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A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine®) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters
Abstract
Theacrine (1,3,7,9-tetramethyluric acid) is a naturally occurring purine alkaloid, present in Camellia assamica variety kucha tea. Using a two-part approach in humans, the impact of theacrine (TeaCrine®, TC) was used to examine subjective dose-response, daily changes in cognitive and psychometric parameters, and changes in gas exchange and vital signs. All indicators were chosen to better ascertain the previously reported animal and human outcomes involving theacrine administration. Part 1 was a randomized, open-label, dose-response investigation in nine healthy participants whereby three participants ingested 400 mg TC per day and six participants ingested 200 mg/day. Participants recorded subjective changes in cognitive, psychometric, and exercise attributes using 150-mm anchored visual analog scale (VAS) before, and 1, 4, and 6 hours after ingestion every day for 7 consecutive days. Part 2 was a randomized, double-blind, placebo-controlled, crossover investigation in 15 healthy subjects in which all participants ingested a single 200 mg dose of TC or Placebo (PLA). Anchored VAS questionnaires were used to detect subjective changes in various aspects of physical and mental energy along with changes in gas exchange and hemodynamic parameters before, and 1, 2, and 3 hours after acute ingestion. Energy, focus, and concentration increased from baseline values in both doses with no dose-response effect. VAS responses in the 200 mg for willingness to exercise, anxiety, motivation to train and libido increased across the measurement period while no such change was seen with the 400 mg dose. After consuming a single 200 mg dose, significant group × time interaction effects were seen for energy, fatigue, and concentration. No changes in resting heart rate, gas exchange, systemic hemodynamics or side effect profiles were noted.
... Daily intake of up to 300 mg of theacrine across eight weeks had no negative effect on blood pressure, heart rate, electrocardiogram indicators of cardiac function, or blood safety markers in sixty healthy adults 14 . Similarly, the intake of 200 mg across seven days had no negative effect on heart rate, blood pressure, or gas exchange in fifteen healthy adults 15 . Despite the emerging interest in theacrine as an alternative to caffeine, there is limited evidence available regarding its cognitive and behavioural effects. ...
... Despite the emerging interest in theacrine as an alternative to caffeine, there is limited evidence available regarding its cognitive and behavioural effects. The initial data support a positive effect on self-reported arousal [14][15][16] , with objective improvements in cognitive performance observed only when theacrine is consumed in a supplement blend containing caffeine 17,18 . Furthermore, there is no evidence currently available regarding the effect of theacrine on subsequent sleep. ...
... Previous studies investigating theacrine have shown mixed effects on self-reported level of arousal. For example, an acute dose of 200 mg significantly increased energy and reduced fatigue when assessed using visual analogue scales 15 , while the acute intake of 300 mg had no significant effect on arousal when assessed using visual analogue scales 39 or an adapted Profile of Moods States questionnaire 14 . Comparatively, the intake of 100 to 400 mg of caffeine typically results in positive impacts on markers of perceived arousal 40 , with subsequent reports of poor subjective sleep outcomes 7 . ...
Psychostimulants can be employed as a countermeasure to cognitive declines resulting from insufficient sleep. Although caffeine is the most consumed psychostimulant, consumption can cause adverse side-effects, including sleep disturbance. Therefore, there is interest in identifying alternative supplements that improve cognitive performance without compromising subsequent sleep. Here we investigate the influence of the dose and timing of theacrine consumption on cognitive performance and subsequent sleep using conditions that replicate a low (100 mg) and high (400 mg) dose consumed in the morning (12 h prior to bedtime), afternoon (eight hours prior to bedtime), and evening (four hours prior to bedtime). We found no significant effect of the low or high theacrine dose on subsequent sleep although the high dose showed small non-significant effects on sleep efficiency and wake after sleep onset at each timepoint of consumption. However, consuming theacrine within eight hours of bedtime improved next-morning cognitive performance, with the 400 mg dose reducing the number of lapses on the Psychomotor Vigilance Task, although there were no significant effects on reaction time. Our findings provide initial scientific evidence suggesting that theacrine consumption may improve some aspects of next-morning cognitive performance but not others, with small non-significant effects on nighttime sleep.
... Theacrine may nevertheless amend this issue being inherently less addictive than caffeine, whereby individuals are able to consume relatively higher doses without adverse effect 7,19,20 . Previous mouse data illustrates that a lethal dose of theacrine was shown to be around 810.6mg/kg, which is an inordinately large dose relative to typical dosing regimens (200-400mg/day) 21,22 . In humans, this compound was found to have no tachyphylatic (reduced response of a drug, rendering it less effective) response in doses upwards of 300mg a day 21,23 . ...
... Research supporting this compound on aerobic/endurance demographics is meager. Ziegenfuss et al. 22 found that 200mg nor 400mg of theacrine saw any changes in gas exchange, attenuating this supplement's ability to promote a nootropic effect in aerobic/endurance outcomes. Conversely, in strength-and-power activities, findings of caffeine supplementation are inconsistent but can potentially training protocols, subject training ages/ fitness levels, and/or a multiplicity of other extraneous factors. ...
... Additionally, many of the individual dosing and genetic-mediated differences in theacrine supplementation require elucidation. Regardless, this promising compound has substantial evidence among existing data to back its claims as a nootropic 9,13,22,33,41,63,64 . Therefore, players, sport physicians, coaches, and average gym goers should consider employing theacrine either by itself or coupled with caffeine as an alternative to combating fatigue 30,33,35 . ...
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.
... Theacrine has been attracted great attentions academically owing to its diverse healthy benefits (1-3), including reducing inflammation (12), providing stimulatory effects without adaptation or habituation (13), antioxidant effect (14), enhancing sustained energy (15), promoting positive mood elevation, and mental clarity (15)(16)(17) and etc. However, these researches lack systematic summarization and some important mechanisms remain to be further investigated. ...
... Theacrine has been attracted great attentions academically owing to its diverse healthy benefits (1-3), including reducing inflammation (12), providing stimulatory effects without adaptation or habituation (13), antioxidant effect (14), enhancing sustained energy (15), promoting positive mood elevation, and mental clarity (15)(16)(17) and etc. However, these researches lack systematic summarization and some important mechanisms remain to be further investigated. ...
... There were many studies showing that theacrine activated locomotor and reduced fatigue. In comparison to placebo under double-blind conditions, oral administration of TeaCrine R at a dose equivalent 200 mg theacrine resulted in more energy, less fatigue, better concentration and mood (15). Dietary supplement with 5-850 mg theacrine would improve mood, energy and focus, accompanying with reduction of anxiety or fatigue (25). ...
Theacrine, i.e., 1,3,7,9-tetramethyluric acid, is one of the major purine alkaloids found in leaf of a wild tea plant species Camellia kucha Hung T. Chang. Theacrine has been attracted great attentions academically owing to its diverse health benefits. Present review examines the advances in the research on the health beneficial effects of theacrine, including antioxidant effect, anti-inflammatory effect, locomotor activation and reducing fatigue effects, improving cognitive effect, hypnotic effect, ameliorating lipid metabolism and inhibiting breast cancer cell metastasis effect. The inconsistent results in this research field and further expectations were also discussed.
... Due to purported synthesis from caffeine in some plants and structural similarities to caffeine [5,11], both theacrine and methylliberine are theorized to produce similar physiological effects with less side effects, potentially due to their different affinities with adenosine receptors [11,12]. Although theacrine was first discovered in 1937 [13], little research (to our knowledge, only seven studies) was conducted on theacrine's effects on human health and performance until recently [14][15][16][17][18][19][20]. Previous cell and animal model investigations on theacrine reported improved antioxidant capacity [20] and anti-inflammatory responses [21], as well as analgesic [21], antidepressive [22], and sedative/hypnotic [23] mood states. ...
... As methylliberine was never studied in humans, a four-week time period was selected based on previous studies on novel dietary supplements [28][29][30]. Based on previous findings [14,17,25], we hypothesized that DYM alone or with TCR would not produce significant abnormal changes in cardiovascular function parameters of heart rate, blood pressure, or electrical conduction of the heart assessed via an electrocardiogram, nor hematological markers of health for both men and women. ...
... Likewise, TCR supplemented at doses of 200 mg and 300 mg by male and female human subjects for eight weeks did not negatively affect resting heart rate [17]. Similar null results were found by Ziegenfuss et al. [14], whose team investigated the acute influence of a 200-mg dose of TCR on heart rate before, as well as 30-minP, 60-minP, 90-minP, 120-minP, 150-minP, and 180-minP supplementation, compared to placebo. Moreover, another study by Kuhman and colleagues [15] compared the effects of men and women's acute consumption (baseline, and 1 h, 2 h, 3 h, and 4 h post supplementation) of a multi-ingredient dietary supplement containing TCR and caffeine (150 mg) (product name = TheaTrim) to caffeine alone and placebo, and they also found no differences in resting heart rate response across groups. ...
Methylliberine (Dynamine®; DYM) and theacrine (Teacrine®; TCR) are purine alkaloids purported to have similar neuro-energetic effects as caffeine. There are no published human safety data on DYM, and research on TCR is limited. The purpose of this study was to examine the effect of four weeks of DYM supplementation with and without TCR on cardiovascular function and blood biomarkers. One-hundred twenty-five men and women (mean age 23.0 yrs, height 169.7 cm, body mass 72.1 kg; n = 25/group) were randomly assigned to one of five groups: low-dose DYM (100 mg), high-dose DYM (150 mg), low-dose DYM with TCR (100 mg + 50 mg), high-dose DYM with TCR (150 mg + 25 mg) , and placebo. Regardless of group and sex, significant main effects for time were noted for heart rate, systolic blood pressure, and QTc (p < 0.001), high-density lipoproteins (p = 0.002), mean corpuscular hemoglobin (p = 0.018), basophils (p = 0.006), absolute eosinophils (p = 0.010), creatinine (p = 0.004), estimated glomerular filtration rate (p = 0.037), chloride (p = 0.030), carbon dioxide (p = 0.023), bilirubin (p = 0.027), and alanine aminotransferase (p = 0.043), among others. While small changes were found in some cardiovascular and blood biomarkers, no clinically significant changes occurred. This suggests that DYM alone or in combination with TCR consumed at the dosages used in this study does not appear to negatively affect markers of health over four weeks of continuous use.
... Although caffeine has been shown to improve several aspects of performance, there are several undesirable side effects potentially associated with it, including the increases in cardiovascular responses, habituation from chronic use, and timing effects that should be taken into consideration [4,11,26]. A recently developed compound similar to caffeine, theacrine (1,3,7,9-tetramethyluric acid), may hold some promise given that it has a longer onset of action at approximately 2 h and has been shown to increase mood and subjective measures of cognitive function with no adverse side effects or habituation [27][28][29]. Theacrine appears to operate similarly to caffeine as an adenosine receptor antagonist, so it can be hypothesized that the use of TeaCrine® might mimic and provide longer-lasting effects than caffeine, without the sharp decline in effectiveness that usually occurs as the concentration of caffeine decreases in the body [28,[30][31][32]. ...
... Theacrine appears to operate similarly to caffeine as an adenosine receptor antagonist, so it can be hypothesized that the use of TeaCrine® might mimic and provide longer-lasting effects than caffeine, without the sharp decline in effectiveness that usually occurs as the concentration of caffeine decreases in the body [28,[30][31][32]. Currently, there is only one study that has investigated the effects of theacrine independently on subjective measures of mental well-being including such things as energy, focus, and fatigue, with significant improvements noted [29]. An additional study has tested the effects on muscular strength and endurance in resistance trained males, with few significant beneficial effects on strength training and endurance during bench and leg presses [30]. ...
... Additionally, Caf 's effect on endurance has also been shown to have a glycogen sparing effect through increasing plasma free fatty acids and the rate of lipid metabolism [55,56]. Additional research needs to be conducted on the mechanistic side of TCr to determine if there is a similar influence on the mobilization of substrates [29], as well as its effects as a dopamine agonist [32]. ...
Abstract Background Theacrine (1,3,7,9-tetramethyluric-acid) is a pure alkaloid with a similar structure to caffeine and acts comparably as an adenosine receptor antagonist. Early studies have shown non-habituating effects, including increases in energy and focus in response to Teacrine®, the compound containing pure theacrine. The purpose of this study was to determine and compare the effects of Teacrine® and caffeine on cognitive performance and time-to-exhaustion during a simulated soccer game in high-level male and female athletes. Methods Male and female soccer players (N = 24; MAge = 20.96 ± 2.05y, MMaleVO2max = 55.31 ± 3.39 mL/O2/kg, MFemaleVO2max = 50.97 ± 3.90 mL/O2/kg) completed a 90-min simulated treadmill soccer match over four randomized sessions (TeaCrine®, caffeine, TeaCrine® + caffeine, placebo). Cognitive testing at halftime and end-of-game including simple reaction time (SRT), choice RT (CRT), and cognitive-load RT with distraction questions (COGRT/COGRTWrong) was performed, with a run time-to-exhaustion (TTE) at 85% VO2max following end-of-game cognitive testing. Session times and pre-exercise nutrition were controlled. RM-MANOVAs with univariate follow-ups were conducted and significance was set at P
... 23 A randomized, open-label doseresponse (200 vs. 400 mg daily for seven consecutive days) study was conducted to evaluate the effect of theacrine (as TeaCrine) on subjective changes in cognitive, psychometric, and exercise attributes in healthy human subjects. 24 Theacrine was found to be well tolerated with robust increases in energy, focus, and concentration compared to baseline values. Interestingly, no temporal response differences were reported, leading the authors to suggest that theacrine, unlike caffeine, does not appear to induce pharmacodynamic tolerance with chronic use, an intriguing suggestion requiring further study. ...
... Our data are consistent with other studies demonstrating that theacrine supplementation (up to 400 mg/day for 8 weeks) appears to be safe in humans with no adverse effects on hemodynamic parameters. 19,24 Perhaps the most intriguing finding in repeat dose theacrine studies 19,24 is the absence of either sensitization or pharmacodynamic tolerance. Caffeine is a mixed A 1 /A 2 AR antagonist. ...
... Our data are consistent with other studies demonstrating that theacrine supplementation (up to 400 mg/day for 8 weeks) appears to be safe in humans with no adverse effects on hemodynamic parameters. 19,24 Perhaps the most intriguing finding in repeat dose theacrine studies 19,24 is the absence of either sensitization or pharmacodynamic tolerance. Caffeine is a mixed A 1 /A 2 AR antagonist. ...
Objective:
Theacrine, a methylurate class purine alkaloid, triggers diverse pharmacologic responses, including psychostimulatory activity by modulation of adenosinergic and dopaminergic pathways. In a double-blind, placebo-controlled study, theacrine increased energy, concentration, and mood, while reducing fatigue. Because caffeine, a methylxanthine purine alkaloid, is frequently coadministered with theacrine, we sought to determine if a pharmacokinetic and/or pharmacodynamic interaction existed between theacrine and caffeine.
Methods:
Eight healthy adults received theacrine, as TeaCrine® (25 or 125 mg), caffeine (150 mg), or a combination of theacrine (125 mg) and caffeine (150 mg) in a randomized, double-blind crossover study. Blood samples were collected over a 24-hour period and analyzed by Liquid chromatrography-mass spectrometry/mass spectrometry (LC-MS/MS) for theacrine, caffeine, and paraxanthine. Pharmacodynamic response markers, heart rate and blood pressure, were recorded.
Results:
Theacrine pharmacokinetics was similar following administration of theacrine alone. Caffeine coadministration increased maximum plasma concentration and area under the curve of theacrine without altering theacrine half-life. Theacrine had no impact on caffeine or paraxanthine pharmacokinetics. There was no difference between treatment groups with regard to heart rate or systolic/diastolic blood pressure.
Conclusions:
Coadministration of theacrine and caffeine results in a clinically significant pharmacokinetic interaction, viz., increased theacrine exposure. Enhanced oral bioavailability is the most likely mechanism by which caffeine alters theacrine exposure. However, further studies examining the contribution of presystemic elimination mechanisms, for example, efflux transport and/or gut metabolism, to theacrine bioavailability are needed to confirm the exact mechanism(s). Hemodynamic parameters were unaltered despite the pharmacokinetic interaction, suggesting that coadministration of caffeine and theacrine is safe at the doses administered.
... The primary aim of this study was to evaluate the effects of combined caffeine + TeaCrine + Dynamine (CTD) measures of physiological changes and first-person shooter game performance in e-gamers. Based on previous studies utilizing similar ingredients [9,14,15], the researchers hypothesized that measures of gamer performance would improve following the acute ingestion of supplementation. Additionally, measures of mood, stress, and physiological arousal (salivary cortisol and EEG frequency bands) were assessed. ...
... Subjective assessments of gaming performance provide important insight into an e-gamers perceived mental effort and task difficulty. Previous studies report increased subjective feelings of motivation, focus, and attention following supplementation with a combination of CTD [9,10,15,27]. Our findings are in line with La Monica et al. [27] where CTD supplementation improved subjective ratings of performance in firstperson shooter video games and improvements in their gaming performance compared to the caffeine group [27]. ...
Introduction: Video games require precise motor skills, quick reaction times, and cognitive engagement. The tremendous growth of the electronic (e)-gaming industry has increased the demands for cognitive supplements (e.g., nootropics) to help e-athletes gain a competitive edge. The primary aim of this study was to evaluate the effects of combined caffeine + TeaCrine + Dynamine measures of neurophysiological and first-person shooter game performance in e-gamers.
Methods: Using a randomized double-blinded, crossover design, we assessed the effects of an acute, single-dose treatment of caffeine (200 mg) vs. caffeine (200 mg) + TeaCrine (10 mg) + Dynamine (50 mg) (CTD) vs. Ppacebo (maltodextrin). Each participant was tested under all three conditions one week apart. Baseline and post-dose measures were tested one hour apart. Participants [n = 49 male (24.4 ±, 4.5 yr)] were amateur e-gamers who play a first-person video game for at least 10 hours/week. Gaming performance was assessed through a series of first-person shooter training games through AIMLAB (State Space Labs, Inc., New York, USA). These included Reflex Shot (RS) standard, speed, and precision. The neurophysiological activity was captured while participants played three games through a single-channel EEG.
Results: In the standard game, the caffeine and the CTD conditions shot significantly more targets relative to the placebo, and both caffeine and the CTD condition had significantly greater targets post-dose compared to pre-dose. However, both the placebo and caffeine conditions had significantly slower reaction times post-dose compared to pre-dose. In the speed game, both the caffeine and placebo conditions shot a significantly greater number of targets, while the placebo and caffeine conditions had significantly more shots post-dose compared to pre-dose. Only the CTD condition had a significant increase in total kills post-dose compared to pre-dose. In the precision game, only the CTD condition significantly improved the number of kills per second post-dose, while only the caffeine condition had more shots post-dose. EEG data collected concomitantly with game playing showed that the CTD condition resulted in significantly lower alpha power compared to the placebo condition. The CTD group also showed increased theta activity post-dose during game playing compared to both the placebo caffeine conditions.
Conclusion: CTD appears to improve overall shooting gaming performance and neurophysiological measures of cognitive activity compared to caffeine and placebo. Collectively, these findings suggest that CTD assists with speed-accuracy tradeoffs where caffeine-only can lead to erratic play; thus, CTD may be particularly beneficial for shooting precision. The EEG data support this notion since the CTD exhibited lower alpha power suggesting increased cognitive flexibility and arousal and higher theta power suggesting greater cognitive control and decision-making under pressure.
... Additionally, theacrine has been reported to positively alter mood and fatigue and exhibit anti-inflammatory and analgesic properties in rats [2,3]. Limited studies exist which examine TeaCrine® supplementation in humans [4][5][6][7][8], but it appears to positively influence cognitive perceptions of energy, focus, and motivation, similarly to caffeine, while notably unaltering hemodynamics (blood pressure, heart rate) which has been reported with caffeine use [9]. The unaltering hemodynamics with TeaCrine® use poses an interesting concept: if TeaCrine® can exert similar or enhanced ergogenic effects to that of caffeine without the possible side effects reported with caffeine use, then TeaCrine® may be an applicable replacement supplement for caffeine, or, a lower dose of caffeine can be used in conjunction with TeaCrine® to mitigate/minimize unwanted side effects while utilizing elicited ergogenic effects. ...
... While neither TEA300 or COMBO treatment resulted in significant differences to PLA, there were trends for mean differences from baseline to 90-min post-treatment in measures of motivation (COMBO > TEA300; p = 0.06, η p 2 = 0.21) and fatigue (COMBO < PLA; p = 0.07, η p 2 = 0.34) which is similar to previous research that reported no significant effects or trends towards significance with TeaCrine® consumption [4,5]. In contrast, Ziegenfuss et al. [6] utilized a twopart approach of TeaCrine® supplementation on subjective cognitive parameters. In the first part, energy, focus, and motivation to exercise significantly increased from baseline with no dose-response effect in TeaCrine® (200 mg vs 400 mg) compared to placebo, with significant group x time effects for energy (TeaCrine®: + 8.6% vs PLA: − 5.7%, p = 0.049) and fatigue (TeaCrine®: − 6.7% vs PLA: − 1.3%, p = 0.05). ...
Background:
TeaCrine® is the synthetic version to naturally occurring theacrine (1, 3, 7, 9-tetramethyluric acid) found in the leaves of Camellia kucha tea plants. A few studies have examined the effects of TeaCrine® on cognitive perception, but no research exists examining its effects on resistance exercise performance. The purpose of this study was to determine the efficacy of TeaCrine®, a caffeine-like compound, on maximal muscular strength, endurance, and power performance in resistance-trained men.
Methods:
Twelve resistance-trained men participated in a randomized, double-blind, cross-over designed study. Each participant performed one-repetition maximum (1RM) bench press, 1RM squat, bench press repetitions to failure (RTF) at 70% 1RM, squat RTF at 70% 1RM, and 2-km rowing time trial 90 min after consumption of: (1) Caffeine 300 mg (CAFF300); (2) TeaCrine® 300 mg (TEA300); (3) TeaCrine® + Caffeine (COMBO; 150 mg/150 mg); (4) Placebo 300 mg (PLA). Power and velocity were measured using a TENDO Power Analyzer. Visual analogue scales for energy, focus, motivation to exercise, and fatigue were administered at baseline and 90 min post-treatment ingestion (pre-workout). Rating of perceived exertion was assessed after bench press RTF and squat RTF.
Results:
There were no differences between groups for 1RM, RTF, and power in the bench press and squat exercises. Only CAFF300 resulted in significant increases in perceived energy and motivation to exercise vs. TEA300 and PLA (Energy: + 9.8%, 95% confidence interval [3.3-16.4%], p < 0.01; + 15.3%, 95% CI [2.2-28.5%], p < 0.02; Motivation to exercise: + 8.9%, 95% CI [0.2-17.6%], p = 0.04, + 14.8%, 95% CI [4.7-24.8%], p < 0.01, respectively) and increased focus (+ 9.6%, 95% CI [2.1-17.1%], p = 0.01) vs. TEA300, but there were no significant differences between CAFF300 and COMBO (Energy + 3.9% [- 6.9-14.7%], Focus + 2.5% [- 6.3-11.3%], Motivation to exercise + 0.5% [- 11.6-12.6%]; p > 0.05).
Conclusion:
Neither TEA300, CAFF300, COMBO, or PLA (when consumed 90 min pre-exercise) improved muscular strength, power, or endurance performance in resistance-trained men. Only CAFF300 improved measures of focus, energy, and motivation to exercise.
... In addition, tyrosine has the potential, as an acute treatment, to prevent stress-related decline in cognitive function, [20][21][22][23][24][25] while tetramethyluric acid has been shown to increase excitability and locomotor activity in rats similar to caffeine. 26 Studies in humans have shown an increase in subjective feelings of energy and mood 27,28 and concentration 28 without undesirable perturbations in clinical markers such as heart rate, blood pressure, lipid profiles, hematologic blood counts, and biomarkers of liver/kidney/immune function. 29 Finally, human studies using up to 250 mg/day have shown pterostilbene to decrease blood pressure and body weight 30,31 and potentially enhance glycogen replenishment through enhanced insulin sensitivity by enhancing hepatic enzymes associated with glucose uptake. ...
... In addition, tyrosine has the potential, as an acute treatment, to prevent stress-related decline in cognitive function, [20][21][22][23][24][25] while tetramethyluric acid has been shown to increase excitability and locomotor activity in rats similar to caffeine. 26 Studies in humans have shown an increase in subjective feelings of energy and mood 27,28 and concentration 28 without undesirable perturbations in clinical markers such as heart rate, blood pressure, lipid profiles, hematologic blood counts, and biomarkers of liver/kidney/immune function. 29 Finally, human studies using up to 250 mg/day have shown pterostilbene to decrease blood pressure and body weight 30,31 and potentially enhance glycogen replenishment through enhanced insulin sensitivity by enhancing hepatic enzymes associated with glucose uptake. ...
Background: We examined the effects of ingesting two preworkout supplements (PWSs) on selective attention and response inhibition, perceived exercise readiness (herein, readiness), and exercise performance-related parameters.
Methods: Resistance-trained participants (N = 19) were randomized to a double-blind, crossover (7-day washout) placebo (PLA)-controlled study supplementing with (1) PLA; (2) PWS [beta-alanine (3.2 g), arginine alpha ketoglutarate (2.0 g), creatine nitrate (2.0 g), ascorbic acid (500 mg), N-acetyl tyrosine (300 mg), caffeine (300 mg), tetramethyluric acid (10 mg), Mucuna pruriens extract standardized for 15% l-Dopa (1.0 g), theacrine (10 mg), pyridoxal 5-phosphate (1.48 mg), folic acid (0.50 mg), and methylcobalamin (1.8 mg)]; and (3) PWS150 at ∼150% the PWS dose. Primary outcomes were Stroop test responses for congruent, incongruent, and interference tasks. Secondary outcomes were readiness and exercise performance (bench and leg press/Wingate). Data were analyzed by general linear models and presented as mean (standard deviation) or mean change [95% confidence interval, CI].
Results: Significant improvements in Stroop word testing were observed for PWS (6.57, 95% CI [1.36–11.8]) and PWS150 (11.5, 95% CI [6.26–16.6]), but not PLA (1.31, 95% CI [−3.89 to 6.52]). Significant changes in Stroop color testing were observed for PWS150 (8.1, 95% CI [4.52–11.6]) and PLA (4.47, 95% CI [0.89–8.05]), but not PWS (2.31, 95% CI [−1.26 to 5.89]). Similar results were observed for word–color. When all domains were summed, PWS150 (27.42 counts, 95% CI [16.08–38.76]) and PWS (12.26 counts, 95% CI [0.92–23.60]) showed significant improvements, but not PLA (11.26 counts, 95% CI [−0.077 to 22.60]). No significant changes in readiness, exercise performance, or adverse changes were otherwise observed.
Conclusion: Consistent improvements in selective attention and response inhibition were observed with PWS150, but not readiness or exercise performance.
... Primary outcomes included fasting clinical safety markers (heart rate, blood pressure, lipid profiles, and hematologic and liver/kidney/immune function biomarkers), all of which fell within normal limits with no group × time interactions and no differences in side effect profiles as compared to controls. Theacrine was also given to 15 healthy subjects in a randomized double-blinded crossover study [25,26]. A single 200 mg dose (or placebo) was administered, and side effect reports, hemodynamics, and biochemical markers of safety were collected over a 3hour postdosing period, with no significant findings noted. ...
... A single 200 mg dose (or placebo) was administered, and side effect reports, hemodynamics, and biochemical markers of safety were collected over a 3hour postdosing period, with no significant findings noted. Six subjects additionally participated in a separate 7-day open-label repeated-dose study comparing 100, 200, and 400 mg of theacrine, in which no side effects were noted [25,26]. ...
A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.
... TeaCrine® appears to provide a mild stimulant and calming effect acting through the adenosine and dopamine systems 18 , thereby potentially allowing for a smaller dose of caffeine which can negate the potential side effects in caffeine sensitive individuals. Ziegenfuss et al. 19 showed increased energy, focus, lower anxiety, increased motivation to exercise and concentration without jitteriness during acute supplementation with TeaCrine®. TeaCrine® has been shown to be safe after eight weeks of use 20 and does not appear to exhibit a tachyphylaxis or habituation effect like caffeine, likely due to different structure-activity relationships and allosteric modulation at the adenosine and dopamine receptors 18 . ...
Purpose: To compare the effects of purported cognitive enhancing dietary bioactive ingredients on subjective and objective measures of cognitive and motor performance during a first-person shooter video game.Methods: Using a placebo-controlled crossover design, nine healthy men (23.4±5.7 yr, 178.9±5.8cm, 86.0±17.1kg) completed four 20-minute gaming sessions designed to assess cognitive, motor, and perceptual skills via artificial intelligence-driven battery of tasks (Aim Lab). Participants ingested either a placebo (PL), caffeine (CAFF), or caffeine + methylliberine (Dynamine™) + theacrine (TeaCrine®) (CMT). Before and after each gaming session participants rated various feelings of affect. Data were analyzed using mixed factorial ANOVA, bootstrapping post-hoc tests with 95% confidence intervals, and effect sizes.Results: Compared to PL, self-assessed performance was significantly increased in CMT vs. PL (p=0.035) and self-assessed jitteriness was increased by CAFF vs. PL (p=0.043). CMT was associated with a greater improvement of participants’ visuo-spatial working memory from baseline vs. PL (p=0.04) and CAFF (p=0.033). CAFF had a greater decrease in reaction time for false alarms (indicating diminished cognitive control) from baseline vs. PL (p=0.002) and CMT (p=0.001) and a greater increase for time on target tracking vs. PL (p=0.008) and CMT (p=0.047). Compared to PL, CMT was associated with a greater decrease in median kill time (indicating improved speed) (p=0.017). Compared to PL, systolic blood pressure was significantly increased by CAFF (p=0.025) and CMT (p=0.020) but remained within normal limits.Conclusions: Acute CMT supplementation improved cognitive and motor abilities in recreational gamers. The addition of theacrine and methylliberine to caffeine may lessen some undesirable effects of isolated caffeine ingestion on cognitive control and jitteriness.
... However, in addition to having a longer supplementation period than the current study, the results of Stratton et al. (2018) provide vague differences over time regardless of group and do not indicate a positive or negative influence from either investigational product. In comparison, there have been mixed results observed with an acute dose of TeaCrine ® , showing increased energy, reduced fatigue, and possibly improved concentration [28], while an 8-week dose regimen increased vigor (via POMS), but had negligible effects on focus, concentration, and energy [29]. Meanwhile, the acute ingestion of CMT did not impact energy, alertness, focus, creativity, or decision making compared to PLA and caffeine [6], but positively impacted mood compared to PLA in egamers [7]. ...
This study assessed the acute effects of oral methylliberine (DynamineTM) supplementation on cognitive function and indices of well-being. This was a double-blind, randomized, within-subject crossover trial. In total, 25 healthy men and women (33.5 ± 10.7 yr, 172.7 ± 8.6 cm, 73.3 ± 11.0 kg) underwent pretesting before ingesting methylliberine (100 mg) or a placebo (PLA) for 3 days. On the fourth day, the participants were tested before their fourth dose (baseline) and every hour post-ingestion for 3 h. After a one-week washout period, the participants repeated testing with the alternate investigational product. The testing battery consisted of vitals, Stroop test, Trail Making Test-B, and visual analog scales that assessed various indices of well-being. Mixed factorial ANOVAs with repeated measures were used to assess all variables. There were significant (p ≤ 0.050) interactions in terms of concentration, motivation, and mood. Methylliberine improved concentration at 1 and 3 h, motivation at 3 h, and mood at 1, 2, and 3 h (p ≤ 0.050). Methylliberine improved energy, sustained energy, and mood in all participants to a greater extent than PLA at 1 h and 3 h relative to baseline (p ≤ 0.050). PLA improved motivation at 1 and 2 h and mood at 2 h (p ≤ 0.050). Methylliberine improved concentration, well-being, and the ability to tolerate stress to a greater extent than PLA at 3 h relative to baseline (p ≤ 0.050). Women observed elevations in sustained energy at 1 and 3 h (p ≤ 0.050) with methylliberine vs. PLA. Methylliberine had a negligible influence on cognitive function and vitals (p > 0.050), and no adverse events were reported. Methylliberine significantly improved subjective feelings of energy, concentration, motivation, and mood, but not cognitive function. PLA improved motivation and mood at hours 1 and 2, while methylliberine sustained these benefits for longer. Methylliberine also improved concentration, well-being, and the ability to tolerate stress to a greater degree than PLA, while having no detrimental effects on vital signs. Methylliberine also seemed to have a positive impact on sustained energy in women.
... TeaCrine® appears to provide a mild stimulant and calming effect acting through the adenosine and dopamine systems 18 , thereby potentially allowing for a smaller dose of caffeine which can negate the potential side effects in caffeine sensitive individuals. Ziegenfuss et al. 19 showed increased energy, focus, lower anxiety, increased motivation to exercise and concentration without jitteriness during acute supplementation with TeaCrine®. TeaCrine® has been shown to be safe after eight weeks of use 20 and does not appear to exhibit a tachyphylaxis or habituation effect like caffeine, likely due to different structure-activity relationships and allosteric modulation at the adenosine and dopamine receptors 18 . ...
Purpose
To compare the effects of purported cognitive enhancing dietary bioactive ingredients on subjective and objective measures of cognitive and motor performance during a first-person shooter video game.
Methods
Using a placebo-controlled crossover design, nine healthy men (23.4±5.7 yr, 178.9±5.8cm, 86.0±17.1kg) completed four 20-minute gaming sessions designed to assess cognitive, motor, and perceptual skills via artificial intelligence-driven battery of tasks (Aim Lab). Participants ingested either a placebo (PL), caffeine (CAFF), or caffeine + methylliberine (Dynamine™) + theacrine (TeaCrine®) (CMT). Before and after each gaming session participants rated various feelings of affect. Data were analyzed using mixed factorial ANOVA, bootstrapping post-hoc tests with 95% confidence intervals, and effect sizes.
Results
Compared to PL, self-assessed performance was significantly increased in CMT vs. PL (p=0.035) and self-assessed jitteriness was increased by CAFF vs. PL (p=0.043). CMT was associated with a greater improvement of participants’ visuo-spatial working memory from baseline vs. PL (p=0.04) and CAFF (p=0.033). CAFF had a greater decrease in reaction time for false alarms (indicating diminished cognitive control) from baseline vs. PL (p=0.002) and CMT (p=0.001) and a greater increase for time on target tracking vs. PL (p=0.008) and CMT (p=0.047). Compared to PL, CMT was associated with a greater decrease in median kill time (indicating improved speed) (p=0.017). Compared to PL, systolic blood pressure was significantly increased by CAFF (p=0.025) and CMT (p=0.020) but remained within normal limits.
Conclusions
Acute CMT supplementation improved cognitive and motor abilities in recreational gamers. The addition of theacrine and methylliberine to caffeine may lessen some undesirable effects of isolated caffeine ingestion on cognitive control and jitteriness.
... Some studies have shown that theacrine may be effective in improving focus or disposition in general, including disposition to exercise [9,11,24]. In addition to the benefits mentioned in clinical trials, animal model data have indicated that theacrine increases locomotive activity in rodents, without promoting tolerance of the body to supplementation, as occurs with caffeine [4,12]. ...
The search to increase physical performance is inherent to physical activity practitioners, and nutrition features are among the alternatives to seeking such an increase. The literature from the area has shown that different substances can promote beneficial effects over physical performance. One substance that has come into the spotlight is theacrine, an alkaloid similar to caffeine, which aims to increase physical performance. However, the studies on this supplement are scarce. Therefore, this study is a randomized, controlled trial that aimed to verify the effects of theacrine supplementation over physical performance in young male athletes, by applying a battery of physical tests. Twenty-two male amateur flag-football athletes were recruited. Subjects were divided into two groups and assessed at two moments, which were 72 h apart. The first assessment served as a basal measurement. In the second, the subjects ingested the supplement or a placebo 60 min before the following tests: sextuple jump, agility T test, 30 m sprint, 40 s run test (Matsudo test), and 12 min run test (Cooper test). There was no difference between the groups in any of the tests. Therefore, the findings of this study do not support the use of theacrine to increase physical performance.
... Variation in caffeine sensitivity has spurred the discovery of wider therapeutic index natural stimulant platforms that include a unique class of purine alkaloids known as methylurates, e.g., theacrine, also exert their pharmacologic effects via adenosine receptor modulation 2,4,10,11,12,13 . Intriguingly, however, the pharmacologic profile of theacrine appears distinct from caffeine in that it does not alter cardiovascular parameters (e.g., heart rate) [14][15][16] . For this reason, theacrine is frequently combined ("stacked") with caffeine in energy, mood, and focus dietary supplements; unfortunately, with little regard for pharmacokinetic and pharmacodynamic interaction potential. ...
Introduction: Methylliberine and theacrine are methylurates found in the leaves of various Coffea species and Camellia assamica var. kucha, respectively. We previously demonstrated that the methylxanthine caffeine increased theacrine’s oral bioavailability in humans. Methods: Consequently, we conducted a double-blind, placebo-controlled pharmacokinetic study in humans administered methylliberine, theacrine, and caffeine to determine methylliberine’s pharmacokinetic interaction potential with either caffeine or theacrine. Subjects received an oral dose of either methylliberine, caffeine, methylliberine plus caffeine, or methylliberine plus theacrine using a randomized, double-blind, crossover design. Blood samples were analyzed using UPLC-MS/MS. Results: Methylliberine exhibited linear pharmacokinetics that were unaffected by co-administration of either caffeine or theacrine. However, methylliberine co-administration resulted in decreased oral clearance (41.9 ± 19.5 vs. 17.1 ± 7.80 L/hr) and increased half-life (7.2 ± 5.6 versus 15 ± 5.8 hrs) of caffeine. Methylliberine had no impact on caffeine’s maximum concentration (440 ± 140 vs. 458 ± 93.5 ng/mL) or oral volume of distribution (351 ± 148 vs. 316 ± 76.4 L). Conclusions: We previously demonstrated theacrine bioavailability was enhanced by caffeine, however, caffeine pharmacokinetics were unaffected by theacrine. Herein, we found that methylliberine altered caffeine pharmacokinetics without a reciprocal interaction, which suggests caffeine may interact uniquely with different methylurates.
... On the other hand, supplementation with theacrine is safe and does not cause side effects commonly caused by caffeine, moreover some studies showed improvement in focus and willingness to exercise with its use (Clewell et al., 2016;Sheng et al., 2020;Ziegenfuss et al., 2017), however with regard to physical performance, our data do not provide evidence that support the use of theacrine. ...
Fatigue is a condition that may affect physical performance during training sessions. Consequently, this will impact
training performance and will also affect the performance of the individual in the long term. Caffeine is extensively
used to counteract fatigue; however, it contains several side effects. Theacrine might be used as an alternative to
caffeine, providing the same benefits without the side effects. The current study aimed to investigate the effects of
8 weeks of supplementation with theacrine on physical performance and training status of young amateur athletes.
Twenty-two subjects were divided into two groups – Theacrine Group (T) and Placebo Group (P) – and evaluated
before and after the intervention period. Evaluations included physical tests and hormonal values of insulin like
growth factor (IGF)-I and IGF binding protein (IGFBP)-3, used as markers of training status. Results demonstrated
that theacrine was not capable of promoting benefits regarding the physical performance of the subjects. It also
had no effects on serum secretion of IGF-I and its binding protein, IGFBP-3. Therefore, the findings of this study
do not support the use of theacrine to increase physical performance.
... Theacrine is a pure alkaloid isolated from the Kucha tea leaf and other plant species, and, like caffeine, is an adenosine receptor antagonist and activates dopamine D1 and D2 receptors [22,23]. TeaCrine® (pure theacrine; Compound Solutions, Inc., Carlsbad, CA, USA) also serves as a prospective supplement to improved egamer performance given its ability to improve the subjective ratings of energy, focus, and concentration [24,25]. However, a study involving soccer players showed that TeaCrine combined with caffeine only conferred modest cognitive benefits [26]. ...
Background
Involvement in video game activities and competitive video gaming (esports) is a rapidly growing field. Moreover, there is a marked interest in identifying nutritional supplements to safely improve egamer performance.
Methodology
We conducted a repeated-measure, randomized crossover study to compare the effects of caffeine (125 mg), caffeine (125 mg) + Dynamine® (75 mg) + TeaCrine® (50 mg) (CDT), and matched placebo across three testing sessions (one week apart) among 50 young male egamers. We tested the effect of each product on multiple measures of cognition, self-reported mood (anxiety, alertness, and headache), and biomarkers of arousal (cortisol and salivary alpha-amylase). We also measured electroencephalogram power during the cognitive tasks. Finally, we tested whether individual differences in xenobiotic metabolism would affect the study outcome measures by genotyping each participant for cytochrome P450 1A2*1F (CYP1A2*1F) allele status.
Results
Compared to pre-dose, CDT improved performance on the Flanker Test of Inhibitory Control and improved reaction time on the Psychomotor Vigilance Task post-dose. Compared to the placebo, caffeine increased self-reported anxiety whereas the CDT combination increased self-reported alertness. Compared to the CDT combination, caffeine increased self-reported headaches. Physiological measures suggested that increases in delta EEG power and cortisol production are associated with the effects observed in the CDT condition to optimize certain aspects of egamer performance. CYP1A2*1F allele status did not moderate outcome variables between conditions in this study.
Conclusions
CDT is a safe and effective product for improving cognitive performance among egamers without increasing self-reported anxiety or headaches. EEG changes demonstrate that CDT increased attention to internal processing (i.e., increased cortical delta power) and potentially increased cognitive control (i.e., increased cortical theta frequency), while the increases in cortisol suggest increased energy mobilization. Future work should aim to clarify the physiological underpinnings of CDT-induced changes in performance and examine the effects of CDT under naturalistic egamer conditions.
... All visual analog scales were similarly constructed using a 100-mm line anchored by "Lowest Possible" and "Highest Possible" to assess subjective ratings of energy, willingness to exercise, muscle soreness, and sleep quality. The validity and reliability of VAS to assess fatigue and energy have been previously established 11 and our methods have been published elsewhere [12][13][14][15] . ...
Introduction: Purple tea exhibits a unique composition of chemical constituents that may exert favorable outcomes related to recovery from muscle damage, improvements in blood flow, perfusion, and recovery. The purpose of this study was to examine the impact of a brief oral dosing period of purple tea in exercising humans after stressful, damaging exercise. Methods: Using a randomized, placebo-controlled, double-blind, crossover study design, 30 healthy men (33.5 ± 11.4 years, 178.4 ± 7.6 cm, 92.5 ± 13.3 kg) completed an eight day supplementation regimen consisting of either a maltodextrin placebo or 100 mg of purple tea extract (PurpleForce™, Oryza Oil & Fat, Ltd.) interspersed with a two week washout period. After five and eight days of supplementation, changes in muscle oxygenation, body composition, reactive hyperemia, visual analog responses, exercise performance, and muscle damage markers were assessed. Data were analyzed using mixed factorial ANOVA, t-tests with 95% confidence intervals, and effect sizes (ES). Results: Lactate dehydrogenase was significantly reduced (p = 0.04) in PT in comparison to PLA after eight days of supplementation and exercise performance challenge. In comparison to PT, arm circumference increased in PLA after five days of supplementation (p=0.04) and tended to be greater after eight days (p=0.06). Significantly greater decreases in impedance were observed in PT (p=0.02) while between-group differences in oxygen saturation post-leg extension exercise were greater in PT 30s into recovery (p=0.04) and tended to be greater 60s after recovery (p=0.06). Total bench press repetitions completed were greater in purple tea than PLA (p = 0.001). Total leg extension repetitions completed tended to be different between groups (p=0.09) while the total number of repetitions completed in purple tea increased from day five to day eight (p<0.001) with no change in PLA (p=0.37). No between-group changes were observed in the visual analog scales; however, only the PT condition experienced a significant improvement in Willingness to Exercise (p=0.02). Conclusions: Acute supplementation of PT decreased lactate dehydrogenase, a marker of muscle damage, while also improving lower body muscle endurance performance.
... Tea is also used as one of the ingredients of traditional Chinese medicine to treat inflammation. The role of the anti-inflammatory effect of TC in an inflammation model was reported to inhibit the nuclear factor-kB (NF-kB) transcription factor [18] and reduce proinflammatory factors (TNF-a, IL-6 and IL-1b) [19], cyclooxygenase, phospholipase and reactive oxygen production to regulate inflammation and induce apoptosis of synoviocytes in rheumatoid arthritis [20]. ...
Rheumatoid arthritis is a chronic and systemic autoimmune disease, which affects approximately 1% of the adult population worldwide. The present study investigated the therapeutic effect of theacrine (TC) on arthritis and its mechanisms in Freund's incomplete adjuvant (FIA)-induced SD rats. Rats were randomly divided into 5 groups: i) healthy control; ii) model; iii) positive control with methotrexate (MTX); iv) treatment with 12.5 mg/kg TC; and v) treatment with 25.0 mg/kg TC. The apparent scores, including changes in body weights, degree of paw swelling and arthritis indicators, were analyzed to evaluate the anti-chronic inflammatory effect of TC. The levels of interleukin (IL)-6 and transforming growth factor-β (TGF-β) in serum were measured by enzyme-linked immunosorbent assay. The protein and RNA expression levels of the critical factors in rats were measured to elucidate the mechanisms responsible for chronic inflammation and to verify molecular indexes of chronic inflammatory conditions. TC notably suppressed the severity of FIA-induced rat by attenuating the apparent scores, animal weight and inflammatory indexes in the 25 mg/kg TC group compared with the FIA rat model. Furthermore, TC significantly decreased the levels of IL-6 and increased the levels of TGF-β. Histopathological examinations indicated that TC rescued the synovial hyperplasia and inflammatory cell infiltration in joint tissues. In addition, TC enhanced TGF-β-mediated shifts in inflammatory marker expression in joint tissue. Overall, the present study demonstrated that TC exerted a superior anti-arthritic effect via the suppression of IL-6 and the activation of TGF-β by the TGF-β/SMAD pathway.
... Due to structural similarities to the methylxanthine caffeine, methylliberine is hypothesized to have similar physiological properties but without undesirable stimulant effects, as has previously been demonstrated for the related methoxiurate, theacrine [2][3][4][5]. e slight structural differences between theacrine and methylliberine have been hypothesized to result in slight differences in the pharmacokinetic profiles of the two compounds, with methylliberine thought to have a shorter time to reach maximum plasma concentration and a shorter half-life with respect to theacrine. Because of these hypothetical properties, there is interest in methylliberine as an ingredient in functional foods and dietary supplements, and clinical trials to investigate all three hypotheses are currently underway. ...
Methylliberine (CAS 51168-26-4), a methoxiuric acid, is a caffeine metabolite present at low levels in various Coffea plants; however, very little has been published regarding this compound and we could find no toxicological data in the public domain. Therefore, we undertook the toxicological investigation of a pure, synthetic form of methylliberine in order to evaluate its potential health hazards as a food ingredient. A (1) bacterial reverse mutation test, (2) in vitro mammalian chromosomal aberration test, (3) in vivo mammalian micronucleus test, and (4) 90-day repeated-dose oral toxicity study in rats with a 28-day recovery period were conducted. No in vitro mutagenic or clastogenic activity was observed in the presence or absence of metabolic activation up to the maximum OECD recommended test concentrations. No genotoxicity was observed in the mammalian micronucleus study up to the highest dose tested of 700 mg/kg bw. In the 90-day study, methylliberine was administered to Han:WIST rats at doses of 0, 75, 112, 150, 187, and 225 mg/kg bw/day. No mortality or morbidity was observed and no toxicologically relevant clinical effects or effects on clinical pathology parameters were observed. In male animals, test item-related effects on body weight and sexual organs, which were not reversible after a 28-day recovery period without treatment, were observed in the high-dose group. Body weight development was also slightly and reversibly depressed in the 187 mg/kg bw/day male group. No toxicological effects were observed in females. The NOAEL for females was determined to be 225 mg/kg bw/day, the highest dose tested, while the NOAEL for males was determined to be 150 mg/kg bw/day. Future studies are encouraged to corroborate the safety, and assess efficacy, of methylliberine in humans.
... In plants, caffeine is typically synthesised as the most prominent of a group of structurally related methylxanthines. However, controlled trials suggest that non-caffeine methylxanthines such as theobromine and theacrine, which is present in some tea plants, have inconsistent or negative effects on mood, and no interpretable beneficial effects on cognitive function [231][232][233][234][235][236]. Caffeine, on the other hand, has consistent central nervous system effects, rapid bioavailability, with a half-life of 3-5 h, and the propensity to rapidly cross the blood-brain barrier [237]. ...
Subjective alertness and optimal cognitive function, including in terms of attention, spatial/working memory and executive function, are intrinsic to peak performance in many sports. Consumption of a number of plant-derived ‘secondary metabolite’ phytochemicals can modulate these psychological parameters, although there is a paucity of evidence collected in a sporting context. The structural groups into which these phytochemicals fall—phenolics, terpenes and alkaloids—vary in terms of the ecological roles they play for the plant, their toxicity and the extent to which they exert direct effects on brain function. The phenolics, including polyphenols, play protective roles in the plant, and represent a natural, benign component of the human diet. Increased consumption has been shown to improve cardiovascular function and is associated with long-term brain health. However, whilst short-term supplementation with polyphenols has been shown to consistently modulate cerebral blood-flow parameters, evidence of direct effects on cognitive function and alertness/arousal is currently comparatively weak. Terpenes play both attractant and deterrent roles in the plant, and typically occur less frequently in the diet. Single doses of volatile monoterpenes derived from edible herbs such as sage (Salvia officinalis/lavandulaefolia) and peppermint (Mentha piperita), diterpene-rich Ginkgo biloba extracts and triterpene-containing extracts from plants such as ginseng (Panax ginseng/quinquefolius) and Bacopa monnieri have all been shown to enhance relevant aspects of cognitive function and alertness. The alkaloids play toxic defensive roles in the plant, including via interference with herbivore brain function. Whilst most alkaloids are inappropriate in a sporting context due to toxicity and legal status, evidence suggests that single doses of nicotine and caffeine may be able to enhance relevant aspects of cognitive function and/or alertness. However, their benefits may be confounded by habituation and withdrawal effects in the longer term. The efficacy of volatile terpenes, triterpene-rich extracts and products combining low doses of caffeine with other phytochemicals deserves more research attention.
... kucha) that appears to act through both the adenosine and dopamine systems to provide a mild stimulant effect, as well as a calming effect (Feduccia et al., 2012;Taylor et al., 2016). Acute supplementation of theacrine has been shown to improve energy, concentration, and mood while reducing fatigue ( Ziegenfuss et al., 2016). Kuhman, Joyner, and Bloomer (2015) also demonstrated that the combination of theacrine and caffeine improved multiple subjective feelings related to energy and mood compared to placebo and caffeine alone; however, cognitive performance was not significantly altered (Kuhman, Joyner, & Bloomer, 2015). ...
This study assessed whether a multi-ingredient energy supplement (MIES) could enhance cerebral-cortical activation and cognitive performance during an attention-switching task. Cerebral-cortical activation was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via electroencephalography (EEG) both at rest and during the attention-switching task before (pretest) and 30 min after (posttest) consumption of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or a placebo (PL) in a double-blinded, randomized crossover experimental design. EEG upper-alpha power was assessed at rest and during the task, wherein d′ (Z[hit rate]–Z[false alarm rate]) and median reaction time (RT) for correct responses to targets on attention-hold and attention-switch trials were analyzed. For both d′ and RT, the Session (MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached statistical significance (p = .07, η²p = 0.106). Exploring these interactions with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (ps ≤.034), suggesting the pretest-to-posttest improvement in sensitivity to task target stimuli (d′) and RT increased as a function of supplement dose. With respect to upper-alpha power, the Session × Time interaction was significant (p < .001, η²p = 0.422). Exploring this interaction with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (p < .001), suggesting pretest-to-posttest increases in cerebral-cortical activation were a function of supplement dose. In conclusion, our findings suggest that MIES can increase cerebral-cortical activation and RT during task performance while increasing sensitivity to target stimuli in a dose-dependent manner.
Acute kidney injury (AKI) is a frequent and serious complication of sepsis, which results in a rapid decline of kidney function. Currently, there are no curative therapies for AKI. Theacrine is a purine alkaloid and exerts significant role in regulating inflammation, oxidative stress, and mood elevation. The study aims to evaluate the biological role and potential mechanism of theacrine in septic AKI. The murine and cellular models of septic AKI were established in lipopolysaccharide (LPS)-treated C57BL/6 mice and HK-2 cells, respectively. The effect of theacrine on alleviating septic AKI was assessed after pretreatment with theacrine in vivo and in vitro . We found that theacrine treatment significantly alleviated LPS-induced kidney injury, as evidenced by decreased levels of kidney injury markers (blood urea nitrogen and creatinine), inflammatory factors (IL-1 β and IL-18), and cell apoptosis in vivo and in vitro . Mechanistically, theacrine markedly repressed the activation of NOD-like receptor (NLR) pyrin domain-containing protein 3 (NLRP3)inflammasome. As expected, MCC950 (a specific inhibitor of NLRP3) treatment also decreased LPS-induced production of IL-18 and IL-1 β and cell apoptosis in HK-2 cells. More important, Nigericin sodiumsalt (a NLRP3 agonist) damaged the effect of theacrine on repressing kidney injury markers (blood urea nitrogen and creatinine), pro-inflammatory cytokines (IL-18 and IL-1 β ), and cell apoptosis. Taken together, these results demonstrate that theacrine alleviates septic AKI, at least in part by repressing the activation of NLRP3 inflammasome.
Background: Fatigue is a condition that may affect physical performance during training sessions. Consequently, this will impact training performance, moreover in the performance of the individual in long-term. Caffeine is broadly utilized to this purpose, however contains several side effects. Thus, teacrine emerges as an alternative to the use of caffeine, providing the same benefits without the side effects. Thus, the current work had as an objective to investigate the effects of 8 weeks of supplementation with teacrine on physical performance and the training status of young amateur athletes.
Methods: 22 subjects were divided into two groups – Teacrine Group (T) and Placebo Group (P) – and evaluated before and after the intervention period. Evaluations included physical tests and hormonal doses of IGF-I and IGFBP-3, utilized as markers of training status.
Results: Results demonstrated that teacrine was not capable of promoting benefits in relation to physical performance of the subjects. Neither produced effects on serum secretion of IGF-I and its binding protein, IGFBP-3.
Conclusion: Therefore, the findings of the present study do not support the use of teacrine for the purpose of increasing physical performance.
We determined the effects of a commercially available, GRAS (Generally Recognized As Safe) by independent conclusion, CBD-containing hemp oil extract on stress resilience, perceived recovery, mood, affect, body composition, and clinical safety markers in healthy human subjects.
Methods: Using a randomized, placebo-controlled, double-blind design, 65 overweight, but otherwise healthy men and women (35.2 ± 11.4 years, 28.5 ± 3.3 kg/m²) ingested either Hemp Oil Extract [Hemp, 60 mg/d PlusCBDTM Extra Strength Hemp Extract Oil (15 mg hemp-derived CBD)] or a placebo (PLA) every day for six weeks while continuing to follow their normal diet and physical activity patterns. Outcome variables included changes in stress resilience, a 14-item panel of various psychometric parameters, heart-rate variability, plasma chromogranin A, body composition, and general markers of health. Data were analyzed using mixed factorial ANOVA, t-tests with 95% confidence intervals, and effect sizes (ES).
Results: HDL cholesterol significantly improved in the Hemp group (p = 0.004; ES = 0.75). No other statistically significant group x time interaction effects were observed. Statistical tendencies for between-group differences were found for ‘I Get Pleasure From Life’ (p = 0.06, ES = 0.48) and ‘Ability to Cope with Stress’ (p = 0.07, ES = 0.46). Sleep quality (Hemp, p = 0.005, ES = 0.54) and sleep quantity (Hemp, p = 0.01, ES = 0.58) exhibited significant within-group changes. All values for hepato-renal function, cardiovascular health, fasting blood lipids, and whole blood cell counts remained within normal clinical limits with no between-group differences over time being identified.
Conclusions: Hemp supplementation improved HDL cholesterol, tended to support psychometric measures of perceived sleep, stress response, and perceived life pleasure and was well tolerated with no clinically relevant safety concerns. Registered at clinicaltrials.gov: NCT04294706.
A cafeína é conhecida por melhorar o foco, retardar a fadiga e melhora tempo de reação. A teacrina é um metabólico da cafeína, alguns estudos sugerem que esta molécula também exerce os mesmos efeitos ergogênicos atribuídos à cafeína. O futebol exerce grande estresse metabólico induzindo a fadiga periférica e central, no final do jogo atletas se demonstram mais cansados, com falta de foco, queda na performance técnica e com queda acentuado nos sprint. O objetivo deste estudo é verificar o efeito da suplementação aguda de cafeína e teacrina em parâmetros de foco, tempo de reação, velocidade e técnica em de atletas de futebol de elite em estado de fadiga.
Males seeking to improve body composition may ingest thermogenic dietary supplements with the goal of elevating resting metabolic rate. The purpose of this study was to examine the effects of a commercially available dietary supplement (containing ingredients that promote thermogenesis) on resting metabolic rate (RMR) in a randomized, double-blind, placebo-controlled cross-over study. Ten healthy, physically active males (age: 26.5 ± 6.4 years; height: 177.6 ± 7.2 cm; body weight: 80.5 ± 10.8 kg) underwent two testing sessions separated by approximately 7 days. Following baseline assessments of RMR, heart rate (HR), and blood pressure (BP), each participant ingested a thermogenic dietary supplement or a placebo. Assessments were repeated at 60, 120, and 180 minutes postingestion. Approximately 1 week later, participants ingested the alternative supplement and the assessments were repeated. Post hoc analyses revealed that the dietary supplement treatment demonstrated significant elevations in RMR during the postingestion period (p < 0.05) from 1,859 ± 266 kcal to 2,027 ± 288 kcal (increase of 9%) to 2,072 ± 292 kcal (increase of 11.5%) and to 2,040 ± 271 kcal (increase of 9.7%) at 60, 120, and 180 minutes postingestion, respectfully. No significant elevations were observed in the placebo treatment at any time point. HR and BP measures were within normal clinical values throughout the intervention.
Background:
Theacrine (1,3,7,9-tetramethyluric acid) is a purine alkaloid found in certain coffee (Coffea) species, fruits (Cupuacu [Theobroma grandiflorum]), and tea (Camellia assamica, var. kucha) that has anti-inflammatory, analgesic, and neuro-locomotor properties. Recent preliminary research has also reported increased feelings of energy, reduced fatigue, and strong effects on improving focus, concentration, and motivation to exercise. The purpose of this study was to examine the safety and non-habituating effects of TeaCrine®, a nature-identical, chemically equivalent bioactive version of theacrine.
Methods:
Sixty healthy men (mean ± SD age, height, weight: 22.9 ± 4.7 years, 183.5 ± 9.2 cm, 86.5 ± 13.7 kg) and women (22.3 ± 4.5 years, 165.2 ± 12.3 cm, 69.0 ± 17.4 kg) were placed into one of three groups: placebo (PLA, n = 20), 200 mg TeaCrine® (LD, n = 19) or 300 mg Teacrine® (HD, n = 21) and ingested their respective supplement once daily for 8 weeks. Primary outcomes were fasting clinical safety markers (heart rate, blood pressure, lipid profiles, hematologic blood counts, biomarkers of liver/kidney/immune function) and energy, focus, concentration, anxiety, motivation to exercise, and POMS measured prior to daily dosing to ascertain potential tachyphylactic responses and habituation effects. Data were analyzed via two-way (group × time) ANOVAs and statistical significance was accepted at p < 0.05.
Results:
All values for clinical safety markers fell within normal limits and no group × time interactions were noted. No evidence of habituation was noted as baseline values for energy, focus, concentration, anxiety, motivation to exercise, and POMS remained stable in all groups across the 8-week study protocol.
Conclusions:
These findings support the clinical safety and non-habituating neuro-energetic effects of TeaCrine® supplementation over 8 weeks of daily use (up to 300 mg/day). Moreover, there was no evidence of a tachyphylactic response that is typical of neuroactive agents such as caffeine and other stimulants.
Theacrine is a purine alkaloid found primarily in the leaves of the Camellia Kucha plant and is now included within dietary supplements. To compare the effects of a theacrine-containing dietary supplement with caffeine and placebo on energy and mood, as well as objective measures of cognitive performance, heart rate, and blood pressure, 10 healthy men (20.8 ± 0.7 years) and 10 healthy women (22.2 ± 1.1 years) ingested the dietary supplement TheaTrim (Purus Labs; containing a branded form of theacrine (Teacrine™) and caffeine (150 mg)), caffeine only (150 mg), or a placebo on three different days, separated by approximately one week. Before, and for up to 4 h following, ingestion of the assigned condition, subjects completed a subjective assessment of energy and mood, as well as tests of cognitive performance (trail making test (TMT), digit symbol substitution test (DSST)), and reaction time. Heart rate and blood pressure were measured. No condition or interaction effects were noted for TMT, DSST, or reaction time, despite a trend for improvement in selected variables with both TheaTrim and caffeine treatment. Condition effects or trends were noted for subjective feelings, with values for attentive, alert, focused, and energetic higher for TheaTrim than for placebo and caffeine, while values for lethargic and groggy were lower for TheaTrim than for placebo and caffeine. Heart rate and blood pressure were largely unaffected by treatment. These data indicate that TheaTrim treatment does not result in a statistically significant improvement in cognitive performance but may favorably impact multiple subjective feelings related to energy and mood.
Single-dose oral administration of 100 mg caffeine increased the resting metabolic rate of both lean and postobese human volunteers by 3-4% (p less than 0.02) over 150 min and improved the defective diet-induced thermogenesis observed in the postobese subjects. Measurements of energy expenditure (EE) in a room respirometer indicate that repeated caffeine administration (100 mg) at 2-h intervals over a 12-h day period increased the EE of both subject groups by 8-11% (p less than 0.01) during that period but had no influence on the subsequent 12-h night EE. The net effect was a significant increase (p less than 0.02) in daily EE of 150 kcal in the lean volunteers and 79 kcal in the postobese subjects. Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity.
Although subjective appetite scores are widely used, studies on the reproducibility of this method are scarce. In the present study nine healthy, normal weight, young men recorded their subjective appetite sensations before and during 5 h after two different test meals A and B. The subjects tested each meal twice and in randomized order. Visual analogue scale (VAS) scores, 10 cm in length, were used to assess hunger, satiety, fullness, prospective food consumption and palatability of the meals. Plasma glucose and lactate concentrations were determined concomitantly. The repeatability was investigated for fasting values, delta-mean 5 h and mean 5 h values, delta-peak/nadir and peak/nadir values. Although the profiles of the postprandial responses were similar, the coefficients of repeatability (CR = 2SD) on the mean differences were large, ranging from 2.86 to 5.24 cm for fasting scores, 1.36 to 1.88 cm for mean scores, 2.98 to 5.42 cm for delta-mean scores, and 3.16 to 6.44 cm for peak and delta-peak scores. For palatability ratings the CR values varied more, ranging from 2.38 (taste) to 8.70 cm (aftertaste). Part of the difference in satiety ratings could be explained by the differences in palatability ratings. However, the low reproducibility may also be caused by a conditioned satiation or hunger due to the subjects' prior experience of the meals and therefore not just be a reflection of random noise. It is likely, however, that the variation in appetite ratings is due both to methodological day-to-day variation and to biological day-to-day variation in subjective appetite sensations.
To examine reproducibility and validity of visual analogue scales (VAS) for measurement of appetite sensations, with and without a diet standardization prior to the test days.
On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 4.5 h postprandial period under exactly the same conditions.
55 healthy men (age 25.6+/-0.6 y, BMI 22.6+/-0.3 kg¿m2).
VAS were used to record hunger, satiety, fullness, prospective food consumption, desire to eat something fatty, salty, sweet or savoury, and palatability of the meals. Subsequently an ad libitum lunch was served and energy intake was recorded. Reproducibility was assessed by the coefficient of repeatability (CR) of fasting, mean 4.5 h and peak/nadir values.
CRs (range 20-61 mm) were larger for fasting and peak/nadir values compared with mean 4.5 h values. No parameter seemed to be improved by diet standardization. Using a paired design and a study power of 0.8, a difference of 10 mm on fasting and 5 mm on mean 4.5 h ratings can be detected with 18 subjects. When using desires to eat specific types of food or an unpaired design, more subjects are needed due to considerable variation. The best correlations of validity were found between 4.5 h mean VAS of the appetite parameters and subsequent energy intake (r=+/-0.50-0.53, P<0.001).
VAS scores are reliable for appetite research and do not seem to be influenced by prior diet standardization. However, consideration should be given to the specific parameters being measured, their sensitivity and study power. International Journal of Obesity (2000)24, 38-48
Theacrine (1,3,7,9-tetramethyluric acid) and caffeine were the major purine alkaloids in the leaves of an unusual Chinese tea known as kucha (Camellia assamica var. kucha). Endogenous levels of theacrine and caffeine in expanding buds and young leaves were ca. 2.8 and 0.6-2.7% of the dry wt, respectively, but the concentrations were lower in the mature leaves. Radioactivity from S-adenosyl-L-[methyl-14C]methionine was incorporated into theacrine as well as theobromine and caffeine by leaf disks of kucha, indicating that S-adenosyl-L-methionine acts as the methyl donor not only for caffeine biosynthesis but also for theacrine production. [8-14C]Caffeine was converted to theacrine by kucha leaves with highest incorporation occurring in expanding buds. When [8-14C]adenosine, the most effective purine precursor for caffeine biosynthesis in tea (Camellia sinensis), was incubated with young kucha leaves for 24 h, up to 1% of total radioactivity was recovered in theacrine. However, pulse-chase experiments with [8-14C]adenosine demonstrated much more extensive incorporation of label into caffeine than theacrine, possibly because of dilution of [14C]caffeine produced by the large endogenous caffeine pool. These results indicate that in kucha leaves theacrine is synthesized from caffeine in what is probably a three-step pathway with 1,3,7-methyluric acid acting an intermediate. This is a first demonstration that theacrine is synthesized from adenosine via caffeine.
Metabolism of purine alkaloids in the leaves of Coffea dewevrei De Wild et Durand var excelsa Chev, Coffea liberica Bull ex Hiern and Coffea abeokutae Cramer was studied by analyzing leaf discs collected during vegetative development and by feeding the following radioactive tracers: [(14)C]theobromine, [(14)C]caffeine, and [(14)C]theacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites were quantitatively and qualitatively determined. All three species convert the precursors to the same radioactive products, and proceed through the same four maturity stages characterized by the alkaloid accumulation pattern and by a particular transformation potency: (stage 1) young plant accumulating caffeine, transforms theobromine to caffeine; (stage 2) caffeine is gradually replaced by theacrine, theobromine and caffeine are converted to theacrine; (stage 3) theacrine disappears whereas liberine (O(2), 1,9-thrimethyluric acid) accumulates, theacrine is metabolized to liberine; (stage 4) branched-out plant containing liberine but no theacrine, caffeine is converted rapidly to liberine via theacrine. Methylliberine (O(2),1,7,9-tetramethyluric acid), presumably the direct precursor of liberine, is occasionally found in low concentrations at stage 3 and 4.The collective term ;liberio-excelsoid' introduced by geneticists for the numerous races or species of Pachycoffea is in accordance with the phytochemical equality found in this work.
Aim: To investigate the antidepressant effects of theacrine (TC). Methods: The antidepressant effects of TC were examined by a series of experiments including tail suspension test, forced swimming test, ambulatory activity test, yohimbine induced toxicity test, reserpine test and 5-HTP induced head-twitching test (The doses of groups were 3, 10, 30 mg · kg-1, bid respectively for continued 7 days of intragastric administration). Results: Compared with the control group, TC could effectively shorten the immobility time in the tail suspension test (P < 0.05) and enhance the rotatory locomotor activities during forced swimming test (P < 0.05), but didn't affect the ambulatory activity. Moreover, TC also enhanced the mortality induced by yohimbine, and increased the head-twitching number induced by 5-HTP (P < 0.01). In addition, TC could markedly improve such symptoms as hypothermia (P < 0.01), akinesia (P < 0.05), and eye ptosis of mice (P < 0.01) induced by reserpine. Conclusions: TC has antidepressant effects in various depression models of mice, which may be contributed to its influence on monoamine neurotransmitter.
Two kinds of green tea were prepared with the young shoots of Camellia kucha and C. ptilophylla, and antioxidative activities of the chemical constituents were determined. Levels of alkaloids, catechins, total polyphenols, flavonoids and amino acids were determined by high‐performance liquid chromatography and UV‐Vis spectrophotometer. Antioxidative activity was evaluated by applying 2,2‐diphenyl‐1‐picrylhydrazyl radical assay and ferric reducing antioxidant power assay. Our results showed that theobromine was the only alkaloid in C. ptilophylla, while there was theacrine in C. kucha, which was coexisting with the caffeine. We confirmed the high content of (−)‐gallocatechin gallate in C. ptilophylla was not the epimerisation of (−)‐epigallocatechin gallate during the heating procedure. These wild teas had higher content of tea polyphenols, water extracts, amion acids and stronger antioxidative activity compared with the longjing tea. They could be used for the development of noncaffeine beverages and new types of tea.
Caffeine is the psychostimulant substance consumed in greatest quantities in the world. The repeated administration of psychostimulants can either decrease or increase the drug effect, inducing tolerance or sensitization, respectively, depending on administration procedure. Not only the dose and regimen, but also the environment where drug is administered, seem to modulate the changes in locomotor activity following repeated psychostimulant administration. The purpose of the present study was to examine the influence of the environmental context on caffeine-induced psychomotor stimulation following repeated administration of this drug. Our results showed that repeated caffeine induced psychomotor sensitization when drug injections were paired with the environment in which the animals were subsequently tested, whereas tolerance occurred when the animals received repeated caffeine in an environment different from that where the tests were performed. In conclusion, the present results demonstrated that the environmental context where caffeine is administered is a key factor modulating the adaptations of the organism to drug effects.
Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.
The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and lambda-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8-32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8-32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities.
In humans caffeine stimulates thermogenesis by unknown mechanisms and its effect on body weight has not been studies. The effect of placebo and 100, 200, and 400 mg oral caffeine on energy expenditure, plasma concentrations of substrates and hormones, blood pressure, and heart rate was investigated in a double-blind study in healthy subjects who had a moderate habitual caffeine consumption. Caffeine increased energy expenditure dose dependently and the thermogenic response was positively correlated with the response in plasma caffeine (r = 0.52; p less than 0.018), plasma lactate (r = 0.79; p less than 0.000001), and plasma triglyceride (r = 0.53; p less than 0.02). Stepwise regression analysis with the thermogenic response as the dependent variable excluded plasma caffeine and yielded the following equation: thermic effect (kcal/3 h) = -0.00459 X heart rate + 0.30315 X (triglyceride) + 0.53114 X (lactate) + 15.34 (r = 0.86; p = 0.0001). The results suggest that lactate and triglyceride production and increased vascular smooth muscle tone may be responsible for the major part of the thermogenic effect of caffeine.