|Matthan, Nirupa - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Meng, Huicui - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Shapses, Sue - Rutgers University|
|Schneider, Stephen - Rutgers University|
|Lichtenstein, Alice - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: American Society for Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 1/15/2018
Publication Date: 6/10/2018
Citation: Matthan, N., Meng, H., Shapses, S.A., Schneider, S.H., Lichtenstein, A.H. 2018. High-dose vitamin D supplementation interferes with cholesterol absorption and affects circulating cholesterol levels in overweight/obese post-menopausal women [abstract]. American Society for Nutrition. Abstract No. OR14-01.
Technical Abstract: Objective: Data on the relationship between vitamin D and CVD risk is inconsistent. This may be due to unaccounted for variability among individuals at the intestinal level. We assessed whether high-dose vitamin D3 supplementation alters in vivo cholesterol homeostasis (absorption and synthesis) and subsequently circulating plasma 25-hydroxyvitamin D (25-OHD) and total cholesterol (TC) levels, and whether these responses are modified in individuals with inherently high versus low cholesterol absorption rates (hyper- and hypo-absorbers). Methods: Archived serum aliquots from a randomized double-blind controlled trial designed to determine the effect of 1-year supplementation with 600, 2000 or 4000 IU daily of vitamin D3 on bone parameters in overweight/obese (BMI, 30.2 +/- 3.8 kg/m2) post-menopausal women (n=12-16/group; 58+/-6 years; 25-OHD <30 ng/mL at screening; not taking lipid lowering medication) were analyzed for markers of cholesterol absorption (campesterol, B-sitosterol) and synthesis (squalene, desmosterol, lathosterol) by gas chromatography. Participants were classified as hypo- or hyper-responders based on serum campesterol levels below or above the median value (9.6umol/L) at baseline. Results were merged with available data for serum 25-OHD and TC levels. Results: The 4000 IU dose resulted in significantly lower serum campesterol (-16%), B-sitosterol (-11%) and TC (-4%) levels compared to baseline as well as the lower doses. Interestingly, hyper-absorbers had a trend toward lower 25-OHD levels (35 vs. 42 ng/mL, p=0.09) and less reduction in TC (-2% vs. -7%, p<0.05) than hypo-absorbers to 4000 IU vitamin D3 supplementation. Markers of cholesterol synthesis remained unchanged at all doses and among hypo- and hyper-absorbers. Conclusion: Chronic high-dose vitamin D3 supplementation interferes with cholesterol absorption, without a compensatory increase in synthesis, thus resulting in lower TC levels. This pleotropic effect of high-dose vitamin D3 supplementation was diminished in hyper- compared to hypo-absorbers. This may be due to diminished bioavailability of the nutrient secondary to competition with cholesterol at the level of intestinal transport proteins, thereby attenuating potential beneficial effects of supplementation in cholesterol hyper-absorbers.