A Pilot Trial of Nicotinamide Riboside and Coenzyme Q10 on Inflammation and Oxidative Stress in CKD

Abstract

Key Points:

1. Nicotinamide riboside and coenzyme Q10 supplementation showed distinct beneficial effects on whole-blood transcriptome, inflammatory cytokines, and oxidative stress.

2. Nicotinamide riboside treatment altered the expression of genes associated with metabolism and immune response coinciding with a decrease in markers of oxidative stress.

3. Coenzyme Q10 supplementation altered genes associated with lipid metabolism coinciding with reductions in markers of oxidative stress and inflammatory cytokines.

Background: Mitochondria-driven oxidative/redox stress and inflammation play a major role in CKD pathophysiology. Compounds targeting mitochondrial metabolism may improve mitochondrial function, inflammation, and redox stress; however, there is limited evidence of their efficacy in CKD.

Methods: We conducted a pilot, randomized, double-blind, placebo-controlled crossover trial comparing the effects of 1200 mg/d of coenzyme Q10 (CoQ10) or 1000 mg/d of nicotinamide riboside (NR) supplementation with placebo in 25 patients with moderate-to-severe CKD (eGFR <60 ml/min per 1.73 m²). We assessed changes in blood transcriptome using 3′-Tag-Seq gene expression profiling and changes in prespecified secondary outcomes of inflammatory and oxidative stress biomarkers. For a subsample of participants (n=14), we assessed lymphocyte and monocyte bioenergetics using an extracellular flux analyzer.

Results: The (mean±SD) age, eGFR, and body mass index of the participants were 61±11 years, 37±9 ml/min per 1.73 m², and 28±5 kg/m², respectively. Of the participants, 16% had diabetes and 40% were female. Compared with placebo, NR-mediated transcriptomic changes were enriched in gene ontology terms associated with carbohydrate/lipid metabolism and immune signaling, whereas CoQ10 changes were enriched in immune/stress response and lipid metabolism gene ontology terms. NR increased plasma IL-2 (estimated difference, 0.32; 95% confidence interval [CI], 0.14 to 0.49 pg/ml), and CoQ10 decreased both IL-13 (estimated difference, −0.12; 95% CI, −0.24 to −0.01 pg/ml) and C-reactive protein (estimated difference, −0.11; 95% CI, −0.22 to 0.00 mg/dl) compared with placebo. Both NR and CoQ10 reduced five-series F2-isoprostanes (estimated difference, −0.16 and −0.11 pg/ml, respectively; P < 0.05 for both). NR, but not CoQ10, increased the Bioenergetic Health Index (estimated difference, 0.29; 95% CI, 0.06 to 0.53) and spare respiratory capacity (estimated difference, 3.52; 95% CI, 0.04 to 7 pmol/min per 10,000 cells) in monocytes.

Conclusions: Six weeks of NR and CoQ10 improved markers of oxidative stress, inflammation, and cell bioenergetics in patients with moderate-to-severe CKD.

Clinical Trial registry name and registration number:: NCT03579693.