Few substances are more beloved than caffeine. Every day, as many as nine in 10 Americans drink a caffeinated beverage, increasingly in a stronger form such as an energy drink. But the stimulant has a massive drawback: consume too much after a certain hour, and you can kiss your sleep schedule goodbye. To get around this, biohackers are turning to an unproven supplement to try flush caffeine out their bodies fast. It promises the best of both worlds: a quick, anytime energy boost and a good night’s sleep. But does it work?
Caffeine has a half-life of roughly five hours, meaning it takes about that time, on average, for the initial dosage to reduce by 50 percent in your bloodstream. Depending on the person, caffeine’s stimulant effects can take up to 12 hours to fully wear off. That’s why some people find themselves unable to wind down at night after a 3 P.M. coffee.
That’s where rutaecarpine comes in. Among biohacking enthusiasts and one of Silicon Valley’s most influential blogs, the substance has been touted as a way to process caffeine much faster than the body does naturally. Rutaecarpine by itself hasn’t been tested in humans, but it has been shown to help metabolize caffeine more rapidly in rats.
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More recently, rutaecarpine has been picked up by fitness influencers such as Thomas DeLauer, a YouTuber with more than four million subscribers. It’s also been promoted as a weight-loss aid that allows users to enjoy the appetite-suppressing effects of caffeine in large doses without the sleep deprivation.
We dug into what the science behind rutaecarpine is and whether the claims about its caffeine-canceling effects hold up. Here’s what you need to know.
How rutaecarpine works
Rutaecarpine is derived from the fruit of a plant called Tetradium ruticarpum; it has also been known as Evodia rutaecarpa, among other names. This fruit has been used in traditional Chinese medicine to treat ailments such as headaches, vomiting, diarrhea, abdominal pain and period pain for more than 2,000 years. Rutaecarpine hasn’t been studied, however, in clinical trials in humans.
In rats, rutaecarpine works by provoking the liver into producing more CYP1A2, an enzyme that breaks down caffeine in the body and first converts it into a compound called paraxanthine. Rats with higher-than-normal concentrations of CYP1A2 break down caffeine much faster than untreated rats.
People who promote rutaecarpine say it increases the level of CYP1A2 in your body, allowing you to enjoy the benefits of coffee without delaying sleep. Humans vary naturally in how quickly their bodies clear caffeine, which is in part because of individual differences in CYP1A2 and caffeine sensitivity, which is linked primarily to ADORA2A, the gene for the adenosine receptor that caffeine blocks.
Despite the lack of clinical evidence, rutaecarpine is readily available at mainstream online retailers such as Amazon and iHerb, both in its concentrated form and in its traditional herbal form. When sold as a supplement, it doesn’t require the same approval from the U.S. Food and Drug Administration as a medication does, meaning it is not tested for safety or effectiveness.
Is rutaecarpine safe?
A 2024 paper in Toxics that looked at mice and human cell cultures suggests that rutaecarpine could present a serious danger when it is mixed with one of the most common drugs on the planet: acetaminophen, or Tylenol. Bill Baldwin, a professor of biological sciences at Clemson University, who edited the study, says the evidence we have so far “suggests that you have to be careful with this co-treatment. You have to be very careful.”
The reason why has to do with how rutaecarpine works.
“CYP1A2, along with a couple of other enzymes, is known to take acetaminophen and produce NAPQI, which is a powerful oxidant,” Baldwin explains. “This leads to damage within the liver, and this damage would typically not happen due to acetaminophen unless you would overdose or you would take [acetaminophen] with alcohol.”
The broader research into rutaecarpine’s safety profile is more mixed, however. A 2021 mouse study, for example, found that mice that were given rutaecarpine every day for a week actually appeared protected against acetaminophen-related liver damage. Meanwhile the fruit that rutaecarpine comes from has repeatedly been linked to liver toxicity in animal studies. Again, rutaecarpine has never been through a clinical trial, so it’s hard to say what it does in humans.
Acetaminophen isn’t the only potential interaction. CYP1A2 breaks down numerous other common drugs, such as the asthma drug theophylline and the antipsychotics clozapine and olanzapine.
Pieter Cohen, an associate professor of medicine at Harvard Medical School, says that rutaecarpine “does not have safety data to support its use.” In addition, there are potential concerns around heart and liver damage raised by animal studies that should give pause, he says.
Cohen adds that he is “not aware” of any medication or substance that can “safely offset the effects of caffeine.”
If people do choose to take supplements, Cohen recommends picking substances that have only one plant extract on the label, do not make health claims and have been certified by a high-quality third-party supplement screening organization, such as the U.S. Pharmacopeia.
Are there better alternatives?
The best strategy for consuming caffeine later in the day without sacrificing sleep is to switch to beverages with a lower concentration, such as green tea. Another option is to try engaging in natural energy-boosting activities, such as taking light exercise or a quick nap. Cohen recommends not consuming more than 100 milligrams of caffeine, roughly equivalent to an eight-ounce (237-milliliter) cup of coffee, after 1 P.M.
If you must go the chemical route, safer alternatives may exist. Paraxanthine, the compound that caffeine is converted to in the body, has also been picking up steam as a supplement among biohackers. And it’s started to appear in mainstream energy drinks and supplements, including one recently co-founded by Kim Kardashian. One of the selling points of paraxanthine is that it has a shorter half-life than caffeine, meaning it reaches 50 percent of initial dosage sooner in the bloodstream.
Small-scale studies in humans indicate that paraxanthine may improve attention, reaction time and short-term memory compared with a placebo, with no known safety issues at doses of up to 200 mg. The evidence of these benefits is substantially lacking compared with that of the effects of caffeine, however, and many of the existing studies of paraxanthine were funded by supplement companies looking to sell the compound.
Considering how ever present caffeine is in our society, wanting to mitigate its unwanted side effects is understandable. T. ruticarpum may have a centuries-long history in traditional Chinese medicine, but that isn’t the same as clinical evidence.
“Any highly concentrated individual compound, regardless of whether it originated in a plant or a chemist’s laboratory, poses the same challenges,” Cohen reiterates. “We must first determine if it is safe for human consumption.”