Optimizing Nuclear Techniques to Assess Vitamin A Status

Closed for proposals

Project Type

Coordinated Research Project

Project Code

E43030

CRP

2049

Approved Date

6 February 2015

Status

Closed

Start Date

6 February 2015

Expected End Date

6 February 2020

Completed Date

28 May 2020

Participating Countries

United Kingdom of Great Britain and Northern Ireland
United States of America

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.

CRP Publications

Type

Peer-reviewed publication

Year

2017

Publication URL

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569465/

Description

Low plasma vitamin A concentration is associated with tuberculosis in Moroccan population: a preliminary case control study

Country/Organization

Morocco

Type

Peer-reviewed publication

Year

2018

Publication URL

https://academic.oup.com/cdn/article/2/11/nzy071/5076022

Description

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data

Country/Organization

USA

Type

Peer-reviewed publication

Year

2020

Publication URL

https://www.sciencedirect.com/science/article/pii/S002231662202380X?via%3Dihub

Description

Overlapping Vitamin A Intervention Programs: Should We Be Concerned with Excessive Intakes?

Country/Organization

UK

Type

Peer-reviewed publication

Year

2019

Publication URL

https://academic.oup.com/jn/article/149/11/2065/5514147

Description

Addition of Vitamin A Intake Data during Compartmental Modeling of Retinol Kinetics in Theoretical Humans Leads to Accurate Prediction of Vitamin A Total Body Stores and Kinetic Parameters in Studies of Reasonable Duration

Country/Organization

USA

Type

Peer-reviewed publication

Year

2022

Publication URL

https://www.sciencedirect.com/science/article/pii/S2475299123121044?via%3Dihub

Description

Filipino Children with High Usual Vitamin A Intakes and Exposure to Multiple Sources of Vitamin A Have Elevated Total Body Stores of Vitamin A But Do Not Show Clear Evidence of Vitamin A Toxicity

Country/Organization

Philippines

Type

Peer-reviewed publication

Year

2023

Publication URL

https://www.sciencedirect.com/science/article/abs/pii/S0022316623065902?via%3Dih…

Description

Comparison of Total Body Vitamin A Stores Using Individual versus Population (13)C-Natural Abundance of Serum Retinol in Preschool Children and Women Residing in 6 Diverse African Countries

Country/Organization

USA/global

Type

Peer-reviewed publication

Year

2023

Publication URL

https://www.sciencedirect.com/science/article/pii/S0022316622131226?via%3Dihub

Description

Association between Biomarkers of Inflammation and Total Liver Vitamin A Reserves Estimated by (13)C-Retinol Isotope Dilution among Preschool Children in 5 African Countries

Country/Organization

USA/global

Type

Peer-reviewed publication

Year

2021

Publication URL

https://www.sciencedirect.com/science/article/pii/S002231662200092X?via%3Dihub

Description

Development of a Compartmental Model to Investigate the Influence of Inflammation on Predictions of Vitamin A Total Body Stores by Retinol Isotope Dilution in Theoretical Humans

Country/Organization

USA

Type

Peer-reviewed publication

Year

2022

Publication URL

https://www.sciencedirect.com/science/article/pii/S0022316622006538

Description

Time Since Dose and Dietary Vitamin A Intake Affect Tracer Mixing in the 13C-Retinol Isotope Dilution Test in Male Rats

Country/Organization

USA

Type

Peer-reviewed publication

Year

2022

Publication URL

https://www.sciencedirect.com/science/article/abs/pii/S0022316623086583?via%3Dih…

Description

Total Liver Vitamin A Reserves, Determined With C-13(2)-Retinol Isotope Dilution, are Similar Among Tanzanian Preschool Children in Areas With Low and High Vitamin A Exposure

Country/Organization

Tanzania

Type

Peer-reviewed publication

Year

2020

Publication URL

https://academic.oup.com/jn/article/150/8/2223/5866527

Description

Vitamin A Absorption Efficiency Determined by Compartmental Analysis of Postprandial Plasma Retinyl Ester Kinetics in Theoretical Humans

Country/Organization

USA

Type

Peer-reviewed publication

Year

2020

Publication URL

https://www.sciencedirect.com/science/article/pii/S0022316622022301?via%3Dihub

Description

Vitamin A Absorption Determined in Rats Using a Plasma Isotope Ratio Method

Country/Organization

USA

Type

Peer-reviewed publication

Year

2020

Publication URL

https://academic.oup.com/jn/article/150/5/989/5680470

Description

Better Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method Are Possible with Deeper Understanding of the Mathematics and by Applying Compartmental Modeling

Country/Organization

USA

Type

Peer-reviewed publication

Year

2020

Publication URL

https://academic.oup.com/jn/article/150/2/411/5571550

Description

Use of Model-Based Compartmental Analysis and a Super-Child Design to Study Whole-Body Retinol Kinetics and Vitamin A Total Body Stores in Children from 3 Lower-Income Countries

Country/Organization

USA/global

Type

Peer-reviewed publication

Year

2023

Publication URL

https://onlinelibrary.wiley.com/doi/full/10.1111/mcn.13486

Description

Comparing two simplified questionnaire-based methods with 24-h recalls for estimating fortifiable wheat flour and oil consumption in Mandaluyong City, Philippines

Country/Organization

Philippines

Type

Peer-reviewed publication

Year

2021

Publication URL

https://www.sciencedirect.com/science/article/pii/S0022316622001699?via%3Dihub

Description

Determination of Vitamin A Total Body Stores in Children from Dried Serum Spots: Application in a Low- and Middle-Income Country Community Setting

Country/Organization

UK

Type

Peer-reviewed publication

Year

2022

Publication URL

https://www.sciencedirect.com/science/article/pii/S0002916522002222?via%3Dihub

Description

Chronic and acute hypervitaminosis A are associated with suboptimal anthropometric measurements in a cohort of South African preschool children

Country/Organization

South Africa

Type

Peer-reviewed publication

Year

2019

Publication URL

https://www.sciencedirect.com/science/article/pii/S0002916522011558?via%3Dihub

Description

South African preschool children habitually consuming sheep liver and exposed to vitamin A supplementation and fortification have hypervitaminotic A liver stores: a cohort study

Country/Organization

South Africa

Type

Peer-reviewed publication

Year

2019

Publication URL

https://academic.oup.com/jn/article/149/7/1282/5490312

Description

Inclusion of Vitamin A Intake Data Provides Improved Compartmental Model-Derived Estimates of Vitamin A Total Body Stores and Disposal Rate in Older Adults

Country/Organization

USA

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