The randomized control trial (RCT), which included 165 vitamin D-deficient African Americans, found the combination led to a significant reduction in several inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP), compared to vitamin D supplementation alone.
Vitamin D and L-cysteine also reduced insulin resistance (measured using the homeostatic model assessment: HOMA-IR) more than vitamin D alone, reported researchers from Louisiana State University.
“This pilot study suggests that compared with supplementation with [vitamin D] alone, [vitamin D plus L-cysteine] co-supplementation could be a better approach for increasing the levels of total 25(OH)VD in men and the bioavailable 25(OH)VD in both sexes while reducing inflammation among [African Americans],” they wrote.
Looking beyond bone health
Vitamin D affects essential physiological functions beyond maintaining bone health. Previous research has shown vitamin D deficiency is associated with a greater incidence of chronic diseases—including diabetes and heart disease —yet RCTs have reported limited success with supplementation of vitamin D alone.
L-cysteine, an antioxidant, is reported to lower both inflammation biomarkers and upregulate the vitamin D-regulating genes. Consequently, the authors set out to investigate whether co-supplementation with vitamin D and L-cysteine provides greater benefits than supplementation with the sunshine vitamin alone in African Americans.
African Americans have a higher incidence of vitamin D deficiency compared to the white population (70% vs 25%), as well as an increased risk of diabetes, heart disease and other chronic diseases.
Benefits of vitamin D and L-cysteine co-supplementation
In total, 165 African Americans between the ages of 18 and 65 years were included in the study. The participants were randomized into four groups—placebo, L-cysteine (1,000 mg/day), vitamin D (2,000 IU/day) and a combination of the two at the same doses—and instructed to take their oral supplement(s) daily for six months. Forty-nine subjects either dropped out or withdrew from the study after randomization.
Blood samples were collected from each group at baseline and after the six-month treatment period to measure total, free and bioavailable 25(OH)D. The researchers suggest that serum bioavailable 25(OH)D rather than total 25(OH)D may be a better biomarker of vitamin D status and predictor of its health consequences.
Participants receiving the combination showed a significant two-fold increase in bioavailable 25(OH)D compared to those taking vitamin D alone. While there was also a significant difference in total 25(OH)D levels after supplementation with only the vitamin, this difference was only seen in men. The researchers explain that the higher levels of testosterone found in men may upregulate the vitamin D metabolism genes, which leads to an increase in total vitamin D levels.
“Thus, co-supplementation with [vitamin D plus L-cysteine] is superior to supplementation with [vitamin D] alone in raising bioavailable 25(OH)VD levels in men and women,” the authors wrote.
Anti-inflammatory effects
The combination group also experienced significant reductions in key inflammatory markers compared to the vitamin D only group, indicating a superior anti-inflammatory effect.
It was also associated with changes to free/total testosterone and sex hormone-binding globulin (SHBG). SHBG transports testosterone and estradiol to target tissues and regulates their free concentrations. Increased SHBG levels can upregulate insulin signaling pathways, improve glucose metabolism and contribute to the decrease in HbA1c and the proinflammatory biomarker CRP and the NLR.
“The results suggest a synergistic effect between LC and testosterone, leading to an increased expression of genes related to VD metabolism and testosterone biosynthesis, along with the production of SHBG in monocytes,” the researchers explained.
“Further clinical trials are needed to investigate whether LC co-supplementation with VD could be used to successfully treat VD deficiency,” they concluded.
Source: BMJ Nutrition, Prevention & Health
doi: 10.1136/bmjnph-2023-000856
“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.”
Authors: Sushil K Jain, et al.