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Methylliberine (Dynamine®): Science, Safety, and Side Effects

Although it’s found in trace amounts in coffee, chocolate, and other common sources of caffeine, researchers have only recently begun to investigate the effects of methylliberine (Dynamine®), a natural coffee analog.

There’s currently a relative lack of scientific research on methylliberine supplements compared to more well-known compounds like caffeine, but there are some things we do know about its use and safety. You can read this free guide to get up to speed and learn directly from all the latest studies about methylliberine.

What Is Methylliberine (Dynamine®)?

Methylliberine, like other caffeine analogs, methylliberine has mildly stimulating effects when ingested.†

Methylliberine, also commercially available under the trade name Dynamine®, is a purine xanthine that’s structurally similar to caffeine, theobromine, theophylline, and theacrine.

Researchers have documented its presence in cola nuts, guarana, cacao, green and black tea, mate, and coffee.[1]https://web.archive.org/web/20141210224333/http://www.cabdirect.org/abstracts/20003008257.html;jsessionid=9F32FB941DCD1B7597BDCAE41579154E

Want to learn how to use methylliberine and other cognitive enhancers to make your work and life easier? Take the free quiz to learn the perfect combination and dosage for your brain and lifestyle.

What Scientific Studies Say About Methylliberine

Although it occurs naturally in common sources such as coffee, methylliberine is normally found in very low concentrations.[2]https://pubmed.ncbi.nlm.nih.gov/31911801/. So while you’ve probably consumed it before without realizing it, it’s also likely that you didn’t obtain a very high dosage.

Prior to 2019, there were virtually no scientific examinations of this compound.[3]https://pubmed.ncbi.nlm.nih.gov/31911801/ Since then, there have been a handful of small studies, which we’ll cover below.

Methylliberine’s Effects on Heart Rate, Blood Pressure, and Mood

In a 2020 study at the University of Memphis, researchers tested the effects of a single dose of methylliberine (25 mg or 100 mg), theacrine (50 mg), caffeine (150 mg), or a combination of these compounds on 6 male and 6 female subjects over several days.[4]https://www.memphis.edu/healthsciences/pdfs/pdfs2020/acuteimpact2020.pdf The researchers found that methylliberine, alone or in combination with caffeine or theacrine, did not result in significant increases in heart rate, blood pressure, respiratory rate, or body temperature.†

The same study also found that the combination of methylliberine and caffeine augmented mood compared to methylliberine without caffeine.[5]https://www.memphis.edu/healthsciences/pdfs/pdfs2020/acuteimpact2020.pdf Methylliberine alone was not found to positively alter mood compared to other treatments, although the study was small and lacked a negative control group.

Methylliberine Taken With or Without Theacrine

In a separate 2020 study, researchers randomized 125 healthy men and women, aged 18-55, into one of 5 groups receiving either low-dose methylliberine (100 mg), high-dose methylliberine (150 mg), low-dose methylliberine with theacrine (100 mg and 50 mg respectively), high-dose methylliberine with theacrine (150 mg and 25 mg respectively) or 125 mg maltodextrin as placebo.[6]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146520/

 

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After 4 weeks of taking one or both supplements or placebo, researchers reported that participants experienced no abnormal changes in heart rate, blood pressure, electrical conductivity of the heart, or hematological safety markers (comprehensive blood work). [7]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146520/

Out of 125 original subjects, 3 participants discontinued the study due to “flu-like symptoms” including chills, sweats, or muscle aches.[8]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146520/ There were no serious adverse events reported.

Interaction Between Methylliberine and Caffeine

In a 2021 double-blind, placebo-controlled study, researchers gave 12 subjects an oral dose of either methylliberine (25 mg or 100 mg), caffeine (150 mg), methylliberine and caffeine (100 mg and 150 mg), or methylliberine plus theacrine (100 mg and 50 mg).[9]https://www.medrxiv.org/content/10.1101/2021.01.05.21249234v1.full

While methylliberine’s pharmacokinetics (processing and movement within the body) were unaffected by caffeine or theacrine, in subjects who received methylliberine and caffeine, the oral clearance of caffeine decreased and the half-life more than doubled (from 7.2 +/- 5.6 hours to 15 +/- 5.7 hours).†

Participants tolerated all compounds well, and no adverse effects were reported during the study.

How to Take Methylliberine and What to Expect

Common dosage of methylliberine used in recent studies range from 25 mg to 100 mg, taken alone or in combination with caffeine or theacrine.

If you’ve never used methylliberine before and want to try it, it’s wise to take a relatively low dose separately from other stimulants so you can gauge your reaction.

Although there is limited data on the subjective effects of methylliberine, some users report anecdotal effects including increased feelings of energy, mood, and focus.

Anecdotally, some users report more noticeable results when combining 50-100 milligrams of methylliberine with 100-150 milligrams of caffeine or 50-100 milligrams of theacrine, a strategy also used in some studies.

Before you combine multiple stimulants, start with a lower dose of each one individually and work your way up to determine how your body responds.

As with other stimulants, avoid taking methylliberine before bedtime as it may interfere with sleep.

Safety and Side Effects

There are currently very few human studies investigating the safety and side effects of methylliberine, but the available safety evidence appears to be favorable.

In most studies, zero adverse effects were reported.

In one methylliberine study, 3 out of 125 participants dropped out of the research because of mild flu-like symptoms including chills, sweats, and muscle aches.[10]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146520/

No human studies of nethylliberine have reported any serious adverse effects.

If you have a medical condition or take prescription drugs, be sure to speak to your physician before you add any new supplements to your regimen just to be on the safe side.

Frequently Asked Questions (FAQs) About Methylliberine

Will Methylliberine Cause Caffeine Tolerance?

There’s no direct evidence that methylliberine will cause cross-tolerance with caffeine. However, it is an analog that’s structurally similar to caffeine, so there’s still a possibility that habitual use of methylliberine or caffeine (or a combination of the two stimulants) could result in tolerance for the other compound.

A 2021 study found that taking methylliberine doubled the half-life of caffeine, but did not measure the effects on caffeine tolerance.

Will Methylliberine Cause Me to Fail a Drug Test?

While it may sound similar to banned substances like methamphetamine, methadone, and methylphenidate, methylliberine (Dynamine®) is chemically unrelated to all of these compounds and should not trigger a false positive.† For athletes, methylliberine doesn’t appear to be banned as a doping agent, but check with your organization to be certain.

Is Methylliberine Safe?

Methylliberine is a mild stimulant shown to have less effect on blood pressure, heart rate, and mood than caffeine.† Early evidence suggests a promising safety profile, but there have only been a handful of human studies. Ask your doctor first if you have a medical condition or take medication.

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