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.
Wishing you the best of health, and don't forget - if you want to stay
ahead of the pack on health and nutrition news then join my 100%health Club.
References
1. http://oregonstate.edu/dept/ncs/newsarch/2007/Feb07/vitaminstudy.html
2. 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
From Patrick Holfords 100% Health E-News
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