Mechanisms
Ribose-cysteine supplementation raises antioxidant glutathione and lowers Lp(a) in transgenic mice, a mechanistic study (Atherosclerosis 2014)
Original title: Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice
Researchers tested whether ribose-cysteine, a cysteine analogue designed to boost glutathione (GSH) synthesis, affects oxidative stress markers and lipids in human Lp(a) transgenic mice treated with 4 mg/day ribose-cysteine for 8 weeks (n=9 per group vs untreated controls). Ribose-cysteine increased liver and plasma GSH (P<0.05) and glutathione peroxidase activity in liver (1.7-fold, P<0.01) and erythrocytes (3.5-fold, P<0.05), while significantly reducing lipid peroxidation markers TBARS and 8-isoprostanes in liver, plasma and aorta (P<0.01 to P<0.0005). Ribose-cysteine treated mice also showed significant decreases in LDL, Lp(a) and apoB (P<0.05, P<0.01, and P<0.05, respectively), associated with LDL receptor upregulation. The findings suggest ribose-cysteine, by lowering LDL, Lp(a) and oxidised lipids, could be a promising intervention for atherosclerosis protection.
Original abstract
Objective: D-ribose-L-cysteine (ribose-cysteine) is a cysteine analogue designed to increase the synthesis of glutathione (GSH). GSH is a cofactor for glutathione peroxidase (GPx), the redox enzyme that catalyses the reduction of lipid peroxides. A low GPx activity and increased oxidised lipids are associated with the development of cardiovascular disease (CVD). Here we aimed to investigate the effect of ribose-cysteine supplementation on GSH, GPx, lipid oxidation products and plasma lipids in vivo.
Methods: Human lipoprotein(a) [Lp(a)] transgenic mice were treated with 4 mg/day ribose-cysteine (0.16 g/kg body weight) for 8 weeks. Livers and blood were harvested from treated and untreated controls (n = 9 per group) and GSH concentrations, GPx activity, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes and plasma lipid concentrations were measured.
Results: Ribose-cysteine increased GSH concentrations in the liver and plasma (P < 0.05). GPx activity was increased in both liver (1.7 fold, P < 0.01) and erythrocytes (3.5 fold, P < 0.05). TBARS concentrations in the liver, plasma and aortae were significantly reduced with ribose-cysteine (P < 0.01, P < 0.0005 and P < 0.01, respectively) as were the concentrations of 8-isoprostanes in the liver and aortae (P < 0.0005, P < 0.01, respectively). Ribose-cysteine treated mice showed significant decreases in LDL, Lp(a) and apoB concentrations (P < 0.05, P < 0.01 and P < 0.05, respectively), an effect which was associated with upregulation of the LDL receptor (LDLR).
Conclusions: As ribose-cysteine lowers LDL, Lp(a) and oxidised lipid concentrations, it might be an ideal intervention to increase protection against the development of atherosclerosis.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.