02 Mar 2007
-
On the 28 February 2007, five newspapers (1-6) reported that vitamin supplements can increase risk of death. All five newspapers reported that beta carotene, vitamin A, and vitamin E appear to increase the risk of death but reported no effect of vitamin C and selenium. Two newspapers (3, 6) reported that two thirds of the included participants were chronically ill.
-
The newspaper reports were based on a well-conducted systematic review (7) of 68 trials, collectively involving 232,606 adults from primary and secondary prevention trials comparing antioxidant supplementation (beta carotene, vitamin A, vitamin C, vitamin E or selenium) with placebo or no intervention. The authors concluded that there is no evidence that antioxidant supplements have beneficial effects on mortality, and state that beta carotene, vitamin A, and vitamin E appear to increase the risk of death. They added that further trials are needed to establish the effects of vitamin C and selenium.
-
The newspaper reports accurately described key details of the review. This was a generally well conducted review but some of its conclusions may be overstated.
Evaluation of the evidence base for the effect of antioxidant supplements on mortality in primary and secondary prevention.
Where does the evidence come from?
The evidence comes from research led by Dr Goran Bjelakovic, University of Nis, Department of Internal Medicine, Nis, Serbia. This Cochrane review was supported by The Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark. The funding source had no role in the conduct of the study, collection of data, or preparation of the manuscript.
What were the authors' objectives?
The objective was to investigate the effect of antioxidant supplements on mortality in randomised primary and secondary prevention trials.
What was the nature of the evidence?
The study was a systematic review, which included 68 randomised controlled trial (RCTs), involving 232,606 adults from primary and secondary prevention trials. Trials including general or healthy groups of adults were classified as primary prevention, and trials including individuals with a specific disease were classified as secondary prevention. Tertiary prevention trials were excluded from the review. Where reported, the mean age of included participants ranged from 47 to 84 years. The authors searched four electronic databases, and the reference lists of relevant articles for published studies. Each stage of the review, study selection, data extraction and quality assessment, was carried out in duplicate to reduce the risk of errors and bias.
What interventions were examined in the research?
RCTs that compared beta carotene, vitamin A, vitamin C, vitamin E or selenium with placebo or no intervention were included. The primary outcome measure was all-cause mortality at maximum follow-up. Studies were combined using a random effects meta-analysis. Differences between studies that could have influenced the findings were investigated. Results were presented as relative risks for all mortality. Analyses to determine how sensitive results are to changes in how the study was conducted were carried out, looking at trial quality (low or high risk of bias) and method of administration (singly or in combination).
What were the findings?
The authors classify 47 of the 68 included studies as having high methodological quality; for example, allocating participants randomly to the different treatment groups, using an approach that does not allow one to predict to which treatment group a participant will be allocated.
No statistically significant difference was found in risk of mortality between all supplements versus placebo or no intervention. When only trials with a low risk of bias were considered, a statistically significant increased risk of mortality (5%) was found for antioxidant supplements compared to placebo or no intervention.
A statistically significant increase in risk of mortality was found in those taking beta carotone (7%), vitamin A (16%), and vitamin E (4%) supplements (either singly or in combination) compared to placebo or no intervention after exclusion of high bias trials and selenium trials. Selenium supplementation was found to reduce the risk of mortality by 10% although this was not statistically significant after excluding trials with a high risk of bias. No statistically significant difference in the risk of mortality was shown between those taking vitamin C supplements and placebo or no intervention.
What were the authors' conclusions?
The authors concluded that there is no evidence that antioxidant supplements have beneficial effects on mortality. They also state that beta carotene, vitamin A, and vitamin E appear to increase the risk of death, but that further RCTs are needed to establish the effects of vitamin C and selenium.
How reliable are the conclusions?
The authors searched several relevant sources without language restrictions, so they are likely to have found most or all of the relevant research studies. Study selection, quality assessment and data extraction were carried out in duplicate, reducing the risk of error and bias. Trials included varied populations (general population, patients with gastrointestinal, cardiovascular, neurological, skin, ocular, renal and rheumatoid diseases), and compared antioxidants with different properties, at different doses and duration, singly or in combination with different additional supplements, and the results should be interpreted in light of these variations. Differences between the studies, particularly in terms of trial quality, were assessed. It might have been useful to separate healthy populations from disease specific populations. In addition, all cause mortality was not a primary outcome for a number of the included trials. The authors also state that many of the included trials investigated the effects of supplements administered at higher doses than those found in a balanced diet and some trials used doses well above recommended daily allowances, as such generalisability to recommended levels might be difficult.
The authors also add that the trials assessed the influence of synthetic antioxidants and that findings should not be translated to potential effects of fruits or vegetables.
Systematic reviews
Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.
There was one related systematic review identified on the Cochrane Database of Systematic Reviews (CDSR) (8) and five on the Database of Abstracts of Reviews of Effects (DARE) (9-13).
References and resources
1. Medical backlash over health foods. The Times, 28 February 2007, p1.
2. Food and vitamin pills are 'bad for you'. The Times, 28 February 2007, p7.
Taking vitamin supplements may increase risk of death, says study
Sarah BoseleyWednesday February 28, 2007
The Guardian
The three supplements are marketed on the premise they deliver antioxidants to the body to mop up free radicals, thought to be responsible for some of the effects of ageing. But none was found to lengthen the lives of those who took them, according to an analysis in the Journal of the American Medical Association of all the substantial trials done to date.
Scientists of the respected Cochrane collaboration, which regularly pools data from trials to evaluate drugs and medical treatments, discovered the three supplements had the opposite effect. Those who took them, in 47 trials with 180,938 people, had a 5% greater risk of dying than those who did not.
Other common supplements with similar claims made for them, vitamin C and selenium, did not increase risk of death, the researchers from Copenhagen University hospital in Denmark found, but only selenium may have some benefit. "Our systematic review contains a number of findings. Beta carotene, vitamin A, and vitamin E given singly or combined with other antioxidant supplements significantly increase mortality," wrote Goran Bjelakovic and colleagues.
"There is no evidence that vitamin C may increase longevity. We lack evidence to refute a potential negative effect of vitamin C on survival. Selenium tended to reduce mortality, but we need more research on this question." Around 10% to 20% of people in Europe and North America take these supplements regularly, so "the public health consequences may be substantial", they say. People are exposed to "intense marketing" they add, but consumers would be better obtaining antioxidants from fruit and vegetables.
But Balz Frei, director of the Linus Pauling Institute at Oregon State University, said the study and the data were flawed, because more than two-thirds of research examined used people with heart disease, cancer, or other risks, treated to see if the supplements worked: "Over the years it has become clear ... antioxidants don't work in disease treatment."
4. What's up doc? Experts claim 'carrot' vitamin pill can kill you. The Sun, 28 February 2007, p25.
5. Vitamin pills can help send you to an early grave, say scientists. Daily Mail, 28 February 2007, p4.
6. Anti-ageing vitamins increase death risk, finds study. Daily Telegraph, 28 February 2007, p6.
9. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of Internal Medicine 2005;142(1):37-46. [DARE Abstract]
10. Shekelle PG, Morton SC, Jungvig LK, Udani J, Spar M, Tu W, Suttorp MJ, Coulter I, Newberry SJ, Hardy M. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. Journal of General Internal Medicine 2004;19(4):380-9. [DARE Abstract]
11. Ritenbaugh C, Streit K, Helfand M. Routine vitamin supplementation to prevent cancer: a summary of the evidence from randomized controlled trials for the U.S. Preventive Services Task Force. Rockville, MD, USA: Agency for Healthcare Research and Quality; 2004. [DARE Abstract]
12. Alkhenizan AH, Al-Omran MA. The role of vitamin E in the prevention of coronary events and stroke: meta-analysis of randomized controlled trials. Saudi Medical Journal 2004;25(12):1808-14. [DARE Abstract]
13. Lonn EM, Yusuf S. Is there a role for antioxidant vitamins in the prevention of cardiovascular diseases: an update on epidemiological and clinical trials data. Canadian Journal of Cardiology 1997;13(10):957-65. [DARE Abstract]
Consumer information
Food Standards Agency - Vitamins and minerals
NHS Direct - Do I need vitamin supplements?
Previous Hitting the Headlines summaries on this topic
'Vitamins health fear'. Hitting the Headlines archive, 4 April 2005.
Vitamin E 'could raise risk of heart failure'. Hitting the Headlines archive, 17 March 2005.
Too many vitamins may be bad for you. Hitting the Headlines archive, 9 May 2003.
Vitamin pills 'are useless'. Hitting the Headlines archive, 8 July 2002.
reposted from: NHS
my: highlights / emphasis / key points / comments
2 comments:
It is frustrating to see yet another study from Bjelakovic et al. receive widespread media attention, without a single mention of why its conclusions are completely wrong.
They published similar articles in The Lancet (2004), and in Alimentary Pharmacology & Therapeutics (2006). The flaw in all three studies is the same.
They used multiple linear regression, a technique that averages in people who took moderate doses of vitamins along with people who took highly toxic doses of vitamins.
The average dosage for vitamins A and E in their new study were at levels already known to be toxic; the maximum dosages were about 20 times the recommended levels. Of course there was some mortality - just as a study of people who took 1 to 100 tablets for a headache would show that "aspirin increases mortality".
People frequently cite the many numbers and measures of statistical significance in Bjelakovic's studies as evidence of the validity of their results. Statistical significance means nothing if the test being performed is nonsensical.
More details on how to correctly interpret the study data are on my livejournal page, shagbark.livejournal.com .
- Dr. Phil Goetz, NIH
It is frustrating to see yet another study from Bjelakovic et al. receive widespread media attention, with no mention of why its conclusions are completely wrong.
They published similar articles in The Lancet (2004), and in Alimentary Pharmacology & Therapeutics (2006). The flaw in all three studies is the same. They used multiple linear regression, a technique that averages in people who took moderate doses of vitamins along with people who took highly toxic doses of vitamins.
The average dosage for vitamins A and E in their new study were at levels already known to be toxic; the maximum dosages were about 20 times the recommended levels. Of course there was some mortality - just as a study of people who took 1 to 100 tablets for a headache would show that "aspirin increases mortality".
People frequently cite the many numbers and measures of statistical significance in Bjelakovic's studies as evidence of the validity of their results. Statistical significance means nothing if the test being performed is nonsensical.
More details on how to correctly interpret the study data are on my livejournal page, shagbark.livejournal.com .
- Dr. Phil Goetz, NIH
Post a Comment