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Paraxanthine Supplement Review: Dose, Benefits, Uses


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Caffeine without the downsides?

Enter one of its hottest (yet safest) recently discovered molecular cousins.

Paraxanthine.

Could paraxanthine be the ultimate coffee alternative? Compared to caffeine, paraxanthine results in:

All existing research has found this caffeine metabolite called paraxanthine superior across the board. Anything caffeine does, paraxanthine does better.

Without the caffeine-fueled addiction, sleep disruption, nervousness, jitters, heart palpitations, or other unfortunate side effects caused by the world’s favorite drug.

In this post, I will cover the science, benefits, and uses of paraxanthine as a nootropic supplement and ergogenic aid. At the end, I’ll review DrinkUpdate, my favorite source of paraxanthine.

What is Caffeine

Caffeine belongs to a family of stimulating drugs called methylxanthines. Caffeine is an alkaloid both naturally occurring in certain plants (and fruits) and is also synthesized. Humans mostly consume it through coffee and tea, but also in soda, chocolate, and energy drinks. Caffeine acts as a central nervous system stimulant. It mainly works by increasing stress hormones, blocking the tiredness chemical called adenosine from working properly, and altering neurotransmitter levels. 30-45 minutes after consumption, users feel a hit of energy, motivation, productivity, euphoria, and focus.

Yet caffeine has a dark side. Well, multiple.

Side effects of caffeine

selfdecode report caffeine metabolism cyp1a2
The powerful & actionable genetic analysis tool called SelfDecode shows that I am a fast metabolizer of caffeine (less sensitive) yet it still harms my sleep. That review explains it all.

While caffeine is one of the most used and researched cognitive enhancers, it certainly has issues.

Here are just a few of the drawbacks of using caffeine.

Lowered baseline. Most habitual users experience diminished baseline alertness due to reducing adenosine sensitivity. For them, drinking coffee only results in a short-lived return to baseline cognitive performance and energy.

Genetic differences. We metabolize caffeine via multiple pathways, most notably CYP1A2. Our DNA determines if we can drink an evening coffee or lay up all night tossing and turning from just a pre-sunrise “Cup of Joe”. Thus caffeine tolerability varies significantly from person to person.

Reduced sleep quality. Caffeine consumption can set up a vicious spiral of tolerance and waning performance. Much of that comes from its impact on sleep. The half-life of caffeine is 5-7 hours. So for some, 2 cups of coffee (200mg) at 10 AM results in 0.5 cups still in their bloodstream at midnight! Reducing REM, Deep Sleep, and other biomarkers of good sleep while simultaneously impairing the brain’s natural glymphatic drainage detoxification process.

Dependency & tolerance. Consume caffeine habitually, and you build tolerance. You’ll need larger and larger doses to clear adenosine from neurons and feel awake. This becomes a vicious treadmill, leading to insane caffeine consumption for a waning effect. While also increasing the severity of symptoms and the danger of quitting down the road.

GI upset. Coffee and caffeine promote acidity throughout the body and commonly contribute to nausea, diarrhea, stomach pain, and other digestive upset. That’s one reason I always recommend combining coffee with a fat source.

Dehydration. Caffeine is a diuretic, causing you to pee more often and leading to dehydration. It also promotes faster gastric emptying, further dehydrating. Some newer coffee companies are fortifying their products with minerals to help combat this issue.

Stress. This molecule is basically synthetic stress. Whether you pop a capsule, drink a coffee, or ingest caffeine in another form, it all adds to your allostatic load. While stress promotes short-term alertness, over time it causes profound bodily degeneration.

Jitters & nervousness. When you exceed the caffeine sweet spot, you quickly discover these two prominent side effects. The nervousness and jitters you experience throughout the day may simply be a consequence of your caffeine indulgence.

Crash. At the end of your caffeine experience, you return below baseline as your body recovers. This is because the body has been producing and accumulating adenosine. As caffeine undocks from receptors, adenosine floods in. Then you’re hit by a wave of tiredness and lethargy.

These are but a few of the more common side effects and problems with caffeine.

What is Paraxanthine

caffeine metabolism

Paraxanthine (1,7-dimethylxanthine) is another stimulating drug, naturally produced when caffeine is broken down. In fact, the metabolism of caffeine produces three metabolites. Paraxanthine is the primary (~80%) of the three. AND it’s responsible for virtually all of the desirable effects. Its mechanisms are largely the same as caffeine. Paraxanthine naturally occurs in certain plants like coffee beans, tea leaves, grapefruit, and cacao.

Paraxanthine has a large therapeutic window, meaning it’s easy to dose properly. It’s also more potent and safer than the other two metabolites.

Paraxanthine side effects

So far, the research hasn’t uncovered many side effects specific to paraxanthine.

Existing research that’s investigated the methylxanthine family of drugs has so far concluded, “Paraxanthine… is the major metabolite of caffeine in humans, in whom its toxicological potency appears to be very low.”

A December 2021 rat study found no toxicity even at the highest doses administered.

That said, high doses of paraxanthine may cause similar side effects (but weaker) to that of caffeine.

Paraxanthine dose

Paraxanthine exhibits benefits with dosages as low as 50mg.

The best paraxanthine dose, however, appears to be 100mg – 300mg. Ideally taken in the morning.

Although paraxanthine dose is roughly equivalent to caffeine, it’s better tolerated, more effective, and shown safer in large doses.

Paraxanthine vs Caffeine

Both caffeine and paraxanthine belong to the same methylxanthine family of central nervous system stimulants.

Paraxanthine results from the metabolization of caffeine and appears to exert virtually all of the benefits without the side effects.

ParaxanthineCaffeine
FeelsClean, Light, SmoothHeavy, Slow, Cardiovascularly Intense
Ideal Dose200-300mg50mg-200mg
Peak Effects300 Minutes75 Minutes
Effects DurationConsistentGene-Dependent
Side EffectsFewSignificant
PriceExpensiveCheap
FindabilityHardUbiquitous
Caffeine vs paraxanthine comparison

Although caffeine is cheap and easier to find, it’s generally a sloppier molecule with more drawbacks.

It disrupts sleep, is habit-forming, varies dramatically based on personal genetics, has a “dirtier” feeling, and can cause feelings of panic and nervousness.

Potential Benefits of Paraxanthine

benefits of
Primary health & performance benefits of paraxanthine supplementation

Although paraxanthine comes from the metabolization of caffeine and shares some properties, it has its own distinct mechanisms, effects, and uses too.

To summarize the benefits of paraxanthine:

  • Energy
  • Attention
  • Reaction time
  • Short-term memory
  • Fat burning thermogenesis
  • Athletic performance
  • Motivation and drive
  • Alertness and wakefulness

For such a novel ergogenic aid, paraxanthine actually has garnered some scientific evidence of its health and performance benefits.

During my research, I was surprised to uncover investigations into paraxanthine dating back to the late 20th century. Although the patent holder and manufacturer, enfinity, has undertaken most of the recent paraxanthine research.

Athletic performance

Caffeine, essential amino acids, and creatine are perhaps the three most popular athletic performance supplements used by virtually every trainee. As well as contained within most peri-workout products.

Paraxanthine has the same ergogenic properties as caffeine, but with key advantages. First, it’s a stronger dopamine agonist making it better to increase motivation, willpower, and drive. Next, it actually improves nutrient delivery throughout the body by increasing levels of a molecule called nitric oxide.

Third and most impressive, paraxanthine has stronger movement-enhancing benefits than caffeine or any of the other metabolites. Better, easier movement means higher sports performance.

Strength & muscle building

Bodybuilders and strength trainers love paraxanthine for all of the same reasons as athletes.

Paraxanthine amplifies the ease and efficacy of movements. The greater our ability to move and activate muscles, the more potential strength and muscle increase.

It also increases nitric oxide (NO) levels, ensuring muscle tissues receive all the nutrients needed to grow optimally.

A 2022 study titled Paraxanthine Supplementation Increases Muscle Mass, Strength, and Endurance in Mice found,

“Paraxanthine significantly increased forelimb grip strength by 17% (p < 0.001), treadmill exercise performance by 39% (p < 0.001), gastrocnemius and soleus muscle mass by 14% and 41% respectively (both p < 0.001), and nitric oxide levels by 100% compared to control…”

Those are some pretty incredible improvements!

Additionally, paraxanthine improved various different biomarkers and parameters of health (more on that later).

Overall, I expect elite physical performers to rapidly adopt this newer molecule over caffeine.

Cognition

The cognitive enhancement community has been the first to study, use, and adopt paraxanthine.

This is because of its multi-faceted nootropic properties. It improves:

One December 2021 study titled Dose-Response of Paraxanthine on Cognitive Function: A Double Blind, Placebo Controlled, Crossover Trial found (emphasis mine),

…acute ingestion of 100 mg and 200 mg of [paraxanthine] may affect some measures of cognition, memory, reasoning, and response time as well as help sustain attention.

And the nootropic/cognitive benefits start at a low dose of just 50mg of paraxanthine.

This molecule will become an invaluable tool for students, workers, and those that want to get the most out of their minds without long-term health consequences.

Attention & wakefulness

Methylxanthines, like caffeine and paraxanthine, are powerful agents of attention and vigilance.

They facilitate deeply focusing on particular tasks. Caffeine, however, increases attention at the expense of accuracy. One trial found that participants on caffeine focused better, but also made more mistakes than the placebo group.

Paraxanthine increases focus while also improving task accuracy.

This beneficial metabolite also increases wakefulness better than caffeine. As a December 2021 study concluded,

“[Paraxanthine] sustained vigilance during Trial 2 after 2 h (PXN 840 ms [103, 1576], p = 0.03) and 4 h (PXN 1466 ms [579, 2353], p = 0.002) compared to [Placebo]. As testing progressed, the response time improved during the 20 trials and over the course of the 6 h experiment in the PXN treatment, whereas it significantly increased in the PL group.”

Meaning that paraxanthine increased distraction-free work capacity while simultaneously reducing cognitive fatigue.

Other researchers agreed,

The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period.”

This is theorized to occur due to paraxanthine’s greater affinity for the brain’s A1/A2 adenosine receptors.

Memory

Another major nootropic benefit of paraxanthine worth discussing is memory improvement.

Memory is a core cognitive function, key to learning and normal daily living. While I haven’t yet seen any research on paraxanthine’s effect on long-term memory, it does seem to improve short-term (working) memory.

This paper concluded (emphasis mine),

[Paraxanthine] ingestion improved STT two-letter length absent and present reaction times over time as well as improving six-letter length absent reaction time after 2 h (PXN -86.5 ms [-165, -7.2], p = 0.03; PXN -9.0% [-18.1, 0.2], p = 0.05), suggesting that [paraxanthine] enhanced the ability to store and retrieve random information of increasing complexity from short-term memory.

Other research also supports paraxanthine’s beneficial impact on memory.

There are better memory-enhancing nootropics available, but this one is still worth considering.

Neuroprotection & mental health

Can paraxanthine really protect the brain?

Its mental health benefits are thought to work in two ways.

First, this compound exhibits very low toxicity, especially when compared to other stimulants (including caffeine). It induces less jitters and anxiety than these other stimulants too.

It also directly protects neurons from overexcitation and cell death (emphasis mine),

“Epidemiological evidence suggests that caffeine or its metabolites reduce the risk of developing Parkinson disease, possibly by protecting dopaminergic neurons. Guerreiro et al. showed that paraxanthine, but not caffeine, was strongly protective against neurodegeneration and loss of synaptic function in a culture system of selective dopaminergic cell death.”

Protecting against the death of dopaminergic cells helps stave off neurodegenerative diseases and keeps the brain’s reward circuitry running optimally. Which, as a side benefit, safeguards motivation and ambition.

Biomarker & blood improvements

Paraxanthine uniquely improves multiple biomarkers that are usually hampered by stimulants.

Several studies have clearly demonstrated that this compound boosts levels of the anabolic signaling molecule nitric oxide. Which, in turn, is cardioprotective and facilitates nutrient delivery throughout the body.

Leading a group of researchers to hypothesize that paraxanthine has cardio benefits,

“…reducing triglyceride (p < 0.001), total cholesterol (p < 0.001), LDL (p < 0.05), and increasing HDL (p < 0.001) compared to control, and compared to L-theanine, alpha-GPC, and taurine.”

All of this without negatively impacting heart rate, respiratory rate, blood pressure, or heart rate variability to the same extent as caffeine.

Smooth stimulation

Paraxanthine is an ideal stimulant drug because of its beneficial effects profile—especially relative to the side effects.

When compared head-to-head with popular stimulants like caffeine and even modafinil, researchers stated,

“Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases”

Although I strategically use modafinil for hyper-productivity on occasion, it’s much harder on the central nervous system and can dramatically worsen sleep quality. Even when I micro-dose it at 6 AM. Plus, modafinil feels harsh.

Paraxanthine is clean and smooth. No tightness in the chest, no jitters, no nervousness, no cold sweats, no headache, no GI distress. Not even tolerance or withdrawal symptoms. More on my experience shortly.

Where to Buy Paraxanthine Supplements Online

I scoured the internet for a good, clean paraxanthine supplement powder to no avail. Since it is patented for now (by Ingenious Ingredients), you can only buy enfinity’s paraxanthine products.

Right now, they do not sell it alone. You cannot buy pure paraxanthine isolate powder. You can only get it in select pre-made nootropic stacks.

These are the only three paraxanthine products available:

  • Drink Update
  • MuscleTech Burn iQ
  • MuscleTech EuphoriQ Pre-Workout

After significant research, and comparison between each of those products, I chose to use Drink Update. They manufacture a high-quality, caffeine-free nootropic energy drink that stars 300mg of paraxanthine.

Which is also the largest and most effective dose of any of those products.

It does contain other biosynergistic ingredients, so I cannot comment on the exact feel of 300mg of pure paraxanthine isolate. Nonetheless, DrinkUpdate’s formula is quite good.

DrinkUpdate Paraxanthine Supplement Review: A Powerful Nootropic Coffee Alternative?

Update sent me an eight-pack, and I immediately began testing it out.

I drank Update every day for a week straight to get the best idea of what it’s like and to simultaneously compare the experience to a very familiar drug—caffeine.

The taste of the flavors is decent, especially considering that this contains quality allulose and stevia sweeteners instead of cheap and toxic artificial sweeteners. None of the flavors are overly sweet, so I’d imagine it wouldn’t be an issue even for those that dislike the aftertaste of stevia (which I didn’t notice here).

Update currently comes in four flavors: peach, berry, lime, and mandarin.

Each DrinkUpdate can contains:

  • Paraxanthine (enfinity) – 300mg
  • N-Acetyl-L-Tyrosine
  • Alpha-GPC
  • Taurine
  • L-Theanine
  • 5-HTP
  • Vitamin B-12
  • Malic Acid
  • Citric Acid
  • Allulose
  • Stevia (Reb A & Reb M)

I really like the formula. Each ingredient serves a purpose and amplifies the qualities of the paraxanthine. That said, I wish the team would disclose the exact dosages of each ingredient.

You can get your own Update drinks here.

Use exclusive DrinkUpdate code URBAN10 for 10% off

What paraxanthine feels like

Like coffee, I generally use paraxanthine 90-180 minutes after waking. Usually, I take it at about 9 AM, unless I am combining nootropics.

This is after meditating and going on my morning circadian walk around the neighborhood.

I was a bit nervous to test this product since it contains a version of bioavailable tyrosine called N-Acetyl-L-Tyrosine. Usually, this ingredient gives me a splitting headache and makes me feel robotic (in a bad way). This is the first and only formula that does not give me those side effects at all.

About 25 minutes pass between my first sip and starting to notice paraxanthine’s nootropic effects.

Overall, paraxanthine feels much smoother and lighter. Caffeine has a certain “heavy” feel to it that PX does not. I feel more clearheaded. Cognitive tasks feel easier and require less willpower.

I don’t fall into the caffeine tunnel vision I usually experience.

Facilitating pattern recognition and abstract thinking. For motivation and ambition, there’s no comparison. Although Update contains other dopamine-enhancing nootropics too, existing research clearly demonstrates that paraxanthine alone dramatically increases drive.

Two hours in, paraxanthine is working at full force. I never felt the classic side effects of central nervous system stimulants:

  • No racing heart rate
  • No massive blood pressure spike
  • No plummeting heart rate variability (as measured by my Hanu Health continuous HRV system)
  • No tightening of the chest, shallowing of breath, or cold sweats
  • No lightheadedness, anxiety, irritability, or digestive upset
  • No dehydration or hourly trips to the bathroom

I felt less like I was on a drug, and more like my optimal self after a night of kick-butt sleep.

300mg of paraxanthine felt like the elusive caffeine sweet spot. The one we chase… and inevitably end up overshooting.

I found the motivation, focus, mental clarity, and energy to hold steady for a very long time. Five hours later, and still no sign of coming down. I tried to nap five hours after my initial dose and quickly gave up.

The appetite-suppressing effect didn’t feel all that strong. Perhaps weaker than caffeine.

Finally, nine hours later, the effects began to wane. Despite that, I didn’t experience any rebound fatigue or lethargy. No zombie mode comedown.

I did try combining it with coffee on a few days, and it dramatically increased the effects.

I am not an energy drink guy, so my biggest reservation about Update is giving up my Genius Coffee ritual. I guess switching to decaf would be one option.

How to Upgrade the Effects & Benefits of Paraxanthine

Paraxanthine alone is an exciting and potentially powerful new nootropic.

As with all nootropics, however, we can do a few easy things to get better results or to amplify the effects.

You can even use other ingredients to highlight particular attributes of the paraxanthine.

Best paraxanthine stacks

A nootropic stack is simply combining two or more ingredients together to capitalize on the principle of biosynergy: increasing benefits and reducing side effects.

Please note that none of these are scientifically proven but born out of my own experience. I am adding to this list as I continue to research and experiment.

Zen Master (Paraxanthine + Theanine). Caffeine paired with the amino acid theanine is perhaps the original nootropic stack. Theanine rounds out the harsh effects of caffeine and smoothes out the entire experience. With paraxanthine, theanine strengthens the calm alertness qualities. Putting the brain into an optimal state, as advanced meditators call it, of restful alertness. Great for creative work.

Flow State (Paraxanthine + Kava). As I wrote in my full guide to quality kava (not the junk “kava kava”), this is another powerful duo to downregulate the nervous system and enter the realm of easy deep work. Kava acts as a natural (and reversible) MAOI which boosts the effects of stimulants while simultaneously adding dimensionality to them. I like this stack to naturally enhance EQ, socialize, and quickly build rapport (podcasting, selling, negotiating, etc).

Launch Mode (Paraxanthine + Modafinil). Modafinil is actually a commonly used off-label smart prescription drug. At a micro-dose of ~25mg, it pairs nicely with paraxanthine to provide steady, all-day energy and focus. It’s also one of the few combos that’ve been studied together. For days requiring absolute peak output for 12+ hours, modafinil combines far better with paraxanthine than caffeine. Overall, it’s hard to beat.

Super Learner (Paraxanthine + Nicotine). Nicotine is one of the most commonly overlooked yet efficacious nootropics. In fact, I had a neuroscience professor that showed us data favorably comparing the ergogenic benefits of nicotine compared to off-label Adderall. But only when administered via a clean delivery system (patches, gum, or lozenges) and used semi-infrequently. This is a powerful combo for learning and memory. Especially when the paraxanthine is consumed in the AM and the nicotine in the PM. Nicotine doesn’t last long, but I find that it temporarily “re-activates” the paraxanthine for a smooth focus session.

Those are some of the popular paraxanthine supplement stacks. Equally important, however, is how you take it.

Tips to boost the benefits of your paraxanthine

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Nootropics aren’t cheap.

You can skip this entire section, but these tips will help ensure that you get the most out of your experience.

Caffeine-free. If you’re new to nootropics, start with the non-caffeinated versions. I drink coffee most days. Sometimes two cups. But I always get my nootropics caffeine-free. For several reasons. First, nootropics potentiate caffeine. One coffee can feel like 3. If you’re not used to the combo, going caff-free gives you more control. Caff-free also means that I can take nootropics later in the day. Also, the health benefits of coffee don’t come from caffeine but from the polyphenols, flavonoids, and other phytochemicals. Plus, I just like the taste of coffee.

DNA decoded. Every human has profound uniquenesses. Even more so, in the brain. My favorite ingredients might give you migraines, and vice-versa. By taking a ~$50 once-in-a-lifetime test and running it through the powerful SelfDecode genetic software, you can easily understand your neurodiversity. To figure out what will work for your brain specifically. Without wasting time, energy, and money on ineffective (or even harmful) nootropics.

Optimal fuel. Nootropics love dietary fat. Certain fats, like a special extract of coconut called C8 MCT Oil, deliver some compounds into the brain more effectively. It also slows their absorption and metabolism. Resulting in a smoother and stronger nootropic experience (with even less crash).

Avoid kryptonite. If fat is a nootropic’s best friend, protein is the enemy. Now don’t get me wrong, I’m a huge advocate for consuming protein and aminos (especially essential amino acids). These aminos, however, compete with nootropics for absorption. If taken too close together, protein can reduce the effects you feel. A rule of thumb is to take nootropics at least 1 hour before eating or wait one hour after.

Optimize recovery. Nootropics are like the gas pedal for your brain. If you don’t recover (while sleeping), eventually you’ll burn out and they’ll lose their charm. There are many ways to improve your recovery. First, increase your sleep time and quality. Your brain needs some extra downtime to compensate for working so hard. Next, feed it the right nutrients. I feel a pronounced difference when I take Shilajit and Magnesium with my nootropics. I’m able to cut back my dose and still feel stronger effects.

If you like this kind of thing, join my FREE nootropics mini-course where you’ll learn:

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Paraxanthine: The Ultimate New Cognitive Enhancing Supplement?

understanding caffeine

The vast majority of the world uses stimulants. Most often, coffee.

Despite some of the optimistic headlines, coffee (and especially caffeine) have dark sides.

Once ingested, humans convert caffeine into three metabolites.

Only one of which appears responsible for virtually all of the beneficial effects of caffeine, and none of the side effects.

That metabolite is called paraxanthine, and it’s one of the hottest new nootropics on the market.

Although paraxanthine-focused research is only recently gaining steam, I came across multiple studies investigating this compound back in the late 20th century.

So far, the benefits of paraxanthine look promising:

  • Energy
  • Mental clarity
  • Neuroprotection
  • Cardioprotection
  • Memory
  • Endurance
  • Focus
  • Fat burning
  • Strength & muscle
  • Motivation & drive

Currently, only one company is licensed to manufacture it, and it is unavailable as a standalone ingredient.

Now, I don’t usually use energy drinks.

My favorite paraxanthine-containing supplement is a special caffeine-free, unhealthy artificial sweetener-free, nasty chemical-free energy drink called Update.

Click the button below to try Update yourself.

Use exclusive DrinkUpdate code URBAN10 for 10% off

If you’ve used paraxanthine supplements or managed to find a source of pure powder, let me know in the comments below!

DrinkUpdate
Paraxanthine Supplements Review

The ultimate caffeine replacement. 300mg of pure paraxanthine, blended together with a stack of high-quality, high-bioavailability nootropics to round out the effects. Get all the benefits of caffeine, without the drawbacks.

Editor's Rating:
4.5

Pros

  • Clean stimulation
  • Deep mental clarity
  • Strong motivation
  • Synergistic formula
  • Quality ingredients
  • Non habit-forming
  • No stomach upset
  • No jitters or nervousness
  • Consistent
  • Non-dehydrating & non-sleep disruptive
  • Good taste

Cons

  • Expensive
  • Harder to dose
  • Not available in store
  • Less researched than caffeine

Nick Urban

Nick Urban is the Founder of Outliyr, an expert Biohacker of 10+ years, Data Scientist, Certified CHEK Practitioner, Host of the Mind Body Peak Performance Podcast, and a High-Performance Coach. Click here to read how Nick went from struggling pre-diabetic, to collegiate rugby national champion. If you want to send Nick a quick message, then visit his Contact Page.

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