Paraxanthine Supplementation Increases Muscle Mass, Strength, and Endurance in Mice

Jäger, Ralf; Purpura, Martin; Wells, Shawn; Liao, K.C.; Godavarthi, Ashok

doi:10.3390/nu14040893

Cited by 14 publications

(8 citation statements)

References 48 publications

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“…A dose-response study confirmed the nootropic effects of paraxanthine in acute doses as little as 50 mg [ 24 ]. Moreover, Jäger and coworkers [ 65 ] reported that paraxanthine supplementation increased muscle mass, strength, and endurance in mice. While preclinical and mechanistic data suggest some advantages of paraxanthine over caffeine, no study has compared the nootropic effects of ingesting paraxanthine with or without caffeine on cognition after intense exercise.…”

Section: Discussionmentioning

confidence: 99%

Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run

Yoo,

Xing,

Gonzalez

et al. 2024

Journal of the International Society of Sports Nutrition

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Rationale Intense exercise promotes fatigue and can impair cognitive function, particularly toward the end of competition when decision-making is often critical for success. For this reason, athletes often ingest caffeinated energy drinks prior to or during exercise to help them maintain focus, reaction time, and cognitive function during competition. However, caffeine habituation and genetic sensitivity to caffeine (CA) limit efficacy. Paraxanthine (PX) is a metabolite of caffeine reported to possess nootropic properties. This study examined whether ingestion of PX with and without CA affects pre- or post-exercise cognitive function. Methods 12 trained runners were randomly assigned to consume in a double-blind, randomized, and crossover manner 400 mg of a placebo (PL); 200 mg of PL + 200 mg of CA; 200 mg of PL + 200 mg of PX (ENFINITY®, Ingenious Ingredients); or 200 mg PX + 200 mg of CA (PX+CA) with a 7–14-day washout between treatments. Participants donated fasting blood samples and completed pre-supplementation (PRE) side effects questionnaires, the Berg-Wisconsin Card Sorting Test (BCST), and the Psychomotor Vigilance Task Test (PVTT). Participants then ingested the assigned treatment and rested for 60 minutes, repeated tests (PRE-EX), performed a 10-km run on a treadmill at a competition pace, and then repeated tests (POST-EX). Data were analyzed using General Linear Model (GLM) univariate analyses with repeated measures and percent changes from baseline with 95% confidence intervals. Results BCST correct responses in the PX treatment increased from PRE-EX to POST-EX (6.8% [1.5, 12.1], p = 0.012). The error rate in the PL (23.5 [−2.8, 49.8] %, p = 0.078) and CA treatment (31.5 [5.2, 57.8] %, p = 0.02) increased from PRE-EX values with POST-EX errors tending to be lower with PX treatment compared to CA (−35.7 [−72.9, 1.4] %, p = 0.059). POST-EX perseverative errors with PAR rules were significantly lower with PX treatment than with CA (−26.9 [−50.5, −3.4] %, p = 0.026). Vigilance analysis revealed a significant interaction effect in Trial #2 mean reaction time values ( p = 0.049, = 0.134, moderate to large effect) with POST-EX reaction times tending to be faster with PX and CA treatment. POST-EX mean reaction time of all trials with PX treatment was significantly faster than PL (−23.2 [−43.4, −2.4] %, p = 0.029) and PX+CA (−29.6 [−50.3, −8.80] %, p = 0.006) treatments. There was no evidence that PX ingestion adversely affected ratings of side effects associated with stimulant intake or clinical blood markers. Conclusions Results provide some evidence that pre-exercise PX ingestion improves prefrontal cortex function, attenuates attentional decl...

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Section: Discussionmentioning

confidence: 99%

Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run

Yoo,

Xing,

Gonzalez

et al. 2024

Journal of the International Society of Sports Nutrition

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…Despite the fact that further trials are needed to corroborate the causal path, caffeine and some of its metabolites, including the main one, paraxanthine, show notable potential pharmacological interests, sometimes different from caffeine, for example on nitric oxide (NO) neurotransmission [ 44 , 45 ]. Jäger and colleagues showed interesting results of paraxanthine supplementation on grip strength, muscle mass, treadmill performance and NO in mice, all with seemingly less toxicity compared to caffeine [ 45 , 46 ]. On the other hand, theophylline has already shown an effect of reducing susceptibility to fatigue by improving ventilatory functions through its bronchodilator effect and on the contractility of the diaphragm [ 47 ] and is commonly used in the elderly in the context of asthma or chronic airway diseases [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Coffee Drinking and Adverse Physical Outcomes in the Aging Adult Population: A Systematic Review

et al. 2022

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Declining physical functioning covers a prominent span of later life and, as a modifiable driver to be leveraged, lifestyle plays a critical role. This research aimed to undertake a systematic review investigating the association between levels of coffee consumption and declining conditions of physical functioning during aging, such as sarcopenia, frailty, weakness, falls, and disability, while trying to explain the underlying mechanisms, both from a metabolic and social angle. The literature was reviewed from inception to May 2022 using different electronic databases, not excluding the grey literature. Two independent researchers assessed the eligibility of 28 retrieved articles based on inclusion criteria; only 10 met the eligibility requirements. Different levels of coffee consumption were considered as exposure(s) and comparator(s) according to PECO concepts, while middle age was an inclusion criterion (40 + years). No limitations were set on the tool(s) assessing physical functioning, type of dietary assessment(s), study setting, general health status, country, and observational study design (cohort, cross-sectional). The cross-sectional design outnumbered the longitudinal (90%, n = 9/10). The overall quality rating was judged poor (70%) to good (30%). It was found that higher exposure to coffee drinking is strongly associated with better physical functioning outcomes, and the findings showed consistency in the direction of association across selected reports. Countering physical decline is a considerable challenge in easing the burden of population aging. For preventive models that aim to allow a better lifestyle, it has to be kept in mind that increased coffee consumption does not lead to poor physical functioning.

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“…Paraxantine, the primary metabolite of caffeine, has similar pharmacological properties to caffeine but has been claimed to have reduce anxiogenic effects and reduced toxicity [39] compared with caffeine. It is unclear whether the therapeutic vs. deleterious effects of paraxanthine would differ from those of caffeine in the setting of headache disorders.…”

Section: Potential Alternatives To Caffeinementioning

confidence: 99%

The role of caffeine in headache disorders

Charles

2024

Current Opinion in Neurology

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Purpose of review Caffeine is known to have both beneficial and adverse effects in individuals with headache disorders. This review describes recent findings regarding caffeine that are relevant to headache disorders and puts these findings into the context of clinical management. Recent findings Preclinical studies show that caffeine has complex effects on sleep, brain blood flow, and intracranial pressure that may depend on the timing of caffeine intake relative to the sleep-wake cycle. Caffeine metabolism may have significant inter-individual variation that influences its therapeutic and/or adverse effects. Caffeine has acute therapeutic benefit for some primary headache disorders. For migraine, this benefit is predominantly in milder headache without cutaneous allodynia. High levels of caffeine intake may contribute to progression of headache disorders. Caffeine-containing combination analgesics commonly cause medication overuse headache. Abrupt reduction in caffeine consumption is a trigger for migraine that may be important in situations including the hospital setting, religious and cultural fasting, and pregnancy. Summary There is not sufficient evidence to support universal guidelines for the use of dietary and medicinal caffeine in headache disorders. A sensible approach based upon available evidence is to limit dietary caffeine intake to moderate amounts with consistent timing before noon, and to use caffeine-containing combination analgesics infrequently for milder headache.

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Paraxanthine Supplementation Increases Muscle Mass, Strength, and Endurance in Mice

Cited by 14 publications

References 48 publications

Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run

Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run

Coffee Drinking and Adverse Physical Outcomes in the Aging Adult Population: A Systematic Review

The role of caffeine in headache disorders

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