Ontwikkeling van een methode voor het bestuderen van de omzetting van beta-caroteen in vitamine A.

Rationale: Vitamin A (retinol) deficiency is still a public health concern in developing countries. Stable isotope techniques are now used to accurately assess vitamin A status and to determine bioequivalence and bioconversion of β-carotene (provitamin A) to retinol.
Objective: To explore the potential of a novel retinol stable isotope dilution technique to assess the bioconversion and bioequivalence of dietary provitamin A.
Study design: This pilot study will be a 4-week double blind parallel interventional trial.
Study population: Female (n = 16) volunteers aged between 18-35 years will be recruited from the human volunteer database kept at Wageningen University and Research.
Intervention: Subjects will be randomly allocated to four treatment groups of equal size (n=4; group A–D). All subjects will be provided with a standardised meal on the evening before start of the study which they will consume at home between 18h00 and 20h00. They will additionally be asked to abstain from any food or beverage consumption, except water, until the next morning. At baseline (day 0) fasted blood samples will be collected from subjects, where after they will receive a once-off dose of 13C10-labelled β-carotene (2 mg) dissolved in high oleic sunflower oil as a capsule. Blood will subsequently be collected at 2, 4, 6, 8, 10, and 12 hours post dose via cannulation. Subjects will be provided with a standardized breakfast (after 2h blood draw), lunch (after 4h blood draw), and dinner (after 8h blood draw). The next day, after a fasting blood sample has been drawn (24h), subjects will receive a once-off dose of 13C10-labelled retinol (1 mg). For the duration of the rest of the study all subjects will daily receive a capsule containing 80 µg 13C10-labeled retinol (as retinyl acetate) and a capsule with a varying dose of unlabelled retinol (as retinyl acetate): group A, 150 µg; group B, 300 µg; group C, 500 µg; and group D, 800 µg. Additional fasting blood samples will be collected at day 7, day 14, day 21 and day 28 (end point). Subjects will be asked not to deviate from their habitual diets during the study, and intake of vitamin A rich products such as liver and supplements will be restricted.
Main study parameters/endpoints: Percentage of 13C10-labelled retinol in plasma with intakes of varying doses of unlabelled retinol over time (4 weeks), and the shape of the dose response curve. In addition, we will measure the area under the curve (AUC) of 13C10-labelled β-carotene and 13C5-labelled retinol in blood plasma over a 24h period.

We hypothesize that with this new stable isotope dilution method we will be able to assess the bioequivalence of dietary pro-vitamin A intake in future studies.

Day 1: 0h, 2h, 4h, 6h, 8h, 12h and 24h
Thereafter: Days 7, 14, 21, 28

Group A: 150 mcg retinol/day; Group B: 300 mcg retinol/day; Group C: 500 mcg retinol/day; Group D: 800 mcg retinol/day