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

• Published in: BMJ nutrition, prevention & health prevention & health, 2024-07, p.e000856
• Main Authors: Jain, Sushil K, Justin Margret, Jeffrey, Zachary, Alonzo, Lally, Marissa M, Vanchiere, John A, Mhanna, Maroun J, Shi, Runhua, Levine, Steven N
• Format: Article
• Language: English
• Subjects: African Americans; Bioavailability; Biomarker; Biomarkers; Body mass index; Cardiovascular disease; Chronic illnesses; Clinical trials; Diabetes; Inflammation; Laboratories; Metabolism; Metabolites; Nutritional treatment; Original research; Testosterone; Vitamin D; Vitamin deficiency; White people
• ISSN: 2516-5542; 2516-5542
• DOI: 10.1136/bmjnph-2023-000856

BackgroundSubjects 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.ObjectiveThis 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).MethodsAA 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.ResultsBaseline 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.ConclusionsVD 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.