Headlines in today's papers such as 'Vitamin Pills "Increase Risk of Early Death"' claim that anti-oxidants are not good for you and could even do you harm. But, don't believe everything you read!

What's this review about?

This is the fourth time Bjekalovic and his group have reviewed the effects on selected studies on antioxidants. Anyone following the science of antioxidants over the past 20 years will be aware of a vast number of studies reporting positive results. So, how do you end up with a headline that implies antioxidants increase mortality?

In this review, which is a rehash of their paper published last year in the Journal of American Medical Association (JAMA), they first excluded over 400 trials, that had no deaths. They then decided which trials they liked (low risk bias) and did not like (high risk bias), a factor that has received criticism in mainstream medical journals.

What the experts say

One of the world's leading experts in this field, Dr Balz Frei said "This is a flawed analysis of flawed data, and it does little to help us understand the real health effects of antioxidants, whether beneficial or otherwise," (1)

Dr Bernadine Healey, former director of the National Institute of Health said, "Blenderizing these diverse trials into one giant 232,606-patient-strong study to come up with a seductively simple proclamation is just silly. When the researchers tallied up the mortality from the 68 trials, there was no difference based on vitamin intake. The headlines that these supplements significantly increase the risk of death by 5 percent overall came only when the researchers pulled out the 47 trials they deemed to have been the best executed. Actually, in the 21 randomized trials they peeled off, mortality was decreased by 9 percent among those taking the vitamins." (2)

How did they come up with the reported results?

Not surprisingly, the selection process in today's review excluded many of the most positive studies. For example, quoting the review itself, 'In secondary prevention trials (meaning people with disease) with high-bias risk, mortality was significantly reduced by supplements.' In those they called 'low-bias risk' there was no significant change in mortality.

To report an even more negative result, which is what newspapers often home in on, they also excluded all trials on selenium, which actually reduced mortality the most of all the antioxidants considered.

Beta-carotene

As an example, let's look at beta-carotene, which is given the worst rating. The review states 'Beta-carotene used singly or in combination with other antioxidants had no significant effect on mortality when including all 24 trials' BUT 'After exclusion of high-bias risk and selenium trials, however,
beta-carotene singly or combined significantly increased mortality in 12 trials.'

Antioxidants and cancer

Even if we were to accept the exclusion of the so-called high-bias risk trials let's look more closely at the apparently negative studies. A graph of all these trials shows five that skew the results towards a negative (p.167). I thought I'd look closer at these trials. The first was by Dr Correa from the pathology department at the Louisiana State University Health Sciences Centre, and showed a clear protective effective of antioxidant supplements against gastrointestinal cancer. (3)

I decided to contact Dr Correa and he was "amazed", he said, because his research, "far from being negative, had shown clear benefit from taking vitamins". Correa told us there was no way the study could show anything about mortality. "Our study was designed for evaluation of the progress of
pre-cancerous lesions", he said. "It did not intend, and did not have the power, to study mortality and has no value to examine mortality of cancer."

Vitamin E and statins

The next, called the DATOR trial, gave people with high cholesterol, high dose vitamin E (750iu) and statins. (4) As nutritionists we caution against this because statins stop you making CoQ10 which results in vitamin E becoming a potentially harmful oxidant. That's exactly what this trial reported, "These results indicate that the antioxidant effect of Vitamin E is attenuated (reduced) when given in conjunction with this statin." So these negative effects of vitamin E might actually be because it's taken
with a drug that makes it harmful! Given that the majority of the trials included in this review were on sick people, presumably taking medication, this kind of confounding variable really should be taken into account. It is not.

Selenium's protective effects

The next trial, published on the Mayo Clinic's journal, that skewed the results to a negative reported a positive outcome. (5) It investigated the effect of selenium of oesophageal cancer. It found that 'among subjects with mild esophageal squamous dysplasia (early stage) at baseline, selenomethionine did have a protective effect.' For those with more advanced cancer it did not.

In January this year the authors published a paper 'Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis.'(6) Their conclusion was that 'beta carotene supplementation appeared to increase cancer incidence and cancer mortality among smokers, whereas vitamin E supplementation had no effect. Selenium supplementation might have anticarcinogenic effects in men and thus requires further research.'

So, what does all this mean?

Well, if you look at all the studies reviewed, strictly for reducing mortality, not for other benefits, Bjekalovic concludes 'Beta-carotene, vitamin A and vitamin C, used singly or in combination with other
antioxidants had no significant effect' although a number of vitamin C studies did report reduced mortality. 'Selenium used singly or in combination with other antioxidants significantly decreased mortality.' (7).
Beta-carotene, as we know, is best not taken singly by smokers. Vitamin E in high dose, as we know, should not be taken by those on statins without additional CoQ10. Selenium and vitamin C are most likely to be beneficial.

So, should we throw away our antioxidants?

Certainly not. Personally, I haven't recommended isolated antioxidant supplementation for 20 years and doubt they would produce much effect in sick people with advanced disease states, except for vitamin C at high doses - a subject not examined in this review. Antioxidants are team players. I take a combination of vitamin E, CoQ10, vitamin C, glutathione, anthocyanidins, resveratrol, beta-carotene, alpha lipoic acid and selenium. There's good reason to do so if you look at what's known about their effects in reducing markers of ageing. But these are as well as eating loads of fruit and veg, nuts and seeds.

References

1. http://oregonstate.edu/dept/ncs/newsarch/2007/Feb07/vitaminstudy.html
<http://oregonstate.edu/dept/ncs/newsarch/2007/Feb07/vitaminstudy.html>

2. http://health.usnews.com/usnews/health/articles/070304/12healy_print.htm
<http://health.usnews.com/usnews/health/articles/070304/12healy_print.htm>

3. P Correa et al, 'Chemoprevention of gastric dysplasia: Randomized trial
of antioxidant supplements and anti-Helicobacter pylori therapy', Journal of
the National Cancer Institute (2000), vol 92, pp1881-8.

4. Manuel-Y-Keenoy B et al Impact of Vitamin E supplementation on
lipoprotein peroxidation and composition in Type 1 diabetic patients treated
with Atorvastatin. Atherosclerosis. 2004 Aug;175(2):369-76]

5. Bardia et al Randomized, placebo-controlled, esophageal squamous cell
cancer chemoprevention trial of selenomethionine and
celecoxib.Gastroenterology. 2005 Sep;129(3):863-73

6. Bardia A et al Efficacy of antioxidant supplementation in reducing
primary cancer incidence and mortality: systematic review and meta-analysis.
Mayo Clin Proc. 2008 Jan;83(1):23-34.

7. Bjelakovic et al, Antioxidant supplements for prevention of mortality in
healthy participants and patients with various diseases (Review), Cochrane
Library, Issue 2, 2008


 

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