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Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study

  • C. F. Dolopikou
  • I. A. Kourtzidis
  • N. V. Margaritelis
  • I. S. Vrabas
  • I. Koidou
  • A. Kyparos
  • A. A. Theodorou
  • V. Paschalis
  • Michalis G. NikolaidisEmail author
Original Contribution

Abstract

Purpose

Older individuals suffer from low NADH levels. We have previously shown that nicotinamide riboside [NR; a NAD(P)(H) precursor] administration impaired exercise performance in young rats. It has been suggested that supplementation of redox agents exerts ergogenic effect only in deficient individuals. We hypothesized that old individuals would more likely benefit from NR supplementation. We investigated the effect of acute NR supplementation on redox homeostasis and physical performance in young and old individuals.

Methods

Twelve young and twelve old men received NR or placebo in a double-blind cross-over design. Before and 2 h after NR or placebo supplementation, blood and urine samples were collected, while physical performance (VO2max, muscle strength, and fatigue) was assessed after the second blood sample collection.

Results

At rest, old individuals exhibited lower erythrocyte NAD(P)H levels, higher urine F2-isoprostanes and lower erythrocyte glutathione levels compared to young (P < 0.05). NR supplementation increased NADH (51% young; 59% old) and NADPH (32% young; 38% old) levels in both groups (P < 0.05), decreased F2-isoprostanes by 18% (P < 0.05), and tended to increase glutathione (P = 0.078) only in the old. NR supplementation did not affect VO2max and concentric peak torque, but improved isometric peak torque by 8% (P = 0.048) and the fatigue index by 15% (P = 0.012) in the old. In contrast, NR supplementation did not exert any redox or physiological effect in the young.

Conclusions

NR supplementation increased NAD(P)H levels, decreased oxidative stress, and improved physical performance only in old subjects, substantiating that redox supplementation may be beneficial only in individuals with antioxidant deficiencies.

Keywords

Ergogenic supplements Exercise physiology Performance Sports nutrition 

Notes

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Bieganowski P, Brenner C (2004) Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss–Handler independent route to NAD+ in fungi and humans. Cell 117:495–502.  https://doi.org/10.1016/S0092-8674(04)00416-7 CrossRefGoogle Scholar
  2. 2.
    Agledal L, Niere M, Ziegler M (2010) The phosphate makes a difference: cellular functions of NADP. Redox Rep 15:2–10.  https://doi.org/10.1179/174329210X12650506623122 CrossRefGoogle Scholar
  3. 3.
    Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K (2012) The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab 15:838–847.  https://doi.org/10.1016/j.cmet.2012.04.022 CrossRefGoogle Scholar
  4. 4.
    Trammell SA, Weidemann BJ, Chadda A, Yorek MS, Holmes A, Coppey LJ, Obrosov A, Kardon RH, Yorek MA, Brenner C (2016) Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice. Sci Rep 6:26933.  https://doi.org/10.1038/srep26933 CrossRefGoogle Scholar
  5. 5.
    Vaur P, Brugg B, Mericskay M, Li Z, Schmidt MS, Vivien D, Orset C, Jacotot E, Brenner C, Duplus E (2017) Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration. FASEB J 31:5440–5452.  https://doi.org/10.1096/fj.201700221RR CrossRefGoogle Scholar
  6. 6.
    Frederick DW, Loro E, Liu L, Davila A, Chellappa K, Silverman IM, Quinn WJ 3rd, Gosai SJ, Tichy ED, Davis JG, Mourkioti F, Gregory BD, Dellinger RW, Redpath P, Migaud ME, Nakamaru-Ogiso E, Rabinowitz JD, Khurana TS, Baur JA (2016) Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab 24:269–282.  https://doi.org/10.1016/j.cmet.2016.07.005 CrossRefGoogle Scholar
  7. 7.
    Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D’Amico D, Ropelle ER, Lutolf MP, Aebersold R, Schoonjans K, Menzies KJ, Auwerx J (2016) NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352:1436–1443.  https://doi.org/10.1126/science.aaf2693 CrossRefGoogle Scholar
  8. 8.
    Kourtzidis IA, Stoupas AT, Gioris IS, Veskoukis AS, Margaritelis NV, Tsantarliotou M, Taitzoglou I, Vrabas IS, Paschalis V, Kyparos A, Nikolaidis MG (2016) The NAD+ precursor nicotinamide riboside decreases exercise performance in rats. J Int Soc Sports Nutr 13:32.  https://doi.org/10.1186/s12970-016-0143-x CrossRefGoogle Scholar
  9. 9.
    Kourtzidis IA, Dolopikou CF, Tsiftsis AN, Margaritelis NV, Theodorou AA, Zervos IA, Tsantarliotou MP, Veskoukis AS, Vrabas IS, Paschalis V, Kyparos A, Nikolaidis MG (2018) Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: implications for exercise performance. Exp Physiol.  https://doi.org/10.1113/EP086964 Google Scholar
  10. 10.
    Mouchiroud L, Houtkooper RH, Auwerx J (2013) NAD+ metabolism: a therapeutic target for age-related metabolic disease. Crit Rev Biochem Mol Biol 48:397–408.  https://doi.org/10.3109/10409238.2013.789479 CrossRefGoogle Scholar
  11. 11.
    Yoshino J, Mills KF, Yoon MJ, Imai SI (2011) Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet-and age-induced diabetes in mice. Cell Metab 14:528–536.  https://doi.org/10.1016/j.cmet.2011.08.014 CrossRefGoogle Scholar
  12. 12.
    Margaritelis NV, Paschalis V, Theodorou AA, Kyparos A, Nikolaidis MG (2018) Antioxidants in personalized nutrition and exercise. Adv Nutr.  https://doi.org/10.1093/advances/nmy052 Google Scholar
  13. 13.
    Paschalis V, Theodorou AA, Kyparos A, Dipla K, Zafeiridis A, Panayiotou G, Vrabas IS, Nikolaidis MG (2016) Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation. Eur J Nutr 55:45–53.  https://doi.org/10.1007/s00394-014-0821-x CrossRefGoogle Scholar
  14. 14.
    Paschalis V, Theodorou AA, Margaritelis NV, Kyparos A, Nikolaidis MG (2018) N-Acetylcysteine supplementation increases exercise performance and reduces oxidative stress only in individuals with low levels of glutathione. Free Radic Biol Med 115:288–297.  https://doi.org/10.1016/j.freeradbiomed.2017.12.007 CrossRefGoogle Scholar
  15. 15.
    Bonkowski MS, Sinclair DA (2016) Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol 17:679.  https://doi.org/10.1038/nrm.2016.93 CrossRefGoogle Scholar
  16. 16.
    Reid MB (2016) Redox interventions to increase exercise performance. J Physiol 594:5125–5133.  https://doi.org/10.1113/JP270653 CrossRefGoogle Scholar
  17. 17.
    Schultz MB, Sinclair DA (2016) Why NAD+ declines during aging: it’s destroyed. Cell Metab 23:965–966.  https://doi.org/10.1016/j.cmet.2016.05.022 CrossRefGoogle Scholar
  18. 18.
    Verdin E (2015) NAD+ in aging, metabolism, and neurodegeneration. Science 350:1208–1213.  https://doi.org/10.1126/science.aac4854 CrossRefGoogle Scholar
  19. 19.
    Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C (2016) Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun 7:12948.  https://doi.org/10.1038/ncomms12948 CrossRefGoogle Scholar
  20. 20.
    Golding LA, Myers CR, Sinning WE (eds) (1982) Y’s way to physical fitness. YMCA of the USA, ChicagoGoogle Scholar
  21. 21.
    Beekley MD, Brechue WF, Dehoyos DV, Garzarella L, Werber-Zion G, Pollock ML (2004) Cross-validation of the YMCA submaximal cycle ergometer test to predict VO2max. Res Q Exerc Sport 75:337–342.  https://doi.org/10.1080/02701367.2004.10609165 CrossRefGoogle Scholar
  22. 22.
    Jamnick NA, Pettitt CD, Pettitt RW (2016) Comparison of the YMCA and a Custom submaximal exercise test for determining VO2max. Med Sci Sports Exerc 48:254–259.  https://doi.org/10.1249/MSS.0000000000000763 CrossRefGoogle Scholar
  23. 23.
    Veskoukis AS, Kyparos A, Paschalis V, Nikolaidis MG (2016) Spectrophotometric assays for measuring redox biomarkers in blood. Biomarkers 21:208–217.  https://doi.org/10.3109/1354750X.2015.1126648 CrossRefGoogle Scholar
  24. 24.
    Veskoukis AS, Margaritelis NV, Kyparos A, Paschalis V, Nikolaidis MG (2018) Spectrophotometric assays for measuring redox biomarkers in blood and tissues: the NADPH network. Redox Rep 23:47–56.  https://doi.org/10.1080/13510002.2017.1392695 CrossRefGoogle Scholar
  25. 25.
    Wellek S, Blettner M (2012) On the proper use of the crossover design in clinical trials: part 18 of a series on evaluation of scientific publications. Dtsch Arztebl Int 109:276–281.  https://doi.org/10.3238/arztebl.2012.0276 Google Scholar
  26. 26.
    Airhart SE, Shireman LM, Risler LJ, Anderson GD, Gowda GN, Raftery D, Tian R, Shen DD, O’Brien KD (2017) An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PloS one 12:e0186459.  https://doi.org/10.1371/journal.pone.0186459 CrossRefGoogle Scholar
  27. 27.
    Dellinger RW, Santos SR, Morris M, Evans M, Alminana D, Guarente L, Marcotulli E (2017) Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis 3:17.  https://doi.org/10.1038/s41514-017-0016-9 CrossRefGoogle Scholar
  28. 28.
    Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR (2018) Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun 9:1286.  https://doi.org/10.1038/s41467-018-03421-7 CrossRefGoogle Scholar
  29. 29.
    Nikolaidis MG, Kyparos A, Vrabas IS (2011) F2-isoprostane formation, measurement and interpretation: the role of exercise. Prog Lipid Res 50:89–103.  https://doi.org/10.1016/j.plipres.2010.10.002 CrossRefGoogle Scholar
  30. 30.
    van’t Erve TJ, Kadiiska MB, London SJ, Mason RP (2017) Classifying oxidative stress by F2-isoprostane levels across human diseases: a meta-analysis. Redox Biol 12:582–599.  https://doi.org/10.1016/j.redox.2017.03.024 CrossRefGoogle Scholar
  31. 31.
    Margaritelis NV, Cobley JN, Paschalis V, Veskoukis AS, Theodorou AA, Kyparos A, Nikolaidis MG (2016) Principles for integrating reactive species into in vivo biological processes: examples from exercise physiology. Cell Signal 28:256–271.  https://doi.org/10.1016/j.cellsig.2015.12.011 CrossRefGoogle Scholar
  32. 32.
    Reid MB (2001) Invited Review: redox modulation of skeletal muscle contraction: what we know and what we don’t. J Appl Physiol 90:724–731.  https://doi.org/10.1152/jappl.2001.90.2.724 CrossRefGoogle Scholar
  33. 33.
    Margaritelis NV, Veskoukis AS, Paschalis V, Vrabas IS, Dipla K, Zafeiridis A, Kyparos A, Nikolaidis MG (2015) Blood reflects tissue oxidative stress: a systematic review. Biomarkers 20:97–108.  https://doi.org/10.3109/1354750X.2014.1002807 CrossRefGoogle Scholar
  34. 34.
    Pamp K, Bramey T, Kirsch M, De Groot H, Petrat F (2005) NAD(H) enhances the Cu(II)-mediated inactivation of lactate dehydrogenase by increasing the accessibility of sulfhydryl groups. Free Radic Res 39:31–40.  https://doi.org/10.1080/10715760400023671 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • C. F. Dolopikou
    • 1
  • I. A. Kourtzidis
    • 1
  • N. V. Margaritelis
    • 1
    • 2
  • I. S. Vrabas
    • 1
  • I. Koidou
    • 1
  • A. Kyparos
    • 1
  • A. A. Theodorou
    • 3
  • V. Paschalis
    • 3
    • 4
  • Michalis G. Nikolaidis
    • 1
    Email author
  1. 1.School of Physical Education and Sport Science at SerresAristotle University of ThessalonikiSerresGreece
  2. 2.Intensive Care Unit424 General Military Hospital of ThessalonikiThessalonikiGreece
  3. 3.Department of Health Sciences, School of SciencesEuropean University CyprusNicosiaCyprus
  4. 4.School of Physical Education and Sport ScienceNational and Kapodistrian University of AthensAthensGreece

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