Glutathione stimulates vitamin D regulatory genes, and lowers inflammation and increases 25-hydroxy-vitamin D levels in blood: A novel approach to treat 25-hydroxy-vitamin D-deficiency.
Antioxid Redox Signal. 2018 Aug 30. Epub 2018 Aug 30. PMID: 30160165
Sushil K Jain
AIMS: 25-hydroxyvitamin D [25(OH)VD] deficiency/inadequacy is a major public health issue affecting over 1 billion people worldwide. A convincing association exists between low levels of circulating 25(OH)VD and the poor health outcomes associated with chronic diseases. However, high supraphysiological doses of VD are needed to achieve the required 25(OH)VD levels in blood, because many subjects respond poorly to supplementation.
RESULTS: This study reports a link between 25(OH)VD deficiency and a reduction in glutathione in obese adolescents. The improvement in glutathione status that results from co-supplementation with VD and L-cysteine (a glutathione precursor) significantly reduced oxidative stress in a mouse model of 25(OH)VD deficiency. It also positively upregulated VD-regulatory genes (VDBP/VD-25-hydroxylase/VDR) in liver and glucose-metabolism genes (PGC-1α/VDR/GLUT-4) in muscle, boosted 25(OH)VD, and reduced inflammation/insulin resistance levels in the blood compared with supplementation with VD-alone. In vitro glutathione-deficiency caused increased oxidative stress and downregulation of VDBP/VD-25-hydroxylase/VDR and upregulation of CYP24a1 in hepatocytes and downregulation of PGC-1α/VDR/GLUT-4 in myotubes. This study demonstrates that improvement in GSH status exerts beneficial effects on the blood levels of 25(OH)VD, as well as on the inflammation/insulin resistance in a VD-deficient mouse model. Thus, the VD-supplements widely consumedby the public are unlikely to be successful unless the glutathione status is also corrected.
INNOVATION: These studies demonstrate a previously undiscovered mechanism by which glutathione status positively upregulates the bioavailability of 25(OH)VD.
CONCLUSION: Supplementation with a combination of VD and L-cysteine or glutathione precursor, rather than supplementation with VD alone, is beneficial and helps achieve more successful VD supplementatio.