JAMA Goofs Again

DO ANTIOXIDANTS INCREASE MORTALITY?

Here we go again. It’s almost an annual occurrence. Mainstream media announces the latest bad news about the natural health care industry and the public panics. Usually it involves vitamin toxicity or “proof” that vitamins don’t work as advertised. The natural health product (NHP) industry panics.

The stories always seem to be front-page news and alarmist enough to adversely affect the health of patients reading them. Temporarily, NHP sales plummet only to rebound once it is realized by one and all that the conclusions are exaggerated at best. Without exception, the attacks are based on very poorly done studies, anecdotes or the ramblings of crackpot opponents of natural health care.

The most recent case in point is the JAMA article (2007 Feb 28;297(8):842-57) that concludes that “Treatment with beta carotene, vitamin A, and vitamin E may increase mortality.” Do we now all stop taking our daily vitamin supplements? Before we do that, let’s first examine this study.

“This is a flawed analysis…the totality of the evidence indicates that antioxidants from foods or supplements have many health benefits, including reduced risk for cardiovascular disease, some types of cancer, eye disease, and neurodegenerative disease…they are a key to an enhanced immune system and resistance to infection.”

Dr. Jeffrey Blumberg, Director of the Antioxidants Research Laboratory at Tufts University in Boston, Massachusetts
First of all, the conclusions of this JAMA study were based entirely on a statistical review of selected old data. There was really no experimental design or actual study done here. Further, it was published by the same “scientists” that denounced antioxidants in a Lancet article in 2004. The latter was dismissed as science fiction by most credible scientists but the authors are back again with even more nonsense. They discount most of the well-established scientific support for antioxidants and go on to conclude that antioxidant vitamins increase death from all causes.
Wrong Dosages Evaluated
If one wants to see whether or not a nutrient is effective in preventing or curing illness one must at least use the correct dosage. The JAMA statistical review used suboptimal, very wide and inconsistent dosage ranges for the antioxidants evaluated.
Supplement Dose range
Vitamin A (synthetic) 1,333-200,000*** IU
Alpha Tocopherol (synthetic) 10-5,000 IU
Vitamin C (synthetic) 60 – 2,000 mg
Selenium (natural) 20 – 200 mcg

Who in their right mind takes 200,000 IU of vitamin A for 3 months of time on their own? The way this review is put together one would assume that everyone does this and ends up poisoning himself or herself.
Proven Beneficial Nutrients Omitted
The nutrients that were evaluated in this negative JAMA article are a small percentage of the total available antioxidants that most people who are serious about disease prevention take on a regular basis. Isolating the four nutrients from the dozens recommended by most antioxidant authorities and drawing conclusions from those four alone is not valid.
The authors failed to include a long list of proven disease preventing nutrients such as gamma tocopherol, natural alpha tocopherol succinate and tocotrienols in the case of vitamin E, bioflavonoids like those found in bilberry and grape seed extract, CoQ10 and resveretrol just to name a few. The use of synthetic alpha tocopherol has long ago been warned about by experts in the natural health care industry and does not warrant any further study. Extrapolating its adverse effects to all natural antioxidants is unscientific.
Other very important life extending nutrients ignored by the review were omega-3 fatty acids, alpha lipoic acid, carnitine, arginine, standardized fruit & vegetable extracts, carotenoids, B-vitamins, and minerals such as calcium, magnesium and zinc.
Poor Selection of the Study Population for Too Short Duration
The studies selected for review used an average age of 62 for their subjects for an average of 3.3 years. No one in their right mind could possibly hope that the use of suboptimal doses of selected antioxidants could somehow be beneficial in prolonging life in those that had already endured a lifetime of oxidative damage.
In other words, giving 60 year old plus smokers who had been taking at least 3 or more drugs some antioxidants is like using gasoline to put out a fire. Yet, this is similar to what these authors did. Why the prestigious JAMA would allow this review to be published in the first place is the real question.
Manipulating Statistics Leads to Erroneous Conclusions
An old professor of mine at McGill University once told me that one could manipulate statistics in such a way as to “prove” that cigarette smoking is good for you. Just leave out the results of a few studies here and include the results of some poorly done studies there for your statistical review and you have that conclusion.
“One of the major premises of doing such a meta-analysis is that the studies should be comparable…here, they looked at primary prevention, treatment, old people, young people, smokers, nonsmokers. Only when they used their own criteria of what was good and what was bad were they able to show an increase in all-cause mortality."
Dr. Jeffrey Blumberg, Director of the Antioxidants Research Laboratory at Tufts University in Boston, Massachusetts
http://www.washingtonpost.com/wp-dyn/content/article/2007/02/27/AR2007022700925.html
Exclusion of over 90% of Favorable Antioxidant Studies
With the JAMA review the authors chose only 68 out of a potential of 815 studies that favorably supported the use of antioxidants in disease prevention. Out of these excluded studies, 405 failed to show any deaths at all either in the study or placebo group.
The deaths reported by the JAMA review were incorrectly reported from a 2001 study where only one death occurred in the placebo group, one death in the drug and antioxidant group and no deaths in the group given only the antioxidants (Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345: 1583-1592).

Overwhelming Antioxidant Safety and Efficacy Studies Ignored
Several hundred studies published in peer reviewed medical journals like JAMA have used large populations of individuals studied for decades (not 3.3 years) and concluded highly significant life extending benefits of antioxidant supplements. Three of the most striking of these taken from the Life Extension Foundation site rebuttal of the JAMA review (http://www.lef.org/featuredarticles/consumer_alert_020307.htm) are summarized below:
“1)A study involving over 29,092 male smokers aged 50-69 years followed prospectively for 19 years showed that men with the highest serum alpha-tocopherol levels had a 28% lower risk of total and cause-specific mortality than did those with the lowest levels, and a 21%, 29%, and 30% lower risk of deaths due to cancer, cardiovascular disease, and other causes. (Wright ME, Lawson KA, Weinstein SJ, Pietinen P, Taylor PR, Virtamo J, Albanes D. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 2006 Nov;84(5):1200-7).

2)A study in 3,254 people (1,260 males and 1,994 females) aged from 39 to 85 years followed from 1989 to 1995 showed that higher serum levels of carotenoids with pro-vitamin A activity significantly reduces the risk of mortality from cardiovascular disease and colorectal cancer. (Ito Y, Suzuki K, Ishii J, Hishida H, et al. A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants. Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):533-46).

3)A study in aging women that showed those with the lowest levels of alpha- and beta-carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely to have increasing IL-6 levels over a period of 2 years, and those aging women with the lowest selenium levels had a significantly higher 54% risk of death over a 5-year period. (Walston J, Xue Q, Semba RD, Ferrucci L, Cappola AR, Ricks M, Guralnik J, Fried LP. Serum antioxidants, inflammation, and total mortality in older women. Am J Epidemiol. 2006 Jan 1;163(1):18-26).”

For details of dozens of other such studies, see http://www.lef.org/featured-articles/consumer_alert_020307.htm

The Bottom Line

Hopelessly flawed studies like this recent JAMA review article only serves to reinforce the fact that antioxidants play a major role in disease prevention. I expect the attacks on antioxidants to continue for years to come. Maybe the next attack can be more founded in science and less in ignorance. Until then, I’ll continue taking my antioxidants and I suspect you should do so as well.

THE PUBLISHED JAMA ARTICLE ABSTRACT
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 Feb 28;297(8):842-57

The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. goranb@junis.ni.ac.yu

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.

REFERENCE

http://www.lef.org/featured-articles/consumer_alert_020307.htm

Comments

[Tim]

It really is disgusting how the FDA, and mainstream medicine are against the natural health indursty.

[Orac Dan]

That's an excellent rebuttal to that study. We have learned a lot in the past few years about how to measure antioxidants and their ORAC values, but there is still a lot of work to be done.

[Nowheet Owl]

I agree.

Most of the time, statistic is blown out of proportion and makes a great excuse to kill natural supplements.

[Increase Penis Size]

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