RT Journal Article SR Electronic T1 Effects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: a placebo-controlled double-blind clinical trial JF BMJ Nutrition, Prevention & Health JO BMJ Nutrition FD BMJ Publishing Group Ltd SP e000856 DO 10.1136/bmjnph-2023-000856 A1 Jain, Sushil K A1 Justin Margret, Jeffrey A1 Zachary, Alonzo A1 Lally, Marissa M A1 Vanchiere, John A A1 Mhanna, Maroun J A1 Shi, Runhua A1 Levine, Steven N YR 2024 UL http://nutrition.bmj.com/content/early/2024/08/07/bmjnph-2023-000856.abstract AB Background Subjects with metabolic syndrome and obesity have higher levels of inflammation with depression of the vitamin D (VD) hydroxylase/metabolising genes (CYP2R1/CYP27A1/CYP27B1/VDR) required to convert VD consumed in the diet into 25(OH)VD. Compared with total 25(OH)VD levels, measurement of bioavailable 25(OH)VD is a better method to determine the beneficial effect of VD.Objective This study investigates whether cosupplementation with VD and L-cysteine (LC), which downregulates inflammation and upregulates VD-regulating genes, provides a better therapeutic benefit than supplementation with VD-alone in African Americans (AA).Methods AA participants (men/women, aged 18–65 years; n=165) were block randomised into one of four groups and received daily, oral supplementation for 6 months with placebo, LC (1000 mg/day), VD (2000 IU/day) or VD+LC. Fasting blood collected at the baseline and final visits was analysed for total, free and bioavailable 25(OH)VD along with insulin, VD-binding protein (VDBP), sex hormone-binding globulin (SHBG), free and total testosterone, and inflammatory marker levels. Studies were carried out in THP-1 monocytes to elucidate the direct effect of LC and testosterone on VD-regulating genes.Results Baseline data showed no differences in age, body mass index, calcium, liver or kidney function among the groups. Compared with levels in the group that received VD-alone supplementation, levels of neutrophil-to-lymphocyte ratio, C reactive protein, HOMA-IR, VDBP and HbA1c were significantly lower in the VD+LC group while the VD+LC group showed a significant increase in bioavailable 25(OH)VD in both sexes, total 25(OH)VD levels were significantly elevated in men but not in women treated with VD+LC. Blood levels of SHBG and free/total testosterone were elevated in the VD+LC group but not in the VD-alone group. LC and testosterone treatment significantly upregulated VD-metabolising genes (CYP2R1/CYP27A1/CYP27B1/VDR) and SHBG in THP-1 monocytes.Conclusions VD cosupplemented with LC upregulates circulating bioavailable 25(OH)VD and reduces inflammation. Total 25(OH)VD levels were higher in men but not in women in the VD+LC group. This pilot study suggests that compared with supplementation with VD-alone, VD+LC cosupplementation could be a better approach to raising the total 25(OH)VD in men and the bioavailable 25(OH)VD in both sexes and lowering the inflammatory risk in the AA population.Trial registration number NCT04939792.All data relevant to the study are included in the article or uploaded as online supplemental information. Additional data are available on reasonable request.