Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.38427.404259.8F (Published 12 May 2005) Cite this as: BMJ 2005;330:1109
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Sir,
We read with interest the article by Ciliberto et al. (1)
demonstrating that supplementation with antioxidants did not prevent the
onset of kwashiokor in high risk children. Although the study was well
designed, we believe that there are major problems in the interpretation
of data. How can authors ascertain that the antioxidant supplementation
utilized could attenuate oxidative stress in that population? Since
authors did not measure markers of oxidative stress before and after
antioxidant supplementation, one can argue that antioxidant
supplementation at the doses used did not attenuate oxidative stress.
Thus, authors could not conclude that antioxidant depletion may be a
consequence rather than a cause of kwashiorkor. In order to propose that
oxidative stress mediates the pathogenesis of a clinical condition two
basic conditions must be observed. First, it is necessary to show the
occurrence of oxidative stress associated with the disease, and, second,
it is necessary to demonstrate that the resolution of oxidative stress is
associated with the resolution of the disease or condition. Ciliberto et
al did not investigate oxidative stress parameters in their study, thus it
cannot be conclude that oxidative stress is not associated to the
development of kwashiorkor. In addition, the redox balance during protein
malnutrition seemed to be complex, and it is possible that the antioxidant
supplementation used did not adequately decrease oxidative damage in those
conditions. We had previously demonstrated that supplementation with
methionine (a substrate for glutathione synthesis and an endogenous
antioxidant due to its thiol group) could either decrease or increase,
depending on the animal age and the kind of damage analyzed (lipid or
protein oxidative damage), oxidative damage in the hippocampus of rats
submitted to protein malnutrition (2). We thus believe that the
involvement of oxidative stress in malnutrition should be analyzed with
more caution; a more profound knowledge of the redox state during protein
malnutrition is necessary before the design of clinical trials aiming to
treat or prevent kwashiorkor with antioxidant supplementation.
1. Ciliberto H, Ciliberto M, Briend A, Ashorn P, Bier D, Manary M.
Antioxidant supplementation for the prevention of kwashiorkor in Malawian
children: randomised, double blind, placebo controlled trial. BMJ
2005;330: 1109. Epub 2005 Apr 25.
2. Bonatto F, Polydoro M, Andrades ME, da Frota Junior ML, Dal-Pizzol
F, Rotta LN, et al. Brain Res 2005;1042: 17-22.
Felipe Dal Pizzol, MD, PhD, Associate Professor of Medicine
Experimental Physiopathology Laboratory, Department of Medicine
University of Southern Santa Catarina (UNESC), 88806-000 Criciúma, SC,
Brazil
E-mail address: pizzol.ez@terra.com.br
Fernanda Bonatto, BSc, Graduate Researcher
Center for Oxidative Stress Studies, Department of Biochemistry
Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS,
Brazil
José Cláudio Fonseca Moreira, PhD, Associate Professor of
Biochemistry
Center for Oxidative Stress Studies, Department of Biochemistry
Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS,
Brazil
Rafael Roesler, PhD, Associate Professor of Pharmacology
Department of Pharmacology
Federal University of Rio Grande do Sul, 90046-900 Porto Alegre, RS,
Brazil
Competing interests:
None declared
Competing interests: No competing interests
Sir,
The article about the use of antioxidants to prevent the development
of kwashiorkor made interesting reading. Kwashiorkor, a disease of
maladapatation to malnutrition was common in India until recently. But in the
last few years the number of children admitted to hospitals in India with
the classical syndrome of kwashiorkor is becoming less and less. In my
institution, which is situated in a rural area, we have not seen a case so
far. I am sure it is the same all over India, except in a few places, the reason
being that the children are immunised even in remote areas and have less
number of infections. The prevalence of undernutrition, marasmus is still
the same, but these children have less number of serious infections. The
infections tilted the balance of the adaptation in previous generations and
resulted in higher number of Kwashiorkor children. It is not the
micronutrients, nor the antioxidants or the proteins which determined the
occurrence of Kwashiorkor. It is the infections. The marasmus,
underweight, under statured manifestations of malnutrition in developing
nations can only be prevented by providing adequate amount food. The
quantity is more important than the quality.
Competing interests:
None declared
Competing interests: No competing interests
Dear Editor,
When children are born to malnourished mothers in rapid succession
(one who comes after), the child hardly gets mother's milk. When the
child is brought up on artificial milk substitutes,there would be protein
mal-nutrition, as the protein is foreign to the child. This results in
early liver damage and oedema.
In Marasmus the child gets too little mother's milk, resulting in
protein sub-nutrition and the liver does not get damaged early, hence no
oedema. This hypothesis was put forward by Dr. C. Goplalan, an Indian
nutrition expert. He went on to show how early liver damage could release
iron in ferric state into the blood stream that could stimulate the
posterior pituitary, setting a chain reaction which results in oedema at
the end.
I wonder if this hypothesis is still valid?
I remember to have read this when I was a young registrar in London
getting ready for the membership examination! Antioxidants are the in
thing now for every ill. They make good business sense resulting in very
high profit margins for the seller-net profit after adjusting for any
risk, which is negligible in this instance.
yours ever,
bmhegde
Competing interests:
None declared
Competing interests: No competing interests
Spirit of the unborn child
Dear Sir
Re :- Anti-oxidant supplementation for the prevention of kwashiorkor
in Malawian children. Ciliberto et al 14th May
The authors are to be congratulated on carrying out a study of the
link between anti-oxidants status and oedema in PEM, in the community,
where the complexity of simultaneous exposures may blunt the effect of an
intervention.
As stated in the accompanying editorial1, failure to demonstrate
protection by antioxidant supplementation does not in itself deny the
importance of antioxidant status in the progression of PEM, but rather
confirms the paradox that is kwashiorkor. Theories about its aetiology are
toppled every decade or so, but the traditional explanation still holds
true.
Thirty years ago , when kwashiorkor was explained by protein
deficiency, MacLaren 2 complained of a ‘ protein fiasco’, in which
enormous efforts were being made to develop high protein beans, rather
than feeding hungry children. Even earlier, Cecily Williams3 had
introduced the Ga term ‘kwashiorkor’ ( translated poetically as ‘ spirit
of the unborn child’ by Pobee J (personal communication) ) to explain the
disease which followed the sudden cessation of breastfeeding of her
toddler by a newly pregnant mother. The ‘deposed’ child was weaned onto
maize porridge, later recognised to be both low in (quality) protein and
of low energy density, after which he often developed diarrhoea and died.
The authors’ speculation that ‘intrinsic’ characteristics may
determine the way that children on poor diets metabolise nutrients,
mentioning differences in amino-acid pattern between children with
kwashiorkor and marasmus, is not new. However, such differences in amino-
acid pattern may reflect differences in hormonal response to (infection)
stress, and some differences are obliterated within a matter of hours
after the start of re-feeding 4. The idea that genetic mapping may be
informative is of interest, but I wonder whether or not communities would
have recognised ‘at risk’ blood lines many years ago.
1. Fuchs GJ 2005 Antioxidants for children with kwashiorkor editorial
British Medical Journal 330 1095
2. Williams C 1933 ( reprinted 1983) A nutritional disease of
childhood associated with a maize diet, Archives of Disease in Childhood
57:550-560
3. Maclaren D 1975, The protein fiasco , The Lancet, 2: 93-96
4. Whitehead RG and Dean RFA 1964 Serum amino acids in kwashiorkor,
American Journal of Clinical Nutrition 14 : 320-330.
Competing interests:
None declared
Competing interests: No competing interests