# Optimization of Glutathione Levels and Alzheimer Disease Risk in African Americans

> **NIH NIH R33** · LOUISIANA STATE UNIV HSC SHREVEPORT · 2022 · $507,204

## Abstract

Optimization of 25(OH) vitamin D levels in African Americans
Public Health Issue: Low circulating levels of 25(OH) vitamin D (VD) have been correlated with many
adverse health conditions and health disparities in African Americans (AA). Supraphysiological high-dose VD
supplementation is required to eliminate the differences observed in the levels of circulating 25(OH)VD in AA
and white subjects. However, recent studies have questioned the therapeutic effects of high-dose VD
supplementation.
Rationale: Glutathione (GSH) is a major physiological antioxidant. Recent studies report that low levels of
GSH are linked to 25(OH)VD deficiencies in both animal and human studies. Animal studies using ZDF rats
and a mouse model of 25(OH)VD deficiency have shown that, compared to supplementation with VD-alone,
co-supplementation with VD (cholecalciferol) + L-cysteine (LC, a GSH precursor) led to an improvement in
GSH status that resulted in significant increases in circulating levels of 25(OH)VD and reduced oxidative
stress, TNF-α, and insulin resistance (IR).
Approach: AA have reduced levels of glutathione (GSH), as well as a high incidence of insulin resistance (IR)
and inflammatory disorders. This R33 application presents our design for a randomized, double-blind, placebo-
controlled clinical trial to test the hypothesis that supplementation with VD in combination with L-cysteine (a
GSH precursor) is more successful at optimizing the statuses of 25(OH)VD and GSH [biological signatures]
and simultaneously decreasing TNF-α and IR [functional or clinical outcomes], suggesting a better therapeutic
approach compared with supplementation with VD alone in AA subjects.
Impact on Public Health: The successful completion of this R33 clinical trial will have a significant impact on
the design of future efficacy clinical trials examining co-supplementation using a GSH precursor coupled with
lower VD doses to reduce 25(OH)VD deficiency/inadequacy, inflammation, and IR biomarkers. The
development of a safe, low-cost dietary supplement that can improve 25-hydroxy vitamin D status and reduce
insulin resistance and inflammation would provide significant benefits in the treatment of pre-diabetes and
health disparities, including chronic pain, in the African American population.
This application, which is highly responsive to PAR-18-828, will replicate previous human studies and examine
the outcome of biological signatures by combining the natural product L-cysteine with VD to optimize its
supplementation and efficacy.

## Key facts

- **NIH application ID:** 10475166
- **Project number:** 5R33AT010637-03
- **Recipient organization:** LOUISIANA STATE UNIV HSC SHREVEPORT
- **Principal Investigator:** Sushil K Jain
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $507,204
- **Award type:** 5
- **Project period:** 2020-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475166

## Citation

> US National Institutes of Health, RePORTER application 10475166, Optimization of Glutathione Levels and Alzheimer Disease Risk in African Americans (5R33AT010637-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10475166. Licensed CC0.

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