|vitamin A doses in malnutrition|
|vitamin A doses in malnutrition||Fathia Abdalla||??|
|vitamin A doses in malnutrition||Michael Golden||20.02.98|
|Therapeutic doses of Vitamin A||Andy Seal||23.02.98|
|F100 and vitamin A||Michael Golden||23.02.98|
|vitamin A doses in malnutrition||Emorn Udomkesmalee||23.02.98|
|vitamin A dose in severely malnourished < 6 month old infants||Michael Golden||07.08.98|
from: Fathia Abdalla <00071E09.1865atsmtplink.unicef.org>
" Dear Professor Golden
It is me again Fathia, hope this is not a disturbance for you, I will
try to keep it short. It is a question of VIT A dose during emergency
in severely malnourished children. The practice here is to give
200,000IU oral to all severely malnourished children in the first day,
to be repeated in the following day and before discharge total
600,000IU. Some NGOs think this is very high dose and it is not
necessary unless there are signs of vit a deficiency and prefer to
give one high dose of 200,000 to children >12 months and half dose to
6-12 months. I would appreciate very much your point of view. Thanks a
Date: Fri, 20 Feb 1998 12:16:54 +0000
From: Michael Golden <m.goldenatabdn.ac.uk>
Subject: Ngonut: vitamin A doses in malnutrition
Dear NGONUTs Concerning Fathia's email I have responded as shown below. However, there are those on the list who know more about vitamin A than I do (e.g. George Fuchs, Benny Torun, Andrew Tomkins etc) and I would appreciate comments. There is also the point about having global guidelines which are meant to cover every situation - or at least the average situation, and the ways in which these guidelines (they are ONLY guidelines) should be adapted to local circumstances. Brewer's comments about the differences in the expression of malnutrition are very apposite here - I myself have seen a different spectrum of clinical cases in different regions - and some complications are definitely much more common in one area than another. For example copper deficiency seems to be very common in Kivu province in Congo(Zaire), very rare elsewhere, and there is copper toxicity in Bangladesh. In what way and to what extent should recommendations be tailored? What data is necessary to vary the "standard" practice. If we need different formulae for different places how should this be decided? I should point out that the F100 formula is not designed to TREAT specific nutrient deficiencies - if there were therapeutic levels of nutrients in these diets then they would be given daily throughout the whole of the time the child was taking the diet (in other words there would be to little at the beginning and to much at the end of the child's stay).
F75 is also not designed for specific treatment, although as it is given for only a few days at the start of treatment to severely sick children then is an argument for having a different vitamin/mineral mix for this diet which does treat the common deficiencies.
So, at the moment, if there are specific deficiencies then they need to be specifically treated. Because vitamin A and folate deficiencies are almost universal the recommendation is that every child should get these treatments.
The forthcoming WHO manual advocates:
200,000 IU orally on day 1 and 2 and then again on discharge for children over 12 months (giving 600,000 in all).
HALF this dose for those less than 12 months.
HALF the dose again for the severely malnourished if the dose is given by injection.
(so that a 7 month old being given by injection would get 50,000 IU)
Using conversions (100,000 IU vitamin A = 55 mg retinyl palmitate = 33 mg retinly acetate).
I would defend these on the following basis:
a) the severely malnourished child on day 1 and 2 has much decreased availability of vitamin A, particularly the fat soluble preparations. AND the more he/she needs the vit A the worse the status of the intestine.
Most studies of absorption have been done after the day of admission and with proper treatment the gut improves quite rapidly.
However, there are a lot of other unknowns! For example, the body fat is very low in these children, chylomicron formation and beta-lipoprotein synthesis are much reduced so we do not know much about the transport of vit A either. REtinol binding proteins are also very low. Furthermore, the liver function is very much disturbed in most children, particularly those with kwashiorkor - the function of Ito cells (the special cells that store vitamin A in the liver) has not been investigated at all - in fact I do not know if Ito cells have ever been identified in a malnourished child's liver biopsy.
b) The expression of vitamin A deficiency is not the same in different regions - for example Bitots spots are not seen in Haiti even though severe keratomalacia is quite common. Someone with "experience" in one region but practicing in another may not realise this
c) the diagnosis of vitamin A deficiency in its early stages is not easy - I have had the experience of physicians in a Caribbean island saying that vitamin A def does not occur, because they were diagnosing all the cases as viral/bacterial conjunctivitis and not following up their patients! When the eyes deteriorated the mothers (quite rightly) did not bring the children back to that same doctor who had made a balls-up in the first place but went elsewhere - the result was an unfortunate controversy that cost a lot of children their sight.
d) Even where there is almost no overt clinical deficiency there is almost always a sub-clinical deficiency with low plasma levels - the level is related to mortality quite closely in several studies around the world (Lebanon, Guatamala, Indonesia, Bangladesh). BY the time that there are overt eye signs it is often too late for that child's sight and the other effects. Furthermore, the conversion of carotene into vitamin A is probably impaired in severe malnutrition (interaction with zinc deficiency), and Clive west has shown that the bioavailability of carotene is very variable and usually low in the diets these children take. This may not be the case in the general population.
e) there is a synergy between measles and vitamin A deficiency so that the higher doses are definitely indicated where there is any question of measles as a complication.
f) PERHAPS the most important is the vitamin A does not only function to preserve eyes - indeed, eye lesions could be said to be a LATE sign of vitamin A deficiency. It is also important for mucosal integrity (which is almost universally breached in malnutrition) and for the immune system, which are impaired with vitamin A deficiency before any eye signs appear.
The doses needed to rapidly reverse these effects of vitamin A deficiency are not to my knowledge known.
g) In some places like Bangladesh, there can be progression of eye lesions despite giving vitamin A - we do not really understand why, but it could be related to the zinc interaction (Sultana Khanum investigated this).
h) MALNOURISHED children seem to benefit from vitamin A even in areas where there is plenty in the native diet - for example where red-palm oil is used extensively.
HOWEVER, the guidelines are meant to be universal. To be generic guidelines to cover all the world and every situation! I have no doubt that there may be some places where lower doses of vitamin A - or even none at all, may be justified. And I would be happy for people to vary the guideline regimen - PROVIDED they really know what they are doing!!!!
However, such a decision should NOT be based upon either a clinicians "opinion" or on the field workers "experience", or some such "whim". If the guide lines are going to be varied, in a particular program, then this has to be done 1) with measurements of vitamin A status in the malnourished population, before and after treatment with the standard dose and the proposed new dose. 2) the decisions have to be made by people with specific expertise in vitamin A after the data are obtained. If this is not possible and the management of the children is being left to one expatriate nurse on her first or second or third mission, with locally trained staff - and the co-ordinator is making infrequent pastoral visits - and it is reported that they are not seeing vitamin A deficiency or it is thought that the antecedent diets "probably" have plenty of vitamin A in them - then this is not sufficient to deviate from the guidelines! I can see disasters from not having a systematic method for deciding how to deviate from established guidelines..
Prof. Michael H.N.Golden
Date: Wed, 25 Feb 1998 17:08:29 GMT
From: Andy Seal <A.Sealatich.ucl.ac.uk>
Subject: Ngonut: Therapeutic doses of Vitamin A
With regards to the discusion over therapeutic doses of vitamin A it is interesting to see that the recent MSF pulication "Refugee Health" (1997) recommends that treatment doses of vitamin A should not be administered if "therapeutic milk (e.g. Nutriset) is given" (p.103). It also recommends that preventative doses should be withheld if red palm oil is given in the ration. Any comments?
A draft version of another WHO document aimed at standardising protocols for the treatment of severe malnutrition and other childhood diseases also uses the doses quoted in the e-mail from Emorn Wasantwisut. It is would seem extremely desireable for different WHO publications to present standardised treatment plans for malnutrition.
While guidance exists on maximum levels of intake for vitamin A replete healthy people, e.g. UK DRVs publication (DOH, 1991), is there in fact any scientific basis for asigning a safe or unsafe level for therapeutic intake?
While there are a number of case reports in the literature is there any harder evidence available?
Andrew Seal PhD
Centre for International Child Health Institute of Child Health
30 Guilford Street, London WC1 1EH
Tel. (0171)242 9789 Ex.2468, FAX (0171)404 2062
Date: Mon, 23 Feb 1998 19:21:20 +0000
From: Michael Golden <refugeesatabdn.ac.uk>
Subject: Ngonut: F100 and vitamin A
The drafters of the MSF publication must have misunderstood the function of F100 (Thereapeutic Milk) and the levels of nutrients that are formulated in it - there is not sufficient in this product to treat vitamin A deficiency adequately - giving F100 is not a reason for failing to treat any specific micronutrient deficiency.
Prof. Michael H.N.Golden
Date: Mon, 23 Feb 1998 14:52:32 +0700 (GMT+0700)
From: Emorn Udomkesmalee <numdkatmahidol.ac.th>
Re: Ngonut: vitamin A doses in malnutrition
The practice of vitamin A supplementation in severely malnourished children that you described is the recommended treatment schedule for individuals with clinical signs of vitamin A deficiency or "active xerophthalmia", including those with nightblindness, conjunctival xerosis with Bitot's Spots, corneal xerosis, corneal ulceration and keratomalacia.
I would like to refer you to the 1997 WHO publication of the WHO/UNICEF/IVACG Task Force on "Vitamin A Supplements: a guide to their use in the treatment and prevention of vitamin A deficiency and xerophthalmia". Based on this, they recommended a prevention schedule for children at high risk of vitamin A deficiency who are children with measles, diarrhoea, respiratory disease, chickenpox, other severe infections or "severe protein-energy malnutrition" or those lived within the vicinity of children with clinical vitamin A deficiency. The schedule is as follows:
Infants <6 months of age 50,000 IU orally
Infants 6-12 months of age 100,000 IU orally
Children >12 months of age 200,000 IU orally
The supplements should be given every 4-6 months. To achieve wider coverage and cost-effectiveness, the supplementation should be coupled with other ongoing public health activities for example, immunization, growth monitoring etc.
About Mike's comments, on the issue of retinol binding protein (RBP), based on personal communication with Dr. Barbara Underwood a while back, she was able to do the relative dose response (RDR) test which is a technique to estimate the liver store of vitamin A in malnourished children. The technique entails giving an oral dose of vitamin A (450 to 1000 ug retinyl palmitate or acetate) and she can detect the blood response of holo-RBP (retinol + apo-RBP). There appears to be some RBP accumulated in the liver, although not a whole lot, but perhaps enough to prevent the eruption of eye signs. It is true that detection of early stages of vitamin A deficiency or subclinical level is not simple and poses a challenge everywhere. Children affected by subclinical deficiency are large, WHO Expert estimated around 190 to 240 million children are at risk of subclinical deficiency. Therefore, the efforts to find them and do something are worthed. Based on 1996 WHO publication on "Indicators for assessing vitamin A deficiency and their application in monitoring and evaluating intervention programs", there are a list of indicators, for example: functional indicator - night blindness, history of night blindness is helpful when a local term exists to describe it.
Biochemical indicators - breast milk vitamin A is helpful and rather non-invasive, serum retinol distribution of a population is useful, the dose response techniques should be used on a subsample basis to validate the problem.
Histological indicator - conjunctival impression cytology (CIC), impression cytology with transfer (ICT) - these are population indicator and should be used with others for best interpretation.
Ecologic and demographic indicators: nutritional status and diet,illness and diet patterns and socioeconomic variables.
These are helpful in mapping or locating vitamin A deficient areas/populations.
For the effect of vitamin A on epithelial integrity, the only thing I can comment on is that it took conjunctival epithelium from 2 weeks to several months to come back to normal after given vitamin A.
Please let me know if I can help in anyway.
Emorn U. Wasantwisut, PhD
Institute of Nutrition, Mahidol University at Salaya Phutthamonthon, Nakkon Pathom 73170, Thailand E-mail numdkatmahidol.ac.th, Tel. 662-889-3309, Fax: 662-441-9344