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Unstable oxygen
f d l
Sources of free radicals
Trauma
free radical
lacking an electron
Radiaon
Microbes
Heat
Stress Stress
Immune injury
Toxins
Free radicals seek to stabilize themselves by stealing an
electron from other compounds or molecules such as lipids /
DNA / mitochondria which in turn become a free radical which
steals an electron : a damaging chain reacon is thus created.
Donates electron
Anoxidant
Anoxidant
Stabilised radical
Anoxidant remains stable despite
of loss of electron
(Endogenous superoxide dismutases, glutathione etc
Exogenous - Vit C, Vit E,beta carotene etc)
Fig. 1. Interaction of oxygen free radicals and antioxidants.
V.S. Talaulikar, I.T. Manyonda / European Journal of Obstetrics & Gynecology and Reproductive Biology 157 (2011) 1013 11
amelioration of diseases associated with oxidative stress. The
popular range of antioxidants includes vitamin E, vitamin C,
carotenoids (including beta carotene and lycopene) and poly-
phenols (including avonoids), although the full list of compounds
with antioxidant properties is extensive. Vitamin E is the most
abundant fat-soluble antioxidant in the body and one of the most
efcient chain-breaking antioxidants available, and therefore a
primary defender against oxidation. Vitamin C is the most
abundant water-soluble antioxidant in the body and acts primarily
in cellular uid, being especially effective in combating free-radical
formation caused by pollution and cigarette smoke. In the western
world and especially in America it is estimated that up to 50% of the
adult population take antioxidant pills on a daily basis to promote
health and stave off disease. The question is whether these
supplements are effective.
5. The myth of vitamin supplementation in the prevention of
disease
The epidemiologic evidence of the benets of antioxidants on
staving off cancer, cardiovascular and other diseases of ageing
spawned a series of preventative studies. Although there have been
conicting data published by various study groups, the results of
recent large studies using vitamin E supplements have been almost
universally disappointing, with one study even suggesting that
vitamin E might increase the risk of heart failure. Other studies
failed to nd a benet for vitamin E against cancers or the
progression to Alzheimers disease in people with mild cognitive
impairment. There is even evidence that vitamin E supplements
could be harmful [12], although the report has been challenged. In
a study focussing on beta carotene and its potential for protecting
against lung cancer, 29,133 male smokers 5069 years of age from
southwestern Finland were randomly assigned to one of four
regimens: alpha-tocopherol alone, beta carotene alone, both
alpha-tocopherol and beta carotene, or placebo. Follow-up
continued for ve to eight years and, unexpectedly, a higher
incidence of lung cancer was observed among the men who
received beta carotene than among those who did not [13]. Apart
from failing to show benet in the prevention or amelioration of
PE, vitamin C has not fared well elsewhere, with reports suggesting
that it may accelerate atherosclerosis in some people with
diabetes, and fail to confer benet in patients with advanced
cancer [14] despite early promise. However, while it should nowbe
fully accepted that vitamin C does not prevent or ameliorate PE in
its current form and dose, it should also be recognized that overall
the jury is still out on a role for vitamin antioxidant therapy for a
range of diseases, since a PubMed search for 2010 still yields a
mixed bag of recent positive and negative studies.
6. Why vitamin supplements may not be effective antioxidants
That many vitamins, including E and C, are antioxidants and
exhibit vigorous antioxidant activity in the test tube is beyond
dispute. Why then, when packaged in pure form in a capsule and
swallowed in large quantities, do these vitamins fail to prevent
disease? There are several potential explanations. Firstly, the
antioxidants in fruit and vegetables may be tightly bound within
the tough brous material of these foodstuffs and may exert their
antioxidant activity not in the blood or tissues but in the
gastrointestinal tract where free radicals are constantly generated
from food [15] Supplements, on the other hand, are probably
digested too quickly to replicate the effect. Elegant studies by Lean
et al. [16] showed that oxidative stress plays a crucial role in
oophorectomy-induced osteoporosis in mice, and that vitamin C
will prevent the development of osteoporosis when given
intraperitoneally at a dose of 1 mmol/kg twice a day. The human
equivalent of the vitamin C dose they used is 20 g per day. The
equivalent serum levels of vitamin C cannot be achieved if the
supplement is given by the oral route, since there is an upper limit
for absorption of vitamin C of about 500 mg, which is why this is
normally the highest dose given. Any more vitamin C stays in the
gut and may cause osmotic diarrhoea and other gastrointestinal
upset [17]. In contrast, plasma levels up to 70 times greater can be
achieved by parenteral administration [18]. Finally, antioxidants
such as glutathione are present in cells at huge (millimolar)
concentrations, and vitamin C prevented oxidant-induced bone
loss in the work described by Lean et al. [16] because a sufcient
dose was given to normalize antioxidant levels. In contrast, while a
dose of 5001000 mg (used in the clinical trials involving pre-
eclampsia) is sufcient to full the need for a cofactor in collagen
synthesis, it may be far too small a proportion of a cells antioxidant
reserve to exert a detectable antioxidant effect.
7. Where to now?
A careful pre-trial consideration of what was already known
about vitamin C could have provided hints that vitamin C in its
current dose and form was highly unlikely to be the holy grail in
combating pre-eclampsia, and it may not have required so many
largeinternational clinical trials toarrive wherewearetoday. Wedo
appreciate that research studies with negative ndings add to the
existing knowledge on the subject and that they are critical for
acceptance/refusal of novel healthcare interventions. Nevertheless,
the propagation of the same fundamental aw of assuming benet
from intervention has cost huge amounts of precious research
resources. The need of the hour is for robust laboratory scientic
research to explore new routes of administration or doses of novel
antioxidants, before any more large trials are planned for future.
Role of funding source
No funding was received for this review.
Disclosure of interest
None of the authors reports any conict of interest concerning
this review.
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