On TVOne's Breakfast Show, they have a Health Correspondent, Lorelei Mason. As can be seen from TVNZ's profile of Lorelei, she is a reporter, which is fine, but not medically, or more specifically research trained.
This became totally apparent when she reported (video available here) on the paper below.
References
Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. JAMA. 2007;297(8):842-857
Abstract
CONTEXT: Antioxidant supplements are used for prevention of several diseases. OBJECTIVE: To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. Data Sources and Trial Selection We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials. DATA EXTRACTION: We included 68 randomized trials with 232 606 participants (385 publications). DATA SYNTHESIS: When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality. CONCLUSIONS: Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.
In the news piece, Lorelei comments "As always with these studies, the devil is in the detail. Uhh, what they did, it's called an epidemiological study. Which is a big word for saying what these researchers did is not look at a whole lot of new people in new trials, they took 68 trials, which involved 230 thousand people, and they looked at those people's, uhh, data that hadn't perhaps been exposed, umm, in those trials... ...and worked out the vitamin intake of these people, um, who later went on to die and from that they extrapolated, if you like, the data they got, to show if you take Vitamin A, you got a 16% higher death risk, um, if you take too much of it of course, and this is what I am saying about the detail, um, vitamin Beta-carotene 7% and Vitamin E, which surprised some, a 4% increase..."
She went on to attempt to pick apart the trial due to the inclusion of asbestosis sufferers (One trial, Lorelei made it sound like a large number).
The trial was a meta-analysis of randomised controlled trials, not epidemiology. While Meta-analyses have been termed the epidemiology of controlled research, this is not the same as the common usage of the term epidemiology, which is usually limited to large scale observational trials, case-control, cohorts, surveys etc.
The meta-analysis collected 16'111 references from five research databases, Central, Medline, Embase, Web of Science and the very basic - reading bibliographies. Due to a very specific selection process, this number was reduced to a total of 68 trials that met the requirements, with 14,003 references removed due to reference duplication (multiple databases will find the same reference and this added up to a large, but not unreasonable number).
These trials involved supplementation with single or combined antioxidant supplementation, at different doses from each other.
The researchers performed multiple statistical regression analysis, but this is not "extrapolated", but the use of this term was an interesting way of weakening the results of this trial to the audience, which is a recurrent theme through the presentation.
When looking at the low biased (high quality) studies the researchers found a small, significant increase in risk of death with three of the antioxidants, Vitamin A, E and Beta-Carotene, as mentioned above.
Performing a meta-regression, there was an extremely small, significant, effect of dose on risk from beta-carotene (RR,1.004 ;95%CI,1.001-1.007; P=.012), an even smaller effect of dose on risk from Vitamin A (RR,1.000006;95%CI, 1.000002-1.000009; P=.003), no effect of dose on Vitamin E risk, and a small reduced risk of dose of selenium (RR,0.998;95%CI,0.997-0.999;P=.002).
Interestingly, in the news reports that are presented on the Breakfast show every half hour, Professor Jim Mann of Otago University presented a more favourable view of the meta-analysis than Lorelei. Maybe because he has more of a background understanding research in this area?
Sure, meta-analyses are not perfect, but they are currently the best tool we have to pick out an effect of diet/treatment on disease risk. The overall analysis is ultimately only as good as the research under the covers, and a large proportion of these trials are performed on older or sick individuals.
Ultimately it points to couple of things. Large supplemental (and in reality food based) doses of Vitamin A may not be the best thing for your mortality risk. Beta-Carotene is an interesting one, but the increase in risk is small, 7% (range 2-11%). Vitamin E is the most interesting one, with a number of the trials pointing towards supplemental Vitamin E increasing risk of death, where observational trails generally show a reduced risk from (food sourced) Vitamin E.
The Vitamin manufacturers were quick to point out that the type of Vitamin E used in these trials is alpha-tocopherol, which is only one of the eight isomers found in food, and they typically questioned the natural/synthetic concept. But strangely, a lot of the supplement industry keep selling products containing these exact mixtures, and making claims with these.
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