Current knowledge about pyruvate supplementation: A brief review

Robert A. Olek, Sylwester Kujach, Zsolt Radak

Sports Medicine and Health Science ›› 2024, Vol. 6 ›› Issue (4) : 295-301. DOI: 10.1016/j.smhs.2024.02.007
Review

Current knowledge about pyruvate supplementation: A brief review

Author information +
History +

Abstract

Pyruvate is a three-carbon ketoacid that occurs naturally in cells. It is produced through enzymatic reactions in the glycolytic pathway and plays a crucial role in energy metabolism. Despite promising early results, later well-controlled studies of physically active people have shown that pyruvate supplementation lasting more than 1 week has no ergogenic effects. However, some data suggest that ingested pyruvate may be preferentially metabolized without accumulation in the bloodstream. Pyruvate exhibits antioxidant activity and can affect the cellular redox state, and exogenous pyruvate can influence metabolism by affecting the acid-base balance of the blood. This brief review focuses on the potential effects of pyruvate as a supplement for active people. The current state of understanding suggests that studies of the effects of pyruvate supplementation should prioritize investigating the timing of pyruvate intake.

eywords Acidosis; Bicarbonate; Lactate; Nicotinamide adenine dinucleotide; Sirtuins

Cite this article

Download citation ▾
Robert A. Olek, Sylwester Kujach, Zsolt Radak. Current knowledge about pyruvate supplementation: A brief review. Sports Medicine and Health Science, 2024, 6(4): 295‒301 https://doi.org/10.1016/j.smhs.2024.02.007

References

[[1]]
P.A. Mole, K.M. Baldwin, R.L. Terjung, J.O. Holloszy. Enzymatic pathways of pyruvate metabolism in skeletal muscle: adaptations to exercise. Am J Physiol, 224 (1) ( 1973), pp. 50-54, DOI: 10.1152/ajplegacy.1973.224.1.50
[[2]]
L.R. Gray, S.C. Tompkins, E.B. Taylor. Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci, 71 (14) ( 2014), pp. 2577-2604, DOI: 10.1007/s00018-013-1539-2
[[3]]
R.T. Stanko, D.L. Tietze, J.E. Arch. Body composition, energy utilization, and nitrogen metabolism with a 4.25-MJ/d low-energy diet supplemented with pyruvate. Am J Clin Nutr, 56 (4) ( 1992), pp. 630-635, DOI: 10.1093/ajcn/56.4.630
[[4]]
R.T. Stanko, D.L. Tietze, J.E. Arch. Body composition, energy utilization, and nitrogen metabolism with a severely restricted diet supplemented with dihydroxyacetone and pyruvate. Am J Clin Nutr, 55 (4) ( 1992), pp. 771-776, DOI: 10.1093/ajcn/55.4.771
[[5]]
R.T. Stanko, H.R. Reynolds, K.D. Lonchar, J.E. Arch.Plasma lipid concentrations in hyperlipidemic patients consuming a high-fat diet supplemented with pyruvate for 6 wk. Am J Clin Nutr, 56 (5) ( 1992), pp. 950-954, DOI: 10.1093/ajcn/56.5.950
[[6]]
R.T. Stanko, H.R. Reynolds, R. Hoyson, J.E. Janosky, R. Wolf. Pyruvate supplementation of a low-cholesterol, low-fat diet: effects on plasma lipid concentrations and body composition in hyperlipidemic patients. Am J Clin Nutr, 59 (2) ( 1994), pp. 423-427, DOI: 10.1093/ajcn/59.2.423
[[7]]
D. Kalman, C.M. Colker, I. Wilets, J.B. Roufs, J. Antonio. The effects of pyruvate supplementation on body composition in overweight individuals. Nutrition, 15 (5) ( 1999), pp. 337-340, DOI: 10.1016/s0899-9007(99)00034-9
[[8]]
P.K. Koh-Banerjee, M.P. Ferreira, M. Greenwood, et al.. Effects of calcium pyruvate supplementation during training on body composition, exercise capacity, and metabolic responses to exercise. Nutrition, 21 (3) ( 2005), pp. 312-319, DOI: 10.1016/j.nut.2004.06.026
[[9]]
I. Onakpoya, K. Hunt, B. Wider, E. Ernst. Pyruvate supplementation for weight loss: a systematic review and meta-analysis of randomized clinical trials. Crit Rev Food Sci Nutr, 54 (1) ( 2014), pp. 17-23, DOI: 10.1080/10408398.2011.565890
[[10]]
M.H. Stone, K. Sanborn, L.L. Smith, et al.. Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr, 9 (2) ( 1999), pp. 146-165, DOI: 10.1123/ijsn.9.2.146
[[11]]
S.M. Ostojic, Z. Ahmetovic.The effect of 4 weeks treatment with a 2-gram daily dose of pyruvate on body composition in healthy trained men. Int J Vitam Nutr Res, 79 (3) ( 2009), pp. 173-179, DOI: 10.1024/0300-9831.79.3.173
[[12]]
D. Kalman, C.M. Colker, R. Stark, A. Minsch, I. Wilets, J. Antonio. Effect of pyruvate supplementation on body composition and mood. Curr Ther Res Clin Exp, 59 (11) ( 1998), pp. 793-802, DOI: 10.1016/S0011-393X(98)85105-9
[[13]]
R.T. Stanko, R.J. Robertson, R.W. Galbreath, J.J. Reilly Jr. K. D. Greenawalt, F.L. Goss. Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone and pyruvate. J Appl Physiol ( 1985), 69 (5) ( 1990), pp. 1651-1656, DOI: 10.1152/jappl.1990.69.5.1651
[[14]]
R.T. Stanko, R.J. Robertson, R.J. Spina, J.J. Reilly Jr. K. D. Greenawalt, F.L. Goss. Enhancement of arm exercise endurance capacity with dihydroxyacetone and pyruvate. J Appl Physiol ( 1985), 68 (1) ( 1990), pp. 119-124, DOI: 10.1152/jappl.1990.68.1.119
[[15]]
K.T. Ebersole, J.R. Stout, J.M. Eckerson, T.J. Housh, T.K. Evetovich, D.B. Smith. The effect of pyruvate supplementation on critical power. J Strength Condit Res, 14 (2) ( 2000), pp. 132-134, DOI: 10.1519/00124278-200005000-00002
[[16]]
M.A. Morrison, L.L. Spriet, D.J. Dyck. Pyruvate ingestion for 7 days does not improve aerobic performance in well-trained individuals. J Appl Physiol ( 1985), 89 (2) ( 2000), pp. 549-556, DOI: 10.1152/jappl.2000.89.2.549
[[17]]
R.J. Maughan, L.M. Burke, J. Dvorak, et al.. IOC consensus statement: dietary supplements and the high-performance athlete. Int J Sport Nutr Exerc Metabol, 28 (2) ( 2018), pp. 104-125, DOI: 10.1123/ijsnem.2018-0020
[[18]]
Y.P. Yang, J.Q. Qiu, M.Y. Wang, et al.. Effects of sodium pyruvate supplementation on repeated sprint exercise performance and recovery in male college soccer players: a randomized controlled trial. Ann Palliat Med, 11 (2) ( 2022), pp. 598-610, DOI: 10.21037/apm-21-3862
[[19]]
C. Waterhouse, J. Keilson. Cori cycle activity in man. J Clin Invest, 48 (12) ( 1969), pp. 2359-2366, DOI: 10.1172/JCI106202
[[20]]
R.A. Olek, M. Luszczyk, S. Kujach, et al.. Single pyruvate intake induces blood alkalization and modification of resting metabolism in humans. Nutrition, 31 (3) ( 2015), pp. 466-474, DOI: 10.1016/j.nut.2014.09.012
[[21]]
K. LaNoue, W.J. Nicklas, J.R. Williamson. Control of citric acid cycle activity in rat heart mitochondria. J Biol Chem, 245 (1) ( 1970), pp. 102-111
[[22]]
D. Constantin-Teodosiu, E.J. Simpson, P.L. Greenhaff. The importance of pyruvate availability to PDC activation and anaplerosis in human skeletal muscle. Am J Physiol, 276 (3) ( 1999), pp. E472-E478, DOI: 10.1152/ajpendo.1999.276.3.E472
[[23]]
R.C. Poole, A.P. Halestrap. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am J Physiol, 264 (4 Pt 1) ( 1993), pp. C761-C782, DOI: 10.1152/ajpcell.1993.264.4.C761
[[24]]
F.Q. Zhou. Pyruvate in the correction of intracellular acidosis: a metabolic basis as a novel superior buffer. Am J Nephrol, 25 (1) ( 2005), pp. 55-63, DOI: 10.1159/000084141
[[25]]
P.D. Mongan, J.L. Fontana, R. Chen, R. Bunger. Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. Am J Physiol, 277 (6) ( 1999), pp. H2253-H2263, DOI: 10.1152/ajpheart.1999.277.6.H2253
[[26]]
R.A. Olek, S. Kujach, D. Wnuk, R. Laskowski. Single sodium pyruvate ingestion modifies blood acid-base status and post-exercise lactate concentration in humans. Nutrients, 6 (5) ( 2014), pp. 1981-1992, DOI: 10.3390/nu6051981
[[27]]
R.T. Mallet, A.H. Olivencia-Yurvati, R. Bunger. Pyruvate enhancement of cardiac performance: cellular mechanisms and clinical application. Exp Biol Med (Maywood), 243 (2) ( 2018), pp. 198-210, DOI: 10.1177/1535370217743919
[[28]]
S. Andres, R. Ziegenhagen, I. Trefflich, et al.. Creatine and creatine forms intended for sports nutrition. Mol Nutr Food Res, 61 (6) ( 2017), Article 10.1002/mnfr.201600772, DOI: 10.1002/mnfr.201600772
[[29]]
R.B. Kreider, R. Jäger,M. Purpura. Bioavailability, efficacy, safety, and regulatory status of creatine and related compounds: a critical review. Nutrients, 14 (5) ( 2022), p. 1035, DOI: 10.3390/nu14051035
[[30]]
A.F. Holleman.Notice sur l'action de l'eau oxygénée sur les acides α-cétoniques et sur les dicétones 1. 2. Recueil des Travaux Chimiques des Pays-Bas et de la Belgique, 23 (5) ( 1904), pp. 169-172, DOI: 10.1002/recl.19040230504
[[31]]
R.A. Olek, J. Antosiewicz, J. Popinigis, R. Gabbianelli, D. Fedeli, G. Falcioni. Pyruvate but not lactate prevents NADH-induced myoglobin oxidation. Free Radic Biol Med, 38 (11) ( 2005), pp. 1484-1490, DOI: 10.1016/j.freeradbiomed.2005.02.018
[[32]]
W. Ziolkowski, T.H. Wierzba, J.J. Kaczor, et al.. Intravenous sodium pyruvate protects against cerulein-induced acute pancreatitis. Pancreas, 37 (2) ( 2008), pp. 238-239, DOI: 10.1097/MPA.0b013e31816726e7
[[33]]
R.A. Olek, W. Ziolkowski, J.J. Kaczor, T.H. Wierzba, J. Antosiewicz. Higher hypochlorous acid scavenging activity of ethyl pyruvate compared to its sodium salt. Biosci Biotechnol Biochem, 75 (3) ( 2011), pp. 500-504, DOI: 10.1271/bbb.100728
[[34]]
X.M. Zhang, H. Deng, J.D. Tong, et al.. Pyruvate-enriched oral rehydration solution improves glucometabolic disorders in the kidneys of diabetic db/db mice. J Diabetes Res, 2020 ( 2020), Article 2817972, DOI: 10.1155/2020/2817972
[[35]]
J. Vasquez-Vivar, A. Denicola, R. Radi, O. Augusto. Peroxynitrite-mediated decarboxylation of pyruvate to both carbon dioxide and carbon dioxide radical anion. Chem Res Toxicol, 10 (7) ( 1997), pp. 786-794, DOI: 10.1021/tx970031g
[[36]]
P. Dobsak, C. Courderot-Masuyer, M. Zeller, et al.. Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia. J Cardiovasc Pharmacol, 34 (5) ( 1999), pp. 651-659, DOI: 10.1097/00005344-199911000-00005
[[37]]
D. Fedeli, G. Falcioni, R.A. Olek, et al.. Protective effect of ethyl pyruvate on msP rat leukocytes damaged by alcohol intake. J Appl Toxicol, 27 (6) ( 2007), pp. 561-570, DOI: 10.1002/jat.1236
[[38]]
B. Hassel. Pyruvate carboxylation in neurons. J Neurosci Res, 66 (5) ( 2001), pp. 755-762, DOI: 10.1002/jnr.10044
[[39]]
J.W. Park, Y.S. Chun, M.S. Kim, Y.C. Park, S.J. Kwak, S.C. Park. Metabolic modulation of cellular redox potential can improve cardiac recovery from ischemia-reperfusion injury. Int J Cardiol, 65 (2) ( 1998), pp. 139-147, DOI: 10.1016/s0167-5273(98)00117-x
[[40]]
L.L. Spriet, R.A. Howlett, G.J. Heigenhauser. An enzymatic approach to lactate production in human skeletal muscle during exercise. Med Sci Sports Exerc, 32 (4) ( 2000), pp. 756-763, DOI: 10.1097/00005768-200004000-00007
[[41]]
P.G. Schantz. Plasticity of human skeletal muscle with special reference to effects of physical training on enzyme levels of the NADH shuttles and phenotypic expression of slow and fast myofibrillar proteins. Acta Physiol Scand Suppl, 558 ( 1986), pp. 1-62
[[42]]
Z. Radak, K. Suzuki, A. Posa, Z. Petrovszky, E. Koltai, I. Boldogh.The systemic role of SIRT1 in exercise mediated adaptation. Redox Biol, 35 ( 2020), Article 101467, DOI: 10.1016/j.redox.2020.101467
[[43]]
L.L. Ji, D. Yeo. Maintenance of NAD+ homeostasis in skeletal muscle during aging and exercise. Cells, 11 (4) ( 2022), p. 710, DOI: 10.3390/cells11040710
[[44]]
L. Zhou, R. Pinho, Y. Gu, Z. Radak. The role of SIRT3 in exercise and aging. Cells, 11 (16) ( 2022), p. 2596, DOI: 10.3390/cells11162596
[[45]]
J. Gambini, M.C. Gomez-Cabrera, C. Borras, et al.. Free [NADH]/[NAD(+)] regulates sirtuin expression. Arch Biochem Biophys, 512 (1) ( 2011), pp. 24-29, DOI: 10.1016/j.abb.2011.04.020
[[46]]
K. Ide, I.K. Schmalbruch, B. Quistorff, A. Horn, N.H. Secher. Lactate, glucose and O2 uptake in human brain during recovery from maximal exercise. J Physiol, 522 (Pt 1) ( 2000), pp. 159-164, DOI: 10.1111/j.1469-7793.2000.t01-2-00159.xm
[[47]]
M.K. Dalsgaard, K. Ide, Y. Cai, B. Quistorff, N.H. Secher. The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in humans. J Physiol, 540 (Pt 2) ( 2002), pp. 681-689, DOI: 10.1113/jphysiol.2001.013062
[[48]]
M. Zilberter, A. Ivanov, S. Ziyatdinova, et al.. Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer's disease. J Neurochem, 125 (1) ( 2013), pp. 157-171, DOI: 10.1111/jnc.12127
[[49]]
H. Koivisto, H. Leinonen, M. Puurula, et al.. Chronic pyruvate supplementation increases exploratory activity and brain energy reserves in young and middle-aged mice. Front Aging Neurosci, 8 ( 2016), p. 41, DOI: 10.3389/fnagi.2016.00041
[[50]]
E. Isopi, A. Granzotto, C. Corona, et al.. Pyruvate prevents the development of age-dependent cognitive deficits in a mouse model of Alzheimer's disease without reducing amyloid and tau pathology. Neurobiol Dis, 81 ( 2015), pp. 214-224, DOI: 10.1016/j.nbd.2014.11.013
[[51]]
Y. Zilberter, O. Gubkina, A.I. Ivanov.A unique array of neuroprotective effects of pyruvate in neuropathology. Front Neurosci, 9 ( 2015), p. 17, DOI: 10.3389/fnins.2015.00017
[[52]]
Y. He, J. An, J.J. Yin, et al.. Ethyl pyruvate-derived transdifferentiation of astrocytes to oligodendrogenesis in cuprizone-induced demyelinating model. Neurotherapeutics, 18 (1) ( 2021), pp. 488-502, DOI: 10.1007/s13311-020-00947-x
[[53]]
J. Wang, S. Zhang, H. Ma, et al.. Chronic intermittent hypobaric hypoxia pretreatment ameliorates ischemia-induced cognitive dysfunction through activation of ERK1/2-CREB-BDNF pathway in anesthetized mice. Neurochem Res, 42 (2) ( 2017), pp. 501-512, DOI: 10.1007/s11064-016-2097-4
[[54]]
K.K. Kao, M.P. Fink. The biochemical basis for the anti-inflammatory and cytoprotective actions of ethyl pyruvate and related compounds. Biochem Pharmacol, 80 (2) ( 2010), pp. 151-159, DOI: 10.1016/j.bcp.2010.03.007
[[55]]
M. Fukushima, S.M. Lee, N. Moro, D.A. Hovda, R.L. Sutton. Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury. J Neurotrauma, 26 (7) ( 2009), pp. 1095-1110, DOI: 10.1089/neu.2008.0771
[[56]]
S.W. Suh, K. Aoyama, Y. Matsumori, J. Liu, R.A. Swanson. Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment. Diabetes, 54 (5) ( 2005), pp. 1452-1458, DOI: 10.2337/diabetes.54.5.1452
[[57]]
N. Ullah, M.I. Naseer, I. Ullah, T.H. Kim, H.Y. Lee, M.O. Kim. Neuroprotective profile of pyruvate against ethanol-induced neurodegeneration in developing mice brain. Neurol Sci, 34 (12) ( 2013), pp. 2137-2143, DOI: 10.1007/s10072-013-1350-8
[[58]]
Y. Miao, Y. Qiu, Y. Lin, Z. Miao, J. Zhang, X. Lu. Protection by pyruvate against glutamate neurotoxicity is mediated by astrocytes through a glutathione-dependent mechanism. Mol Biol Rep, 38 (5) ( 2011), pp. 3235-3242, DOI: 10.1007/s11033-010-9998-0
[[59]]
N. Nakamichi, Y. Kambe, H. Oikawa, et al.. Protection by exogenous pyruvate through a mechanism related to monocarboxylate transporters against cell death induced by hydrogen peroxide in cultured rat cortical neurons. J Neurochem, 93 (1) ( 2005), pp. 84-93, DOI: 10.1111/j.1471-4159.2005.02999.x
[[60]]
M.G. Ryou, G.R. Choudhury, A. Winters, L. Xie, R.T. Mallet, S.H. Yang. Pyruvate minimizes rtPA toxicity from in vitro oxygen-glucose deprivation and reoxygenation. Brain Res, 1530 ( 2013), pp. 66-75, DOI: 10.1016/j.brainres.2013.07.029
[[61]]
C.T. Sheline, M.M. Behrens, D.W. Choi. Zinc-induced cortical neuronal death: contribution of energy failure attributable to loss of NAD(+) and inhibition of glycolysis. J Neurosci, 20 (9) ( 2000), pp. 3139-3146, DOI: 10.1523/JNEUROSCI.20-09-03139.2000
[[62]]
A. Zlotnik, B. Gurevich, E. Cherniavsky, et al.. The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury. Neurochem Res, 33 (6) ( 2008), pp. 1044-1050, DOI: 10.1007/s11064-007-9548-x
[[63]]
A. Zlotnik, I. Sinelnikov, B.F. Gruenbaum, et al.. Effect of glutamate and blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome and pathohistology of the hippocampus after traumatic brain injury in rats. Anesthesiology, 116 (1) ( 2012), pp. 73-83, DOI: 10.1097/ALN.0b013e31823d7731
[[64]]
A.S. Carvalho, L.B. Torres, D.S. Persike, et al.. Neuroprotective effect of pyruvate and oxaloacetate during pilocarpine induced status epilepticus in rats. Neurochem Int, 58 (3) ( 2011), pp. 385-390, DOI: 10.1016/j.neuint.2010.12.014
[[65]]
J.B. Kim, Y.M. Yu, S.W. Kim, J.K. Lee. Anti-inflammatory mechanism is involved in ethyl pyruvate-mediated efficacious neuroprotection in the postischemic brain. Brain Res, 1060 (1-2) ( 2005), pp. 188-192, DOI: 10.1016/j.brainres.2005.08.029
[[66]]
J.S. Yi, T.Y. Kim, D. Kyu Kim, J.Y. Koh. Systemic pyruvate administration markedly reduces infarcts and motor deficits in rat models of transient and permanent focal cerebral ischemia. Neurobiol Dis, 26 (1) ( 2007), pp. 94-104, DOI: 10.1016/j.nbd.2006.12.007
[[67]]
Y. He, J. An, J.J. Yin, et al.. Ethyl pyruvate enhances spontaneous remyelination by targeting microglia phagocytosis. Int Immunopharm, 77 ( 2019), Article 105929, DOI: 10.1016/j.intimp.2019.105929

Accesses

Citations

Detail

Sections
Recommended

/