Vit-A megadoses
vit-A megadoses Rubina Hakeem 29.11.99
Re: vit-A megadoses George Beaton 29.11.99
Re: vit-A megadoses George Beaton 29.11.99

Date: Fri, 26 Nov 1999 18:46:57 +0500

From: hakeem <>

Subject: health screening


We are planning to assess food and nutrient intake and growth status of healthy Urban Pakisitani children. I would be grateful if I could get refernce to rapid methods of screening for healthy children through parents interviews or questionnaire.



Dr R Hakeem



Subject: Re: vit-A megadoses

Date: Mon, 29 Nov 1999 00:09:08 -0500


Dear Dr Rubina Hakeem:

Two points in response to your query:

1. The risk of true toxicity with single megadosing of well nourished children should not be a concern. This has been examined in several publications of WHO, IVACG and others. You should be prepared for the expectation that a very small proportion of children will have transient reactions to the dose. These do not represent toxicity but unless you are prepared for it, might have some adverse effect in the community, particularly if there is an anti-dosing movement underway.

2. As to benefit to be expected, I refer you to the 'meta analysis" by Beaton et al. ["Effectiveness of Vitamin A Supplementation in the Control of Young Child Morbidity and Mortality in Developing Countries" Beaton, Martorell, Aronson, Edmonston, McCabe, Ross and Harvey, ACC/SCN State-of -the-Art Series Nutrition Policy Discussion Paper No. 13. December, 1993 Available from the United Nations Administrative Committee on Cordination, Subcommittee on NUtrition (ACC/SCN) c/o WHO, Geneva, Switzerland; email ACCSCNatWHO.CH] Overall, for ages 6 months through 6 years (at least), the expected reduction in general mortality for populations in which vitamin A deficiency is present (not in every child but in the population group) is in the order of 28%. The Sudan study was included in that analysis. while we included it in the analysis, I have since become convinced that it must have had serious design problems since further reports of analyses in the same children appear to give conflicting conclusions about whether or not the design of the primary study was implemented with sufficient care. I do not now consider that it produced valid evidence pro or con effectiveness and safety of vitamin A. Our analyses also included the negative study in Hyderabad mentioned by Dr.

Gopalan as well as the extremely successful study in Tamil Nadu not mentioned by Dr. Gopalan. We concluded that the accumulated evidence was sufficiently strong that there was no merit in continuing to ask the question for children over 6 months. I have had no reason to change that view since then. I continue to believe that a definitive answer is available.

I would urge that you lend your support to the supplementation campaign that you mention. At the same time, you can try to ensure that such campaigns are managed such that they are not repeated too often (spacing of doses) and that the same child is not dosed more than once during the campaign.

Good luck

George Beaton



GHB Consulting, 9 Silverview Drive, Willowdale, Ontario, Canada M2M 2B2

Date: Mon, 29 Nov 1999 06:52:56 -0500 (EST)

From: Wafaie Fawzi <>

Subject: Re: vit-A megadoses


Dear Dr. Hakeem,

I do agree with Dr. Beaton that the risk of toxicity from a single dose is minimal and transient. There should be concern about receiving multiple large doses in a short period of time, as might inadvertently occur as a result of programmatic problems.

I also agree with Dr. Beaton that there is demonstrated efficacy of large doses of vitamin A on mortality. Although the results from the Sudan and Hyderabad studies clearly do not support efficacy of large doses of vitamin A, these results are real and cannot be dismissed as "due to poor design". This forum may not be the right place to debate the pros and cons of the various vitamin A mortality and morbidity trials; suffice it to say that the Sudan study was similar in design to many others that showed efficacy, and to my knowledge had no major implementation problems that affect confidence in the results. We also carried out a metanalyses of the various vitamin A trials (published in JAMA in 1993) and conclude that, overall the supplements had a significant reduction of 23% in mortality.

However, efficacy ranged from about 20% (Ghana) to 54% in Tamil Nadu. The efficacy of the supplements in different communities will depend on several factors including the prevalence of vitamin A deficiency, frequency and dose, and parasitic infections and other dietary deficiencies (such as fat, protein, and zinc) that limit the bioavailability of vitamin A.

Distribution of large doses of vitamin A should not be seen as an endpoint. The supplements are clearly efficacious in reducing mortality in communities where deficiency is a public health problem. In these, and other settings, the long term and sustainable solution is improving dietary intake of vitamin A.



Wafaie Fawzi