Exploring the effect of vitamin D3 supplementation on surrogate biomarkers of cholesterol absorption and endogenous synthesis in patients with type 2 diabetes-randomized controlled trial

Authors: MENG, HUICUI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ANGELLOTTI, EDITH - Tufts Medical Center; PITTAS, ANASTASSIOS - Tufts Medical Center; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/20/2020
Publication Date: 6/19/2020
Citation: Meng, H., Matthan, N., Angellotti, E., Pittas, A.G., Lichtenstein, A.H. 2020. Exploring the effect of vitamin D3 supplementation on surrogate biomarkers of cholesterol absorption and endogenous synthesis in patients with type 2 diabetes-randomized controlled trial. The American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqaa149.
DOI: https://doi.org/10.1093/ajcn/nqaa149

Interpretive Summary: Concentrations of serum 25-hydroxyvitamin D [25-(OH)D] have been inversely associated with circulating plasma cholesterol concentrations. Postulated mechanisms include lower rates of cholesterol absorption and/or synthesis. To address this knowledge gap, we used samples from the Vitamin D for Established Type 2 Diabetes trial, in which. participants with established type 2 diabetes were randomly assigned to receive either 4000 IU vitamin D3 or placebo daily. At 24 weeks, vitamin D3 supplementation increased serum 25-(OH)D concentrations and had no significant effect on surrogate markers of cholesterol absorption or endogenous synthesis, consistent with the lack of effect on serum LDL-cholesterol and HDL-cholesterol concentrations or LDL-cholesterol:HDL-cholesterol ratio.

Technical Abstract: Background: Inverse associations have been reported between serum 25-hydroxyvitamin D [25(OH)D] and circulating cholesterol concentrations in observational studies. Postulated mechanisms include reduced bioavailability of intestinal cholesterol and alterations in endogenous cholesterol synthesis. Objective: To explore the effect of daily supplementation with 4000 IU/d vitamin D3 for 24 wk on surrogate biomarkers of cholesterol absorption (campesterol and beta-sitosterol) and endogenous synthesis (lathosterol and desmosterol). Methods: Ancillary study of The Vitamin D for Established Type 2 Diabetes (DDM2) trial. Patients with established type 2 diabetes (N = 127, 25-75 y, BMI 23-42 kg/m^2) were randomly assigned to receive either 4000 IU vitamin D3 or placebo daily for 24 wk. Of participants without changes in cholesterol-lowering medications (n = 114), plasma surrogate cholesterol absorption and endogenous synthesis biomarker concentrations were measured and merged with available measures of serum LDL cholesterol and HDL cholesterol concentrations. Results: At week 24, vitamin D3 supplementation significantly increased 25(OH)D concentrations (+21.5 +\-13.4 ng/mL) but not insulin secretion rates (primary outcome of the parent study) as reported previously. In this ancillary study there was no significant effect of vitamin D3 supplementation on serum cholesterol profile or surrogate biomarkers of cholesterol absorption and endogenous synthesis. Compared with participants not treated with cholesterol-lowering medications, those who were treated exhibited a greater reduction in plasma campesterol concentrations in the vitamin D3 but not placebo group (P-interaction = 0.011). Analyzing the data on the basis of cholesterol absorption status (hypo- versus hyperabsorbers) or cholesterol synthesis status (hypo- versus hypersynthesizers) did not alter these results. Conclusions: Vitamin D3 supplementation for 24 wk had no significant effect on surrogate biomarkers of cholesterol absorption or endogenous synthesis, consistent with the lack of effect on serum cholesterol profile. Vitamin D3 supplementation resulted in greater reduction in campesterol concentrations in participants not using compared with those using cholesterol-lowering medications. Further studies are required. This trial was registered at clinicaltrials.gov as NCT01736865.