The Science Behind Caffeine’s Next Evolution: Paraxanthine

Nov 9, 2025

If you’re like most athletes or fitness enthusiasts, you’ve probably experimented with different caffeine doses, timing strategies, and delivery methods to dial in your pre-workout routine or mental performance. But here’s something that might surprise you: when you take caffeine, you’re also feeling the effects of another compound called paraxanthine. In fact, for several reasons, supplement companies are starting to offer paraxanthine directly. The early research is intriguing, but before you swap out your trusty caffeine, let’s break down what the science actually shows about paraxanthine, from its unique mechanisms to the human performance data that’s starting to accumulate.

 

What Is Paraxanthine?

Paraxanthine (1,7-dimethylxanthine) is caffeine’s primary active metabolite, meaning it’s what caffeine becomes after your body starts to process it. Your liver converts approximately 70-80% of ingested caffeine into paraxanthine via the enzyme CYP1A2. 

Unlike caffeine, paraxanthine isn’t meaningfully present in foods. You encounter it either after consuming caffeine (when your body creates it) or by taking it directly as a supplement, which is increasingly available in the sports nutrition market3,5.

 

How Does Paraxanthine Work? 

Just like caffeine, paraxanthine blocks adenosine receptors. This prevents adenosine from delivering its “slow down and rest” signal to your brain, promoting wakefulness and alertness. However, there are a few key ways paraxanthine may differ from caffeine.

 

More Blood Flow to the Brain

Research indicates paraxanthine inhibits an enzyme called phosphodiesterase-9 (PDE9). By inhibiting PDE9, paraxanthine can enhance nitric oxide activity and potentially lead to more blood flow to the brain, an action not observed with caffeine. This effect is the leading hypothesis for why some users report “cleaner focus” with paraxanthine versus caffeine. However, it’s important to note that the PDE9 mechanism hasn’t been directly proven in humans yet1,4.

 

Faster Elimination 

When taken on its own, paraxanthine has a plasma half-life of approximately 3 hours, compared to caffeine’s range of 2-7 hours. That shorter elimination time may explain why some athletes report fewer late-day residual effects when using paraxanthine versus caffeine3.

 

Consistent and Predictable Effects 

For caffeine to be cleared from the body, it must first be converted to paraxanthine by an enzyme called CYP1A2. However, the efficiency of this enzyme can vary between individuals. People who convert caffeine more slowly tend to be sensitive to it and may experience its negative effects (hence the term “slow metabolizer”). By taking paraxanthine directly, this conversion step is largely skipped. As a result, not only could paraxanthine produce consistent and similar effects between individuals, but those who are sensitive to caffeine may be able to use it without experiencing the negative side effects. 

 

What Do Human Studies Show?

Cognitive Performance in Rested Conditions 

In rested, healthy adults a single 200mg dose of paraxanthine and tracked cognitive performance over the course of six hours. Compared with placebo, participants performed better on short-term, working-memory and sustained-attention tasks. Interestingly, these effects were maintained across the multi-hour window, not just after taking the paraxanthine dose7. 

In another study, researchers tested single doses of 50, 100, and 200mg paraxanthine and assessed various aspects of cognitive performance for 6 hours on Day 1. The clearest acute improvements occurred at 100–200 mg across these domains. Participants then took their assigned dose daily on Days 2–6 at home without testing their cognitive performance. They returned on Day 7 for a final dose and a single cognitive assessment at 1 hour post-dose. The assessment showed some carry through on tasks involving working memory, but not a broad, across the board improvement compared to their Day 1 performance. Across the week, daily dosing was well-tolerated with no clinically meaningful changes in safety laboratories or adverse-event rates6. 

Taken together, these trials indicate that paraxanthine can acutely enhance attention and working memory in healthy adults, most consistently at 100–200 mg, with effects sustained over several hours.

 

Cognitive Performance Under Fatigue 

In a double-blind crossover of 12 trained runners, participants ingested 200mg paraxanthine, 200mg caffeine, paraxanthine + caffeine combo (200mg each), or placebo before a 10-km run8. While the 10-km run times themselves were not significantly different, runners on paraxanthine showed better maintenance of cognitive function and reaction time after exercise. Specifically, post-exercise “mental fatigue” was blunted. Subjects on caffeine made 31% more errors in a cognitive test by the end of a run, whereas those on paraxanthine improved correct responses (~+6.8%). The paraxanthine group also reacted faster on a vigilance task than both placebo and paraxanthine + caffeine groups. Interestingly, combining caffeine with paraxanthine did not add benefit beyond paraxanthine alone8.

 

Potential Metabolic Effects 

Beyond cognition, a randomized, double-blind, crossover study in 21 adults mapped metabolic effects across 100, 200, and 300mg doses. At 200mg, the paraxanthine group experienced a very small bump in metabolic rate over the course of 3 hours as well as slightly reduced subjective hunger ratings versus placebo. At 300mg, it raised circulating free fatty acids (a lipolysis marker). Across conditions, blood pressure was unchanged, and at 100mg there was a small reduction in heart rate versus placebo2. 

These are performance-adjacent shifts, potentially useful for weight-management or training-readiness, even though they aren’t direct measures of sport performance.

 

Practical Application: Who Can Benefit and How to Take 

If caffeine works well for you, paraxanthine isn’t a mandatory upgrade. However, it may offer advantages for athletes who: 

  • Experience jitters or anxiety with caffeine 
  • Are slow caffeine metabolizers (based on genetics or lifestyle factors) 
  • Train in the afternoon/evening and need better sleep 
  • Want the cognitive benefits with potentially fewer side effects 

Start with 100-200 mg to assess your individual response, ideally timing it the same way you would caffeine (30-60 minutes pre-training or activity). Pay attention to how you feel not just during your workout, but also in the hours afterward. Due to its shorter half-life, the stimulatory effects may not last as long as caffeine. It’s not recommended to combine it with caffeine. Treat it as a replacement, not an adjunct. For any product using paraxanthine, ensure that it uses the enfinity® brand.

If you’re ready to explore paraxanthine for yourself, look for products featuring enfinity® to ensure quality and research-backed performance. You can find trusted options here.

 

The Bottom Line on Paraxanthine 

So where does this leave you as an athlete? The research suggests it’s worth experimenting with if caffeine gives you trouble, whether that’s jitters, sleep issues, or inconsistent effects. Think of paraxanthine as another tool in your supplement toolkit, one that might solve specific problems for certain athletes. As more research emerges, we’ll get clearer answers about long-term use, optimal dosing strategies, and whether those theoretical mechanistic advantages translate into real performance differences. For now, it remains a promising option for athletes looking to optimize their stimulant use without the downsides that sometimes come with traditional caffeine supplementation.

 

References

  1. Ferré, S., Orrù, M., & Guitart, X. (2013). Paraxanthine: Connecting caffeine to nitric oxide neurotransmission. Journal of Caffeine Research, 3(2), 72–78. https://pubmed.ncbi.nlm.nih.gov/24761277/
  2. Gross, K. N., Allen, L. E., Hagele, A. M., Krieger, J. M., Sutton, P. J., Duncan, E., Mumford, P. W., Jäger, R., Purpura, M., & Kerksick, C. M. (2024). A dose response study to examine paraxanthine’s impact on energy expenditure, hunger, appetite, and lipolysis. Journal of Dietary Supplements, 21(5), 608–632. https://pubmed.ncbi.nlm.nih.gov/38745415/
  3. Lelo, A., Birkett, D. J., Robson, R. A., & Miners, J. O. (1986). Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. British Journal of Clinical Pharmacology, 22(2), 177–182. https://pubmed.ncbi.nlm.nih.gov/3756065/
  4. Orrù, M., Guitart, X., KarczKubicha, M., Solinas, M., Justinova, Z., Barodia, S. K., Zanoveli, J., Cortes, A., Lluis, C., Franco, R., Goldberg, S. R., & Ferré, S. (2013). Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humans. Neuropharmacology, 67, 476–484. https://pubmed.ncbi.nlm.nih.gov/23261866/
  5. Thorn, C. F., Aklillu, E., McDonagh, E. M., Klein, T. E., & Altman, R. B. (2012). PharmGKB summary: Caffeine pathway. Pharmacogenetics and Genomics, 22(5), 389–395. https://pubmed.ncbi.nlm.nih.gov/22293536/
  6. Xing, D., Yoo, C., Gonzalez, D., Jenkins, V., Nottingham, K., Dickerson, B., Leonard, M., Ko, J., Faries, M., Kephart, W., Purpura, M., Jäger, R., Wells, S. D., Sowinski, R., Rasmussen, C. J., & Kreider, R. B. (2021). Doseresponse of paraxanthine on cognitive function: A doubleblind, placebocontrolled, crossover trial. Nutrients, 13(12), 4478. https://pubmed.ncbi.nlm.nih.gov/34960030/
  7. Yoo, C., Xing, D., Gonzalez, D., Jenkins, V., Nottingham, K., Dickerson, B., Leonard, M., Ko, J., Faries, M., Kephart, W., Purpura, M., Jäger, R., Wells, S. D., Liao, K., Sowinski, R., Rasmussen, C. J., & Kreider, R. B. (2021). Acute paraxanthine ingestion improves cognition and shortterm memory and helps sustain attention in a doubleblind, placebocontrolled, crossover trial. Nutrients, 13(11), 3980. https://pubmed.ncbi.nlm.nih.gov/34836235/
  8. Yoo, C., Xing, D., Jenkins, V., Nottingham, K., Dickerson, B., Leonard, M., Ko, J., Lewis, M., Faries, M., Kephart, W., Purpura, M., Jäger, R., Wells, S. D., Liao, K., Sowinski, R., Rasmussen, C. J., & Kreider, R. B. (2024). Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10km run. Journal of the International Society of Sports Nutrition, 21(1), 2352779. https://pubmed.ncbi.nlm.nih.gov/38725238/