Estimation of Vitamin A Stores in Children and Women in Guatemala and Relation With Potential Toxicity Markers

Study Overview
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Brief Summary
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The goal of this study is to assess whether 3-5 years-old children who have Vitamin A intakes above the tolerable upper intake level (UL=900 ug per day) have higher total body Vitamin A stores and biomarkers of excessive vitamin A status, compared to children with Normal Vitamin A intakes (250-600 ug per day).

Detailed Description
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The goal of this study is to assess whether VA intakes above the tolerable upper intake level (UL) and exposure to multiple programs are associated with are associated with 1) exposure to multiple VA intervention programs, and 2) elevated liver vitamin A concentration and biomarkers of excess vitamin A. Guatemala was selected as a study site because the country has a long standing national fortification program for vitamin A in sugar (law since 1975, re-launched and maintained since the 90´s). Typically, fortified sugar is used in more than 90% of households at average concentrations of 9 to 10 µg/g of sugar. VA fortified foods, in the form of fortified sugar, foods prepared with fortified sugar and other fortified foods, reach children from 2 years old to adulthood. On the other hand, high dose VA supplements, provided by local health services, only reached 10.5% of children ages 6-59 month in 2013. Children ages 2-3 and 4-5 years old with VA intakes above and below the UL will be recruited together with their mothers to assess the cumulative effect of fortification on young children and their mothers. Data from Program of Food and Nutrition Security (PROSAN), of the Ministry of Health, Guatemala in 2013, shows that coverage in the 30 Health Areas of the country is 17.9%, the lowest is 4.4% (San Marcos) and the largest 33% (Petén). Four of the 30 Region Areas correspond to the Department of Guatemala, in which urban and peri-urban areas of Guatemala City are included. In Central and North-West Guatemala Areas, coverage is 23 and 22% respectively, both above national average coverage and within the 10 out of 30 top coverages. According to PROSAN data for Micronutrient Powders in 2013, all four regions North-East, North-West, South, and Central Guatemala areas are also around or above the national coverage (14%) with 21.8, 11.2, 17.3 and 13.8% coverage. Another advantage of remaining in the 4 areas of Health around Guatemala city is that the four combined amount for 300,000 children of 0-59 month-old, that is more than 15% of the national children population reported. Even if coverages are low, population density will easier children recruitment.

Official Title
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LOAEL/NOAEL and UL Determination in Guatemala - Estimation of Vitamin A Stores in Children and Women and Correlation With Potential Toxicity Markers

Conditions
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Vitamin A Status

Intervention / Treatment
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* Other: High Vitamin A intake
* Other: Normal Vitamin A intake


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 3-5 years old and their mothers Child VA intake must be above 250 micrograms/day Children must be apparently healthy, Hemoglobin>9 g/dL at recruitment point, C-reactive protein<5 mg/L. For Women, Hemoglobin>10 g/dL, C-reactive protein<5 mg/L Exclusion Criteria: °Children with Congenital or chronical diseases, reported illnesses 1 week before the test. For Women: Pregnancy or lactation, Previously known Chronic Diseases

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal Vitamin A intake<br>Normal Vitamin A intake will be assessed by a questionnaire directed to the consumption of food items with high VA content on the 7 days prior to the questionnaire. The daily consumption will be assessed on average. A child is assigned to Normal Vit. A consumption if daily Vit. A is between 250 and 600 micrograms per day. | Other: Normal Vitamin A intake<br>* Total Vitamin A stores will be assessed by isotopic measurement, 13C-Retinol will be given to the subject and blood wil be drawn on Day 4 to assess the isotopic dilution in the plasma. Other biochemical indicators will be assessed too, along with Dietary assessment (Food Frequency, 24 hours recalls).<br>|
| High Vitamin A intake<br>High Vitamin A intake will be assessed by a questionnaire directed to the consumption of food items with high VA content on the 7 days prior to the questionnaire. The daily consumption will be assessed on average. A child is assigned to High Vit. A consumption if daily Vit. A is above 900 micrograms per day. | Other: High Vitamin A intake<br>* Total Vitamin A stores will be assessed by isotopic measurement, 13C-Retinol will be given to the subject and blood wil be drawn on Day 4 to assess the isotopic dilution in the plasma. Other biochemical indicators will be assessed too, along with Dietary assessment (Food Frequency, 24 hours recalls).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Vitamin A stores among 3-5 years-old children, in micromoles | Estimated using Carbon 13 (13C) 13C-retinol dilution method, by the ratio of Labelled (stable isotope) versus no labelled Vitamin A in plasma 4 days after dose of labelled VA is given. | 28-day study period | 
| Total dietary vitamin A intake among 3-5 years-old children, in micrograms (ug) | Estimated using 24-hour dietary recalls, observed weigh food records, food and supplement frequency questionnaire | 28-day study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma retinol among 3-5 years-old children | Estimated by High Performance Liquid Chromatography (HPLC) | 28-day study period | 
| Plasma retinol binding protein among 3-5 years-old children | Estimated by ELISA | 28-day study period | 
| Plasma Transthyretin among 3-5 years-old children | Estimated by immunometric automated assay | 28-day study period | 
| Bone Health markers among 3-5 years-old children | Estimated by different techniques | 28-day study period | 
| Liver function markers among 3-5 years-old children | Estimated by different techniques | 28-day study period | 
| Plasma retinol among women | Estimated by HPLC | 28-day study period | 
| Plasma retinol binding protein among women | Estimated by ELISA | 28-day study period | 
| Plasma Transthyretin among women | Estimated by immunometric automated assay | 28-day study period | 
| Total dietary vitamin A intake among women, in micrograms (ug) | Estimated using 24-hour dietary recalls, observed weigh food records, food and supplement frequency questionnaire | 28-day study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin A, Isotopic dilution, dietary assessment