The Vitamin A Supplementation (VAS) Controversy

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A recent report and podcast from the British Medical Journalhas revived the controversy on when to scale back high-dose vitamin A supplementation (VAS) to reduce child mortality.We believe only compelling evidence can justify scaling back this intervention for the reasons pointed out below.

VAS is a Safe and Cost-effective Strategy for Reducing Child Mortality

Estimates from the World Health Organization (WHO) indicate that still 190 million children aged under five (U5) are vitamin A deficient (VAD).VAD increases the risk of disease and death from severe infections, and is the leading cause of preventable blindness in children U5. Well-controlled randomized trials in different regions with a high prevalence of VAD have conclusively demonstrated that high-dose vitamin A supplementation (VAS) given every four to six months to children U5 is an efficient and cost-effective strategy for reducing child mortality. VAS programs have largely contributed to the reduction in U5 mortality rates over the last decades.

Vitamin A, VAS, DEVTA, Supplementation, Child mortality 
A 2011 Cochrane review of 17 randomized controlled trials (RCTs) in 9 countries concluded that VAS results in a 24% reduction in U5 child mortality rate.This reduction in all-cause mortality confirmed an earlier meta-analysis from 1993, in which WHO’soriginal VAS guidelines were based upon and adopted by over 80 countries. There is also strong evidence, from both community and clinical trials, that VA prophylaxis and treatment can reduce the severity and fatality from measles, diarrhoea, and reduce the risk of hearing loss following middle ear infections. The most recent 2017 Cochrane reviewof 47 RCTs conducted in 19 countries concluded that vitamin A supplementation to U5 results in a significant 12% reduction for both all-cause mortality and mortality due to diarrhoea.6

DEVTA Contradicts the Evidence of VAS on Child Mortality

Cutting in half VAS effect on mortality between the 2011 and 2017 Cochrane reviews differ due to the latter’s inclusion of the DEVTA (Deworming and Enhanced Vitamin A) study,a large-scale program evaluation in the state of Uttar Pradesh, India. The ‘DEVTA study’ was an attempt to evaluate a large supplementation program providing VAS every six months through routine services. Approximately two million preschool children were reportedly enrolled through the Anganwadi Centres of the Integrated Child Development Scheme (ICDS) for the study and comparisons were made between usual care, 6-monthly VAS, 6-monthly albendazole (for deworming), or both. The intervention continued for 5 years and concluded that VAS did not reduce child mortality, although there was a 4% non-significant decline.

The DEVTA Study Had Limitations in the Program Design, Implementation, and Evaluation

Certain elements in the program design may shed light on the lack of effect in DEVTA. The research activity was vastly under-staffed with only 18 monitors overseeing the work of over 8,300 Anganwadi workers and the participation of two million children. This lack of human resources required the number of children and their levels of compliance to be determined only from a mid-study census using anon-random opportunistic sample of 2,106 children out of two million, therefore leaving the estimate open to bias. Thus, this number represented ‘compliers’ at the time of the census, rather than the numbers of children and capsules taken throughout the intervention. The authors reported an overall compliance of 86%, raising questions about accuracy of record keeping. Finally,the DEVTA evaluation also did not include younger children between 6-12 months, who normally account for one-third of the deaths in children U5 and would have benefited most from VAS.

The DEVTA Results Should Not Be Combined with Other Trials

Delivering VA to children every six months is a well-established intervention to reduce child mortality. The DEVTA study represented an earnest attempt to assess a large VAS program run by the Government of India with only a non-significant reduction in child mortality. The evaluation was expected to have revealed a greater program impact. The reasons for this ineffective program were due to how it was run and evaluated, problems that commonly afflict most large intervention strategies. There are many lessons to be learned from this undertaking, both with respect to VA delivery and program design, implementation, and resources needed for running and evaluating programs. We encourage the global scientific community to resist combining the DEVTA findings (as done in the 2017 Cochrane review) with those of previous, rigorously conducted trials to reset the overall “efficacy” of VA in reducing child mortality. Doing so could send the wrong message that mixing program evaluation results with those of well-controlled randomized human trials is an acceptable strategy, when it is not, especially when millions of children lives are potentially at stake.

Scaling Back of VAS Requires Compelling Evidence

As VAS saves lives, eyesight, and hearing of children only irrefutable evidence can justify scaling back this intervention. While continuing VAS programs, it is also critical to address the direct and underlying causes of VAD through effective interventions (e.g., dietary diversity, breastfeeding, fortification, hygiene, etc.). According to the Global Alliance for Vitamin A (GAVA),9it would only be justifiable to scale back VAS if VAD were no longer a public health issue (<5% biochemical VAD at population level). Only evidence from regular data collection in countries (at least every 10 years for VA intake and status data in children), or other data indicating a reduction in VAD, shall inform decisions to phase out of VAS.10

WHO Recommendations

In settings where VAD is a public health problem (prevalence of night blindness is 1% or higher in children 24–59 months of age or where the prevalence of biochemical VAD (serum retinol 0.70 µmol/L or lower) is 20% or higher in infants and children 6–59 months of age), high-dose VAS (200,000 IU) is recommended for children 12–59 months of age (with a single half-dose for infants 6-11 months of age) every 4-6 months.5

References

1. Mason JB, Benn CS, Sachdev H, West KP Jr, Palmer AC, Sommer A. Should universal distribution of high dose vitamin A to children cease? BMJ. 2018 Mar 1;360:k927. doi: 10.1136/bmj.k927.

2. Mason JB, Sanders D, Greiner T, Shrimpton R, Yukich J. Vitamin A deficiency: policy implications of estimates of trends and mortality in children.Lancet Glob Health. 2016 Jan;4(1):e21. doi: 10.1016/S2214-109X(15)00246-6.

3. WHO. Global prevalence of vitamin A deficiency in populations at risk 1995–2005. WHO Global Database on Vitamin A Deficiency. Geneva, World Health Organization, 2009. (accessed 25 April 2018).

4. Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ. 2011 Aug 25;343:d5094. doi: 10.1136/bmj.d5094.

5. WHO. Guideline: Vitamin A supplementation in infants and children 6–59 months of age. Geneva, World Health Organization, 2011. (accessed 25 April 2018).

6. Imdad A, Mayo-Wilson E, Herzer K, Bhutta ZA.Vitaminsupplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst Rev. 2017 Mar 11;3:CD008524. doi: 10.1002/14651858.CD008524.pub3.

7. Awasthi S, Peto R, Read S, Clark S, Pande V, Bundy D; DEVTA (Deworming and Enhanced Vitamin A) team. Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial. Lancet2013 Apr 27;381(9876):1469-77. doi: 10.1016/S0140-6736(12)62125-4. Epub 2013 Mar 14.

8. Habicht JP, Victora C. Vitamin A supplementation in Indian children. Lancet. 2013 Aug 17;382(9892):592. doi: 10.1016/S0140-6736(13)61736-5.

9. The Global Alliance for Vitamin A (GAVA). Assessing vitamin A status in population based surveys. Draft statement, 2017.

10. Wirth JP, Petry N, Tanumihardjo SA, Rogers LM, McLean E, Greig A, Garrett GS, Klemm RD, Rohner F. Vitamin A Supplementation Programs and Country-Level Evidence of Vitamin A Deficiency.Nutrients. 2017 Feb 24;9(3). pii: E190. doi: 10.3390/nu9030190.

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Introducing Vitamin A

Understanding the basics

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‘’Mommy, Mommy’’, the little girl screams in the middle of the night. A bad dream and afraid of the dark she calls to her mommy who switches on a light. Calm is restored. But what if the girl wakes and cannot see? For many children in the developing word this is a reality. Vitamin A deficiency (VAD) is the leading cause of preventable blindness in children and increases the risk of disease and death from severe infections. Today Vitamin A deficiency remains a public health problem in more than half of all countries, especially in Africa and South-East Asia, with young children and pregnant women in low-income countries at greatest risk.

What Vitamin A Does

Vitamin A plays a central role in our vision, skin, genes, growth, and immune system. It is especially important during the early stages of pregnancy in supporting the developing embryo. Infections and fevers increase the requirement for vitamin A.

Retinol

Three different forms of vitamin A are active in the body: retinol, retinal, and retinoic acid. These are known as retinoids. The cells of the body can convert retinol and retinal to the other active forms of vitamin A as needed.

Each form of vitamin A performs specific tasks. Retinol supports reproduction and is the major transport form of the vitamin. Retinal is active in vision and is an intermediate in the conversion of retinol to retinoic acid. Retinoic acid acts like a hormone, regulating cell differentiation, growth, and embryonic development. Foods derived from animals provide retinol in a form that is easily digested and absorbed.

Carotenoids

Foods derived from plants provide carotenoids, some of which have vitamin A activity. The body can convert carotenoids like β-carotene, α-carotene and β-cryptoxanthin into vitamin A. The conversion rates from dietary carotene sources to vitamin A are 12:1 for β-carotene and 24: 1 for β-cryptoxanthin.

Sources of Vitamin A 

Retinol: Liver, Egg Yolk, Butter, Whole Milk, and Cheese

Carotenoids: Orange flesh fruits (i.e. Sweet Potatoes, Melon, Mangos), Green leafy vegetables (spinach, broccoli), Carrots, Pumpkins, Red pam oil

Bioavailability of Vitamin A 

The degree to which it is absorbed in our bodies, bioavailability, of vitamin A derived from animal sources is high – about 70–90% of the vitamin A ingested is absorbed by the body. Carotenoids from plant sources are absorbed at much lower rates – between 9% and 22% – and the proportion absorbed decreases as more carotenoids are consumed.

Dietary fat enhances the absorption of vitamin A. Absorption of β-carotene is influenced by the food matrix. β-carotene from supplements is more readily absorbed than β-carotene from foods, while cooking carrots and spinach enhances the absorption of β-carotene. Diarrhea or parasite infections of the gut are associated with vitamin A malabsorption.

Risks of Vitamin A

About 90% of vitamin A is stored in the liver. Vegetarians can meet their vitamin A requirements with sufficient intakes of deeply colored fruits and vegetables, with fortified foods, or both. Vitamin A deficiency is a major problem when diets consist of starchy staples, which are not good sources of retinol or β-carotene, and when the consumption of deeply colored fruits and vegetables, animal-source foods, or fortified foods is low. Vitamin A plays a role in mobilizing iron from liver stores, so vitamin A deficiency may also compromise iron status. Excessive intakes of pre-formed vitamin A can result in high levels of the vitamin in the liver – a condition known as hypervitaminosis A. No such risk has been observed with high β-carotene intakes.

Additional information on vitamins and micronutrient deficiencies is available though our partner, Vitamin Angels or download our complete vitamin and mineral guide here

Here are some recipes to easily incorporate Vitamin-A rich foods in your diet!

Sweet Potato Fries 

Betacarotene, vitaminIngredients
95g of sweet potato
¼ tsp cayenne pepper (substitute with whatever spices you have available locally such as chill flakes or chill powder)
½ tsp rapeseed oil

Method
Heat oven to 200C/180C fan/ gas 6. Put the sweet potato fries on a baking tray and mix with the rapeseed oil and cayenne pepper. Bake in the oven for 20 mins

Spanish Tortilla

EggsIngredients
300g of baby spinach leaves
Large white onion, chopped
4 tbsp olive, sunflower or rapeseed oil
25g butter
400g potatoes (peeled and finely sliced)
8 eggs beaten
2 cloves of garlic

Method
Put the spinach in a large colander and pour over a kettleful of boiling water. Drain well and, when cooled a little, squeeze dry, trying not to mush up the spinach too much.

1. Put a large non-stick frying pan on a low heat. Cook the onion slowly in the oil and butter until soft but not brown – this should take about 15 mins. Add the potatoes, cover the pan, and cook for a further 15-20 mins, stirring occasionally to make sure they fry evenly

2. When the potatoes are soft and the onion is shiny, crush 2 garlic cloves and stir together with the spinach followed by the beaten eggs

3. Put the lid back on the pan and leave the tortilla to cook gently. After 20 mins, the edges and base should be golden, the top set but the middle still a little wobbly. To turn it over, slide it onto a plate and put another plate on top, turn the whole thing over and slide it back into the pan to finish cooking. Once cooked, transfer to a plate and serve the tortilla warm or cold.

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