This is another

controversial area because calcium supplements have been

implicated in promoting a higher risk for myocardial

infarction among women.[13] However, in the

Women's Health Initiative trial, the use of calcium plus

vitamin D reduced the risk for some types of cancer without

an overall effect on the risk for mortality.[14]

The findings from the current study offer several lessons

to physicians. First, physicians need to pay close attention

to nonprescription therapies used by patients. These

treatments are routinely omitted from the history of many

patients, but the current study suggests that physicians

make such errors at the peril of their patients.

Physicians should be a trusted resource for patients

interested in dietary supplements. We can help balance

self-treatment practices that might be effective against

those that appear harmful or excessive. The findings of the

current study should be sobering for the most ardent

supporters of supplements, and patients need to understand

the potential risks inherent in the treatment choices they

make.

Clinical Pearls

Nearly half of older adults routinely use dietary

supplements, with higher rates of use among women compared

with men.

The routine use of many dietary supplements is

discouraged in practice guidelines.

The use of multivitamins, vitamin B6, folic acid, iron,

magnesium, zinc, and copper was associated with a higher

risk for mortality among older women in the current study.

Conversely, calcium supplements were associated with a

lower risk for mortality.

Physicians need to analyze nonprescription therapies

used by patients and warn them of potential harms

associated with the use of supplements.

References

Glade MJ. National Institutes of Health

Conference: dietary supplement use in the elderly.

Nutrition. 2003;19:981-987. Abstract

Sadovsky R, N, Tighe AP, et al. Patient

use of dietary supplements: a clinician's

perspective. Curr Med Res Opin. 2008;24:1209-1216. Abstract

Dwyer JT, Picciano MF, Betz JM, et al. Progress in

developing analytical and label-based dietary

supplement databases at the NIH Office of Dietary

Supplements. J Food Composition Analysis.

2008;21:S83-S93.

US Preventive Services Task Force. Routine vitamin

supplementation to prevent cancer and cardiovascular

disease: recommendations and rationale. Ann Intern

Med. 2003;139:51-55. Abstract

Tripp F. The use of dietary supplements in the

elderly: current issues and recommendations. J Am

Diet Assoc. 1997;97:S181-S183. Abstract

Eilat-Adar S, Goldbourt U. Nutritional

recommendations for preventing coronary heart

disease in women: evidence concerning whole foods

and supplements. Nutr Metab Cardiovasc Dis.

2010;20:459-466. Abstract

Bjelakovic G, Nikolova D, Gluud LL, et al.

Antioxidant supplements for prevention of mortality

in healthy participants and patients with various

diseases. Cochrane Database Syst Rev.

2008;16:CD007176.

Albanes D, Heinonen OP, Huttunen JK, et al.

Effects of alpha-tocopherol and beta-carotene

supplements on cancer incidence in the

Alpha-Tocopherol Beta-Carotene Cancer Prevention

Study. Am J Clin Nutr. 1995;62:1427S-1430S. Abstract

Sempos CT, Looker AC, Gillum RF, et al. Body iron

stores and the risk of coronary heart disease. N

Engl J Med. 1994;330:119-124.

Corti MC, Guralnik JM, Salive ME, et al. Serum

iron level, coronary artery disease, and all-cause

mortality in older men and women. Am J Cardiol.

1997;79:120-127. Abstract

Salonen JT, Nyyssönen K, Korpela H, et al. High

stored iron levels are associated with excess risk

of myocardial infarction in eastern Finnish men.

Circulation. 1992;86:803-811. Abstract

Wu T, Sempos CT, Freudenheim JL, Muti P, Smit E.

Serum iron, copper and zinc concentrations and risk

of cancer mortality in US adults. Ann Epidemiol.

2004;14:195-201. Abstract

Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR.

Calcium supplements with or without vitamin D and

risk of cardiovascular events: reanalysis of the

Women's Health Initiative limited access dataset and

meta-analysis. BMJ. 2011;342:d2040.

Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium

and vitamin D supplements and health outcomes: a

reanalysis of the Women's Health Initiative (WHI)

limited-access data set. Am J Clin Nutr.

2011;94:1144-1149. Abstract

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