Paraxanthine: Caffeine’s Major Metabolite for Laser-Targeted Energy

Published on September 25, 2023 by Mike Roberto and Drew Schibsted | No Comments

CAFFEINE.

A whopping 93% of American adults drink some sort of caffeinated beverage on a daily basis.[1]

Paraxanthine: Sold as enfinity and Distributed by TSI Group

Paraxanthine is the primary metabolite of caffeine, providing most of caffeine’s beneficial effects. Now you can take it directly with enfinity!

So, we all pretty much love it, yet some of us hate it while loving it.

If you fall into the latter category, and have a tortured relationship with the western world’s drug of choice, read on, because this article is for you.

Would the Real Caffeine Please Stand Up?

So why do we love caffeine so much? You’re probably thinking, “because it gives us energy”. But that isn’t exactly what caffeine does.

How caffeine works

In short, caffeine works by inhibiting adenosine,[2,3] which builds up in the brain as ATP (adenosine triphosphate) is consumed for energy,[4] eliciting wakeful effects. It can also inhibit phosphodiesterase, the enzyme that breaks down cyclic adenosine monophosphate (cAMP),[2,3] ultimately stimulating the metabolism a bit by liberating free fatty acids (FFAs) from body fat to be used for energy.[5]

This process where caffeine drives the release of fatty acids for energy is called lipolysis and is a main reason caffeine has long been touted as a useful supplement for sports and weight loss.

The problem — and solution — to our caffeine problem

But as we’ve come to learn over the years, we don’t all metabolize caffeine the same, and many of us experience unwanted effects and tolerance build-up, especially as dose increases.[6]

There’s good news, though — it turns out that many of the beneficial aspects of caffeine aren’t from caffeine itself, but instead from caffeine’s main metabolite: paraxanthine. Thanks to modern science, we can zero in on this metabolite, skipping some of the unwanted side effects of caffeine’s other metabolites. This represents a major paradigm shift, as we learn that caffeine isn’t necessarily what we seek when we’re consuming it!

TSI Group: The Exclusive Global Distributor of enfinity paraxanthine

Announced on September 1, 2023, TSI Group is the Exclusive Global Distributor of enfinity paraxanthine

In this article, we focus on paraxanthine, explaining the science behind the potent caffeine metabolite, and why supplementing with it may be a better option than caffeine itself. It’s marketed as enfinity® and is exclusively distributed by TSI Group, the same company that’s known for Peak ATP and myHMB.

The first products with enfinity® were MuscleTech’s iQ Series supplements, including the EuphoriQ pre-workout and Burn iQ fat burner, but paraxanthine can now be formulated into more supplements, so this is a good time to recap the benefits of paraxanthine.

You can sign up for our enfinity® news alerts below, and then keep reading as we explore this fascinating molecule:

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Paraxanthine: The Molecule Responsible for Many of Caffeine’s Benefits

Caffeine’s three major metabolites are paraxanthine (~84%), theobromine (~12%), and theophylline (~4%).

The latter of these two metabolites have much longer half-lives — 6.2 hours for theobromine and 7.2 hours for theophylline, on average.[7] Since these metabolites are stimulatory, they can lead to unwanted side-effects, especially for slow metabolizers or if the caffeine’s taken too late.

Paraxanthine, however, has an average half-life of 3.1 hours, while caffeine itself averages 4.1 hours.[7]

But those are just averages, and that leads us to the next point – caffeine metabolism is not consistent across individuals:

Fast, Medium, and Slow: Bio-individuality of caffeine metabolism

These half-lives are misleading, however. Reason being, there is great bio-individuality. This is largely genetic: The CYP1A2 gene is primarily responsible for demethylating caffeine into its metabolites,[7-9] and this gene’s activity varies greatly within and between individuals, especially with respect to caffeine metabolism.[10-22]

For instance, from person-to-person, caffeine’s half-life can actually be anywhere from 1.5-10.5 hours. In fact, research has shown that caffeine clearance can vary by as much as 40x between individuals![10,11]

A bit more on theophylline and theobromine

Of the three metabolites, it’s worth digging a bit more into theophylline, which is often the main culprit for caffeine’s maladies. First, understand that it’s a prescription drug, sold as a bronchodilator.[23] More importantly, it has much higher toxicity, with toxic doses as low as 7.5mg/kg.[24]

Meanwhile, theobromine is toxic to cats and dogs,[25] which is worth knowing for anyone with dietary supplements or chocolate in the house with pets.

This means that if you’re a slow metabolizer, you can still have caffeine in your system three days later! Talk about poor sleep. With this, we can already see the promise of a supplement with lower side effects — but what effects does paraxanthine itself have?

  • Paraxanthine and Lipolysis

    In 1990, researchers noted that it takes a lot more caffeine to trigger lipolysis in vivo (in actual living organisms) than it does to trigger lipolysis in vitro (in isolated, non-living cells from those organisms).[26]

    Because macroscopic organisms like mammals can have biological systems and organs that metabolize substances like caffeine, whereas cell cultures cannot, researchers began to wonder whether maybe some metabolite of caffeine was driving lipolysis – rather than caffeine itself.

    So in 1990, some researchers set out to answer that question.[26] They gave intravenous caffeine to a group of 10 men and continuously monitored their blood levels of caffeine, paraxanthine, and FFA for the next three hours.[26]

    Caffeine Metabolism: Paraxanthine, Theophylline, and Theobromine

    Caffeine has three major metabolites, and one of them (paraxanthine) does the heavy lifting. The other two have very long half-lives, which could be interfering with your experience. Image courtesy TSI Group

    In the end, they discovered that yes, paraxanthine — and not caffeine — appeared to be driving lipolysis.[26] Specifically, there was a “high positive correlation” between the appearance of paraxanthine and levels of FFA in the bloodstream of the volunteers.[26]

    We hope to see more specific data on this in the coming months and years — stay tuned to PricePlow. Until then, let’s keep moving forward:

  • Paraxanthine and Adenosine

    In a 1995 crossover design study, researchers gave a group of 12 subjects equivalent doses of caffeine and paraxanthine, and measured their physiological response to the drugs. They discovered that caffeine and paraxanthine had similar effects on blood pressure and levels of epinephrine (adrenaline) in the subjects’ blood.[27]

    Caffeine Metabolizers

    In this study, ~46% of all participants were fast caffeine metabolizers (A/A),[12] meaning more than half of individuals aren’t optimal caffeine consumers!

    But more interestingly, the researchers realized that paraxanthine was an adenosine antagonist, just like caffeine.[27]

    So in addition to its effects on lipolysis (which is mediated primarily by epinephrine), paraxanthine also reduces fatigue by the same mechanism of action as caffeine – which is especially interesting because fatigue reduction is far and away the most common reason for caffeine consumption in the first place.

    As we dig into the research literature, we find the effects of caffeine and paraxanthine looking more and more similar.

  • Paraxanthine and Dopamine

    Many people consume caffeine because they’re trying to tap into the dopaminergic benefits of caffeine consumption. The dopamine upregulation caused by caffeine (and other drugs) is known to increase motivation,[28] alertness,[28] and psychomotor competence.[29]

    It turns out that paraxanthine also modulates the dopamine system.[30] Much like caffeine itself, paraxanthine protects dopaminergic neurons against stress and cell death,[31] theoretically lowering the risk of dopamine disorders like Parkinson’s disease (which coffee has long been thought to do[32]).

    enfinity Science

    A brief intro to the science of paraxanthine / enfinity. Image courtesy of MuscleTech, who created the supplement with the iQ Series of supplements.

    Paraxanthine also simply upregulates dopamine, making more of it available for the brain to use – in fact, paraxanthine has been described by researchers as more efficient in its pro-dopaminergic activity than caffeine,[30] at least in particular regions of the brain.

    Anecdotal evidence seems to back this up too — reviews on early paraxanthine-based supplements (which do have other confounding ingredients, admittedly) consistently report on mood and confidence boosts similar to that of similar caffeine-based supplements.

  • Paraxanthine and Cognition

    One of the reasons we reach for caffeine during the workday is the mental boost that we seem to experience after taking caffeine, which makes it easier to focus and be productive.

    But although many people swear up and down that they think and work better under the influence of caffeine, the empirical evidence supporting caffeine’s nootropic properties has been equivocal.[33] Caffeine sems to support some cognitive functions, like working memory, to a very limited extent, but large doses of caffeine can actually worsen cognition – and let’s be honest, none of us are stopping at one cup of coffee.

    So the question now is: Could paraxanthine confer the benefits that most of us are trying to get from caffeine?

    A recent study, published in 2021, set out to answer just that question.[34]

    In a double-blind, placebo-controlled, randomized study – a study design that’s considered the gold standard in medical journals – researchers gave 13 healthy men and women either a trademarked preparation of paraxanthine (known as enfinity®) or a placebo.[34] The subjects’ cognitive performance was then measured hourly for 6 hours afterwards with a series of tests.[34]

    A week later, the experiment was repeated with the same group – except this time, the group that had previously taken paraxanthine got the placebo, and vice-versa.

    Paraxanthine Reaction Time

    Paraxanthine consumption leads to significantly reduced reaction time[34]

    The result was that in the “go/no-go” task, a test in which subjects must respond to the “go” stimulus but not respond (i.e., inhibit their response) to the “no-go” stimulus, the paraxanthine group had significantly lower reaction times at every point in the data collection.[34]

    The paraxanthine group also did better in a straight up reaction time test, although the effect was not as pronounced.[34]

    But the big result from this study was that in a card sorting test, the paraxanthine group made 17.5% fewer errors than the placebo group by the 6 hour mark.[34] Moreover, the number of “perseverative errors” was 32.8% lower – meaning that the paraxanthine group learned from their mistakes better than the placebo group.

    Sounds pretty nootropic to us.

  • 2024 Data: Paraxanthine Increases Energy Expenditure (100 calories in 3 hours) while decreasing hunger!

    New data has been published after this article was originally written: A new study demonstrated that paraxanthine increases energy expenditure and fat oxidation… all while decreasing hunger (Gross, 2024)![35]

    enfinity Paraxanthine Energy Expenditure Study

    New research data has been published on enfinity (paraxanthine), showing increased energy expenditure compared to placebo (100 calories in 3 hours) — yet it decreased appetite and heart rate![35]

    It was a double-blinded, randomized, placebo-controlled study with a crossover design, where participants were given either placebo, 100 milligrams paraxanthine, 200 milligrams paraxanthine, or 300 milligrams of paraxanthine.[35] The data was extremely promising, showing that at 200 milligrams of paraxanthine, energy expenditure increased by 100 calories in 3 hours!

    However, what was really interesting is that such effects are normally paired with increased hunger, but in this case, the paraxanthine groups had reduced hunger! Even more interesting, heart rate went down in the paraxanthine group.[35]

    This is all extremely promising data, and bodes well for anyone looking for weight loss support without cardiovascular consequences.

    You can read more in our full article on the topic titled “Paraxanthine Increases Energy Expenditure, Reduces Heart Rate and Hunger in 2024 Study“.

    enfinity Paraxanthine Weight Management Key Findings

    Key findings from the above energy expenditure study on paraxanthine.[35]

  • More 2024 Data: Paraxanthine Outperforms Caffeine in Post-10k Cognitive Tests

    Another study published in 2024 revealed additional promising results for paraxanthine, showing it enhanced cognitive performance post-exercise better than caffeine. The study, titled “Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run”,[36] involved 12 trained runners in a double-blind, randomized, crossover design. Participants received four treatments:

    Paraxanthine Outforms Caffeine

    A new study finds paraxanthine (found in enfinity®) outperforms caffeine in boosting cognitive function after a 10k run.[36] Clear thinking under pressure is key to winning, and paraxanthine could be the edge you need.

    1. Placebo,
    2. Caffeine
    3. Paraxanthine, and
    4. A combination of caffeine and paraxanthine

    …with a washout period between each.

    Paraxanthine significantly improved post-run cognitive performance compared to caffeine and placebo. Specifically, paraxanthine increased correct responses and decreased errors on the Berg-Wisconsin Card Sorting Test (BCST) post-exercise. Additionally, paraxanthine outperformed caffeine in the Psychomotor Vigilance Task Test (PVTT), promoting faster reaction times and sustained attention.[36]

    Interestingly, the combination of caffeine and paraxanthine did not show any synergistic effects, suggesting that paraxanthine’s cognitive benefits operate through different mechanisms than caffeine. This is speculated to be due to paraxanthine’s inhibition of phosphodiesterase 9 (PDE9), enhancing nitric oxide (NO) neurotransmission, which caffeine does not affect.

    The study concluded that paraxanthine is a potent nootropic with fewer side effects than caffeine, making it a promising alternative for enhancing cognitive function during and after strenuous exercise. For more detailed insights into this study, read our full article titled “Paraxanthine Outperforms Caffeine in Post-10k Cognitive Tests“.

  • More in 2024: Preclinical Study Shows Paraxanthine Enhances Memory and Brain Function Better Than Caffeine

    New Preclinical Study Shows Paraxanthine Enhances Memory and Brain Function Better Than Caffeine

    Pre-clinical data shows paraxanthine improves memory and brain function better than caffeine. By boosting BDNF and neuroplasticity, it supports sharper cognitive performance.[37]

    Research published in Experimental Brain Research shows that paraxanthine, caffeine’s primary metabolite, may actually provide superior cognitive benefits compared to caffeine itself. The groundbreaking study demonstrated enhanced memory and neuroplasticity effects, with significant improvements in both young and aged subjects.

    One of the most exciting findings was paraxanthine’s ability to boost Brain-Derived Neurotrophic Factor (BDNF) levels more effectively than caffeine. BDNF plays a crucial role in forming and strengthening neural connections, essentially serving as a growth factor for the brain. The research also showed impressive reductions in beta-amyloid levels, suggesting potential applications for cognitive longevity.

    These findings build upon previous research showing paraxanthine’s benefits for energy and focus, while demonstrating its potential superiority for cognitive enhancement. Read our complete analysis in our article titled “New Preclinical Study Shows Paraxanthine Enhances Memory and Brain Function Better Than Caffeine“ to learn why this could revolutionize the future of energy and nootropic supplements.

  • Paraxanthine and the Liver

    Coffee is also famous for its ability to protect the liver – in people with existing liver disease, as few as two cups of coffee per day may lower the risk cirrhosis and fibrosis.[38] The power of coffee to protect the liver, perhaps even reducing a person’s risk of liver cancer, is significant enough that researchers have even described coffee as the “magical bean for liver diseases.”[39]

    enfinity Paraxanthine for Weight Management and Thermogenesis

    A slide provided by TSI Group covering the 2024 energy expenditure study.[35]

    But by now we’re smart enough to ask: How much of this liver-protective effect is being caused by caffeine’s primary metabolite, paraxanthine?

    According to a 2009 study, paraxanthine is a powerful anti-fibrotic compound, capable of preventing connective tissue from growing in places where it doesn’t belong, such as the liver.[40]

    Specifically, paraxanthine is the best of all the caffeine metabolites at preventing fibrosis.[40]

    It’s worth noting that the CYP1A2 gene is found only in the liver,[16] forcing the liver to perform potentially unnecessary work when processing caffeine.

So Does Caffeine Itself Do Anything?

Caffeine Metabolism Pathways

The primary pathways and enzymes involved in caffeine metabolism.[16]

Yes – don’t misunderstand, caffeine is itself biologically active, and although it might not trigger lipolysis the way that paraxanthine does, it remains a potent adenosine inhibitor,[27] ergogenic aid and more. Caffeine has independent effects on the dopamine system in the brain,[41] making dopamine more abundant[42] and biologically active.

So it’s not that all the benefits of caffeine are caused by paraxanthine instead – it’s more the case that there’s a broad overlap between the effects of these two substances.

But for many people who want the benefits associated with caffeine, paraxanthine consumption may be a better strategy than taking caffeine itself.

Why it Matters for the Consumer

We pretty much all know that when you drink coffee, or some other caffeine-containing beverage, your caffeine blood levels will rise in response. But few of us understand the mechanism by which the body clears caffeine from the bloodstream, bringing levels back down.

That mechanism is an enzyme called cytochrome P450 1A2 (CYP1A2).[7-9] This is the enzyme that converts caffeine into its metabolites, of which paraxanthine is only one.

The other two, again, are theobromine and theophylline. And, as introduced earlier in this article, CYP1A2 activity varies from individual to individual according to their inherited genetics.[10-22]

MuscleTech enfinity Paraxanthine Explained

MuscleTech’s Raza Bashir and Ingenious Ingredients (and NNB Nutrition CSO) Shawn Wells join the PricePlow Podcast for Episode #072 to talk about MuscleTech’s new iQ Series launch, using enfinity Paraxanthine!

Recall from your high school biology classes that genetic traits are determined by a combination of two alleles – in this case, the alleles are “fast” and “slow” caffeine metabolism. If looking at the CYP1A2 rs762551 polymorphisms, there are three variations:[22]

  • ‘AA’: Fast metabolizer
  • ‘AC’: Intermediate metabolizer
  • ‘CC’: Slow metabolizer

If both of your CYP1A2 alleles are fast, then congratulations: you can drink basically as much coffee or caffeine as you want. In fact, if you’re a fast caffeine metabolizer, heavy coffee consumption is associated with a lower risk of hypertension and cardiovascular disease.

But if one of your two alleles are the “slow” copy of the gene, or both, then you’re going to have problems with caffeine use, potentially big problems.

Where you fall on the caffeine metabolism spectrum can make or break your relationship with the substance. For example, regular coffee consumption raises the risk of high blood pressure in “slow metabolizers” – but not in fast metabolizers.[43]

In fact, in fast metabolizers, caffeine may even be protective against high blood pressure, as researchers have found an inverse correlation between a person’s blood pressure and his or her excretion of caffeine and paraxanthine.[44]

If this sounds unfair, that’s because it totally is.

But fortunately for you, there’s a potential solution. Supplement the compound that gets metabolized more consistently across a broader range of users!

Paraxanthine Is Less Toxic Than Caffeine

Even though paraxanthine is metabolized through the same pathway as caffeine[8] – the CYP1A2 enzyme – research has consistently shown that paraxanthine has less toxicity and causes less anxiety in its users than caffeine does.[27] In fact, no major toxicity from paraxanthine has been found.[45]

This means that even if you’re a “slow paraxanthine metabolizer,” the downside of high paraxanthine levels in your blood is going to be a lot smaller than what you’d feel if you took an equivalent amount of caffeine.

Paraxanthine also has a shorter half-life than caffeine – about three hours, on average, compared to caffeine’s four. So even if you’re a slow metabolizer, you will still clear paraxanthine faster than you clear caffeine.

Paraxanthine Doesn’t Convert to Theobromine

The biggest metabolite of caffeine, after paraxanthine, is theobromine. Compared to caffeine and paraxanthine, theobromine doesn’t do much in the way of central nervous system (CNS) stimulation,[46] but has much bigger effects on heart rate than caffeine or paraxanthine do.[46] So basically, theobromine is giving you the main downside of caffeine (adversely affected cardiovascular function) without much of the upside (wakefulness and vigilance).

Paraxanthine Doesn’t Convert to Theophylline

Part of the reason that paraxanthine is less “toxic” than caffeine is that by taking pure paraxanthine, you sidestep the conversion of caffeine to its next biggest metabolite, theophylline, which is known to cause diarrhea, nausea, and irregular or rapid heartbeat.[47] The conversion of caffeine to theophylline is responsible for many if not most of caffeine’s negative side effects, so avoiding it altogether is a very good thing indeed.

Where to Get Paraxanthine?

Discussed above, there’s a paraxanthine ingredient named enfinity® that’s been studied in new clinical research.[34] enfinity® is the industry’s only paraxanthine ingredient, which has been patented by the group at enfinity energy LLC[48] and is distributed by TSI Group. Many of PricePlow’s readers know TSI Group from our scientific coverage of Peak ATP and myHMB.

Paraxanthine: Sold as enfinity and Distributed by TSI Group

TSI Group is bringing paraxanthine to the market in a stable, lab-tested ingredient – to provide the better parts of caffeine to a customer base who’s been anxious to try something better than caffeine. It’s non-GMO, vegan, kosher, and allergen-free.

We’re excited to see enfinity® in energy drinks, pre-workout supplements, mood enhancers, thermogenic fat burners, nootropics, and far more. At the bottom of this article, you can sign up to get our enfinity® alerts so that you’re notified when a new supplement comes out using it.

Conclusion

It seems too good to be true – a caffeine-like dietary supplement with basically none of the undesirable side effects of caffeine. And of course, since paraxanthine research is still pretty preliminary, it could turn out to be too good to be true… but at this point, we really don’t think that’ll be the case.

If you suspect that you’re a “slow metabolizer”, consider establishing this empirically, either by a genetic test, or by having the paraxanthine-to-caffeine ratio of your blood measured in a laboratory setting.[49] But many of you who can’t take caffeine anywhere remotely late in the day already know.

And if you do turn out to be a slow metabolizer, give paraxanthine a try – your heart and brain will thank you for making the effort.

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About the Author: Mike Roberto

Mike Roberto

Mike Roberto is a research scientist and water sports athlete who founded PricePlow. He is an n=1 diet experimenter with extensive experience in supplementation and dietary modification, whose personal expertise stems from several experiments done on himself while sharing lab tests.

Mike's goal is to bridge the gap between nutritional research scientists and non-academics who seek to better their health in a system that has catastrophically failed the public. Mike is currently experimenting with a low Vitamin A diet.

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References

  1. Food Insight. “Caffeine: Consumer Consumption Habits and Safety Perceptions.” Food Insight, 15 Mar. 2022; https://foodinsight.org/caffeine-consumer-consumption-habits-and-safety-perceptions/
  2. Nehlig A, Daval JL, Debry G.; “Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects”; Brain Res Rev. 1992;17(2):139-170. https://pubmed.ncbi.nlm.nih.gov/1356551/
  3. Goldstein, E.R., Ziegenfuss, T., Kalman, D. et al.; “International society of sports nutrition position stand: caffeine and performance.”; J Int Soc Sports Nutr 7, 5 (2010); https://jissn.biomedcentral.com/articles/10.1186/1550-2783-7-5
  4. Porkka-Heiskanen, Tarja, and Anna V Kalinchuk. “Adenosine, energy metabolism and sleep homeostasis.” Sleep medicine reviews vol. 15,2 (2011): 123-35. doi:10.1016/j.smrv.2010.06.005; https://www.sciencedirect.com/science/article/abs/pii/S1087079210000663
  5. Institute of Medicine (US) Committee on Military Nutrition Research. “Pharmacology of Caffeine.” Nih.gov, National Academies Press (US), 2014; https://www.ncbi.nlm.nih.gov/books/NBK223808/
  6. Meredith, Steven E., et al. “Caffeine Use Disorder: A Comprehensive Review and Research Agenda.” Journal of Caffeine Research, vol. 3, no. 3, Sept. 2013, pp. 114–130, doi:10.1089/jcr.2013.0016; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777290/
  7. Lelo, A et al. “Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man.” British journal of clinical pharmacology vol. 22,2 (1986): 177-82. doi:10.1111/j.1365-2125.1986.tb05246.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401099/
  8. Miners, John O., and Donald J. Birkett. “The Use of Caffeine as a Metabolic Probe for Human Drug Metabolizing Enzymes.” General Pharmacology: The Vascular System, vol. 27, no. 2, Mar. 1996, pp. 245–249, doi:10.1016/0306-3623(95)02014-4; https://pubmed.ncbi.nlm.nih.gov/8919637/
  9. Gu, Lie, et al. “Biotransformation of Caffeine, Paraxanthine, Theobromine and Theophylline by CDNA-Expressed Human CYP1A2 and CYP2E1.” Pharmacogenetics, vol. 2, no. 2, Apr. 1992, pp. 73–77, doi:10.1097/00008571-199204000-00004; https://pubmed.ncbi.nlm.nih.gov/1302044/
  10. Kalow, Werner, and Bing-Kou Tang. “Use of Caffeine Metabolite Ratios to Explore CYP1A2 and Xanthine Oxidase Activities.” Clinical Pharmacology & Therapeutics, vol. 50, no. 5/1, Nov. 1991, pp. 508–519, doi:10.1038/clpt.1991.176; https://pubmed.ncbi.nlm.nih.gov/1934864/
  11. Kashuba, Angela D.M., et al. “Quantitation of Three-Month Intraindividual Variability and Influence of Sex and Menstrual Cycle Phase on CYP1A2, N-Acetyltransferase-2, and Xanthine Oxidase Activity Determined with Caffeine Phenotyping*.” Clinical Pharmacology & Therapeutics, vol. 63, no. 5, May 1998, pp. 540–551, doi:10.1016/s0009-9236(98)90105-9; https://pubmed.ncbi.nlm.nih.gov/9630827/
  12. Sachse, Christoph, et al. “Functional Significance of a C→a Polymorphism in Intron 1 of the Cytochrome P450 CYP1A2 Gene Tested with Caffeine.” British Journal of Clinical Pharmacology, vol. 47, no. 4, Apr. 1999, pp. 445–449, doi:10.1046/j.1365-2125.1999.00898.x; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014233/
  13. Palatini, Paolo, et al. “CYP1A2 Genotype Modifies the Association between Coffee Intake and the Risk of Hypertension.” Journal of Hypertension, vol. 27, no. 8, 1 Aug. 2009, pp. 1594–1601, doi:10.1097/HJH.0b013e32832ba850; https://pubmed.ncbi.nlm.nih.gov/19451835/
  14. Yang, Amy, et al. “Genetics of Caffeine Consumption and Responses to Caffeine.” Psychopharmacology, vol. 211, no. 3, 9 June 2010, pp. 245–257, doi:10.1007/s00213-010-1900-1; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242593/
  15. Arnaud, Maurice J. “Pharmacokinetics and Metabolism of Natural Methylxanthines in Animal and Man.” Methylxanthines, vol. 200, 19 Aug. 2010, pp. 33–91, doi:10.1007/978-3-642-13443-2_3; https://pubmed.ncbi.nlm.nih.gov/20859793/
  16. Nehlig, Astrid. “Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption.” Pharmacological Reviews, vol. 70, no. 2, 7 Mar. 2018, pp. 384–411, doi:10.1124/pr.117.014407; https://pharmrev.aspetjournals.org/content/70/2/384.long
  17. Southward, Kyle, et al. “The Role of Genetics in Moderating the Inter-Individual Differences in the Ergogenicity of Caffeine.” Nutrients, vol. 10, no. 10, 21 Sept. 2018, p. doi:10.3390/nu10101352; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213712/
  18. Fulton, Jacob L., et al. “Impact of Genetic Variability on Physiological Responses to Caffeine in Humans: A Systematic Review.” Nutrients, vol. 10, no. 10, 25 Sept. 2018, doi:10.3390/nu10101373; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212886/
  19. Willson, Cyril. “The Clinical Toxicology of Caffeine: A Review and Case Study.” Toxicology Reports, vol. 5, 2018, pp. 1140–1152, doi:10.1016/j.toxrep.2018.11.002; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247400/
  20. Jin, Taiyue, et al. “Interactions of Habitual Coffee Consumption by Genetic Polymorphisms with the Risk of Prediabetes and Type 2 Diabetes Combined.” Nutrients, vol. 12, no. 8, 26 July 2020, p. 2228, doi:10.3390/nu12082228; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468962/
  21. Cornelis, Marilyn C, et al. “Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction.” JAMA, vol. 295, no. 10, 2006, pp. 1135–41, doi:10.1001/jama.295.10.1135; https://pubmed.ncbi.nlm.nih.gov/16522833/
  22. Gkouskou, Kalliopi G., et al. “CYP1A2 Polymorphisms Modify the Association of Habitual Coffee Consumption with Appetite, Macronutrient Intake, and Body Mass Index: Results from an Observational Cohort and a Cross-over Randomized Study.” International Journal of Obesity, vol. 46, no. 1, 1 Jan. 2022, pp. 162–168, doi:10.1038/s41366-021-00972-6; https://pubmed.ncbi.nlm.nih.gov/34564706/
  23. “Theophylline Uses, Side Effects & Warnings.” Drugs.com; https://www.drugs.com/mtm/theophylline.html
  24. Journey, Jonathan D., and Thomas P. Bentley. “Theophylline Toxicity.” PubMed, StatPearls Publishing, 2020; https://www.ncbi.nlm.nih.gov/books/NBK532962/
  25. Cortinovis, Cristina, and Francesca Caloni. “Household Food Items Toxic to Dogs and Cats.” Frontiers in Veterinary Science, vol. 3, 22 Mar. 2016, doi:10.3389/fvets.2016.00026; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801869/
  26. Hetzler, R. K., et al. “Effect of Paraxanthine on FFA Mobilization after Intravenous Caffeine Administration in Humans.” Journal of Applied Physiology (Bethesda, Md.: 1985), vol. 68, no. 1, 1 Jan. 1990, pp. 44–47, doi:10.1152/jappl.1990.68.1.44; https://pubmed.ncbi.nlm.nih.gov/2312486/
  27. Benowitz, Neal L., et al. “Sympathomimetic Effects of Paraxanthine and Caffeine in Humans*.” Clinical Pharmacology & Therapeutics, vol. 58, no. 6, Dec. 1995, pp. 684–691, doi:10.1016/0009-9236(95)90025-x; https://pubmed.ncbi.nlm.nih.gov/8529334/
  28. Bromberg-Martin, Ethan S et al. “Dopamine in motivational control: rewarding, aversive, and alerting.” Neuron vol. 68,5 (2010): 815-34. doi:10.1016/j.neuron.2010.11.022; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032992/
  29. Wardle, Margaret C et al. “Caffeine increases psychomotor performance on the effort expenditure for rewards task.” Pharmacology, biochemistry, and behavior vol. 102,4 (2012): 526-31. doi:10.1016/j.pbb.2012.06.016; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578395/
  30. Orrú, Marco, et al. “Psychostimulant Pharmacological Profile of Paraxanthine, the Main Metabolite of Caffeine in Humans.” Neuropharmacology, vol. 67C, 1 Apr. 2013, pp. 476–484, doi:10.1016/j.neuropharm.2012.11.029; https://www.sciencedirect.com/science/article/abs/pii/S002839081200576X
  31. Guerreiro, Serge, et al. “Paraxanthine, the Primary Metabolite of Caffeine, Provides Protection against Dopaminergic Cell Death via Stimulation of Ryanodine Receptor Channels.” Molecular Pharmacology, vol. 74, no. 4, 11 July 2008, pp. 980–989, doi:10.1124/mol.108.048207; https://pubmed.ncbi.nlm.nih.gov/18621927/
  32. Ren, Xiangpeng, and Jiang-Fan Chen. “Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms.” Frontiers in neuroscience vol. 14 602697. 17 Dec. 2020, doi:10.3389/fnins.2020.602697; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773776/
  33. Nehlig, Astrid. “Is Caffeine a Cognitive Enhancer?” Journal of Alzheimer’s Disease, vol. 20, no. s1, 14 Apr. 2010, pp. S85–S94, pubmed.ncbi.nlm.nih.gov/20182035/, doi:10.3233/jad-2010-091315; https://pubmed.ncbi.nlm.nih.gov/20182035/
  34. Yoo, Choongsung et al. “Acute Paraxanthine Ingestion Improves Cognition and Short-Term Memory and Helps Sustain Attention in a Double-Blind, Placebo-Controlled, Crossover Trial.” Nutrients vol. 13,11 3980. 9 Nov. 2021, doi:10.3390/nu13113980; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622427/
  35. Gross, Kristen N et al. “A Dose-Response Study to Examine Paraxanthine’s Impact on Energy Expenditure, Hunger, Appetite, and Lipolysis.” Journal of dietary supplements, 1-25. 14 May. 2024, doi:10.1080/19390211.2024.2351222. https://www.tandfonline.com/doi/full/10.1080/19390211.2024.2351222
  36. Yoo, Choongsung et al. “Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run.” Journal of the International Society of Sports Nutrition vol. 21,1 (2024): 2352779. doi:10.1080/15502783.2024.2352779. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089923/
  37. Ralf Jäger, et al. “Paraxanthine Enhances Memory and Neuroplasticity More than Caffeine in Rats.” Experimental Brain Research, vol. 243, no. 1, 2 Dec. 2024, doi:10.1007/s00221-024-06954-0. https://link.springer.com/article/10.1007/s00221-024-06954-0
  38. Wadhawan, Manav, and Anil C. Anand. “Coffee and Liver Disease.” Journal of Clinical and Experimental Hepatology, vol. 6, no. 1, 1 Mar. 2016, pp. 40–46, doi:10.1016/j.jceh.2016.02.003; https://pubmed.ncbi.nlm.nih.gov/27194895/
  39. Heath, Ryan D, et al. “Coffee: The Magical Bean for Liver Diseases.” World Journal of Hepatology, vol. 9, no. 15, 28 May 2017, pp. 689–696, doi:10.4254/wjh.v9.i15.689; https://pubmed.ncbi.nlm.nih.gov/28596816/
  40. Gressner, Olav A., et al. “Identification of Paraxanthine as the Most Potent Caffeine-Derived Inhibitor of Connective Tissue Growth Factor Expression in Liver Parenchymal Cells.” Liver International, vol. 29, no. 6, July 2009, pp. 886–897, doi:10.1111/j.1478-3231.2009.01987.x; https://pubmed.ncbi.nlm.nih.gov/19291178/
  41. Volkow, N D et al. “Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.” Translational psychiatry vol. 5,4 e549. 14 Apr. 2015, doi:10.1038/tp.2015.46; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462609/
  42. Solinas, Marcello, et al. “Caffeine Induces Dopamine and Glutamate Release in the Shell of the Nucleus Accumbens.” The Journal of Neuroscience, vol. 22, no. 15, 1 Aug. 2002, pp. 6321–6324, doi:10.1523/jneurosci.22-15-06321.2002; https://www.jneurosci.org/content/22/15/6321
  43. dePaula, Juliana, and Adriana Farah. “Caffeine Consumption through Coffee: Content in the Beverage, Metabolism, Health Benefits and Risks.” Beverages, vol. 5, no. 2, 1 June 2019, p. 37, doi:10.3390/beverages5020037; https://www.mdpi.com/2306-5710/5/2/37/htm
  44. Guessous, Idris, et al. “Associations of Ambulatory Blood Pressure with Urinary Caffeine and Caffeine Metabolite Excretions.” Hypertension, vol. 65, no. 3, Mar. 2015, pp. 691–696, doi:10.1161/hypertensionaha.114.04512; https://pubmed.ncbi.nlm.nih.gov/25489060/
  45. Stavric, B. “Methylxanthines: Toxicity to Humans. 3. Theobromine, Paraxanthine and the Combined Effects of Methylxanthines.” Food and Chemical Toxicology, vol. 26, no. 8, Jan. 1988, pp. 725–733, doi:10.1016/0278-6915(88)90073-7; https://pubmed.ncbi.nlm.nih.gov/3058562/
  46. Okuro, Masashi et al. “Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice.” Sleep vol. 33,7 (2010): 930-42. doi:10.1093/sleep/33.7.930; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894435/
  47. Barnes, Peter J. “Theophylline”. American Journal of Respiratory and Critical Care Medicine. Volume 188, Issue 8. 03 May 2013. Doi: 10.1164/rccm.201302-0388PP; https://www.atsjournals.org/doi/full/10.1164/rccm.201302-0388PP
  48. Purpura, Martin, et al; “Paraxanthine-based bioactive composition and method of use thereof”. United States Patent and Trademark Office. Patent US20230072854A1. 9 Mar. 2023; https://patents.google.com/patent/WO2021151094A1/
  49. Wittayalertpanya, Supeecha, et al. “Paraxanthine/Caffeine Ratio: As an Index for CYP1A2 Activity in Polycyclic Aromatic Hydrocarbons Exposed Subjects.” Journal of the Medical Association of Thailand = Chotmaihet Thangphaet, vol. 86 Suppl 2, 1 June 2003, pp. S310-317; https://pubmed.ncbi.nlm.nih.gov/12930004/

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