The Effect of Vitamin D and Magnesium Supplementation on Bone Turnover Markers and Glycemic Indices in Individuals with Overweight and Obesity
Authors:   , Dall Rosemary DeLuccia , Sukumar Deeptha 
Published: July 2021

Background: The obesity epidemic in the United States has been associated with the pathogenesis of many chronic diseases, such as prediabetes and type 2 diabetes mellitus, both of which are characterized by poor glycemic control. In individuals who are overweight and obese, a higher prevalence of micronutrient deficiencies, such as vitamin D and magnesium deficiencies, is also more common than it is in individuals of normal weight. Both vitamin D and magnesium deficiencies have been independently associated with poor glycemic control. Additionally, both nutrient deficiencies have also been independently associated with low serum total osteocalcin concentrations. Osteocalcin is a bone formation marker that is produced under the control of 1,25- dihydroxyvitamin D that can also uniquely independently influence glycemic control, as opposed to bone-specific alkaline phosphatase (BAP) and C-terminal cross-linked telopeptide (CTX), which have no causal effect. Since it is known that magnesium acts as a cofactor for vitamin D's metabolism and activation in the body, we hypothesized that increased magnesium status may lead to increased vitamin D metabolism and activation, thereby increasing total osteocalcin concentrations and ultimately resulting in improved glycemic control, characterized by decreased fasting blood glucose and insulin concentrations, a lower homeostatic model assessment of insulin resistance (HOMA-IR) value, and higher serum adiponectin concentrations. Methods: We conducted a 12-week, double-blinded, randomized controlled supplementation trial to determine if combined vitamin D and magnesium supplementation would increase subsequent 25-hydroxyvitamin D (25OHD) concentrations, as well as increase serum total osteocalcin concentrations, and ultimately reduce serum fasting glucose and fasting insulin concentrations, increase serum adiponectin concentrations, and decrease HOMA-IR. This study consisted of 3 supplementation groups - 1000 IU of vitamin D3 and 360 mg of magnesium glycinate combined, 1000 IU of vitamin D3 alone, and a placebo group that received a cellulose- based pill. Blood biomarkers including serum concentrations of 25-hydroxyvitamin D, total osteocalcin, BAP, CTX, parathyroid hormone, fasting glucose, fasting insulin, and adiponectin were assessed through fasting blood sample analyses. The HOMA-IR value was subsequently calculated from the serum glucose and serum insulin concentrations. Vitamin K was not assessed via biochemical analysis since it was not considered an influencer of total osteocalcin concentrations. Additional anthropometric and dietary information was also collected pre- and post-intervention. Results: A total of 67 individuals with overweight and obesity (42F/25M) completed the 12-week intervention. The mean age within the study sample was 42.19 ± 11.76 years and the mean body mass index was 29.44 ± 4.07 kg/m^2. It was determined that participants in the magnesium and vitamin D group had a significantly greater increase in serum 25OHD concentrations compared to the vitamin D group only in individuals with a baseline 25OHD concentrations less than 23.5 ng/mL. Despite this ability to increase serum 25OHD concentrations, no differences in serum concentrations of total osteocalcin, parathyroid hormone, glucose, insulin, adiponectin, or HOMA-IR were observed between groups after the intervention. This was also true when differences in these variables were assessed in the subgroup of individuals (n=15) in the Magnesium and Vitamin D versus Vitamin D groups with baseline serum 25OHD concentrations less than 23.5 ng/mL. Additionally, the bone turnover markers total osteocalcin, BAP, and CTX were not found to be significant predictors of HOMA-IR when included in a regression model. Conclusion: A combined vitamin D and magnesium supplementation may be more effective at improving vitamin D status compared to a vitamin D supplement given alone in normoglycemic individuals with overweight and obesity who have a 25OHD status less than 23.5 ng/mL. However, this improvement of vitamin D status may not influence serum total osteocalcin concentrations or glycemic control in this subgroup of individuals with baseline 25OHD concentrations less than 23.5 ng/mL.