
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.08.23.24312501
preprint
1
Article
Randomized Crossover Clinical Trial of Nicotinamide Riboside and Coenzyme Q10 on Metabolic Health and Mitochondrial Bioenergetics in CKD
Ahmadi Armin
Valencia Ana P.
Begue Gwénaëlle
Norman Jennifer E.
Fan Sili
Durbin-Johnson Blythe P.
Jenner Bradley N.
Campbell Matthew D.
Reyes Gustavo
Kapahi Pankaj
Himmelfarb Jonathan
de Boer Ian H.
Marcinek David J.
Kestenbaum Bryan R.
Gamboa Jorge L.
Roshanravan Baback
23 8 2024
2024.08.23.24312501https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
http://medrxiv.org/lookup/doi/10.1101/2024.08.23.24312501
nihpp-2024.08.23.24312501.pdf
Abstract

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 m 2 ). 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/1.73m 2 , and 28±5 kg/m 2 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.
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