Estimation of Vitamin A Stores in Children and Women in Guatemala and Relation With Potential Toxicity Markers (GloVitAS-GU)

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

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).

Study Overview

• Status: Completed
• Conditions: Vitamin A Status
• Intervention / Treatment: Other: Normal Vitamin A intake; Other: High Vitamin A intake

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 178

Contacts and Locations

Study Locations

• Guatemala
  • Guatemala, Guatemala
    • Sacatepequez City Hall
  • Guatemala City, Guatemala
    • Mixco, La Comunidad City Hall
  • Guatemala City, Guatemala
    • Santa Catarina Pinula City Hall

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children and Women from Guatemala peri-urban areas or areas where High Vitamin A foods intake is reported. Convenience sampling according to the availability (time to participate in the study) of the participant, and acceptance of Blood sampling and Dietary assessments

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal Vitamin A intake; 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; 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).
High Vitamin A intake; 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; 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).

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin concentration in children	Measured with Quik Read Pro portable Device	At recruitment
Children weight and length	Measured with Scale and Measurement Rod	At recruitment
Systemic inflammation in children	Measured with Quik Read Pro portable Device	At recruitment
Iron status in children	Estimated by different techniques	28-day study period
Zinc status in children	Estimated by atomic emission spectrometry	28-day study period

Collaborators and Investigators

• Sponsor: Institute of Nutrition of Central America and Panama
• Collaborators: Bill and Melinda Gates Foundation; Newcastle University; International Atomic Energy Agency
• Investigators: Principal Investigator: Dora I Mazariegos, MsSc, Institute of Nutrition of Central America and Panama

Publications and helpful links

General Publications

• Ford JL, Green JB, Haskell MJ, Ahmad SM, Mazariegos Cordero DI, Oxley A, Engle-Stone R, Lietz G, Green MH. 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. J Nutr. 2020 Feb 1;150(2):411-418. doi: 10.1093/jn/nxz225.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2017
• Primary Completion (Actual): September 13, 2017
• Study Completion (Actual): October 30, 2017

Study Registration Dates

• First Submitted: August 25, 2017
• First Submitted That Met QC Criteria: November 13, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: dietary assessment; Vitamin A; Isotopic dilution
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Micronutrients; Antioxidants; Anticarcinogenic Agents; Vitamins; Vitamin A; Retinol palmitate
• Other Study ID Numbers: CIE-REV 061/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All Collected individual participant data (IPD) will be shared within the researchers group of the Global Project (GLOVITAS, leaded by Newcastle University). Only initials will identify individual participants and the information shared will be on biochemical markers, diet, and general socioeconomic data.
• IPD Sharing Time Frame: Data will become available when, after study data collection is finished, data are cleaned and analyzed.
• IPD Sharing Access Criteria: All pre-defined researchers will have access to database. This includes Georg Lietz, principal coordinator, and local Principal researchers.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No