L-Cysteine Supplementation Improves Bioavailability of Vitamin D

by | Feb 25, 2025 | 2024, Recent Articles, Vitamin D - General

Written by Chrystal Moulton, Science Writer. Researchers observed a significant increase in 25(OH)D availability among participants assigned both L-cysteine and vitamin D versus those assigned vitamin D alone (P<0.05).

aging coupleStudies have shown that vitamin D deficiency is associated with higher incidence of chronic diseases such as diabetes and heart disease1,2. The population most at risk is African Americans who reportedly have a higher incidence of chronic disease associated with vitamin D deficiency3. Furthermore, obesity and metabolic disease is associated with abnormal expression of genes specific to vitamin D metabolism4,5. Supplementation with vitamin D has proven unsuccessful in clinical trials6,7. However, L-cysteine has been shown to increase expression of genes specific to vitamin D metabolism4,8. In the current trial, researchers assessed the effect of L-cysteine and vitamin D supplementation on the bioavailability of vitamin D and its corresponding therapeutic effects in African Americans9.

This study was designed as a randomized, double-blind, placebo-controlled trial. Eligible participants were African American adults between 18-65 years of age. All eligible participants consented to the protocol and completed health questionnaires before and during the study. Eligible participants also had serum levels of 25 (OH) D of <30ng/mL. Individuals who were taking glucocorticoids, dietary supplements, weight loss pills, and anti-epileptic medication were excluded from this trial. Also, individuals who were pregnant, had a history of sickle cell, hyper- or hypothyroidism, CVD, diabetes, uncontrolled hypertension, and hepatic/renal dysfunction were not eligible for this study. Volunteers who met eligibility requirements were required to take a placebo for 30 days. Following this 30-day placebo period, participants are randomly assigned to one of four groups:

  1. Placebo
  2. L-cysteine: 1000mg + placebo
  3. Vitamin D : 2000 IU + placebo
  4. L-cysteine and vitamin D: 1000mg L-cysteine + 2000IU vitamin D

Participants were instructed to take their assigned protocol daily for 6 months. Blood draws were conducted at the start of the 30day placebo period, at randomization, and after 6months. Samples were used to conduct a comprehensive metabolic panel, complete blood count and measure serum 25(OH)D, among other measurements of liver and kidney health. Cell cultures of THP-1 monocytes were used to measure mRNA expression of genes specific to vitamin D metabolism (CYP11A1, CYP19A1, SHBG, VDR, CYP27B1, CYP27A1, and CYP2R1). Participants maintained their usual daily lifestyle during the trial. Statistical analysis was conducted using the paired t-test along with regression analysis.

At 6 months, 96 participants successfully completed the trial. No significant difference was observed in baseline characteristics between the 4 groups. Researchers observed a significant increase in 25(OH)D availability among participants assigned both L-cysteine and vitamin D versus those assigned vitamin D alone (P<0.05). Although both groups had increased in total 25(OH)D concentration, the difference in available 25(OH)D was 2 times higher in the L-cysteine and vitamin D group. When examined based on sex, the L-cysteine and vitamin D group showed a significant increase in bioavailable 25(OH)D in both men and women (P<0.05). Vitamin D binding protein was significantly decreased in the L-cysteine and vitamin D group compared to baseline and vitamin D alone group (P<0.05). Sex hormone binding globulin, which increases insulin signaling and sensitivity, was also significantly increased in the L-cysteine and vitamin D group and L-cysteine group compared to those supplemented with vitamin D alone (P<0.05). Researchers also observed a significant increase in free testosterone levels in the L-cysteine and vitamin D group (P<0.05). When assessed based on sex, the significant increase in free testosterone was observed in women but not in men. Neutrophil to lymphocyte ratio, HbA1C, and c-reactive protein was significantly lower in the L-cysteine and vitamin D group compared to the vitamin D alone group (P<0.05). Insulin resistance was also significantly lower in the L-cysteine and vitamin D group compared to baseline. In examining the effect of L-cysteine on gene expression, researchers observed that L-cysteine significantly increased the expression of vitamin D hydroxylase genes, sex hormone binding genes, and testosterone biosynthesis genes. Researchers noted that an increase in free testosterone in the presence of L-cysteine increases expression of genes specific to vitamin D metabolism.

Results from this clinical trial support the efficacy of L-cysteine in combination with vitamin D as a more effective way to increase bioavailable vitamin D while reducing pro-inflammatory components in the body, particularly in African Americans. Cell culture data also showed a synergistic effect of L-cysteine and testosterone in upregulating gene expression of genes responsible for vitamin D metabolism. Additional studies will be needed to verify these findings.

Source: Jain, Sushil K., Jeffrey Justin Margret, Alonzo Zachary Jr, Marissa M. Lally, John A. Vanchiere, Maroun J. Mhanna, Runhua Shi, and Steven N. Levine. “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.” BMJ Nutrition, Prevention & Health 7, no. 2 (2024): e000856.

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permission

Click here to read the full text study.

Posted February 25, 2025.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

References:

  1. Maretzke F, Bechthold A, Egert S, et al. Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases-An Umbrella Review. Nutrients. Mar 31 2020;12(4)doi:10.3390/nu12040969
  2. Bouillon R, Manousaki D, Rosen C, Trajanoska K, Rivadeneira F, Richards JB. The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol. Feb 2022;18(2):96-110. doi:10.1038/s41574-021-00593-z
  3. Ginde AA, Liu MC, Camargo CA, Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. Mar 23 2009;169(6):626-32. doi:10.1001/archinternmed.2008.604
  4. Elkhwanky MS, Kummu O, Piltonen TT, et al. Obesity Represses CYP2R1, the Vitamin D 25-Hydroxylase, in the Liver and Extrahepatic Tissues. JBMR Plus. Nov 2020;4(11):e10397. doi:10.1002/jbm4.10397
  5. Roizen JD, Long C, Casella A, et al. Obesity Decreases Hepatic 25-Hydroxylase Activity Causing Low Serum 25-Hydroxyvitamin D. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. Jun 2019;34(6):1068-1073. doi:10.1002/jbmr.3686
  6. Boucher BJ. Why do so many trials of vitamin D supplementation fail? Endocr Connect. Oct 2020;9(9):R195-r206. doi:10.1530/ec-20-0274
  7. Lin KW. Vitamin D Screening and Supplementation in Primary Care: Time to Curb Our Enthusiasm. Am Fam Physician. Feb 15 2018;97(4):226-227.
  8. Jain SK, Parsanathan R, Achari AE, Kanikarla-Marie P, Bocchini JA, Jr. Glutathione Stimulates Vitamin D Regulatory and Glucose-Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency. Antioxid Redox Signal. Dec 10 2018;29(17):1792-1807. doi:10.1089/ars.2017.7462
  9. Jain SK, Justin Margret J, Zachary A, Jr., et al. 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. BMJ nutrition, prevention & health. 2024;7(2):e000856. doi:10.1136/bmjnph-2023-000856