Paraxanthine

Paraxanthine (1,7-dimethylxanthine) is a metabolite of caffeine and provides many of the nootropic benefits associated with caffeine.

Caffeine is present in more than sixty plants, including coffee which is prepared from roasted beans of the Coffea arabica plant. Caffeine is the most popular and widely used nootropic on the planet.[i]

Recent human studies have found that after it is consumed, caffeine is metabolized into 3 primary methylxanthines including Paraxanthine (80 %), theophylline and theobromine.

With regular caffeine consumption, average blood levels of Paraxanthine are two thirds those of caffeine.[ii]

And it turns out from recent clinical studies that most of the positive benefits of caffeine consumption can be attributed to Paraxanthine.

This review is a deep dive into what Paraxanthine is, how it works in your brain and body, how much to use for maximum benefit, potential side effects, and where to buy Paraxanthine.

Paraxanthine helps:

• Alertness – Animal studies show Paraxanthine blocks adenosine receptors more effectively than caffeine. It mimics the stimulant qualities of caffeine without the negatives associated with caffeine[iii]
• Decision-making – Paraxanthine increases concentration of the secondary messenger cGMP in the striatum region of the brain and caffeine does not.[iv] The region responsible for decision-making, muscle control, habit formation, and the reward function.
• Cerebral Circulation – Paraxanthine boosts nitric oxide activity which helps dilate blood vessels and increases blood flow in the body and brain. More blood flow means the good stuff like nutrients, oxygen, and water can enter your brain for better brain cell signaling. And helps take the toxins out.

Overview

Paraxanthine (1,7-dimethylxanthine) is a metabolite of caffeine (1,3,7-trimethylxanthine). Caffeine is broken down in your liver using the enzyme CYP1A2. Where 70 – 80% of caffeine is converted to paraxanthine.[v]

Caffeine is the most widely used natural stimulant in the world. And is well known for improving focus, alertness, and concentration.

The most common source of caffeine is the coffee bean from which coffee is extracted. Other natural sources include leaves of the tea plant, Cocao beans, kola nuts, holly leaves, yerba mate leaves, seeds from guarana berries, and guayusa leaves.

Caffeine’s primary metabolite in humans is paraxanthine followed by theobromine and theophylline.[vi]

Paraxanthine belongs to the same methylxanthine family as caffeine, though is the least known of the three caffeine metabolites.

Paraxanthine seems to provide most of the benefits associated with caffeine without the negative side effects associated with caffeine, theobromine, and theophylline.[vii]

Theophylline is used clinically for treating asthma and COPD. But comes with a host of side effects including nausea, diarrhea, increased heart rate, and arrhythmia. So theophylline is falling out of favor as a solution for the health issues it is used to treat.[viii]

Theobromine has similar properties to caffeine but is also less effective. Like theophylline, it also contributes to the side effects associated with caffeine and which can include headaches, sweating, trembling, jitters, and digestive issues.[ix]

Like caffeine, paraxanthine is a stimulant and binds to adenosine receptors. But clinical research has consistently shown that paraxanthine has a higher binding potency for adenosine A₁ and A_2A receptors compared to caffeine.

Meaning that paraxanthine promotes wakefulness and enhances alertness more effectively than simply supplementing with caffeine.[x]

How does Paraxanthine work in the brain?

Paraxanthine boosts brain health in several ways. But two in particular stand out.

1. Paraxanthine is a stimulant. Caffeine is an adenosine binding agonist and widely used as a stimulant. But caffeine’s wake promoting effects are often not strong enough. And higher doses can result in unwanted side effects.

Paraxanthine is also an adenosine binding agonist and as a stimulant is more effective than caffeine but has lower toxicity and produces fewer side effects.

A research team at Stanford used an animal study to compare the effectiveness of Paraxanthine, caffeine, and Modafinil as wake promoting agents.

The researchers found that 100 mg of Paraxanthine was as effective as 200 mg Modafinil as a stimulant. But unlike Paraxanthine, they found that higher doses of caffeine and Modafinil caused a significant drop in body temperature and reduced ‘motor’ activity.

The Stanford team concluded that Paraxanthine may be a better wake-promoting agent and causes less anxiety compared to caffeine.[xi]

2. Paraxanthine boosts response time and short-term memory. Caffeine provides its wake promoting benefits by inhibiting adenosine receptors. But Paraxanthine has even higher binding benefits for adenosine A₁ and A_2a receptors. And has been found to help protect dopamine neurons and prevent loss of synaptic function better than caffeine.

Researchers at Texas A&M University decided to examine the effects of Paraxanthine supplementation on cognition, executive function, and vigilance.

13 healthy male and female participants were randomly assigned a placebo or 200 mg Paraxanthine daily for 7 days in a randomized, double-blind placebo-controlled trial.

The researchers concluded, “results suggest that acute Paraxanthine ingestion (200 mg) may affect some measures of short-term memory, reasoning, and response time to cognitive challenges and help sustain attention.”[xii]

How things go bad

In 1994, scientists confirmed for the first time that caffeine can be addictive. In the same way you can become addicted to cigarettes, alcohol, or drugs.[xiii]

In May 2013, caffeine withdrawal was included as an official mental disorder in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM).[xiv]

Caffeine affects your body for about 4 hours after it is consumed. Withdrawal symptoms set in 12 – 20 hours after your last dose. The worst symptoms set in after about 2 days and can last for up to a week.

↑ Drowsiness increases

↑ Mood swings increase

↑ Headaches increase

↓ Alertness decreases

Next, you’ll see the benefits from using Paraxanthine instead of caffeine.

Paraxanthine benefits

Paraxanthine provides many of the same benefits as caffeine. But research shows Paraxanthine has less abuse potential and does not result in the same negative effects caused by too much Caffeine, or withdrawal.[xv]

Your body naturally converts up to 80% of caffeine into Paraxanthine with no toxic effects. Which suggests the potential for side effects from supplementing with this nootropic is low.

You may also be less prone to anxiety when using Paraxanthine compared to caffeine.

Paraxanthine protects against loss of synapse function and supports the activity of and helps protect dopamine neurons.[xvi] Which sounds promising for possibly slowing the progression of Parkinson’s Disease.

Supplementing with caffeine 60 minutes before exercise has been shown in human studies to increase endurance. Researchers concluded that it was Paraxanthine created in the athlete’s body after caffeine consumption that increased the release of free fatty acids which is a major energy source.[xvii]

The wake-promoting effect of Paraxanthine is greater and longer lasting compared to caffeine.[xviii] Caffeine has a half-life of 2.5 – 4.5 hours and is cleared more quickly than Paraxanthine. So, 8 – 10 hours after caffeine ingestion, Paraxanthine levels exceed caffeine levels.[xix]

Paraxanthine supplementation has been shown to enhance thought, reasoning, learning, executive control, and attention shifting (i.e., cognitive flexibility).[xx]

How does Paraxanthine feel?

Paraxanthine is one of the primary metabolites of caffeine in the human body. When you consume caffeine, your liver metabolizes it into several metabolites, one of which is Paraxanthine.

If you are a coffee drinker, consume energy drinks containing caffeine, drink tea, or use Performance Lab^® Caffeine 2 you are likely feeling the effects of Paraxanthine.

But fewer people report on how they feel on Paraxanthine because it is only recently that scientists have discovered an affordable and faster method of separating Paraxanthine from caffeine and offering Paraxanthine as a separate compound.

Neurohackers who have tried Paraxanthine report it helps keep them awake and alert. Which is backed by studies showing Paraxanthine has higher binding ability to adenosine A₁ and A_2a receptors compared to caffeine.[xxi]

There is some evidence to suggest that Paraxanthine might play a role in increasing lipolysis, or the breakdown of fats. This would release more free fatty acids into your bloodstream, which can then result in an energy boost.

And some report that before and after any type of exercise, Paraxanthine helps reduce cognitive fatigue. Better than when using a caffeine supplement.

Paraxanthine Clinical Research

Paraxanthine for attention & short-term memory

Researchers at Texas A&M University recruited 13 healthy men and women to study the effects of Paraxanthine taken as a supplement.

In this double-blind, placebo controlled study participants received 200 mg Paraxanthine or placebo. Various tests were used to measure attention and impulse control, vigilance, short-term and working memory, and cognitive flexibility.

The study found that Paraxanthine supplementation resulted in:

• faster response times
• increased sustained attention and impulse control
• significantly increased the number of correct answers while reducing the number of errors
• boosted cognitive flexibility
• improved short-term and working memory

The researchers concluded that the study demonstrated “paraxanthine may influence memory, cognition, and attention and therefore have nootropic properties.”[xxii]

Paraxanthine improves response time

In a follow up study researchers at Texas A&M University wanted to find out the effects of varying doses of Paraxanthine and if long-term use resulted in any side effects.

12 healthy men and women were given 50 mg, 100 mg, or 200 mg doses of Paraxanthine daily for 6 days.

This study found that supplementing with Paraxanthine:

• boosted short-term memory
• improved reasoning skills and response times
• better attention and concentration.

The researchers found doses as low as 50 mg of Paraxanthine provided nootropic benefits.

Tolerance was not a problem. Higher doses of Paraxanthine were more effective compared to 50 mg dosages. And there were no reported side effects after a week of using Paraxanthine.[xxiii]

Paraxanthine Recommended Dosage

The recommended adult dosage for Paraxanthine is 200 – 400 mg per day.

But one small human clinical study showed a dose-response curve with higher doses such as 100 – 200 mg of Paraxanthine may improve cognition, memory, reasoning, response time, and help sustain attention.

The researchers in this study concluded that Paraxanthine “may serve as an effective nootropic agent at doses as low as 50 mg.”[xxiv]

Paraxanthine Side Effects

Paraxanthine has been shown in animal studies to be less toxic and with fewer negative side effects than caffeine.

One animal study conducted with Sprague Dawley rats showed Paraxanthine to be safer at higher doses than Caffeine.

The potential mortality in this study was determined to be 185 mg/kg body weight of Paraxanthine and for caffeine was only 150 mg/kg body weight.[xxv]

In other words, the average human adult would need to consume 12 – 15 grams of Paraxanthine before you got into serious trouble.

Paraxanthine, which is the primary xanthine metabolite from caffeine produced in humans appears to be safer to use even at higher doses compared to caffeine.[xxvi]

Avoid combining Paraxanthine with ephedrine, quinolone antibiotics, propranolol, theophylline, or certain birth control pills until more studies have been done demonstrating its safety when used with these drugs.

Check with your doctor or pharmacist if you are using any other medications that may be affected by Paraxanthine.

Where to buy Paraxanthine

Paraxanthine (enfinity^®) is currently available as a core ingredient in the caffeine-free, sugar free energy drink Update.

Update ingredients include Paraxanthine, N-Acetyl L-Tyrosine (NALT), Alpha GPC, L-Theanine, 5-HTP, Taurine, and Vitamin B₁₂ (methylcobalamin).

Update is available in four flavors including Berry, Lime, Mandarin, and Peach.

Try Update – 6-pack $22.99, or an 8-pack Variety Pack for $29.99 if you’d like to sample each flavor.

I’ve tried Update and it provides a nice, clean energy boost for 2 – 4 hours with no crash once it leaves your system.

Get Update now (< click here)

NOTE: Paraxanthine as a supplement is new to the market and difficult for interested dietary supplement companies to source and include in their product line. So, you are unlikely to be able to find this nootropic anywhere else at this time.