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Optimizing Nuclear Techniques to Assess Vitamin A Status
Closed for proposals
Project Type
Project Code
E43030CRP
2049Approved Date
Status
Start Date
Expected End Date
Completed Date
28 May 2020Participating Countries
Description
The proposed CRP will contribute to a better understanding of the appropriate use of the stable isotope dilution technique to assess vitamin A status across the continuum from deficiency to toxicity in children under the age of 5 years. The findings will provide guidance for programme managers and public health nutrition policy makers to optimize the evaluation of their vitamin A programmes, in particular in countries where multiple vitamin A interventions are in place, and enable them to improve national nutrition strategies and plans. The combination of malnutrition, including micronutrient malnutrition, and infectious diseases is the most prevalent and preventable public health problem in the world; responsible for millions of deaths annually, particularly in infants and children. Infections affect nutritional biomarkers making it difficult to assess the real magnitude of some nutritional problems, for example vitamin A deficiency. Vitamin A is involved in numerous physiological processes essential for normal growth and development, the immune system, the visual system, and other functions in the human body. Vitamin A deficiency is a major nutritional concern in low-resource households in low-income countries. Vitamin A fortified foods such as sugar, margarine, vegetable oil, milk, and wheat flour as well as micronutrient powders and supplements, have been used as a complementary approach. The potential risk of excess vitamin A intake is increased due to a lack of coordination to avoid overlap of intervention coverage. Additionally, assessing vitamin A status, and the effectiveness of government interventions, is challenging in settings where infectious diseases and micronutrient deficiencies are endemic, as in most low-income countries. The isotope dilution technique, which will be used in this CRP, is among the most accurate techniques for assessing total body vitamin A pool size in individuals. However, it is not known whether the method is valid under conditions of hypervitaminosis A, inflammation and selected micronutrient deficiencies. Therefore, this CRP will address methodological issues in the application of the stable isotope dilution technique to accurately determine vitamin A stores in children and thus, provide important new knowledge on optimising the stable isotope dilution technique for the assessment of vitamin A status. The CRP will be complementary to a grant of the Bill & Melinda Gates Foundation that assesses the risk of vitamin A toxicity due to large scale food fortification and other interventions with the University of Newcastle as grantee.
Objectives
To provide new knowledge and evidence on the application of the isotope dilution technique to assess vitamin A status and the risk of excess vitamin A intake in children under the age of 5 years, where large scale food fortification and other interventions are in place to reduce vitamin A deficiency.
Specific objectives
Obtain new information on the validity of the stable isotope dilution technique to assess total body stores of vitamin A across the continuum from deficient to sub-toxic and toxic status in the context of selected micronutrient deficiencies, inflammation and infection.
Impact
The CRP explored and applied the retinol isotope dilution (RID) method, which is among the most accurate techniques for assessing vitamin A status across the full range of stores. The method was applied in research studies to assess vitamin A status from deficiency to excess in different populations and in the context of inflammation. The CRP concluded that, in contrast to conventional methods, the RID method can assess vitamin A status in individuals with high vitamin A consumption and body stores. The RID technique also works well during inflammation, although it is not recommended in individuals with active infections at the time of dosing. Recent mathematical modelling indicated that total vitamin A body stores can be accurately predicted in populations with a high burden of infections if blood sampling is not done earlier than 2 weeks after dose administration.
A few research questions remain to be confirmed or addressed, above all, the extent to which the method is affected by inflammation at the time of dosing. In addition, markers of vitamin A toxicity and their cut-offs and relation with total vitamin A body stores and hepatic vitamin A concentration need to be defined as well as ranges of dose amounts and the interaction of the RID method with other micronutrients.
This CRP informed the design of a follow-up CRP E43035 on ‘Optimising nuclear techniques to assess vitamin A status in population surveys – from deficiency to excess (Phase II)’ which was initiated to adapt the RID method and maximise its relevance at larger scale to accurately assess vitamin A status in populations and to address the risk of excess vitamin A intake, ultimately to support decision-making processes in vitamin A programmes.
Relevance
The RID method, a nuclear technique, is the only method that can quantitatively measure vitamin A status over the entire spectrum from deficiency to excess without the need for a liver biopsy. The use of the method will allow data on both vitamin A deficiency and excess to be used to guide public health nutrition programs.
Populations exposed to multiple vitamin A interventions may be at risk of high intake and status. The CRP demonstrated that this is where the RID method can be used to evaluate the safety of vitamin A programmes by estimating the prevalence of “high” liver vitamin A concentrations in target populations. If the prevalence of “high” liver vitamin A concentrations increases in a target population over time, intervention strategies could be reassessed
As more countries start seeing an improvement in vitamin A status in the era of overlapping vitamin A interventions, there is a critical need to monitor the prevalence of vitamin A deficiency and vitamin A excess in the population. In the meantime, vitamin A deficiency still poses a serious public health challenge for children in much of the developing world. Universal distribution of periodic high-dose vitamin A remains vital in countries where vitamin-A-fortified and vitamin-A-rich foods are not widely available or accessible.
One set of studies in this CRP used a super-child model to establish parameters for calculating total vitamin A body and liver stores. The CRP confirmed the importance of using the RID method (1) for determining the prevalence of vitamin A deficiency and high or excessive vitamin A status in a population or selected subgroups, (2) for assessing quantitative impact of experimental interventions, (3) for better understanding of the vitamin A requirements and building reference data for total vitamin A body stores, and (4) in representative samples of the population to help decide whether it is appropriate to modify or withdraw an intervention such as vitamin A high-dose supplements, and to evaluate the effectiveness and safety of ongoing programmes.