Creatine | Malate | Malic Acid
Supports mitochondrial efficiency*
Supports muscle performance*
Supports cardiac function*
Tricreatine malate is made up of three creatines bound to one malate. Both molecules are involved in supporting efficient cellular energy production. Creatine is named from the Greek word from meat (kreas), because it was originally discovered in skeletal muscle. It plays a key role in tissues, like muscles and the brain, that use high amounts of energy. Because it concentrates in muscles, the best food sources are red meat, pork, lamb, poultry, and fish. While we can make some creatine in the body, persons not eating meat might not make sufficient creatine to optimize tissue status. So creatine as a dietary supplement may be more important to take as a supplement for vegans and vegetarians. Creatine is used in the phosphocreatine (phosphagen) system. This system regenerates ATP from ADP in tissues, and is especially important in circumstances with high energy demand. Because of this role, creatine is often described as an ATP “buffer.” Malate is a salt of malic acid, a compound that was first identified in apple juice, leading to it being named for the Latin word for apple (mālum). Malate is an intermediate in the citric acid cycle, a circular pathway that helps turn food into energy (i.e., ATP) and build important biomolecules. Adding intermediates like malate into this cycle helps upregulate the flux (i.e., the cycle can essentially spin faster).*
We opt to use creatine as tricreatine malate, instead of a creatine monohydrate or other form of creatine, when both creatine and malate play a role supporting pathways or processes in a formulation.
Tricreatine malate sourcing is focused on ensuring it is non-GMO, gluten-free and vegan.
Creatine is dose-dependent (see Neurohacker Dosing Principles) in the range it’s commonly dosed (up to about 5 grams a day). Dosage of creatine will vary depending on the purpose of a formulation. If the goal is to quickly saturate muscle stores for sports performance uses, higher doses (3-5 grams) are recommended. If the goal is to augment the diet, a lower dose taken consistently over time is recommended. It’s been estimated that an omnivore diet provides about 1 gram of creatine a day[1,2] and that young adults make about 1 gram a day [1,3]. This combination of what we get in the diet and make (i.e., biosynthesis) is needed to offset the approximately 2 grams of creatine we lose everyday. A low dose of creatine can contribute a significant degree to offsetting this daily loss.*
Supports mitochondrial biogenesis*
Supports peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) 
Supports transcription factors of mitochondrial biogenesis (mitochondrial transcription factor A [TFAM]) 
Supports mitochondrial DNA (mtDNA) 
Supports mitochondrial structure and function*
Supports healthy mitochondrial structure and function [4–6]
Supports mitochondrial membrane potential [4,5]
Supports signaling pathways*
Supports AMP-activated protein kinase (AMPK) signaling [4,7–10]
Promotes exercise performance*
Supports the muscle pool of phosphocreatine to be used for ATP regeneration [10–15]
Supports strength performance [12–14,16–21]
Supports lean mass [14,16–21]
Supports muscle structure and function [12–14,16]
Supports the skeletal muscle glucose transporter GLUT4 [8,9,12,22]
Supports healthy cardiovascular function*
Supports energy generation in cardiac muscle 
Protects cardiac muscle against ischemia/hypoxia 
Supports brain health*
Supports neuroprotective functions [5,6,25–28]
CoQ10 and lipoic acid – support mitochondrial function 
L-carnitine and L-leucine – support muscle mass and strength 
Supports Krebs cycle (citric acid cycle) function*
Supports energy metabolism through the citric acid cycle 
Supports energy metabolism through the malate-aspartate shuttle 
Supports the NAD+/NAPH ratio 
Supports mitochondrial function*
Supports mitochondrial membrane potential [32,33]
Supports mitochondrial complex I-V performance 
Supports antioxidant defenses*
Supports antioxidant enzymes [34–36]
Counters oxidative stress and the generation of reactive oxygen species (ROS) 
Replenishes glutathione (GSH) levels 
Supports cellular signaling*
Downregulates the expression of proinflammatory molecules (tumor necrosis factor alpha [TNF-α]) 
Supports healthy cardiovascular function*
Protects cardiac muscle from ischemic injury 
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, cure, or prevent any disease.
J.T. Brosnan, R.P. da Silva, M.E. Brosnan, Amino Acids 40 (2011) 1325–1331.
M.E. Brosnan, J.T. Brosnan, Amino Acids 48 (2016) 1785–1791.
R. Cooper, F. Naclerio, J. Allgrove, A. Jimenez, J. Int. Soc. Sports Nutr. 9 (2012) 33.
E. Barbieri, M. Guescini, C. Calcabrini, L. Vallorani, A.R. Diaz, C. Fimognari, B. Canonico, F. Luchetti, S. Papa, M. Battistelli, E. Falcieri, V. Romanello, M. Sandri, V. Stocchi, C. Ciacci, P. Sestili, Oxid. Med. Cell. Longev. 2016 (2016) 5152029.
L.M. Rambo, L.R. Ribeiro, I.D. Della-Pace, D.N. Stamm, R. da Rosa Gerbatin, M. Prigol, S. Pinton, C.W. Nogueira, A.F. Furian, M.S. Oliveira, M.R. Fighera, L.F.F. Royes, Amino Acids 44 (2013) 857–868.
P. Klivenyi, R.J. Ferrante, R.T. Matthews, M.B. Bogdanov, A.M. Klein, O.A. Andreassen, G. Mueller, M. Wermer, R. Kaddurah-Daouk, M.F. Beal, Nat. Med. 5 (1999) 347–350.
L. Zhang, X. Wang, J. Li, X. Zhu, F. Gao, G. Zhou, J. Agric. Food Chem. 65 (2017) 6991–6999.
C.R.R. Alves, J.C. Ferreira, M.A. de Siqueira-Filho, C.R. Carvalho, A.H. Lancha Jr, B. Gualano, Amino Acids 43 (2012) 1803–1807.
J.-S. Ju, J.L. Smith, P.J. Oppelt, J.S. Fisher, Am. J. Physiol. Endocrinol. Metab. 288 (2005) E347–52.
R.B. Ceddia, G. Sweeney, J. Physiol. 555 (2004) 409–421.
B. Banerjee, U. Sharma, K. Balasubramanian, M. Kalaivani, V. Kalra, N.R. Jagannathan, Magn. Reson. Imaging 28 (2010) 698–707.
B. Gualano, V. DE Salles Painneli, H. Roschel, G.G. Artioli, M. Neves Jr, A.L. De Sá Pinto, M.E.R. Da Silva, M.R. Cunha, M.C.G. Otaduy, C.D.C. Leite, J.C. Ferreira, R.M. Pereira, P.C. Brum, E. Bonfá, A.H. Lancha Jr, Med. Sci. Sports Exerc. 43 (2011) 770–778.
C.R.R. Alves, B.M. Santiago, F.R. Lima, M.C.G. Otaduy, A.L. Calich, A.C.C. Tritto, A.L. de Sá Pinto, H. Roschel, C.C. Leite, F.B. Benatti, E. Bonfá, B. Gualano, Arthritis Care Res. 65 (2013) 1449–1459.
D.G. Burke, P.D. Chilibeck, G. Parise, D.G. Candow, D. Mahoney, M. Tarnopolsky, Med. Sci. Sports Exerc. 35 (2003) 1946–1955.
J.T. Brosnan, M.E. Brosnan, Annu. Rev. Nutr. 27 (2007) 241–261.
J.S. Volek, N.D. Duncan, S.A. Mazzetti, R.S. Staron, M. Putukian, A.L. Gómez, D.R. Pearson, W.J. Fink, W.J. Kraemer, Med. Sci. Sports Exerc. 31 (1999) 1147–1156.
S.L. Nissen, R.L. Sharp, J. Appl. Physiol. 94 (2003) 651–659.
R.B. Kreider, Mol. Cell. Biochem. 244 (2003) 89–94.
L.A. Gotshalk, W.J. Kraemer, M.A.G. Mendonca, J.L. Vingren, A.M. Kenny, B.A. Spiering, D.L. Hatfield, M.S. Fragala, J.S. Volek, Eur. J. Appl. Physiol. 102 (2008) 223–231.
L.A. Gotshalk, J.S. Volek, R.S. Staron, C.R. Denegar, F.C. Hagerman, W.J. Kraemer, Med. Sci. Sports Exerc. 34 (2002) 537–543.
J.D. Branch, Int. J. Sport Nutr. Exerc. Metab. 13 (2003) 198–226.
B. Op ’t Eijnde, B. Ursø, E.A. Richter, P.L. Greenhaff, P. Hespel, Diabetes 50 (2001) 18–23.
V. Saks, P. Dzeja, U. Schlattner, M. Vendelin, A. Terzic, T. Wallimann, J. Physiol. 571 (2006) 253–273.
C.A. Lygate, S. Bohl, M. ten Hove, K.M.E. Faller, P.J. Ostrowski, S. Zervou, D.J. Medway, D. Aksentijevic, L. Sebag-Montefiore, J. Wallis, K. Clarke, H. Watkins, J.E. Schneider, S. Neubauer, Cardiovasc. Res. 96 (2012) 466–475.
G.J. Brewer, T.W. Wallimann, J. Neurochem. 74 (2000) 1968–1978.
B. Valastro, A. Dekundy, W. Danysz, G. Quack, Behav. Brain Res. 197 (2009) 90–96.
R.T. Matthews, L. Yang, B.G. Jenkins, R.J. Ferrante, B.R. Rosen, R. Kaddurah-Daouk, M.F. Beal, J. Neurosci. 18 (1998) 156–163.
P.G. Sullivan, J.D. Geiger, M.P. Mattson, S.W. Scheff, Ann. Neurol. 48 (2000) 723–729.
M.C. Rodriguez, J.R. MacDonald, D.J. Mahoney, G. Parise, M.F. Beal, M.A. Tarnopolsky, Muscle Nerve 35 (2007) 235–242.
M. Evans, N. Guthrie, J. Pezzullo, T. Sanli, R.A. Fielding, A. Bellamine, Nutr. Metab. 14 (2017) 7.
J.M. Berg, J.L. Tymoczko, G.J. Gatto, L. Stryer, eds., Biochemistry, 8th ed, W.H. Freeman and Company, 2015.
C.B. Edwards, N. Copes, A.G. Brito, J. Canfield, P.C. Bradshaw, PLoS One 8 (2013) e58345.
J.-L. Wu, Q.-P. Wu, Y.-P. Peng, J.-M. Zhang, Physiol. Res. 60 (2011) 329–336.
S. Ding, Y. Yang, J. Mei, Evid. Based. Complement. Alternat. Med. 2016 (2016) 3803657.
X. Zeng, J. Wu, Q. Wu, J. Zhang, Physiol. Res. 64 (2015) 71–78.
J.-L. Wu, Q.-P. Wu, X.-F. Yang, M.-K. Wei, J.-M. Zhang, Q. Huang, X.-Y. Zhou, Physiol. Res. 57 (2008) 261–268.