Enough Is Enough: Stop Wasting Money on Vitamin and
Mineral Supplements
Three articles in this issue address the role of vitamin
and mineral supplements for preventing the occurrence
or progression of chronic diseases. First, Fortmann and
colleagues (1) systematically reviewed trial evidence to up-
date the U.S. Preventive Services Task Force recommenda-
tion on the efficacy of vitamin supplements for primary
prevention in community-dwelling adults with no nutri-
tional deficiencies. After reviewing 3 trials of multivitamin
supplements and 24 trials of single or paired vitamins that
randomly assigned more than 400 000 participants, the
authors concluded that there was no clear evidence of a
beneficial effect of supplements on all-cause mortality, car-
diovascular disease, or cancer.
Second, Grodstein and coworkers (2) evaluated the
efficacy of a daily multivitamin to prevent cognitive decline
among 5947 men aged 65 years or older participating
in the Physicians’ Health Study II. After 12 years of follow-
up, there were no differences between the multivitamin
and placebo groups in overall cognitive performance or
verbal memory. Adherence to the intervention was high,
and the large sample size resulted in precise estimates
showing that use of a multivitamin supplement in a well-
nourished elderly population did not prevent cognitive de-
cline. Grodstein and coworkers’ findings are compatible
with a recent review (3) of 12 fair- to good-quality trials
that evaluated dietary supplements, including multivita-
mins, B vitamins, vitamins E and C, and omega-3 fatty
acids, in persons with mild cognitive impairment or mild
to moderate dementia. None of the supplements improved
cognitive function.
Third, Lamas and associates (4) assessed the potential
benefits of a high-dose, 28-component multivitamin sup-
plement in 1708 men and women with a previous myo-
cardial infarction participating in TACT (Trial to Assess
Chelation Therapy). After a median follow-up of 4.6 years,
there was no significant difference in recurrent cardiovas-
cular events with multivitamins compared with placebo
(hazard ratio, 0.89 [95% CI, 0.75 to 1.07]). The trial was
limited by high rates of nonadherence and dropouts.
Other reviews and guidelines that have appraised the
role of vitamin and mineral supplements in primary or
secondary prevention of chronic disease have consistently
found null results or possible harms (5, 6). Evidence in-
volving tens of thousands of people randomly assigned in
many clinical trials shows that
-carotene, vitamin E, and
possibly high doses of vitamin A supplements increase
mortality (6, 7) and that other antioxidants (6), folic acid
and B vitamins (8), and multivitamin supplements (1, 5)
have no clear benefit.
Despite sobering evidence of no benefit or possible
harm, use of multivitamin supplements increased among
U.S. adults from 30% between 1988 to 1994 to 39% be-
tween 2003 to 2006, while overall use of dietary supple-
ments increased from 42% to 53% (9). Longitudinal and
secular trends show a steady increase in multivitamin sup-
plement use and a decline in use of some individual sup-
plements, such as
-carotene and vitamin E. The decline
in use of
-carotene and vitamin E supplements followed
reports of adverse outcomes in lung cancer and all-cause
mortality, respectively. In contrast, sales of multivitamins
and other supplements have not been affected by major
studies with null results, and the U.S. supplement industry
continues to grow, reaching $28 billion in annual sales in
2010. Similar trends have been observed in the United
Kingdom and in other European countries.
The large body of accumulated evidence has important
public health and clinical implications. Evidence is suffi-
cient to advise against routine supplementation, and we
should translate null and negative findings into action. The
message is simple: Most supplements do not prevent
chronic disease or death, their use is not justified, and they
should be avoided. This message is especially true for the
general population with no clear evidence of micronutrient
deficiencies, who represent most supplement users in the
United States and in other countries (9).
The evidence also has implications for research. Anti-
oxidants, folic acid, and B vitamins are harmful or ineffec-
tive for chronic disease prevention, and further large pre-
vention trials are no longer justified. Vitamin D
supplementation, however, is an open area of investigation,
particularly in deficient persons. Clinical trials have been
equivocal and sometimes contradictory. For example, sup-
plemental vitamin D, which might prevent falls in older
persons, reduced the risk for falls in a few trials, had no
effect in most trials, and increased falls in 1 trial. Although
future studies are needed to clarify the appropriate use of
vitamin D supplementation, current widespread use is not
based on solid evidence that benefits outweigh harms (10).
With respect to multivitamins, the studies published
in this issue and previous trials indicate no substantial
health benefit. This evidence, combined with biological
considerations, suggests that any effect, either beneficial or
harmful, is probably small. As we learned from voluminous
trial data on vitamin E, however, clinical trials are not
well-suited to identify very small effects, and future trials of
multivitamins for chronic disease prevention in well-
nourished populations are likely to be futile.
In conclusion,
-carotene, vitamin E, and possibly
high doses of vitamin A supplements are harmful. Other
antioxidants, folic acid and B vitamins, and multivitamin
and mineral supplements are ineffective for preventing
mortality or morbidity due to major chronic diseases.
Annals of Internal MedicineEditorial
850 © 2013 American College of Physicians
This article has been corrected. The specific correction appears on the last page of this document. The original version (PDF) is available at www.annals.org.
Downloaded From: http://annals.org/ on 08/11/2014
Although available evidence does not rule out small bene-
fits or harms or large benefits or harms in a small subgroup
of the population, we believe that the case is closed—
supplementing the diet of well-nourished adults with
(most) mineral or vitamin supplements has no clear benefit
and might even be harmful. These vitamins should not be
used for chronic disease prevention. Enough is enough.
Eliseo Guallar, MD, DrPH
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland
Saverio Stranges, MD, PhD
Warwick Medical School, University of Warwick
Coventry, United Kingdom
Cynthia Mulrow, MD, MSc
Annals of Internal Medicine, American College of Physicians
Philadelphia, Pennsylvania
Lawrence J. Appel, MD, MPH
Edgar R. Miller III, MD, PhD
Johns Hopkins School of Medicine
Baltimore, Maryland
Potential Conflicts of Interest: Disclosures can be viewed at www
Requests for Single Reprints: Eliseo Guallar, MD, DrPH, Welch Cen-
ter for Prevention, Epidemiology and Clinical Research, 2024 East
Monument Street, Room 2-645, Baltimore, MD, 21287; e-mail,
Current author addresses are available at www.annals.org.
Ann Intern Med. 2013;159:850-851.
1. Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and
mineral supplements in the primary prevention of cardiovascular disease and
cancer: an updated systematic evidence review for the U.S. Preventive Services
Task Force. Ann Intern Med. 2013;159:824-34.
2. Grodstein F, O’Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al.
Long-term multivitamin supplementation and cognitive function in men. A ran-
domized trial. Ann Intern Med. 2013;159:806-14.
3. Lin JS, O’Connor E, Rossom RC, Perdue LA, Eckstrom E. Screening for
cognitive impairment in older adults: a systematic review for the U.S. Preventive
Services Task Force. Ann Intern Med. 2013;159:601-12. [PMID: 24145578]
4. Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M,
et al; TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose
multivitamins and minerals after myocardial infarction. A randomized trial. Ann
Intern Med. 2013;159:797-804.
5. Huang HY, Caballero B, Chang S, Alberg AJ, Semba RD, Schneyer CR,
et al. The efficacy and safety of multivitamin and mineral supplement use to
prevent cancer and chronic disease in adults: a systematic review for a National
Institutes of Health state-of-the-science conference. Ann Intern Med. 2006;145:
372-85. [PMID: 16880453]
6. Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements to prevent
mortality. JAMA. 2013;310:1178-9. [PMID: 24045742]
7. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Gual-
lar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-
cause mortality. Ann Intern Med. 2005;142:37-46. [PMID: 15537682]
8. Miller ER 3rd, Juraschek S, Pastor-Barriuso R, Bazzano LA, Appel LJ,
Guallar E. Meta-analysis of folic acid supplementation trials on risk of cardiovas-
cular disease and risk interaction with baseline homocysteine levels. Am J Cardiol.
2010;106:517-27. [PMID: 20691310]
9. Gahche J, Bailey R, Burt V, Hughes J, Yetley E, Dwyer J, et al. Dietary
supplement use among U.S. adults has increased since NHANES III (1988-
1994). NCHS Data Brief. 2011:1-8. [PMID: 21592424]
10. Moyer VA; U.S. Preventive Services Task Force. Vitamin D and calcium
supplementation to prevent fractures in adults: U.S. Preventive Services Task
Force recommendation statement. Ann Intern Med. 2013;158:691-6. [PMID:
EditorialStop Wasting Money on Vitamin and Mineral Supplements
www.annals.org 17 December 2013 Annals of Internal Medicine Volume 159 • Number 12 851
Downloaded From: http://annals.org/ on 08/11/2014
Current Author Addresses: Drs. Guallar, Appel, and Miller: Depart-
ments of Epidemiology and Medicine and Welch Center for Prevention,
Epidemiology, and Clinical Research, Johns Hopkins Medical Institu-
tions, Baltimore, MD, 21287.
Dr. Stranges: Division of Health Sciences, Warwick Medical School,
University of Warwick, Coventry CV4 7AL, United Kingdom.
Dr. Mulrow: American College of Physicians, 190 N. Independence
Mall West, Philadelphia, PA 19106-1572.
www.annals.org 17 December 2013 Annals of Internal Medicine Volume 159 • Number 12
Downloaded From: http://annals.org/ on 08/11/2014
Correction: Stop Wasting Money on Vitamin and Mineral
In a recent editorial (1), the last sentence of the first paragraph
should read, “After reviewing 3 trials of multivitamin supplements
and 24 trials of single or paired vitamins that randomly assigned
more than 400 000 participants . . .” as opposed to 450 000.
This has been corrected in the online version.
1. Guallar E, Stranges S, Mulrow C, Appel LJ, Miller ER. Enough is enough. Stop
wasting money on vitamin and mineral supplements. Ann Intern Med. 2013;159:
Downloaded From: http://annals.org/ on 08/11/2014
... This implies that if the diet is balanced, then the evidence suggests that vitamin or mineral supplementation may not be required, especially if the goal is for extended lifespan. 13 Even though this multibillion-dollar vitamin industry is built on the belief that vitamins and minerals will hopefully ward off disease and death, the evidence does not support this ideology. 11,14 Therefore, longevity compounds and technologies may very well be the future of the health and life-extending therapies market. ...
Full-text available
Aging is widely considered an immovable fact of life. Cultural conditioning has ensured that therapeutics for extreme human lifespans are considered out of reach technologies. However, longevity therapies such as stem cell replacement, fasting, gene therapies, fasting mimetics such as metformin and rapamycin, regulation and tissue reprogramming with OSK transcription factors, blood dilution, metabolic pathway engineering, reversal of epigenetic drift, heterochronic parabiosis, coenzyme replacement technologies (nicotinamide adenine dinucleotide) and a plethora of other established sciences are showing great potential at slowing down the rate at which tissues enter dysfunction. Recent discoveries have shed light on major mysteries of the aging process. Longevity‐based discoveries are not only landing quickly, but therapies to prevent or reverse those drivers of aging are also being devised regularly and this is opening up an entirely new industry, the longevity industry. This presents the requirement for a new classification system where subjects can be divided into specific groups based on their potential for mortality. This system also enables the public to target which class of this classification system they wish to be on. Moving the population on the classification system to become more disease resistant holds great benefit for society and governments as a whole. The upward curve reflects the vision for humanity to pursue healthier living.
... There was evidence suggesting combination of nutrients in some supplements may be helpful to reduce incidence of chronic disease among at-risk populations such as cardiovascular disease (CVD) and cancer (Comerford, 2013). However, high doses of supplements could be harmful and may be ineffective for preventing mortality and morbidity related to chronic disease (Guallar et al., 2013). ...
... Regarding health remedies, consilience may refer to (i) compelling evidence either supporting or rejecting a remedy's efficacy, (ii) compelling evidence that a remedy causes harm or (iii) a lack of compelling evidence to back up the health claims being made. One remedy not supported by scientific consilience is multivitamin supplementation for healthy individuals: numerous randomised controlled trials have found that multivitamins provide no health benefits (Guallar, Strangers, Mulrow, Appel, & Miller, 2013;Jenkins et al., 2018) and may even be detrimental to health (Mursu, Robien, Harnack, Park, & Jacobs, 2011). Evidence-based interventions are thus needed to help people avoid the negative consequences of such behaviour. ...
Objective: We tested a novel intervention for reducing demand for ineffective health remedies. The intervention aimed to empower participants to overcome the illusion of causality, which otherwise drives erroneous perceptions regarding remedy efficacy. Design: A laboratory experiment adopted a between-participants design with six conditions that varied the amount of information available to participants (N = 245). The control condition received a basic refutation of multivitamin efficacy, whereas the principal intervention condition received a full contingency table specifying the number of people reporting a benefit vs. no benefit from both the product and placebo, plus an alternate causal explanation for inefficacy over placebo. Main outcome measures: We measured participants’ willingness to pay (WTP) for multivitamin products using two incentivized experimental auctions. General attitudes towards health supplements were assessed as a moderator of WTP. We tested generalization using ratings of the importance of clinical-trial results for making future health purchases. Results: Our principal intervention significantly reduced participants’ WTP for multivitamins (by 23%) and increased their recognition of the importance of clinical-trial results. Conclusion: We found evidence that communicating a simplified full- contingency table and an alternate causal explanation may help reduce demand for ineffective health remedies by countering the illusion of causality.
... By contrast, results of intervention studies have invariably shown that long-term intake of these compounds brings no health benefi t, and can even reduce life expectancy. 10 We declare that we have no competing interests. ...
... By contrast, results of intervention studies have invariably shown that long-term intake of these compounds brings no health benefi t, and can even reduce life expectancy. 10 We declare that we have no competing interests. ...
Autier, Philippe Boniol, Mathieu Pizot, Cecile Mullie, Patrick eng Comment Letter England 2014/04/08 06:00 Lancet Diabetes Endocrinol. 2014 Apr;2(4):275-6. doi: 10.1016/S2213-8587(14)70049-X.
Conference Paper
Full-text available
Presently, social media plays a vital role in substituting the power of advertisement. There are approximately 24.5 million social media users in Malaysia. The enormous number of social media users makes it more apparent that social media has become a valuable platform to promote products and services. Wide use of social media made people easily exposed to other users' daily activities, lifestyle as well as sharing of opinions and experience. Hence, the level of awareness on health and beauty among consumers in Malaysia becomes more prevalent. There is a variety of health and dietary supplements available in the market. The purpose of this study was to explore the experience of the dietary supplement consumers in trusting electronic word of mouth which made them convinced to purchase. This paper was a preliminary study on understanding the process of how consumers made their decision. In-depth interviews were conducted in obtaining the experience of the consumers on this. Preliminary results indicated that electronic word of mouth plays as behavior change agent and demographic background influence to the level of trust among consumers. The findings assisted the researchers to improve strategies before embarking into the major study.
Although many Americans take vitamins and supplements, there is little objective data available regarding their benefits and risks, and they are not tightly regulated by the FDA. Studies of multivitamins and anti-oxidant pills have not shown them to be effective in disease prevention. The benefits and risks of eye vitamins, fish oil, Vitamin E, and Folic Acid are also assessed. There continues to be confusion regarding the benefits and risks of supplement use. Information presented to doctors and patients tends to be misleading and difficult to interpret. This is due, in large part, to the use of relative risks rather than absolute values when communicating information on supplement benefits. In light of this situation, a unique graphic, functioning as a decision aid, has been developed to enable physicians and patients to jointly assess the benefits and risks of vitamin and supplement use. By characterizing the complexities of risk analysis in terms patients can understand, means they will be able to make well-informed decisions about their health.
Full-text available
Whether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown. To assess whether oral multivitamins reduce cardiovascular events and are safe. Double-blind, placebo-controlled, 2 x 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) SETTING: 134 U.S. and Canadian academic and clinical sites. 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 mol/L (2.0 mg/dL) or less. Intervention: Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo. The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events. There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety). High-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate. National Institutes of Health.
Full-text available
Key findings: Use of dietary supplements is common among the U.S. adult population. Over 40% used supplements in 1988-1994, and over one-half in 2003-2006. Multivitamins/multiminerals are the most commonly used dietary supplements, with approximately 40% of men and women reporting use during 2003-2006. Use of supplemental calcium increased from 28% during 1988-1994 to 61% during 2003-2006 among women aged 60 and over. Use of supplements containing folic acid among women aged 20-39 did not increase since 1988-1994. In 2003-2006, 34% of women aged 20-39 used a dietary supplement containing folic acid. Use of dietary supplements containing vitamin D increased from 1988-1994 through 1999-2002 for men and women in most age groups. Dietary supplements can contain nutrients in amounts as high as or higher than the Institute of Medicine's Recommended Dietary Reference Intakes, therefore contributing substantially to total nutrient intake. Dietary supplements are widely available to U.S. consumers, and monitoring their use over time is an important component of the National Nutrition Monitoring System. Failure to include these nutrients when assessing the adequacy of diets and nutrition in the U.S. population may lead to inaccurate and misleading results. This report provides estimates of dietary supplement use for specific population groups over time. In addition to overall use of dietary supplements, this report focuses on estimates for specific nutrients consumed through dietary supplement use.
Full-text available
Multivitamin and mineral supplements are the most commonly used dietary supplements in the United States. To synthesize studies on the efficacy and safety of multivitamin/mineral supplement use in primary prevention of cancer and chronic disease in the general population. English-language literature search of the MEDLINE, EMBASE, and Cochrane databases through February 2006 and hand-searching of pertinent journals and articles. Randomized, controlled trials in adults were reviewed to assess efficacy, and randomized, controlled trials and observational studies in adults or children were reviewed to assess safety. Paired reviewers extracted data and independently assessed study quality. 12 articles from 5 randomized, controlled trials that assessed efficacy and 8 articles from 4 randomized, controlled trials and 3 case reports on adverse effects were identified. Study quality was rated fair for the studies on cancer, cardiovascular disease, cataracts, or age-related macular degeneration and poor for the studies on hypertension. In a poorly nourished Chinese population, combined supplementation with beta-carotene, alpha-tocopherol, and selenium reduced the incidence of and mortality rate from gastric cancer and the overall mortality rate from cancer by 13% to 21%. In a French trial, combined supplementation with vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced the rate of cancer by 31% in men but not in women. Multivitamin and mineral supplements had no significant effect on cardiovascular disease or cataracts, except that combined beta-carotene, selenium, alpha-tocopherol, retinol, and zinc supplementation reduced the mortality rate from stroke by 29% in the Linxian study and that a combination of 7 vitamins and minerals stabilized visual acuity loss in a small trial. Combined zinc and antioxidants slowed the progression of advanced age-related macular degeneration in high-risk persons. No consistent adverse effects of multivitamin and mineral supplements were evident. Only randomized, controlled trials were considered for efficacy assessment. Special nutritional needs, such as use of folic acid by pregnant women to prevent birth defects, were not addressed. Findings may not apply to use of commercial multivitamin supplements by the general U.S. population. Evidence is insufficient to prove the presence or absence of benefits from use of multivitamin and mineral supplements to prevent cancer and chronic disease.
Despite widespread use of multivitamin supplements, their effect on cognitive health-a critical issue with aging-remains inconclusive. To date, no long-term clinical trials have studied multivitamin use and cognitive decline in older persons. To evaluate whether long-term multivitamin supplementation affects cognitive health in later life. Randomized, double-blind, placebo-controlled trial of a multivitamin from 1997 to 1 June 2011. The cognitive function substudy began in 1998. Up to 4 repeated cognitive assessments by telephone interview were completed over 12 years. (ClinicalTrials.gov: NCT00270647) SETTING: The Physicians' Health Study II. 5947 male physicians aged 65 years or older. Daily multivitamin or placebo. A global composite score averaging 5 tests of global cognition, verbal memory, and category fluency. The secondary end point was a verbal memory score combining 4 tests of verbal memory, which is a strong predictor of Alzheimer disease. No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessments. Specifically, for the global composite score, the mean difference in cognitive change over follow-up was -0.01 SU (95% CI, -0.04 to 0.02 SU) when treatment was compared with placebo. Similarly, cognitive performance did not differ between the multivitamin and placebo groups on the secondary outcome, verbal memory (mean difference in cognitive change over follow-up, -0.005 SU [CI, -0.04 to 0.03 SU]). Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin. In male physicians aged 65 years or older, long-term use of a daily multivitamin did not provide cognitive benefits. National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.
Vitamin and mineral supplements are commonly used to prevent chronic diseases. To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. Dual quality assessments and data abstraction. Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.94 [95% CI, 0.89 to 1.00]). The study that included women showed no effect in them. High-quality studies (k = 24; n = 324,653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. Agency for Healthcare Research and Quality.
Earlier identification of cognitive impairment may reduce patient and caregiver morbidity. To systematically review the diagnostic accuracy of brief cognitive screening instruments and the benefits and harms of pharmacologic and nonpharmacologic interventions for early cognitive impairment. MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials through December 2012; systematic reviews; clinical trial registries; and experts. English-language studies of fair to good quality, primary care-feasible screening instruments, and treatments aimed at persons with mild cognitive impairment or mild to moderate dementia. Dual quality assessment and abstraction of relevant study details. The Mini-Mental State Examination (k = 25) is the most thoroughly studied instrument but is not available for use without cost. Publicly available instruments with adequate test performance to detect dementia include the Clock Drawing Test (k = 7), Mini-Cog (k = 4), Memory Impairment Screen (k = 5), Abbreviated Mental Test (k = 4), Short Portable Mental Status Questionnaire (k = 4), Free and Cued Selective Reminding Test (k = 2), 7-Minute Screen (k = 2), and Informant Questionnaire on Cognitive Decline in the Elderly (k = 5). Medications approved by the U.S. Food and Drug Administration for Alzheimer disease (k = 58) and caregiver interventions (k = 59) show a small benefit of uncertain clinical importance for patients and their caregivers. Small benefits are also limited by common adverse effects of acetylcholinesterase inhibitors and limited availability of complex caregiver interventions. Although promising, cognitive stimulation (k = 6) and exercise (k = 10) have limited evidence to support their use in persons with mild to moderate dementia or mild cognitive impairment. Limited studies in persons with dementia other than Alzheimer disease and sparse reporting of important health outcomes. Brief instruments to screen for cognitive impairment can adequately detect dementia, but there is no empirical evidence that screening improves decision making. Whether interventions for patients or their caregivers have a clinically significant effect in persons with earlier detected cognitive impairment is still unclear. Agency for Healthcare Research and Quality.
Are antioxidant supplements associated with higher or lower all-cause mortality? Antioxidant supplements are not associated with lower all-cause mortality. Beta carotene, vitamin E, and higher doses of vitamin A may be associated with higher all-cause mortality.
Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. To perform a meta-analysis of the dose-response relationship between vitamin E supplementation and total mortality by using data from randomized, controlled trials. 135,967 participants in 19 clinical trials. Of these trials, 9 tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosages of vitamin E ranged from 16.5 to 2000 IU/d (median, 400 IU/d). PubMed search from 1966 through August 2004, complemented by a search of the Cochrane Clinical Trials Database and review of citations of published reviews and meta-analyses. No language restrictions were applied. 3 investigators independently abstracted study reports. The investigators of the original publications were contacted if required information was not available. 9 of 11 trials testing high-dosage vitamin E (> or =400 IU/d) showed increased risk (risk difference > 0) for all-cause mortality in comparisons of vitamin E versus control. The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10,000 persons (95% CI, 3 to 74 per 10,000 persons; P = 0.035). For low-dosage vitamin E trials, the risk difference was -16 per 10,000 persons (CI, -41 to 10 per 10,000 persons; P > 0.2). A dose-response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d. High-dosage (> or =400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult. High-dosage (> or =400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.
Experimental models and observational studies suggest that homocysteine-lowering therapy with folic acid (FA) may prevent cardiovascular disease (CVD). However, FA also stimulates cell proliferation and might promote progression of atherosclerosis. Our objectives were to perform a meta-analysis of FA supplementation trials on CVD events and to explore a potential interaction between FA supplementation and baseline homocysteine levels on CVD events. We searched MEDLINE for randomized controlled trials of FA supplementation to prevent CVD events (January 1966 to July 2009) and performed meta-analyses using random effects models. For trials that reported responses to FA supplementation stratified by baseline levels of homocysteine, we pooled within-trial estimates of differences in log-relative risks by baseline homocysteine levels using a random effects model. Overall, FA supplementation did not affect primary cardiovascular clinical end points (relative risk 1.02, 95% confidence interval [CI] 0.93 to 1.13, p = 0.66) or stroke (relative risk 0.95, 95% CI 0.84 to 1.08, p = 0.43). However, in trials that reported analyses stratified by baseline homocysteine, effect of FA supplementation differed by strata of baseline homocysteine (p for interaction = 0.030). Specifically, risks of primary clinical CVD events comparing FA supplementation to control were 1.06 (95% CI 1.00 to 1.13) in strata with mean baseline homocysteine levels >12 mumol/L and 0.94 (95% CI 0.86 to 1.03) in strata with baseline homocysteine levels <12 micromol/L. In conclusion, FA had no effect on CVD or stroke. However, analysis of within-trial results stratified by baseline homocysteine suggests potential harm in those with high homocysteine at baseline. This interaction may have important implications for recommendations of FA supplement use. In the meantime, FA supplementation should not be recommended as a means to prevent or treat CVD or stroke.