Theacrine as a Potential Caffeine Alternative for Enhanced Ergogenic and Cognitive Performance in Athletes: A Call to Action and Brief Review

Main Article Content

Harris Dillon
Machek Steven

Keywords

Adenosine, Nootropic, Resistance training

Abstract




Theacrine supplementation has begun recent investigation aimed to increase athletic performance. Although existing literature has examined theacrine’s potential to increase physical and cognitive performance via adenosine receptor inhibition alongside its promotion of overall health and slight cognitive enhancement. Therefore, theacrine ostensibly exists as a caffeine substitute for attenuating both physical and mental fatigue. This article aims to (a) demonstrate the structural/mechanistic similarities of caffeine & theacrine, (b) showcase their existing performance roles, and (c) establish the need for future investigations on theacrine as a potential ergogenic aid in physically active populations to both prophylactically prevent fatigue and augment performance.




Abstract 1191 | PDF Downloads 493

References

1. Silver MD. Use of ergogenic aids by athletes. J Am Acad Orthop Surg. 2001;9(1):61-70.
2. Cappelletti S, Piacentino D, Sani G, Aromatario M. Caffeine: cognitive and physical
performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015;13(1):71-88.
3. Arab L, Khan F, Lam H. Epidemiologic evidence of a relationship between tea, coffee, or
caffeine consumption and cognitive decline. Adv Nutr. 2013;4(1):115-122.
4. Giurgea CE. The nootropic concept and its prospective implications. Drug Development Research.
1982;2(5):441-446.
5. Machek S, Bagley J. Creatine Monohydrate Supplementation: Considerations for Cognitive
Performance in Athletes. Strength and Conditioning Journal. 2018;40:82-93.
6. Kendler KS, Myers J, C OG. Caffeine intake, toxicity and dependence and lifetime risk for psychiatric and substance use disorders: an epidemiologic and co-twin control analysis. Psychol Med. 2006;36(12):1717-1725.
7. Information NCfB. PubChem Compound Summary for CID 2519. 2021;Retrieved April 7, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Caffeine.
8. Lau BYC, Othman A. Evaluation of sodium deoxycholate as solubilization buffer for oil palm proteomics analysis. PLoS One. 2019;14(8):e0221052.
9. Feduccia AA, Wang Y, Simms JA, et al. Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors. Pharmacol Biochem Behav. 2012;102(2):241-248.
10. Li WX, Li YF, Zhai YJ, Chen WM, Kurihara H, He RR. Theacrine, a purine alkaloid obtained from Camellia assamica var. kucha, attenuates restraint stress-provoked liver damage in mice. J Agric Food Chem. 2013;61(26):6328-6335.
11. Information NCfB. PubChem Compound Summary for CID 75324, 1,3,7,9-Tetramethyluric
acid. 2021;Retrieved April 7, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/1_3_7_9-Tetramethyluric-acid.
12. Weil-Malherbe H. The solubilization of polycyclic aromatic hydrocarbons by purines. Biochem J. 1946;40(3):351-363.
13. Duan WJ, Liang L, Pan MH, et al. Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activation. Phytomedicine. 2020;77:153281.
14. Aguiar AS, Jr., Speck AE, Canas PM, Cunha RA. Neuronal adenosine A2A receptors signal ergogenic effects of caffeine. Sci Rep. 2020;10(1):13414.
15. Graham TE. Caffeine and exercise: metabolism, endurance and performance. Sports Med. 2001;31(11):785-807.
16. Snyder SH, Katims JJ, Annau Z, Bruns RF, Daly JW. Adenosine receptors and behavioral actions of methylxanthines. Proc Natl Acad Sci U S A. 1981;78(5):3260-3264.
17. Kovacs EM, Stegen J, Brouns F. Effect of caffeinated drinks on substrate metabolism, caffeine excretion, and performance. J Appl Physiol (1985). 1998;85(2):709-715.
18. Pickering C, Kiely J. What Should We Do About Habitual Caffeine Use in Athletes? Sports Med. 2019;49(6):833-842.
19. PETERS JM. Factors Affecting Caffeine Toxicity: A Review of the Literature. The Journal of Clinical Pharmacology and The Journal of New Drugs. 1967;7(3):131-141.
20. Taylor L, Mumford P, Roberts M, et al. Safety of TeaCrine(R), a non-habituating, naturally- occurring purine alkaloid over eight weeks of continuous use. J Int Soc Sports Nutr. 2016;13:2.
21. Clewell A, Hirka G, Glavits R, et al. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine. J Toxicol. 2016;2016:6206859.
22. Ziegenfuss TN, Habowski SM, Sandrock JE, Kedia AW, Kerksick CM, Lopez HL. A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine(R)) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters. J Diet Suppl. 2017;14(1):9-24.
23. Kinrys G, Gold AK, Pisano VD, et al. Tachyphylaxis in major depressive disorder: A review of the current state of research. J Affect Disord. 2019;245:488-497.
24. Eudy AE, Gordon LL, Hockaday BC, et al. Efficacy and safety of ingredients found in preworkout supplements. Am J Health Syst Pharm. 2013;70(7):577-588.
25. Murray A, Traylor J. Caffeine Toxicity. In: StatPearls. Treasure Island (FL)2021.
26. Andrade A, Sousa C, Pedro M, Fernandes M. Dangerous mistake: an accidental caffeine
overdose. BMJ Case Rep. 2018;2018:bcr2018224185.
27. Willson C. The clinical toxicology of caffeine: A review and case study. Toxicol Rep. 2018;5:1140-
1152.
28. Wang YH, Mondal G, Butawan M, Bloomer RJ, Yates CR. Development of a liquid
chromatography-tandem mass spectrometry (LC-MS/MS) method for characterizing caffeine, methylliberine, and theacrine pharmacokinetics in humans. J Chromatogr B Analyt Technol Biomed Life Sci. 2020;1155:122278.
29. Helms ER, Cronin J, Storey A, Zourdos MC. Application of the Repetitions in Reserve-Based Rating of Perceived Exertion Scale for Resistance Training. Strength Cond J. 2016;38(4):42-49.
30. Bello ML, Walker AJ, McFadden BA, Sanders DJ, Arent SM. The effects of TeaCrine(R) and caffeine on endurance and cognitive performance during a simulated match in high-level soccer players. J Int Soc Sports Nutr. 2019;16(1):20.
31. Mashiko T, Umeda T, Nakaji S, Sugawara K. Position related analysis of the appearance of and relationship between post-match physical and mental fatigue in university rugby football players. Br J Sports Med. 2004;38(5):617-621.
32. Stanton R, Abt, G. Creatine Monohydrate Use Among Elite Australian Power Lifters. The Journal of Strength and Conditioning Research. 2000;14(3).
33. Bloomer RJ BM, Stockton ML, Smith NJG. Effects of a Single Dose of TeacrineÒ, Caffeine, or their Combination on Subjective Feelings, As Well as Heart Rate and Blood Pressure in Adults. Curr Res Complement Altern Med. 2018(CRCAM-134).
34. Cesareo KR, Mason JR, Saracino PG, Morrissey MC, Ormsbee MJ. The effects of a caffeine- like supplement, TeaCrine(R), on muscular strength, endurance and power performance in resistance-trained men. J Int Soc Sports Nutr. 2019;16(1):47.
35. He H, Ma D, Crone LB, et al. Assessment of the Drug-Drug Interaction Potential Between Theacrine and Caffeine in Humans. J Caffeine Res. 2017;7(3):95-102.
36. Snyder CJ. Acute effects of theacrine supplementation on muscular strength and muscular endurance. 2016.
37. In: Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington (DC)2001.
38. Davis JK, Green JM. Caffeine and anaerobic performance: ergogenic value and mechanisms of action. Sports Med. 2009;39(10):813-832.
39. Goldstein ER, Ziegenfuss T, Kalman D, et al. International society of sports nutrition position stand: caffeine and performance. J Int Soc Sports Nutr. 2010;7(1):5.
40. Xin-Qiang Zheng C-XY, Misako Kato, Alan Crozier, Hiroshi Ashihara. Theacrine (1,3,7,9- tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha). Phytochemistry. 2002;60(2).
41. Kuhman DJ, Joyner KJ, Bloomer RJ. Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women. Nutrients. 2015;7(11):9618-9632.
42. SM Habowski JS, AW Kedia & Tim N Ziegenfuss. The effects of TeacrineTM, a nature-identical purine alkaloid, on subjective measures of cognitive function, psychometric and hemodynamic indices in healthy humans: a randomized, double-blinded crossover pilot trial. Journal of the International Society of Sports Nutrition. 2014;11:49.
43. Jacobson BH, Weber MD, Claypool L, Hunt LE. Effect of caffeine on maximal strength and power in elite male athletes. Br J Sports Med. 1992;26(4):276-280.
44. Davenport AD, Jameson TSO, Kilroe SP, et al. A Randomised, Placebo-Controlled, Crossover Study Investigating the Optimal Timing of a Caffeine-Containing Supplement for Exercise Performance. Sports Med Open. 2020;6(1):17.
45. Grgic J, Mikulic P. Caffeine ingestion acutely enhances muscular strength and power but not muscular endurance in resistance-trained men. Eur J Sport Sci. 2017;17(8):1029-1036.
46. Mora-Rodriguez R, Pallares JG, Lopez-Gullon JM, Lopez-Samanes A, Fernandez-Elias VE, Ortega JF. Improvements on neuromuscular performance with caffeine ingestion depend on the time-of-day. J Sci Med Sport. 2015;18(3):338-342.
47. Souza D, Casonatto J, Poton R, Willardson J, Polito M. Acute effect of caffeine intake on hemodynamics after resistance exercise in young non-hypertensive subjects. Res Sports Med. 2014;22(3):253-264.
48. Tarnopolsky M, Cupido C. Caffeine potentiates low frequency skeletal muscle force in habitual and nonhabitual caffeine consumers. J Appl Physiol (1985). 2000;89(5):1719-1724.
49. Van Soeren MH, Sathasivam P, Spriet LL, Graham TE. Caffeine metabolism and epinephrine responses during exercise in users and nonusers. J Appl Physiol (1985). 1993;75(2):805-812.
50. Wang C, Zhu Y, Dong C, Zhou Z, Zheng X. Effects of Various Doses of Caffeine Ingestion on Intermittent Exercise Performance and Cognition. Brain Sci. 2020;10(9).
51. Wilk M, Krzysztofik M, Filip A, Zajac A, Del Coso J. The Effects of High Doses of Caffeine on Maximal Strength and Muscular Endurance in Athletes Habituated to Caffeine. Nutrients. 2019;11(8).
52. Apostolidis A, Mougios V, Smilios I, Frangous M, Hadjicharalambous M. Caffeine supplementation is ergogenic in soccer players independent of cardiorespiratory or neuromuscular fitness levels. J Int Soc Sports Nutr. 2020;17(1):31.
53. Chia JS, Barrett LA, Chow JY, Burns SF. Effects of Caffeine Supplementation on Performance in Ball Games. Sports Med. 2017;47(12):2453-2471.
54. Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol. 2003;284(2):R399-404.
55. Dodd SL, Herb RA, Powers SK. Caffeine and exercise performance. An update. Sports Med. 1993;15(1):14-23.
56. Grgic J, Sabol F, Venier S, et al. What Dose of Caffeine to Use: Acute Effects of 3 Doses of Caffeine on Muscle Endurance and Strength. Int J Sports Physiol Perform. 2019:1-8.
57. Spriet LL. Exercise and sport performance with low doses of caffeine. Sports Med. 2014;44 Suppl 2:S175-184.

58. Tarnopolsky MA. Caffeine and endurance performance. Sports Med. 1994;18(2):109-125.

59. Thyagarajan B, Alagusundaramoorthy SS, Agrawal A. Atrial Fibrillation Due to Over The Counter Stimulant Drugs in A Young Adult. J Clin Diagn Res. 2015;9(8):OD05-07.

60. Shabir A, Hooton A, Tallis J, M FH. The Influence of Caffeine Expectancies on Sport, Exercise, and Cognitive Performance. Nutrients. 2018;10(10).

61. Grgic J, Sabol F, Venier S, et al. Caffeine Supplementation for Powerlifting Competitions: An
Evidence-Based Approach. J Hum Kinet. 2019;68:37-48.

62. Petermann JB, Baumann TW. Metabolic Relations between Methylxanthines and Methyluric
Acids in Coffea L. Plant Physiol. 1983;73(4):961-964.

63. Habowski SM, Sandrock, J.E., Kedia, A.W., & Ziegenfuss, T.N. The effects of TeacrineTM, a
nature-identical purine alkaloid, on subjective measures of cognitive function, psychometric and hemodynamic indices in healthy humans: a randomized, double-blinded crossover pilot trial. Journal of the International Society of Sports Nutrition 2014;11:49.

64. Mumford PW, Osburn SC, Fox CD, Godwin JS, Roberts MD. A Theacrine-Based Supplement Increases Cellular NAD(+) Levels and Affects Biomarkers Related to Sirtuin Activity in C2C12 Muscle Cells In Vitro. Nutrients. 2020;12(12).

65. Wang Y, Yang X, Zheng X, Li J, Ye C, Song X. Theacrine, a purine alkaloid with anti- inflammatory and analgesic activities. Fitoterapia. 2010;81(6):627-631.