Randomized crossover clinical trial of coenzyme Q10 and nicotinamide riboside in chronic kidney disease

Abstract

BackgroundCurrent studies suggest mitochondrial dysfunction is a major contributor to impaired physical performance and exercise intolerance in chronic kidney disease (CKD). We conducted a clinical trial of coenzyme Q10 (CoQ10) and nicotinamide riboside (NR) to determine their impact on exercise tolerance and metabolic profile in patients with CKD.MethodsWe conducted a randomized, placebo-controlled, double-blind, crossover trial comparing CoQ10, NR, and placebo in 25 patients with an estimated glomerular filtration rate (eGFR) of less than 60mL/min/1.73 m2. Participants received NR (1,000 mg/day), CoQ10 (1,200 mg/day), or placebo for 6 weeks each. The primary outcomes were aerobic capacity measured by peak rate of oxygen consumption (VO2 peak) and work efficiency measured using graded cycle ergometry testing. We performed semitargeted plasma metabolomics and lipidomics.ResultsParticipant mean age was 61.0 ± 11.6 years and mean eGFR was 36.9 ± 9.2 mL/min/1.73 m2. Compared with placebo, we found no differences in VO2 peak (P = 0.30, 0.17), total work (P = 0.47, 0.77), and total work efficiency (P = 0.46, 0.55) after NR or CoQ10 supplementation. NR decreased submaximal VO2 at 30 W (P = 0.03) and VO2 at 60 W (P = 0.07) compared with placebo. No changes in eGFR were observed after NR or CoQ10 treatment (P = 0.14, 0.88). CoQ10 increased free fatty acids and decreased complex medium- and long-chain triglycerides. NR supplementation significantly altered TCA cycle intermediates and glutamate that were involved in reactions that exclusively use NAD+ and NADP+ as cofactors. NR decreased a broad range of lipid groups including triglycerides and ceramides.ConclusionsSix weeks of treatment with NR or CoQ10 improved markers of systemic mitochondrial metabolism and lipid profiles but did not improve VO2 peak or total work efficiency.Trial registrationClinicalTrials.gov NCT03579693.FundingNational Institutes of Diabetes and Digestive and Kidney Diseases (grants R01 DK101509, R03 DK114502, R01 DK125794, and R01 DK101509).

Keywords: Chronic kidney disease; Clinical Trials; Mitochondria; Nephrology; Skeletal muscle.

Figure 1. No changes in physical endurance and CRF outcomes after NR and CoQ10 treatments compared with placebo (n = 25).

(A) VO₂ peak, (B and C) absolute VO₂ at 30 and 60 W, (D) test duration, (E) total work, and (F) total work efficiency. Two-way ANOVA was used to compare changes in response to NR and CoQ10 with placebo. The box plots represent median and IQR and the whiskers represent minimum and maximum values. *P < 0.05. NS, not significant.

Figure 2. Heatmap depicting compositional changes within lipid classes in response to NR and CoQ10 supplementation.

The colors of the heatmap are based on effect size obtained from linear mixed effects modeling adjusted for fasting status. *P < 0.05, **P < 0.001. The lipid classes include fatty acyls (fatty acids), glycerolipids (triglycerides and diacylglycerols), glycerophospholipids (PEs, LPEs, LPCs, and PCs), sphingolipids (ceramides and glycosylceramides), steroids, and steroid lipids (cholesterol and cholesteryl ester).