Evidence Concerning Vitamin and Mineral Supplements- Safety and Efficacy

Introduction

I have discussed a number of studies and reviews of the value and risks of vitamin and mineral supplements in humans. While these studies can only be considered supportive, not definitive, in terms of the risks and benefits of such supplements in dogs and cats, it is useful to consider the voluminous and growing evidence in the human healthcare field. The bottom line is quite simple:

1. In the absence of a documented deficiency, there are very few uses of vitamin and mineral supplements that are supported by good scientific evidence.

2. Most people use supplements for vague reasons having to do with promoting general health or preventing disease. The existing evidence in humans does not suggest that vitamin and mineral supplements are likely to be effective when used in this way.

3. Most people also assume that such supplements are inherently safe. Apart from the obvious problems with supplement regulation, leading to significant mislabeling and risk of contamination, even properly manufactured and labeled vitamin and mineral supplements have real and meaningful risks.

Clearly, there are some appropriate uses for vitamin and mineral supplements in which benefits outweigh risks. And there are certainly research studies that show specific supplements to be safe and apparently effective for particular uses. This bibliography is not a systematic review, nor is it intended to be a comprehensive evaluation of the evidence on this subject. Its purpose is to illustrate the conclusions supported by the balance of the evidence, as outlined above, and to counter the pervasive and mistaken belief that taking vitamin and mineral supplements without a specific, science-based purpose, is useful or without risk.

 

Systematic Reviews, Meta-Analyses, & Evidence-Based Guidelines

Autier P., Boniol M., Pizot C., Mullie P. Vitamin D status and ill health: a systematic review. The Lancet Diabetes & Endocrinology, Early Online Publication, 6 December 2013
doi:10.1016/S2213-8587(13)70165-7

Summary

Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 ?g per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 ?g vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

 

Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004 Oct 2-8;364(9441):1219-28.

Abstract

BACKGROUND:

Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality.

METHODS:

With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs.

FINDINGS:

We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer.

INTERPRETATION:

We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.

 

Lydia A. Bazzano, Kristi Reynolds, Kevin N. Holder, Jiang He. Effect of Folic Acid Supplementation on Risk of Cardiovascular Diseases:  A Meta-analysis of Randomized Controlled Trials. JAMA. 2006;296(22):2720-2726.

Objective To evaluate the effects of folic acid supplementation on risk of cardiovascular diseases and all-cause mortality in randomized controlled trials among persons with preexisting cardiovascular or renal disease.

Data Sources Studies were retrieved by searching MEDLINE (January 1966-July 2006) using the Medical Subject Headings cardiovascular disease, coronary disease, coronary thrombosis, myocardial ischemia, coronary stenosis, coronary restenosis, cerebrovascular accident, randomized controlled trial, clinical trials, homofolic acid, and folic acid, and the text words folic acid and folate. Bibliographies of all retrieved articles were also searched, and experts in the field were contacted.

Study Selection From 165 relevant retrieved reports, 12 randomized controlled trials compared folic acid supplementation with either placebo or usual care for a minimum duration of 6 months and with clinical cardiovascular disease events reported as an end point.

Data Extraction Data on study design, characteristics of participants, changes in homocysteine levels, and cardiovascular disease outcomes were independently abstracted by 2 investigators using a standardized protocol.

Data Synthesis Studies including data from 16 958 participants with preexisting vascular disease were analyzed using a random-effects model. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid supplementation compared with controls were 0.95 (0.88-1.03) for cardiovascular diseases, 1.04 (0.92-1.17) for coronary heart disease, 0.86 (0.71-1.04) for stroke, and 0.96 (0.88-1.04) for all-cause mortality. The relative risk was consistent among participants with preexisting cardiovascular or renal disease.

Conclusions Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease. Several ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question.

Figures in this Article

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide, accounting for 30.9% of global mortality and 10.3% of the global burden of disease. Of all deaths in the United States, 37.3% (910 120, or 1 in every 2.7) are due to CVD. According to the latest estimates, approximately 71.3 million persons in the United States have 1 or more forms of CVD, and the estimated annual direct and indirect cost of caring for these individuals is $403.1 billion. Hence, CVD is the most important clinical and public health challenge in the United States and worldwide.

Quiz Ref IDAs early as 1969, homocysteine was hypothesized to affect atherosclerotic processes. Since that time, substantial evidence has accumulated linking homocysteine in plasma and serum to the risk of CVD. Folate and cyanocobalamin (vitamin B12) are important regulators of the metabolism of homocysteine in the body, and studies have shown an inverse relationship between levels of these factors and levels of homocysteine in the blood. Observational epidemiologic studies have indicated that folate intake is inversely related to the risk of CVD, and randomized controlled trials have documented that dietary supplementation with folic acid reduces blood levels of homocysteine. Recently, several randomized controlled trials have been published evaluating the effects of supplemental folic acid and B vitamins on the risk of CVD; all were conducted among patients with preexisting vascular disease. In addition, several large trials are still under way. In general, these trials have insufficient statistical power on their own and have provided inconsistent findings. We thus performed a meta-analysis of randomized clinical trials to qualify the relationship between folic acid supplementation and risk of CVD and all-cause mortality among persons with preexisting vascular disease.

 

Mark J Bolland, Alison Avenell, John A Baron, Andrew Grey, Graeme S MacLennan, Greg D Gamble, Ian R Reid. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691.

Objective To investigate whether calcium supplements increase the risk of cardiovascular events.

Design Patient level and trial level meta-analyses.

Data sources Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010.

Study selection Eligible studies were randomised, placebo controlled trials of calcium supplements (?500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self reports, hospital admissions, and death certificates.

Results 15 trials were eligible for inclusion, five with patient level data (8151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11?921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02 to 1.67, P=0.035). Non-significant increases occurred in the incidence of stroke (1.20, 0.96 to 1.50, P=0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, P=0.057), and death (1.09, 0.96 to 1.23, P=0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01 to 1.59, P=0.038).

Conclusions Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.

 

Douglas RM, Hemilä H, Chalker E, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000980.

Abstract

BACKGROUND:

The role of vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for 60 years, but is widely sold and used as both a preventive and therapeutic agent.

OBJECTIVES:

To discover whether oral doses of 0.2 g or more daily of vitamin C reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of symptoms.

SEARCH STRATEGY:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006); MEDLINE (1966 to December 2006); and EMBASE (1990 to December 2006).

SELECTION CRITERIA:

Papers were excluded if a dose less than 0.2 g per day of vitamin C was used, or if there was no placebo comparison.

DATA COLLECTION AND ANALYSIS:

Two review authors independently extracted data and assessed trial quality. ‘Incidence’ of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. ‘Duration’ was the mean days of illness of cold episodes.

MAIN RESULTS:

Thirty trial comparisons involving 11,350 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold whilst taking prophylactic vitamin C. The pooled RR was 0.96 (95% confidence intervals (CI) 0.92 to 1.00). A subgroup of six trials involving a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95% CI 0.38 to 0.66). Thirty comparisons involving 9676 respiratory episodes contributed to a meta-analysis on common cold duration during prophylaxis. A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adults and 13.6% (95% CI 5% to 22%) for children. Seven trial comparisons involving 3294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C initiated after the onset of symptoms. No significant differences from placebo were seen. Four trial comparisons involving 2753 respiratory episodes contributed to the meta-analysis of cold severity during therapy and no significant differences from placebo were seen.

AUTHORS’ CONCLUSIONS:

The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence suggests that it could be justified in people exposed to brief periods of severe physical exercise or cold environments.

 

Stephen P. Fortmann, Brittany U. Burda, Caitlyn A. Senger, Jennifer S. Lin, Evelyn P. Whitlock. 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(12):824-834-834.

Purpose: 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.

Data Sources: 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.

Study Selection: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms.

Data Extraction: Dual quality assessments and data abstraction.

Data Synthesis: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. 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 ?-carotene prevented CVD or cancer, and ?-carotene increased lung cancer risk in smokers.

Limitations: 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.

Conclusion: 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.

Primary Funding Source: Agency for Healthcare Research and Quality.

 

Virginia A. Moyer, on behalf of the 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(9):691-696.

Description: New U.S. Preventive Services Task Force (USPSTF) recommendation statement on vitamin D and calcium supplementation to prevent fractures in adults.

Methods: The USPSTF commissioned 2 systematic evidence reviews and a meta-analysis on vitamin D supplementation with or without calcium to assess the effects of supplementation on bone health outcomes in community-dwelling adults, the association of vitamin D and calcium levels with bone health outcomes, and the adverse effects of supplementation.

Population: These recommendations apply to noninstitutionalized or community-dwelling asymptomatic adults without a history of fractures. This recommendation does not apply to the treatment of persons with osteoporosis or vitamin D deficiency.

Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men. (I statement)

The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with greater than 400 IU of vitamin D3 and greater than 1000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (I statement)

The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D3 and 1000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (D recommendation)

 

Schürks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010 Nov 4;341:c5702. doi: 10.1136/bmj.c5702.

Abstract

OBJECTIVE:

To evaluate the effect of vitamin E supplementation on incident total, ischaemic, and haemorrhagic stroke.

DESIGN:

Systematic review and meta-analysis of randomised, placebo controlled trials published until January 2010.

DATA SOURCES:

Electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials) and reference lists of trial reports. Selection criteria Randomised, placebo controlled trials with ?1 year of follow-up investigating the effect of vitamin E on stroke. Review methods and data extraction Two investigators independently assessed eligibility of identified trials. Disagreements were resolved by consensus. Two different investigators independently extracted data. Risk ratios (and 95% confidence intervals) were calculated for each trial based on the number of cases and non-cases randomised to vitamin E or placebo. Pooled effect estimates were then calculated.

RESULTS:

Nine trials investigating the effect of vitamin E on incident stroke were included, totalling 118?765 participants (59?357 randomised to vitamin E and 59?408 to placebo). Among those, seven trials reported data for total stroke and five trials each for haemorrhagic and ischaemic stroke. Vitamin E had no effect on the risk for total stroke (pooled relative risk 0.98 (95% confidence interval 0.91 to 1.05), P=0.53). In contrast, the risk for haemorrhagic stroke was increased (pooled relative risk 1.22 (1.00 to 1.48), P=0.045), while the risk of ischaemic stroke was reduced (pooled relative risk 0.90 (0.82 to 0.99), P=0.02). There was little evidence for heterogeneity among studies. Meta-regression did not identify blinding strategy, vitamin E dose, or morbidity status of participants as sources of heterogeneity. In terms of absolute risk, this translates into one additional haemorrhagic stroke for every 1250 individuals taking vitamin E, in contrast to one ischaemic stroke prevented per 476 individuals taking vitamin E.

CONCLUSION:

In this meta-analysis, vitamin E increased the risk for haemorrhagic stroke by 22% and reduced the risk of ischaemic stroke by 10%. This differential risk pattern is obscured when looking at total stroke. Given the relatively small risk reduction of ischaemic stroke and the generally more severe outcome of haemorrhagic stroke, indiscriminate widespread use of vitamin E should be cautioned against.

 

Tanvetyanon T, Bepler G. Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands. Cancer. 2008 Jul 1;113(1):150-7. doi: 10.1002/cncr.23527.

Abstract

BACKGROUND:

Some studies have suggested that beta-carotene supplementation may increase the risk of lung cancer, particularly among smokers or former smokers. Beta-carotene, a provitamin A, is available in multivitamins. In the current study, the authors investigated the risk of lung cancer associated with beta-carotene in smokers or former smokers and surveyed the beta-carotene content in national brand multivitamins.

METHODS:

The authors systemically reviewed the published literature using a search of the MEDLINE database and performed a meta-analysis of large randomized trials that reported on the effect of beta-carotene supplementation on the incidence of lung cancer among smokers or former smokers. A sample of multivitamins was evaluated for their beta-carotene content and the suggested daily dosage.

RESULTS:

Four studies contributing 109,394 subjects were available for analysis. The average daily beta-carotene dosage in these trials ranged from 20 to 30 mg daily. Among current smokers, beta-carotene supplementation was found to be significantly associated with an increased risk of lung cancer (odds ratio [OR], 1.24; 95% confidence interval [95% CI], 1.10-1.39). Among former smokers, there was no significant increase noted (OR, 1.10; 95% CI, 0.84-1.45). In a sample of 47 common multivitamins, beta-carotene was present in 70% of the identified formulas. The median dosage of beta-carotene was 0.3 mg (range, 0-17.2 mg) daily. The beta-carotene content was found to be significantly higher among multivitamins sold to improve visual health than among other multivitamins, with a median daily dosage of 3 mg (range, 0-24 mg).

CONCLUSIONS:

High-dose beta-carotene supplementation appears to increase the risk of lung cancer among current smokers. Although beta-carotene was prevalent in multivitamins, high-dose beta-carotene was observed among multivitamin formulas sold to promote visual health.

 

Clinical Trials & Narrative Reviews

Bernard F. Cole, PhD; John A. Baron, MD; Robert S. Sandler, MD; Robert W. Haile, DrPh; Dennis J. Ahnen, et al. Folic Acid for the Prevention of Colorectal Adenomas:  A Randomized Clinical Trial. JAMA. 2007;297(21):2351-2359.

Objective To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas.

Design, Setting, and Participants A double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma.

Intervention Participants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later).

Main Outcome Measures The primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (?25% villous features, high-grade dysplasia, size ?1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or ?3 adenomas).

Results  During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation.

Conclusions Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.

 

Ebbing M, Bleie Ø, Ueland PM, Nordrehaug JE, Nilsen DW, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008 Aug 20;300(7):795-804.

OBJECTIVE:

To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis.

DESIGN, SETTING, AND PARTICIPANTS:

Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.

INTERVENTIONS:

Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780).

MAIN OUTCOME MEASURES:

The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.

RESULTS:

Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).

CONCLUSIONS:

This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.

 

Ebbing, MD; Kaare Harald Bønaa, MD, PhD; Ottar Nygård, MD, PhD; Egil Arnesen, MD; Per Magne Ueland, et al. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA. 2009;302(19):2119-2126.

Objective To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.

Design, Setting, and Participants Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.

Interventions Oral treatment with folic acid (0.8 mg/d) plus vitamin B12 (0.4 mg/d) and vitamin B6 (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B12 (0.4 mg/d) (n = 1703); vitamin B6 alone (40 mg/d) (n = 1705); or placebo (n = 1721).

Main Outcome Measures Cancer incidence, cancer mortality, and all-cause mortality.

Results During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B12. Vitamin B6 treatment was not associated with any significant effects.

Conclusion Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.

 

Francine Grodstein, Jacqueline O’Brien, Jae Hee Kang, Rimma Dushkes, Nancy R. Cook, et al. Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial. Ann Intern Med. 2013;159(12):806-814-814.

Objective: To evaluate whether long-term multivitamin supplementation affects cognitive health in later life.

Design: 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.

Patients: 5947 male physicians aged 65 years or older.

Intervention: Daily multivitamin or placebo.

Measurements: 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.

Results: 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]).

Limitation: Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin.

Conclusion: In male physicians aged 65 years or older, long-term use of a daily multivitamin did not provide cognitive benefits.

 

Eric A. Klein, Ian M. Thompson, Catherine M. Tangen, John J. Crowley, M. Scott Lucia, et. al. Vitamin E and the Risk of Prostate Cancer: :  The Selenium and Vitamin E Cancer Prevention Trial (SELECT) JAMA. 2011;306(14):1549-1556

Objective To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.

Design, Setting, and Participants A total of 35 533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34 887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.

Interventions Oral selenium (200 ?g/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-?-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.

Main Outcome Measures Prostate cancer incidence.

Results This report includes 54 464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.

Conclusion Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.

This review included 26 studies (24 randomized, controlled trials and 2 cohort studies) that examined the benefits and harms of using vitamin and mineral supplements for primary prevention of CVD, cancer, or all-cause mortality in healthy individuals without known nutritional deficiencies. We found no consistent evidence that the included supplements affected CVD, cancer, or all-cause mortality in healthy individuals without known nutritional deficiencies. Other systematic reviews have arrived at this same conclusion. The certainty of this result is tempered, however, by the fact that few fair- or good-quality studies are available for all supplements except vitamin E and ?-carotene…

Despite its limitations, the current literature on single or paired vitamins and minerals is sufficient to discourage additional studies of ?-carotene or vitamins A, C, and E in general populations not deficient in the nutrients…
In conclusion, we found no evidence of an effect of nutritional doses on CVD, cancer, or mortality in healthy individuals without known nutritional deficiencies for most supplements we examined. In most cases there are insufficient data to draw any conclusion, although for vitamin E and ?-carotene a lack of benefit is consistent across several trials. We identified 2 multivitamin trials that both found lower overall cancer incidence in men. Both these trials were both methodologically sound, but the lack of an effect for women (albeit in 1 trial), the borderline significance in men in both trials, and the lack of any effect on CVD in either study makes it difficult to conclude that multivitamin supplementation is beneficial

Two good-quality trials of multivitamin supplementation found lower cancer incidence in men. The SU.VI.MAX trial included women and did not find an effect in this subgroup. We found a statistically significant protective effect from multivitamin supplementation when we pooled data for men in these 2 trials. The borderline significance level in both studies and the lack of an effect in women in SU.VI.MAX suggest we should not try to overgeneralize these results.

 

Kuanrong Li, Rudolf Kaaks, Jakob Linseisen, Sabine Rohrmann. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart 2012;98:920-925.

Objective To prospectively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality.

Methods Data from 23?980 Heidelberg cohort participants of the European Prospective Investigation into Cancer and Nutrition study, aged 35–64?years and free of major CVD events at recruitment, were analysed. Multivariate Cox regression models were used to estimate HRs and 95% CIs.

Results After an average follow-up time of 11?years, 354 MI and 260 stroke cases and 267 CVD deaths were documented. Compared with the lowest quartile, the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk, with a HR of 0.69 (95% CI 0.50 to 0.94) and 0.68 (95% CI 0.50 to 0.93), respectively. Associations for stroke risk and CVD mortality were overall null. In comparison with non-users of any supplements, users of calcium supplements had a statistically significantly increased MI risk (HR=1.86; 95% CI 1.17 to 2.96), which was more pronounced for calcium supplement only users (HR=2.39; 95% CI 1.12 to 5.12).

Conclusions Increasing calcium intake from diet might not confer significant cardiovascular benefits, while calcium supplements, which might raise MI risk, should be taken with caution.

 

Gervasio A. Lamas, Robin Boineau, Christine Goertz, Daniel B. Mark, Yves Rosenberg, Mario Stylianou, et al. Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial. Ann Intern Med. 2013;159(12):797-805-805.

Objective: To assess whether oral multivitamins reduce cardiovascular events and are safe.

Design: Double-blind, placebo-controlled, 2 × 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213)

Setting: 134 U.S. and Canadian academic and clinical sites.

Patients: 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 µmol/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.

Measurements: The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina.

Results: 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.

Limitation: There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety).

Conclusion: 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.

 

Scott M. Lippman, Eric A. Klein, Phyllis J. Goodman, M. Scott Lucia, Ian M. Thompson, et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: :  The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009;301(1):39-51.

Objective To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.

Design, Setting, and Participants A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.

Interventions Oral selenium (200 ?g/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-?-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.

Main Outcome Measures Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.

Results As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.

Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.

 

Jaakko Mursu, Kim Robien, Lisa J. Harnack, Kyong Park, David R. Jacobs. Dietary Supplements and Mortality Rate in Older Women:  The Iowa Women’s Health Study. Arch Intern Med. 2011;171(18):1625-1633.

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.

 

Marian L. Neuhouser, Sylvia Wassertheil-Smoller, Cynthia Thomson, Aaron Aragaki, Garnet L. Anderson. Multivitamin Use and Risk of Cancer and Cardiovascular Disease in the Women’s Health Initiative Cohorts. Arch Intern Med. 2009;169(3):294-304.

Background  Millions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease (CVD). Therefore, we decided to examine associations between multivitamin use and risk of cancer, CVD, and mortality in postmenopausal women.

Methods  The study included 161 808 participants from the Women’s Health Initiative clinical trials (N = 68 132 in 3 overlapping trials of hormone therapy, dietary modification, and calcium and vitamin D supplements) or an observational study (N = 93 676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993 and 1998; the women were followed up for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease end points were collected through 2005.We documented cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary, and lung; CVD (myocardial infarction, stroke, and venous thromboembolism); and total mortality.

Results  A total of 41.5% of the participants used multivitamins. After a median of 8.0 years of follow-up in the clinical trial cohort and 7.9 years in the observational study cohort, 9619 cases of breast, colorectal, endometrial, renal, bladder, stomach, lung, or ovarian cancer; 8751 CVD events; and 9865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamin use with risk of cancer (hazard ratio [HR], 0.98, and 95% confidence interval [CI], 0.91-1.05 for breast cancer; HR, 0.99, and 95% CI, 0.88-1.11 for colorectal cancer; HR, 1.05, and 95% CI, 0.90-1.21 for endometrial cancer; HR, 1.0, and 95% CI, 0.88-1.13 for lung cancer; and HR, 1.07, and 95% CI, 0.88-1.29 for ovarian cancer); CVD (HR, 0.96, and 95% CI, 0.89-1.03 for myocardial infarction; HR, 0.99, and 95% CI, 0.91-1.07 for stroke; and HR, 1.05, and 95% CI, 0.85-1.29 for venous thromboembolism); or mortality (HR, 1.02, and 95% CI, 0.97-1.07).

Conclusion  After a median follow-up of 8.0 and 7.9 years in the clinical trial and observational study cohorts, respectively, the Women’s Health Initiative study provided convincing evidence that multivitamin use has little or no influence on the risk of common cancers, CVD, or total mortality in postmenopausal women.

 

Paulson G, et al. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized controlled trial. J Physiol. Published online before print.

Abstract

In this double-blind, randomized, controlled trial we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans.Fifty-four young men and women were randomly allocated to receive either 1000 mg vitamin C and 235 mg vitamin E daily or a placebo for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of 3-4 sessions per week (primarily running), divided into high intensity interval sessions (4-6×4-6 minutes; >90% of maximal heart rate (HRmax)) and steady state continuous sessions (30-60 minutes; 70-90% of HRmax). Maximal oxygen uptake (VO2max), submaximal running, and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. The vitamin C and E group increased their VO2max (8±5%) and performance in the 20 m shuttle test (10±11%) to the same degree                     as the placebo group (8±5% and 14±17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4;+59±97%) and cytosolic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha; +19±51%) increased in m. vastus lateralis in the placebo group, but not in the vitamin C and E group (COX4: -13±54%, PGC-1alpha: -13±29%; p?0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group (p?0.05, compared to the placebo group).  Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2max and running performance. Consequently, vitamin C and               E supplementation hampered cellular adaptions in the exercised muscles, and although this was not translated to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

Saremi A, Arora R. Vitamin E and cardiovascular disease. Am J Ther. 2010 May-Jun;17(3):e56-65. doi: 10.1097/MJT.0b013e31819cdc9a.

Abstract

The objective of this article is to review the role of vitamin E in cardiovascular disease. We begin by describing the general characteristics and metabolism of vitamin E and the pathogenesis of atherosclerosis as it relates to oxidation. We also discuss key in vitro studies, animal studies, observational studies, and clinical trials regarding the potentially cardioprotective effect of vitamin E. Lastly, we outline the current recommendations regarding vitamin E in the prevention and treatment of cardiovascular disease as stated by the American Heart Association. Vitamin E is a fat-soluble antioxidant vitamin and alpha-tocopherol is its most naturally abundant and active form. Oxidation is a key step in atherogenesis. Oxidized low-density lipoprotein stimulates endothelial cells to produce inflammatory markers, is involved in foam cell formation, has cytotoxic effects on endothelial cells, inhibits the motility of tissue macrophages, and inhibits nitric oxide-induced vasodilatation. Vitamin E has been shown to increase oxidative resistance in vitro and prevent atherosclerotic plaque formation in mouse models. Consumption of foods rich in vitamin E has been associated with lower risk of coronary heart disease in middle-aged to older men and women. Clinical studies at large have not demonstrated a benefit of vitamin E in the primary and secondary prevention of cardiovascular disease. Vitamin E supplementation might be associated with an increase in total mortality, heart failure, and hemorrhagic stroke. The American Heart Association does not support the use of vitamin E supplements to prevent cardiovascular disease, but does recommend the consumption of foods abundant in antioxidant vitamins and other nutrients.

 

Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2008 Nov 12;300(18):2123-33.

OBJECTIVE:

To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men.

DESIGN, SETTING, AND PARTICIPANTS:

The Physicians’ Health Study II was a randomized, double-blind, placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31, 2007. There were 14,641 US male physicians enrolled, who were initially aged 50 years or older, including 754 men (5.1%) with prevalent cardiovascular disease at randomization.

INTERVENTION:

Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.

MAIN OUTCOME MEASURES:

A composite end point of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular disease death).

RESULTS:

During a mean follow-up of 8 years, there were 1245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1000 person-years; hazard ratio [HR], 1.01 [95% confidence interval {CI}, 0.90-1.13]; P = .86), as well as total myocardial infarction (HR, 0.90 [95% CI, 0.75-1.07]; P = .22), total stroke (HR, 1.07 [95% CI, 0.89-1.29]; P = .45), and cardiovascular mortality (HR, 1.07 [95% CI, 0.90-1.28]; P = .43). There also was no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person-years, respectively; HR, 0.99 [95% CI, 0.89-1.11]; P = .91), as well as total myocardial infarction (HR, 1.04 [95% CI, 0.87-1.24]; P = .65), total stroke (HR, 0.89 [95% CI, 0.74-1.07]; P = .21), and cardiovascular mortality (HR, 1.02 [95% CI, 0.85-1.21]; P = .86). Neither vitamin E (HR, 1.07 [95% CI, 0.97-1.18]; P = .15) nor vitamin C (HR, 1.07 [95% CI, 0.97-1.18]; P = .16) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74 [95% CI, 1.04-2.91]; P = .04).

CONCLUSIONS:

In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men.

 

Rachael Z Stolzenberg-Solomon, Shih-Chen Chang, Michael F Leitzmann, Karen A Johnson, Christine Johnson, et al. Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr April 2006 vol. 83 no. 4 895-904

Objective: We investigated the association between dietary folate, alcohol consumption, and postmenopausal breast cancer in women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort.

Design: Dietary data were collected at study enrollment between 1993 and 2001. Folate content was assigned on the basis of prefortification (ie, pre-1998) databases. Of the 25 400 women participants with a baseline age of 55–74 y and with complete dietary and multivitamin information, 691 developed breast cancer between September 1993 and May 2003. We used Cox proportional hazard models with age as the underlying time metric to generate hazard ratios (HRs) and 95% CIs.

Results: The adjusted HRs were 1.19 (95% CI: 1.01, 1.41; P for trend = 0.04) for women reporting supplemental folic acid intake ?400 ?g/d compared with subjects reporting no supplemental intake. Comparison of the highest with the lowest quintile gave adjusted HRs of 1.04 (95% CI: 0.83, 1.31; P for trend = 0.56) and 1.32 (95% CI: 1.04, 1.68; P for trend = 0.03) for food and total folate intake, respectively. Alcohol consumption was positively associated with breast cancer risk (highest compared with lowest quintile: HR = 1.37; 95% CI: 1.08, 1.76; P for trend = 0.02); the risk was greatest in women with lower total folate intake.

Conclusions: Our results do not support the hypothesis that high folate intake reduces breast cancer risk; instead, they suggest that a high intake, generally attributable to supplemental folic acid, may increase the risk in postmenopausal women. However, our results confirm previous studies showing positive associations between moderate alcohol consumption and breast cancer.

 

Thomas LK, Elinder C, Tiselius H, Wolk A, Åkesson A. Ascorbic Acid Supplements and Kidney Stone Incidence Among Men: A Prospective Study. JAMA Intern Med. 2013;():1-2. doi:10.1001/jamainternmed.2013.2296.

During 11 years of follow-up we ascertained 436 first incident cases of kidney stones. Ascorbic acid use was associated with a statistically significant 2-fold increased risk…Currently there are no well-documented benefits of high-dose ascorbic acid supplement use,7 and, therefore, it seems prudent to advise that high-dose preparations be avoided, particularly by those with a history of kidney stones.

 

Qian Xiao, Rachel A. Murphy, Denise K. Houston, Tamara B. Harris, Wong-Ho Chow, Yikyung Park. Dietary and Supplemental Calcium Intake and Cardiovascular Disease Mortality:  The National Institutes of Health–AARP Diet and Health Study. JAMA Intern Med. 2013;173(8):639-646.

Objective To investigate whether intake of dietary and supplemental calcium is associated with mortality from total cardiovascular disease (CVD), heart disease, and cerebrovascular diseases.

Design and Setting Prospective study from 1995 through 1996 in California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania and the 2 metropolitan areas of Atlanta, Georgia, and Detroit, Michigan.

Participants A total of 388 229 men and women aged 50 to 71 years from the National Institutes of Health–AARP Diet and Health Study.

Main Outcome Measures Dietary and supplemental calcium intake was assessed at baseline (1995-1996). Supplemental calcium intake included calcium from multivitamins and individual calcium supplements. Cardiovascular disease deaths were ascertained using the National Death Index. Multivariate Cox proportional hazards regression models adjusted for demographic, lifestyle, and dietary variables were used to estimate relative risks (RRs) and 95% CIs.

Results During a mean of 12 years of follow-up, 7904 and 3874 CVD deaths in men and women, respectively, were identified. Supplements containing calcium were used by 51% of men and 70% of women. In men, supplemental calcium intake was associated with an elevated risk of CVD death (RR>1000 vs 0 mg/d, 1.20; 95% CI, 1.05-1.36), more specifically with heart disease death (RR, 1.19; 95% CI, 1.03-1.37) but not significantly with cerebrovascular disease death (RR, 1.14; 95% CI, 0.81-1.61). In women, supplemental calcium intake was not associated with CVD death (RR, 1.06; 95% CI, 0.96-1.18), heart disease death (1.05; 0.93-1.18), or cerebrovascular disease death (1.08; 0.87-1.33). Dietary calcium intake was unrelated to CVD death in either men or women.

Conclusions and Relevance Our findings suggest that high intake of supplemental calcium is associated with an excess risk of CVD death in men but not in women. Additional studies are needed to investigate the effect of supplemental calcium use beyond bone health.

 

Expert Opinion & Surveys

Bailey R.L.  Why US Adults Use Dietary Supplements. JAMA Intern Med. 2013;173(5):355-361.

Background Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data. The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements.

Methods Data from adults (?20 years; n = 11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey.

Results The most commonly reported reasons for using supplements were to “improve” (45%) or “maintain” (33%) overall health. Women used calcium products for “bone health” (36%), whereas men were more likely to report supplement use for “heart health or to lower cholesterol” (18%). Older adults (?60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health. Only 23% of products were used based on recommendations of a health care provider. Multivitamin-mineral products were the most frequently reported type of supplement taken, followed by calcium and ?-3 or fish oil supplements. Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers.

Conclusions Supplement users reported motivations related to overall health more commonly than for supplementing nutrients from food intakes. Use of supplements was related to more favorable health and lifestyle choices. Less than a quarter of supplements used by adults were recommended by a physician or health care provider.

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Figures in this Article

Dietary supplement use among adults has increased over the past 30 years in the United States, and currently about half of adults report using 1 or more dietary supplements. Many characteristics of people who choose supplements are known: users tend to be older, have a lower body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), are more physically active, are less likely to smoke, and have higher educational attainment and socioeconomic status compared with nonusers. However, the actual motivations for use, that is, the reasons that people take dietary supplements remain unclear. The National Health and Nutrition Examination Survey (NHANES) began querying motivations for use of dietary supplements for the first time in 2007. The purpose of this analysis was to examine motivations for use of dietary supplements by adults as well as to characterize the types of products that were used and the most common motivations for using them in the 2007-2010 NHANES.

 

Blendon R.J. (2013). Users’ Views of Dietary Supplements. JAMA Internal Medicine, 173 (1) 74.

Our findings indicate that nearly 4 in 10 of the general population are taking dietary supplements, and the reasons for such use are varied, with the most common being general improvements in health and well-being, such as to feel better, to improve overall energy levels, and to boost immune systems. Practicing physicians should be aware that substantial numbers of persons take supplements to treat potentially serious health conditions, and many of them may not share this information with their physicians.

Many of the most commonly stated reasons for use have little connection to specific, measurable health goals and are more likely to be driven by individual perceptions of efficacy than by external scientific statements as to efficacy. As a result, many supplement users are unlikely to change behavior in response to statements from public health authorities about studies showing the ineffectiveness of particular supplements.

 

Carvey C.E., Farina E.K. & Lieberman H.R. (2012). Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel. BMC Complementary and Alternative Medicine, 12 (1) 182.

Background

United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers’ confidence in the efficacy and safety of DS, and assessed Soldiers’ knowledge of federal DS regulatory requirements.

Methods

Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use.

Results

A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS.

Conclusions

Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers’ misperceptions about federal DS safety and efficacy regulations is warranted.

 

Eliseo Guallar, Saverio Stranges, Cynthia Mulrow, Lawrence J. Appel, and Edgar R. Miller III. Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements. Ann Intern Med. 2013;159(12):850-851-851.

The large body of accumulated evidence has important public health and clinical implications. Evidence is suf?cient to advise against routine supplementation, and we should translate null and negative ?ndings into action. The message is simple: Most supplements do not prevent chronic disease or death, their use is not justi?ed, and they should be avoided. This message is especially true for the general population with no clear evidence of micronutrient de?ciencies, who represent most supplement users in the United States and in other countries.

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. Although available evidence does not rule out small benefits 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.

 

Moyer, M.W. The Myth of antioxidants: The hallowed notion that oxidative damage causes aging and that vitamins might preserve our youth is now in doubt. Scientific American. February, 2013. 64-67.

If free radicals are not always bad, then their antidotes, antioxidants, may not al­ways be good—a worrisome possibility given that 52 percent of Americans take considerable doses of antioxidants daily, such as vitamin E and beta-carotene, in the form of multivitamin supplements. In 2007 the Journal of the American Medical Association published a systematic review of 68 clinical trials, which concluded that antioxidant supplements do not reduce risk of death. When the authors limited their review to the trials that were least likely to be affected by bias—those in which assignment of participants to their research arms was clearly random and neither investigators nor participants knew who was getting what pill, for in­stance—they found that certain antioxi­dants were linked to an increased risk of death, in some cases by up to 16 percent.

Several U.S. organizations, including the American Heart Association and the American Diabetes Association, now ad­vise that people should not take antioxi­dant supplements except to treat a diag­nosed vitamin deficiency. “The literature is providing growing evidence that these supplements—in particular, at high dos­es—do not necessarily have the beneficial effects that they have been thought to,” says Demetrius Albanes, a senior investi­gator at the Nutritional Epidemiology Branch of the National Cancer Institute. Instead, he says, “we’ve become acutely aware of potential downsides.”

 

It is hard to imagine, however, that an­tioxidants will ever fall out of favor com­pletely—or that most researchers who study aging will become truly comfort­able with the idea of beneficial free radi­cals without a lot more proof. Yet slowly, it seems, the evidence is beginning to sug­gest that aging is far more intricate and complex than Harman imagined it to be nearly 60 years ago. Gems, for one, be­lieves the evidence points to a new theory in which aging stems from the overactivi­ty of certain biological processes involved in growth and reproduction. But no mat­ter what idea (or ideas) scientists settle on, moving forward, “the constant drill­ing away of scientists at the facts is shift­ing the field into a slightly stranger, but a bit more real, place,” Gems says. “It’s an amazing breath of fresh air.”

SkeptVet Posts

More Evidence Antioxidants May Increase Cancer Risk

Evidence Update-Importance of Vitamin D Supplementation Revealed

Intravenous Vitamin C for Cancer Treatment in Pets

The Myth of Antioxidants?

Vitamin Supplements- Do they prevent cancer?

Posts from Other Blogs

The Routine Use of Multivitamins-What Does the Evidence Say?– December 28, 2013

Three new papers published in the Annals of Internal Medicine add to an accumulated body of research that has studied the health effects of routine vitamin and mineral supplements in healthy populations. The best available evidence gives us good, reliable information to conclude that multivitamins do not offer meaningful health benefits to the generally healthy consumer.  It’s time to bring an end to the era of indiscriminate multivitamin use.

Do Vitamins Prevent Cancer & Heart Disease?– November 21, 2013

Without demonstrated benefit, there’s currently no clear rationale to justify multivitamin supplements or individual vitamins to prevent cardiovascular disease or cancer. Taking vitamins for “insurance” doesn’t appear to be harmful, but the evidence isn’t conclusive. It’s concerning that the two individual supplements for which we do have good evidence also have the least attractive risk/benefit profiles. While the risk of harms do seem low, (especially if you avoid vitamin E and beta-carotene), there’s also no evidence supplementation offers any upside. I’m a believer in the hypothesis that supplement consumption may actually worsen dietary intake, so my advice remains unchanged: If you believe your diet is unhealthy or insufficient to meet your nutritional requirements, then change your diet instead of adding supplements. Supplements should be reserved for when there’s an actual dietary deficiency or medical need that cannot be met through diet. You won’t see this message advertised anytime soon by the supplement industry.

A Closer Look at Vitamin Injections– May 24, 2013

With so many purveyors of vitamin infusions, one would hope the practice was grounded in good science. But it isn’t, and that shouldn’t be a surprise. Despite the lack of good evidence, there is a near-obsessive devotion to touting the benefits of intravenous vitamins while railing against the mysterious entities which are blocking The Truth. But the reality is more mundane. In the absence of a deficiency, vitamin infusions don’t do much of anything. To the worried well, intravenous vitamins are going to be a harmless panacea that just succeed in enriching the revenues of the purveyor. Just as That Mitchell and Web Look said of the homeopath, “Bottle of basically just water in one hand, and a huge invoice in the other.” So if you value health theater over health care, and don’t mind paying mightily for the illusion, vitamin infusions may be your thing.

I have a much different opinion when these products are promoted to patients fighting for their lives, particularly with illnesses like cancer. There is good evidence to show that delaying treatment or substituting CAM for established cancer treatments dramatically worsens outcomes. Touting unproven treatments and then profiting from their administration is appallingly opportunistic. Real diseases require real treatments, not fake ones. They may look sciencey, but the reality is that intravenous vitamin injections are modern-day snake oil.

Calcium Supplements and Heart Attacks- More Data, More Questions– February 28, 2013

Assuming benefit from a drug or supplement, in the absence of confirming evidence, can lead to bad health care decision-making. Yet we do this all the time, particularly with supplements that are generally believed to be safe and effective. These studies show that supplements can indeed be rigorously studied, and that surprising findings can emerge. Not only have calcium supplements been closely scrutinized for therapeutic use in dozens of prospective clinical trials, the evidence suggests that use in the absence of deficiency is at best, probably useless, and at worst, substantially elevating the risk of heart attacks and cardiovascular death. Without any clearly established benefits for most people, but exhibiting worrying signs of harms, it’s time to take the health halo off calcium supplements.

There’s Little Evidence Supplements are Beneficial: So Why do We Take Them?– February 15, 2013

Survey on supplement consumption report widespread use, which seems to be based on perceptions that these products are both safe and effective. While supplement use of all kinds is common, it’s multivitamin/minerals that really push the overall consumption rates up. Take that away, and regular usage of other kinds of supplements drops down to just over 10% of the population. When looked at over longer time frames, however, the Harvard survey suggests that 40% do take some form of non-vitamin supplement at least intermittently.

The reasons for taking supplements varies. In the case of multivitamins, it seems to be based around the belief that their consumption will offer meaningful benefits. Yet on balance, there is little evidence to support general supplementation, and in the absence of a deficiency, no evidence multivitamins will boost mood or energy levels. For the most common reasons cited for supplements, expectations are generalized and fairly non-specific. Many may be taking multivitamins as an insurance policy — not a strategy that I’d routinely endorse, given the evidence, but one that is not uncommon.

Iron Supplements for Fatigue-September 27, 2012

Fatigue can be caused by an array of conditions. Iron deficiency is a common cause, though whether iron supplements offer benefit in the absence of anemia remains to be established. Children and women, particularly pregnant women, need adequate iron in their diet. While low-dose supplements are considered safe and may be helpful in meeting daily requirements, specific supplementation isn’t necessary or advisable in the absence of a clear deficiency. And just because it’s a supplement doesn’t mean it can’t be harmful. Iron supplements can be toxic in children, and should be stored like any other potential poison.

Vitamin B12: The Energy Panacea? December 8, 2011

While there is an important role for supplementing with vitamin B12 in some groups, high dose supplements to treat fatigue should be guided by a medical evaluation. For the energy seekers, supplementation in the absence of deficiency offers no benefits. Even in the deficient, B12 supplements won’t offer any sudden “boost” of energy:  replacement and recovery takes time. Anyone concerned about their B12 intake should ensure they’re looking to dietary sources first. And for vegetarians and other at-risk groups, supplementing with B12 may be appropriate and science-based.

Antioxidants and Exercise: More Harm Than Good– November 24, 2011

Simple solutions can be the wrong ones. Surrogate endpoints, like those that measure oxidative stress, can’t be extrapolated to infer positive health effects in the absence of confirmatory data.   Like other areas of CAM, our ability to draw conclusions is limited by a lack of good data. The evidence is inconsistent and generally unimpressive when it comes to the effects of antioxidant supplements on exercise. So we’re challenged to make decisions based on incomplete information. In light of what we know about antioxidants and exercise, the trend in the data is strongly suggestive of zero benefit, at best, with the real possibility that there may be negative consequences to supplementation. Overlay the epidemiologic evidence that looks at mortality, cancer, and other outcomes, and the attractiveness of antioxidant supplements drops even further. The best advice for those that exercise seems to be to focus on consuming a diet rich in fruits and vegetables, and leaving the antioxidant bottles on the shelf. There appears to be little that is complementary about them.

Vitamins and Mortality– October 12, 2011

As is typical of observational studies, the results are somewhat mixed, depending upon the details of how such studies are conducted. There are also many variables to consider – which vitamins and which doses in which populations with what health conditions. There is therefore a great deal of noise in the data. I do not think we can conclude that the vitamins listed above actually increase risk of mortality. But neither can we conclude that there is any health benefit for routine supplementation. Years of research have failed to provide such evidence, and the mixed results we are seeing is consistent with there being no or only a small effect.

Based upon the totality of evidence the best current recommendation is to have a well-rounded diet with sufficient fruits and vegetables, which should be able to provide most people with all the micronutrients they require. There is no evidence to support routine supplementation. There is also reason to avoid taking megadoses of vitamins, as this can cause toxicity, and even short of toxicity the evidence becomes more compelling at higher doses of the risks of supplementation.

But there are also many situations in which targeted supplementation is evidence-based and appropriate. There is increasing evidence to support the use of vitamin D supplementation for many populations. Many elderly have borderline or  low B12 levels, which correlates with dementia. Pregnant women should take prenanatal vitamins. (To give just a few examples.)

Vitamins are just like any other health care intervention – they have potential risks and benefits and it is best to follow the evidence. For most people the best advice is to ask your primary health care provider which supplements, if any, you should take. Recommendations should be based upon specific health conditions and blood tests to measure levels of vitamins, so that specific deficiencies can be appropriately targeted.

Autism and Prenatal Vitamins– June 14, 2011

In their summary, the authors say: “Our data suggest that supplementation with prenatal vitamins before pregnancy and during the first month of pregnancy might protect against autism, particularly in genetically susceptible individuals. Additionally, COMT genotype may contribute to an elevated risk for autism, especially in offspring of unsupplemented mothers. This evidence for gene-by- environment interaction effects in autism etiology could help explain variations in previous findings across genetic studies. Whether similar interactions exist for susceptibility genes in other pathways, particularly those epigenetically regulated through methylation, remains to be explored. More research is warranted to replicate the findings, explicate potential mechanisms, and explore interactions with other autism candidate genes.”

This is fascinating stuff. It confirms that certain genotypes are associated with autism and that environmental factors can interact with genetics to increase risk…We should never blindly accept the results of a first study. These findings will have to be confirmed by other studies. Meanwhile, should we take action? We already recommend folic acid supplements for women who might become pregnant, and we recommend prenatal vitamins during pregnancy. I can’t see any downside to recommending prenatal vitamins in the pre-conception period for any woman who is likely to become pregnant.

The Benefits and Risks of Folic Acid Supplementation– March 31, 2011

Folic acid reduces neural tube defects but may incr risk of some cancers and seems ineffective, at least, is ineffective at preventing them. Natural dietary intake seems safer than supplementation.

In women of childbearing age, folic acid supplementation has a demonstrable and meaningful benefit, reducing the incidence of NTDs. Its use in this population is evidence-based and demonstrably effective. And for treatments for conditions like end-stage kidney disease, folic acid may be of benefit. But when we look at the use of folic acid for primary prevention, the data are less clear. In children, men, and women beyond their childbearing years, supplementation in the absence of deficiency has no demonstrated health benefits, and there are worrying signals that it may raise cancer risks, possibly by “feeding” existing cancers.

Vitamin E and Stroke– November 10, 2010

The research on vitamins in general and vitamin E in particular is messy and complicated. My overall impression of this research is that there is no consistent signal of net benefit for routine supplementation. There are many specific conditions in which specific supplementation is of benefit, but not routine supplementation for general health.

At the same time there is a consistent signal of benefit to having a healthful diet, the primary feature of which is to have a diet rich in fruits and vegetables. So in the end, after decades of research, what your mother always told you turns out to be the best advice – eat your vegetables.

Antioxidant Supplements for Macular Degeneration– August 24, 2010

Should everyone with moderately severe AMD be taking antioxidant supplements?  I’m not sure. Since there is little else to try, if I had advanced AMD I might be tempted. But I think caution is warranted due to the following red flags:

  • Evidence boils down to one study funded by      manufacturer.
  • Not replicated.
  • Concerns about harmful side effects; no long-term      safety data.
  • Modest effect.
  • No clear rationale for the particular combination and      dosage of ingredients.
  • Hype by the manufacturer.

Another Negative Study of Vitamins– February 11, 2009

There is a clear trend in the evidence we have to date. The benefits of routine supplementation are unproven. High doses of vitamins probably cause more harm than good. If you are concerned about your nutrition then improve your diet.

Further, as with good science-based medicine in general, questions must be specific. We should not ask – do vitamins work. Rather we need to consider specific supplementation in specific situations and conditions.

What may surprise members of the public who have been exposed for years to the propaganda of a supplement industry eager to take their money, or CAM proponents eager to appear legitimate – is that vitamins have always been part of mainstream science-based medicine. There is a tremendous amount of quality research to inform our conclusions about vitamins, and they are part of everyday practice.

Vitamin Cocktail with a Meme Twist (Supplement my gimlet with a dash of dissonance)– November 13, 2008

A trail of recent reports is trying to tell us something. But are we listening, and are “they” listening? If so, does it mean the same to “them” as it does to us?

The report trail is telling us that multiple vitamins fail as preventatives against cardiovascular disease, cancer, or even for anything other than for dietary vitamin deficiency. And that is what we were saying in the first place – forty and more years ago.

These reports…dovetail on more reported over the past decade…A popular Web portal posted a brief questionnaire following one of last week’s reports. It asked readers to answer if they took vitamins regularly, infrequently, or not at all.

The answers to this simple exercise indicate for a large percentage of responders, at least lack of surprise at the negative report on vitamins for disease prevention, and imply prior knowledge of ineffectiveness. Yet a large majority of responders still take vitamins regularly or occasionally, and must have known the vitamins were ineffective.

There are lessons here on human nature, and implications for making of public policy about quackery. The human part is our old friend and nemesis, cognitive dissonance, “don’t bother me with the facts.” Despite having the knowledge of ineffectiveness, people still have a drive to take supplements or get something psychologically out of taking them

 

High Dose Vitamin C and Cancer: Has Linus Pauling Been Vindicated– August 18, 2008

Do these two studies released in the last month vindicate Linus Pauling and all the alternative practitioners of high dose vitamin C therapy for malignancy? Again, it depends on what you mean by “vindicate,” but my answer is nonetheless: Not really, except perhaps in the weakest of ways… The bottom line from my perspective: Yes, vitamin C probably has some antitumor activity for some tumors, but as I contemplate the evidence for this effect the word “underwhelming” comes to mind… If high dose intravenous ascorbate has antitumor activity in humans, that activity is almost certainly quite modest at best, and to achieve even such modest antitumor activity definitely requires incredibly high doses of ascorbate. Once again, I point out that any other experimental drug requiring such high plasma concentrations and high doses to achieve such a modest antitumor effect would probably garner very little interest from anyone, even if it were a potentially patentable product of big pharma. It’s possible that high dose IV ascorbate might ultimately find its way into the armamentarium of science-based oncology, but it’s very unlikely ever to become a mainstay of treatment for any malignancy. It’s just too wimpy.

Should I take a Multivitamin? July 15, 2008

Lots of people believe that vitamin supplements make a difference in our health and give us energy. Lots of people think taking vitamins will make you live longer. Different people believe many things; the real question is whether there is any evidence to support their beliefs.

You can find all sorts of studies and speculations suggesting that various supplements are good for you, but when you stick to rigorous science, the evidence just isn’t there. There are two philosophies: to take everything that is suggested just in case, or to wait for scientific validation before taking anything. Based on long experience, I consider the latter course more reasonable. I can’t begin to tell you how many times I’ve heard strong recommendations for something that was later shown to be useless or harmful…. More and more studies are showing that while vitamins in food are good for you, extra vitamins in pill form may not be so good.

There are many other things we can do to “improve our health” that don’t involve taking pills, vitamins or any other supplements. Eating a healthy diet, exercising, getting enough sleep, reducing stress, and maintaining ideal weight top my list.

Critics of medicine often pick on Big Pharma for its profit motives. How much money do you think Big Vitamin makes? How much money is being spent on unnecessary vitamins that provide no real benefit? Any excess is promptly eliminated. Are we just producing expensive urine? Are our toilets getting the benefit? Are all those vitamins in our sewage good for the environment?

One could argue that multivitamins are good for healthy sewage bacteria and healthy profits for manufacturers. But I’d rather support my own health than theirs.

Antioxidant Hype and Reality– February 6, 2008

Oxidative stress and the effects of antioxidants are an important and interesting aspect of human physiology. We have already learned a great deal, but it seems like just enough to understand that we still have a great deal more to learn. It is clearly playing some role in aging and many diseases, but likely a more complex one than we initially assumed. Antioxidants may one day play an important role in the treatment of certain diseases or in routine health maintenance, but so far there is insufficient evidence to make any confident predictions or to make specific recommendations.

However, when it comes to the marketing hype for antioxidant products I can make a clear recommendation – healthy skepticism.

Posts Updating this Topic

Latest Review of Evidence for Vitamin D & Calcium Supplements

 

 

 

 

 

 

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9 Responses to Evidence Concerning Vitamin and Mineral Supplements- Safety and Efficacy

  1. v.t. says:

    Wow, skeptvet, excellent read, perfect to start off the new year!

  2. Pingback: Dangers of over-supplementing with vitamins etc - Poodle Forum - Standard Poodle, Toy Poodle, Miniature Poodle Forum ALL Poodle owners too!

  3. Dr Amy (veterinarian PA) says:

    I agree with a lot of what is in this post, AND that is why I advocate whole food supplementation only. I am also a skeptic of many things–but I also question some of the “accepted established” veterinary norms when it comes to “complete” nutrition. Therefore: one thing I have lately questioned is why we so easily accept that a dog food, even using NRC has “everything” a dog needs, how can we be so egotistical, even as a nutritionist, to thick we “know all there is to know” about pet nutrition. I do NOT take comfort in AAFCO feeding trials–I don’t think they are statistically sound and I don’t think they examine sufficient parameters . But do we truly know that foods developed to meet requirements to meet AAFCO labeling are going to cause our pets to thrive? I don’t think we do. And using the above thread on Vit/Min supplements: essentially, kibble is taking whole foods and ADDING vitamin and mineral supplements and then cooking them together. If the studies above bring question as to whether or not vitamin/mineral supplements are a good idea, might we want to re-examine our belief that adding vitamin mineral supplements in synthetic isolated forms is “good” for dogs? I am not questioning the intention of AAFCO/NRC and yes we need to start somewhere, but in order to meet NRC, a company adds synthetic vitamin/mineral premixes…maybe we need to start examining what this means to a pet exposed over time to high levels of supplements that are not found in nature. If studies above show supplements may cause harm in us, what are supplements put into food and fed day after day doing to our dogs/cats? Just a thought…I think we NEED to think about the commonly accepted beliefs in veterinary nutrition a little harder. We would not advocate people eating preformed precooked food daily with never eating anything fresh. Evidence is starting to indicate people may do more harm then good in over supplementing themselves. Are we harming our pets with over supplementation??
    Just “food for thought” . I think we need to be more skeptical about calling a processed food “complete”. Dr Amy

  4. skeptvet says:

    I absolutely agree. The established nutrient levels are only well-demonstrated to prevent gross deficiency diseases, and they are not intended to be optimal levels. I don’t think we know what optimal nutrition is for cats or dogs, only what is adequate nutrition. Clearly, commercial diets have reached a point where one can feed them and have a reasonable expectation of a long and healthy life, but that isn’t to suggest there are no deficiencies or excesses in any given diet, or that there isn’t a better way to approach pet nutrition. I don’t think even nutritionists working in the pet food industry would say that their product are optimal or perfect.

    There is, of course a difference between supplementing a diet to a precise level calculated to avoid nutritional deficiencies and adding inconsistent and ill-defined additional supplements, so I’m not sure the issue is that vitamin supplemetns themselves are dangerous, added to foods or taken seperately, but that the notion that “more is better” and that additional supplementation beyond the level needed to avoid known deficiencies is safe and beneficial. The evidence is growing in humans, at least, that this is untrue. Not much veterinary data, unfortunately. If a diet is supplemented well in excess of levels known to be needed to avoid deficiency, you are right in thinking this seems likely to be as harmful as supplements taken seperately from the diet.

    The main problem as I see it is that the alternatives to the imperfect system for developing commercials diets now are almost entirely based on dubious theories, extrapolation from humans, or “common sense” with little data to support them. Even when I agree with the critiques of commercial diets by, say, raw diet proponents, I have to point out there is even less reason to believe the alternative they are proposing is superior. And the evidence that current commercial diets are filled with “toxins” or are a major cause of disease is also non-existent. So we just need to be careful in working to remedy the deficiencies or current practices not to lurch irrationally towards alternatives even less rooted in good evidence.

  5. Pingback: Ocu-Glo Rx: A Nutritional Supplement Marketed to Support Eye Health and Vision | The SkeptVet

  6. Pingback: Latest Review of Evidence for Vitamin D & Calcium Supplements | The SkeptVet

  7. skepdog says:

    I was told by a vet that lysine suppresses the immune system and impairs cell growth. All I can find are studies on antigen presentation and treatment of tumours. People keep giving lysine to their cats even if there seems to be no proof in vivo that it’s effective against FHV, do you have any information on this?

  8. skepdog says:

    I’ve just found your post on lysine, but I’m still curious to know about any proven harmful effects of lysine. I suspect that people might see an improvement because lysine is an anxiolytic, and nothing else.

  9. skeptvet says:

    Though the evidence concerning efficacy is mixed and generally seems to trend towards the conclusion it does not have a meaningful benefit, there is no evidence I am aware of suggesting any significant harm.

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