Bioefficacy of Beta-cryptoxanthin From Biofortified Maize

Vitamin A Deficiency Clinical Trial

— BIOCRYPT  

Official title:

Determination of Relative Bioavailability, Bioconversion and Bioefficacy of β-cryptoxanthin in Comparison to β-carotene From Biofortified Maize and External Stable Isotopes Using Compartmental Modelling

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04153968
• Other study ID #: BH183438
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: November 2020
• Source: Newcastle University
• Contact: Anthony Oxley, PhD
• Phone: 0191 208 1403
• Email: anthony.oxley[@]ncl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Since no quantitative information currently exists on how effectively the pro-vitamin A carotenoid (pVAC) β-cryptoxanthin (βCX) is converted to vitamin A (VA) in humans, this proof of principle study aims to compare the efficacy of both βCX and β-carotene (βC) to yield VA from biofortified maize. This data is critical before the breeding strategy for biofortified maize is directed towards high βCX-containing varieties in order to reduce VA deficiency in low-income countries.

Description:

Despite advances in reducing vitamin A (VA) deficiency worldwide, the prevalence remains highest and unchanged in sub-Saharan Africa and South Asia. Efficacy studies have demonstrated that increasing provitamin A carotenoid (pVAC) intake through consuming pVAC biofortified crops results in increased circulating β-carotene (βC) and VA body stores. It has also been shown that consumption of biofortified maize improved VA total body stores (TBS) as effectively as preformed VA supplementation, and significantly improved visual function in marginally VA deficient children. Despite the fact that βC is the primary focus of breeding programs for pVAC biofortified maize, there is convincing evidence that comparable dietary intakes of βC and β-cryptoxanthin (βCX) would result in 7-fold greater concentrations of βCX in blood.

The study is designed to determine for the first time the bioefficacy of βCX in comparison to βC in humans using state of the art isotope dilution techniques in combination with compartmental modelling. The project is conducted in two phases: Phase 1) the determination of best time points for assessment of βCX bioconversion, intestinal and postintestinal bioefficacy as well as quantifying TBS of VA in healthy volunteers; Phase 2) to test the bioefficacy of βCX and βC in maize by comparing a high βCX and low βC maize variety to a high βC and low βCX maize variety.

Phase 1 of the study involves 1 long study day (D0), where 10 ml of blood will be taken every 2 hours, via cannulation, for a total of 12 hours (70 ml of blood total). Subsequently, there are 13 followup visits on the mornings of Days 1, 2, 4, 7, 11, 14, 21, 28, 35, 49, 63, 77, and 91 where one 10 ml blood sample is taken.

Phase 2 of the study involves 2 whole days (D0 and D21) where approximately 10 ml of blood will be taken every 30-60 minutes, via cannulation, for a total of 8 hours (110 ml of blood total). Subsequently, there are 3 follow-up visits on the mornings of Days 1, 7, and 22 where one 10 ml blood sample is taken on each occasion.

In the mornings of the long/whole study days at either D0 or D21, participants will receive the muffin test meal before stable isotopes, dissolved in sunflower oil, are administered via oral pipette. At D0 or D21, the total dose of pVACs (labelled and unlabelled carotenoids) consumed in the muffin and oil is 3 mg alongside 0.4 mg of pre-formed VA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Females who are pregnant or lactating.

• Not disclosing use and type of contraceptives.

• Acute or chronic illness.

• Concurrent participation in another study.

• Unwillingness to discontinue personal nutritional supplements/vitamins.

• Major food allergies/intolerance to study ingredients.

• Previous history of anorexia or bulimia.

• Inability to refrain from drinking alcohol when requested.

• Fat mal-absorptive disorders or iron deficiency anaemia.

• Dietary preformed vitamin A intake >600 µg/d.

• BMI <20 and >29 kg/m2.

• Smoking.

Related Conditions & MeSH terms

• Night Blindness
• Vitamin A Deficiency

Intervention

Dietary Supplement:
• ß-cryptoxanthin
Phase 1: 2.0mg of [13C14]ß-cryptoxanthin, 1.0mg of [13C10]ß-carotene and 0.4mg [2H6]retinyl acetate are given in sunflower oil at Time 0. Phase 2: 1.5mg of [13C14]ß-cryptoxanthin, 0.75mg of [13C10]ß-carotene, 0.4mg [2H6]retinyl acetate are given in sunflower oil along with 0.25mg ß-carotene and 0.5mg ß-cryptoxanthin from maize are given at Time 0. Then, 0.75mg of [13C14]ß-cryptoxanthin, 1.5mg of [13C10]ß-carotene, and 0.4mg [2H6]retinyl acetate are given in sunflower oil along with 0.5mg ß-carotene and 0.25mg ß-cryptoxanthin from maize are given on day 21.

Locations

Country	Name	City	State
United Kingdom	Newcastle University	Newcastle Upon Tyne	Tyne & Wear

Sponsors (3)

Lead Sponsor	Collaborator
Newcastle University	International Food Policy Research Institute, Penn State University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bioefficacy of ß-cryptoxanthin	Plasma concentrations of [13C14]-ß-cryptoxanthin, [13C7]-retinyl esters, and [13C7]-retinol.	Phase 1 = 91 days. Phase 2 = 22 days.