Genetically determined vitamin D levels and change in bone density during a weight-loss diet intervention: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial

Abstract

Background Obesity is closely associated with bone health. Although diet and weight loss produce many metabolic benefits, studies of weight loss diets on bone health are conflicting. Genetic variations, such as vitamin D levels, may partly account for these conflicting observations by regulating bone metabolism. Objective We investigated whether the genetic variation associated with vitamin D concentration affected changes in bone mineral density (BMD) in response to a weight-loss diet intervention. Design In the 2-y Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, BMD was measured for 424 participants who were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A genetic risk score (GRS) was calculated based on 3 genetic variants [i.e., 7-dehydrocholesterol reductase (DHCR7) rs12785878, cytochrome P450 2R1 (CYP2R1) rs10741657 and group-specific component globulin (GC) rs2282679] related to circulating vitamin D levels. A dual-energy X-ray absorptiometry scan was performed to assess changes in whole-body BMD over 2 y. The final analysis included 370 participants at baseline. Results We found a significant interaction between dietary fat intake and vitamin D GRS on 2-y changes in whole-body BMD (P-interaction = 0.02). In the high-fat diet group, participants with higher GRS showed significantly less reduction in whole-body BMD than those with lower GRS, whereas the genetic associations were not significant in the low-fat diet group. We also found a significant interaction between dietary fat intake and the GRS on 6-mo change in femur neck BMD (P-interaction = 0.02); however, the interaction became nonsignificant at 2 y. Conclusion Our data indicate that dietary fat intake may modify the effect of vitamin D–related genetic variation on changes in BMD. Overweight or obese patients predisposed to sufficient vitamin D may benefit more in maintaining BMD along with weight loss by eating a low-fat diet. This trial was registered at clinicaltrials.gov as NCT03258203.

Blood DNA methylation at TXNIP and glycemic changes in response to weight-loss diet interventions: the POUNDS lost trial

“…Regional DNAm was analyzed continuously; for presentation purpose, we grouped it into tertiles, similar as previous publications by us and others. 22 – 24 All statistical analyses were performed using SAS version 9.4 (SAS Institute). All-p values were 2-sided, and a p-value <0.05 was considered statistically significant.…”

Vitamin D deficiency in the aetiology of obesity‐related insulin resistance

“…Nevertheless, it should also be noted that a universal approach (one size fits all) for vitamin D deficiency–related insulin resistance may not be appropriate. Perhaps ethnic/geographical location and genetic variations of vitamin D–related metabolism may influence responses to, and benefits of, vitamin D supplementation . Therefore, further evaluation of genetic determinants of vitamin D status among different ethnic/geographical groups and metabolic phenotype may enable the identification of population subgroups, which may benefit from vitamin D supplementation.…”

Major Meta-Analysis, Randomized Clinical Studies, and International Consensus on Serum Levels and Importance of Supplementing Vitamin D: State of the art

“…In the high-fat diet group, participants with the highest GRS showed significantly less reduction in full-body BMD with those with the lowest ERG, while genetic associations were not significant in the low-fat diet group. There was also a significant interaction between dietary fat intake and GRS in the 6-month change in femoral neck BMD [14].…”