Concentrations of the Vitamin D Metabolite 1,25(OH)2D and Odds of Metabolic Syndrome and its Components

Abstract

Aim Few epidemiological studies have investigated the association between circulating concentrations of the active vitamin D metabolite 1,25(OH)2D and metabolic syndrome. We sought to determine whether blood levels of 1,25(OH)2D are associated with metabolic syndrome and its individual components, including waist circumference, triglycerides, blood pressure, and glucose, and high-density lipoprotein. We also investigated these associations for the more abundant precursor vitamin D metabolite, 25(OH)D. Methods Participants from two completed clinical trials of colorectal neoplasia with available metabolic syndrome data and blood samples for measurement of 1,25(OH)2D (n=1048) and 25(OH)D (n=2096) were included. Cross-sectional analyses of the association between concentrations of 1,25(OH)2D, 25(OH)D, metabolic syndrome, and its components were conducted. Results A statistically significant inverse association was observed for circulating concentrations of 1,25(OH)2D and metabolic syndrome, with adjusted ORs (95% CIs) of 0.73 (0.52–1.04) and 0.52 (0.36–0.75) for the second and third tertiles of 1,25(OH)2D, respectively (p-trend <0.001). Significant inverse relationships were also observed between 1,25(OH)2D and high triglycerides (p-trend <0.001), and low high-density lipoprotein (p-trend <0.001). For 25(OH)D concentrations, significant inverse associations were found for metabolic syndrome (p-trend <0.01), high waist circumference (p-trend<0.04) and triglyceride levels (p-trend <0.01). Participants with 25(OH)D ≥ 30 ng/ml and in the highest tertile of 1,25(OH)2D demonstrated significantly lower odds of metabolic syndrome, with an OR (95% CI) of 0.38 (0.19–0.75) compared to those in the lowest category for both metabolites. Conclusion These results provide new evidence that the relatively rarely-studied active hormonal form of vitamin D, 1,25(OH)2D, is associated with metabolic syndrome and its components, and confirm prior findings for 25(OH)D. The finding that 1,25(OH)2D is related to high-density lipoprotein, while 25(OH)D is not, suggests that there may be an independent mechanism of action for 1,25(OH)2D in relation to metabolic dysregulation.

Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models

“…Addition to its classical roles in promoting calcium and phosphorus adsorption, vitamin D in its active format as calcitriol functions like sterol hormones to regulate diverse biological functions from the host immune response to cell differentiation (Adams and Hewison, 2010). Although, high calorie diet including high fat diet (HFD) is thought to be a major cause of IR, NAFLD, and MetS, the epidemiologic evidence also shows an association of VDD in development of MetS (Botella-Carretero et al, 2007; Lu et al, 2009; Barchetta et al, 2011; Bea et al, 2015). In animal experiments, dietary vitamin D deficiency was found to exacerbate Toll-like receptor activation and hepatic inflammation in obese rats (Roth et al, 2012).…”

The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women

“…This hormonally active metabolite can directly stimulate expression of the insulin receptor [11] and/or have indirect insulin-sensitizing effects through regulation of extracellular calcium [9]. While production of 1,25(OH) 2 D is tightly regulated to maintain calcium balance [12], more recently, it was suggested that 1,25(OH) 2 D has independent effects on features of the metabolic syndrome [13]. Clinical data, however, have been scarce and inconsistent: some studies reported an association between reduced 25(OH)D and insulin resistance in various populations [2,5,8], whereas others reported no such associations [14,15].…”

Greater Adherence to Cancer Prevention Guidelines Is Associated with Higher Circulating Concentrations of Vitamin D Metabolites in a Cross-Sectional Analysis of Pooled Participants from 2 Chemoprevention Trials

“…Similarly, in a study within the UDCA cohort included in the present study, moderate to vigorous physical activity was positively associated with 1,25 (OH) 2 D, with women experiencing the greatest increase (21). Hibler et al (21) suggested that the association between physical activity and vitamin D may be beyond sun exposure and driven (63). The major strengths of the current study include the availability of data from a prospective cohort of >1300 participants with complete data on a wide range of available baseline nutrition, physical activity, and serum vitamin D metabolite data.…”