Related Experiment Video
Updated: Jun 14, 2025
Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Randomized Crossover Clinical Trial of Nicotinamide Riboside and Coenzyme Q10 on Metabolic Health and Mitochondrial
Armin Ahmadi1, Ana P Valencia2, Gwénaëlle Begue3
1Department of Medicine, Division of Nephrology, University of California, Davis, CA, USA.
Background:
Mitochondria-driven oxidative/redox stress and inflammation play a major role in chronic kidney disease (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 randomized, double-blind, placebo-controlled crossover trial comparing the effects of 1200 mg/day of coenzyme Q10 (CoQ10) or 1000 mg/day of nicotinamide riboside (NR) supplementation to placebo in 25 people with moderate-to-severe CKD (eGFR <60mL/min/1.73 m2). We assessed changes in the blood transcriptome using 3'-Tag-Seq gene expression profiling and changes in pre-specified 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 BMI of the participants were 61±11 years, 37±9 mL/min/1.73m2, and 28±5 kg/m2 respectively. Of the participants, 16% had diabetes and 40% were female. Compared to placebo, NR-mediated transcriptomic changes were enriched in gene ontology (GO) terms associated with carbohydrate/lipid metabolism and immune signaling while, CoQ10 changes were enriched in immune/stress response and lipid metabolism GO terms. NR increased plasma IL-2 (estimated difference, 0.32, 95% CI of 0.14 to 0.49 pg/mL), and CoQ10 decreased both IL-13 (estimated difference, -0.12, 95% CI of -0.24 to -0.01 pg/mL) and CRP (estimated difference, -0.11, 95% CI of -0.22 to 0.00 mg/dL) compared to placebo. Both NR and CoQ10 reduced 5 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 (BHI) (estimated difference, 0.29, 95% CI of 0.06 to 0.53) and spare respiratory capacity (estimated difference, 3.52, 95% CI of 0.04 to 7 pmol/min/10,000 cells) in monocytes.
Conclusion:
Six weeks of NR and CoQ10 improved in oxidative stress, inflammation, and cell bioenergetics in persons with moderate to severe CKD.
Insights
Nicotinamide riboside (NR) and coenzyme Q10 (CoQ10) supplementation improved oxidative stress, inflammation, and cellular energy production in individuals with chronic kidney disease (CKD). These findings suggest potential therapeutic benefits for NR and CoQ10 in managing CKD.
Area of Science:
- Mitochondrial Medicine
- Nephrology
- Nutritional Biochemistry
Background:
- Oxidative stress and inflammation, driven by mitochondrial dysfunction, are key contributors to chronic kidney disease (CKD) pathophysiology.
- Targeting mitochondrial metabolism holds promise for improving CKD, but clinical evidence remains limited.
Purpose of the Study:
- To investigate the effects of nicotinamide riboside (NR) and coenzyme Q10 (CoQ10) supplementation on mitochondrial function, inflammation, and oxidative stress in patients with moderate-to-severe CKD.
- To assess the impact of NR and CoQ10 on blood transcriptome, inflammatory biomarkers, oxidative stress markers, and cellular bioenergetics.
Main Methods:
- A randomized, double-blind, placebo-controlled crossover trial involving 25 participants with CKD (eGFR <60 mL/min/1.73 m²).
- Participants received 1200 mg/day of CoQ10 or 1000 mg/day of NR or placebo for six weeks.
- Evaluated changes in blood transcriptome (3'-Tag-Seq), inflammatory/oxidative stress biomarkers, and lymphocyte/monocyte bioenergetics (extracellular flux analysis).
Main Results:
- NR supplementation altered gene expression related to metabolism and immune signaling, while CoQ10 influenced immune/stress response and lipid metabolism.
- NR increased plasma IL-2, whereas CoQ10 decreased IL-13 and CRP levels compared to placebo.
- Both NR and CoQ10 reduced oxidative stress markers (5 series F2-Isoprostanes), and NR improved monocyte bioenergetics (BHI and spare respiratory capacity).
Conclusions:
- Six weeks of NR and CoQ10 supplementation demonstrated significant improvements in oxidative stress, inflammation, and cellular bioenergetics in individuals with moderate-to-severe CKD.
- These findings highlight the potential of NR and CoQ10 as therapeutic agents for managing CKD by targeting mitochondrial pathways.
