Rationale: Postprandial lipemia, known to be associated with acute leukocyte activation, impairs endothelial function and promotes atherosclerosis. Deficiency of vitamin D is associated with increased cardiovascular risk, but the precise mechanism is still unclear. A recent pilot study performed in our laboratory showed improved postprandial vascular function by pulse wave analysis and decreased postprandial leukocyte activation after vitamin D supplementation. Interestingly, the effects on leukocyte activation were solely found in females.~Hypothesis: The beneficial effects of vitamin D administration on postprandial leukocyte activation are mediated by suppression of oxidative stress. High doses of vitamin D may have a more pronounced effect than low doses.~Objective: To estimate the effect sizes of different doses of vitamin D on postprandial leukocyte activation markers, oxidative stress and arterial stiffness in vitamin D deficient females.~Study design: Randomized, double blind pilot study. Study population: Premenopausal overweight and obese female volunteers with proven vitamin D deficiency, ≥ 18 years of age.~Intervention: Two oral fat load tests (OFLTs) will be performed. After the first OFLT, volunteers will be randomly assigned to receive a single low dose (75 000 IU) or high dose (300 000 IU) of cholecalciferol drink. One week later the OFLT will be repeated.~Main study parameters/endpoints: Postprandial leukocyte activation, oxidative stress parameters and arterial augmentation index.~Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The use of a single dose of 300 000 IU of cholecalciferol has been established to be a safe and effective way to correct vitamin D deficiency. Volunteers will be hospitalized on 2 different days (day 1, day 8) for approximately nine hours each day and receive an oral fat load. Cholecalciferol will be administered once. Volunteers will be instructed not to take vitamin D supplements during the study up until 3 months after the study. The volunteers' general practitioner will be informed on their participation. A total of 222ml (111ml for each postprandial test) of blood will be drawn. Volunteers will be allowed to drink only water during the tests. There is a theoretical risk of hypercalcemia but no excessive risk is involved. Volunteers receive 250 euros for full participation. Furthermore, volunteers will be told and given advice if they turn out to suffer from hyperlipidemia or any other condition.
Administration of vitamin D will have a beneficial effect on postprandial leukocyte activation, oxidative stress and arterial stiffness in vitamin D deficient females. High doses of vitamin D may have a more pronounced effect than low doses.