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Bioefficacy of Beta-cryptoxanthin From Biofortified Maize

Not Applicable
Conditions
Vitamin A Deficiency
Interventions
Dietary Supplement: β-cryptoxanthin
Registration Number
NCT04153968
Lead Sponsor
Newcastle University
Brief 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.

Detailed 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 & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Phase 1β-cryptoxanthinDetermination absorption and bioconversion kinetics of \[13C14\]β-cryptoxanthin and provide external validation for single-sample prediction methods.
Phase 2β-cryptoxanthinTest the bioefficacy of provitamin A carotenoids (pVACs) in maize by comparing a high β-cryptoxanthin:β-carotene (βCX:βC) variety to a low βCX:βC variety in combination with external \[13C\]-labelled pVACs.
Primary Outcome Measures
NameTimeMethod
Bioefficacy of β-cryptoxanthinPhase 1 = 91 days. Phase 2 = 22 days.

Plasma concentrations of \[13C14\]-β-cryptoxanthin, \[13C7\]-retinyl esters, and \[13C7\]-retinol.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Newcastle University

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Newcastle Upon Tyne, Tyne & Wear, United Kingdom

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