A1. Methylliberine (Dynamine™) and theacrine (TeaCrine®) magnify indices of cognitive affect when combined with coffee
B. Raub1, K. Cesareo1, M. Carney1, C. Kerksick2, J. Sandrock1
1The Center for Applied Health Sciences, Canfield, OH, 44406, USA; 2School of Health Sciences, Lindenwood University, MO, 63301, USA
Correspondence: B. Raub (BR@appliedhealthsciences.org)
Methylliberine (Dynamine™) and theacrine (TeaCrine®) are purine alkaloids with pronounced neuro-energetic effects. Based on their pharmacokinetic and pharmacodynamic interaction with caffeine (i.e. threefold increase in AUC vs. caffeine alone [https://pubmed.ncbi.nlm.nih.gov/32829142]), we theorized that combining these compounds with coffee (Coffea arabica) would magnify the beneficial effects of coffee on cognitive affect.
This randomized, double-blind, within-subject crossover trial of 15 male (N=7) and female (N=8) subjects (mean ± age, height, weight: 32.1 ± 9.6 y, 172.9 ± 9.5 cm, 77.5 ± 19.5 kg) assessed perceived changes in eight indices of cognitive affect after the ingestion of coffee plus several combinations of Dynamine™ and TeaCrine®. Using a Latin Square approach to minimize potential order effects, subjects ingested five different combinations of coffee: 1) 8 oz decaffeinated coffee (DECAF), 2) 8 oz regular coffee (COF), 3) 8 oz regular coffee + 50 mg Dynamine™ (COF-D50), 4) 8 oz regular coffee + 50 mg Dynamine™ and 25 mg TeaCrine® (COF-DT), and 5) 8 oz regular coffee + 100 mg Dynamine (COF-D100) and filled out anchored visual analogue scales (VAS) that assessed perceived changes in mood, energy, fatigue, alertness, focus, creativity, concentration, and motivation at 0, 60, 120, and 180 min post-ingestion. Systemic hemodynamics (heart rate, blood pressure, rate pressure product, pulse pressure) were also assessed hourly during each trial. Statistical analyses (mixed factorial ANOVA and paired t-tests) were completed by an independent statistician who was blinded to treatments.
As anticipated, DECAF only improved one VAS (focus, +9.6%, p=0.04) whereas all other treatments improved all eight VAS indices. Mixed factorial ANOVAs revealed positive changes from baseline for COF-DT in mood (+39.4%, p=0.02), energy (+70.8%, p=0.01), and motivation (+49.3%, p=0.03) and trends for improvements in fatigue (-50.4%, p=0.09), alertness (+48.5%, p=0.08), and focus (+60%, p=0.08). Compared to COF, COF-DT tended to reduce fatigue at 180 min (-32%, p=0.09). Aside from a small increase in diastolic blood pressure at 180 min (+4.3 ± 5.1 mm Hg, p=0.04) in COF-D50, no other changes in systemic hemodynamics were noted between treatments.
These findings confirm that combining Dynamine™ and TeaCrine® with caffeinated coffee significantly magnifies the beneficial effects of coffee on mood, energy, motivation while potentially reducing fatigue and improving alertness and focus. This combination was also well tolerated and had no deleterious effects on systemic hemodynamics. Future research should corroborate these findings in a larger sample size and concurrently measure serum methylxanthine and methylurate concentrations.
This study was funded in part by a research grant from Compound Solutions, Inc. The researchers in this study independently collected, analyzed, and interpreted the results without input from the sponsor. All authors declare no conflict of interest.