Dihydromyricetin (DHM) appears to be safe based on the limited evidence available. Human trials lasting up to three months have reported zero adverse events, and animal studies show very low toxicity even at high doses. That said, DHM is a supplement with a relatively small body of human research, and it does interact with liver enzymes that process many common medications.
What the Human Trials Show
Only a handful of human clinical trials have tested DHM, but the safety signal so far is reassuring. In a trial of 60 adults with fatty liver disease who took 150 mg of DHM twice daily for three months, no adverse events were reported in either the DHM or placebo group. A separate trial gave 80 people with type 2 diabetes a larger dose of 760 mg daily for one month, again with “no adverse reactions” in either group. The NIH’s LiverTox database, which tracks supplement-related liver injury, summarizes that short-term DHM therapy in humans has produced no adverse events or evidence of toxicity to date.
These are small studies with relatively short durations. Nobody has published a large trial tracking hundreds of people over six months or a year, so the evidence is encouraging but thin.
Animal Toxicity Data
Animal studies help fill in the gaps. In acute toxicity testing, rats tolerated oral doses up to 5.0 grams per kilogram of body weight, which is an enormous amount relative to typical supplement doses. For context, if you scaled that to a 70 kg (154 lb) human using standard conversion factors, the tolerated dose would be orders of magnitude higher than what any supplement contains.
Longer-term animal studies are also reassuring. A 90-day feeding test of vine tea extract (the plant DHM comes from, naturally rich in the compound) found it was toxicologically safe and actually enhanced immune function in mice. Separate chronic toxicity studies found that continuous administration over extended periods caused no negative effects on growth, blood markers, organ biochemistry, or tissue structure under microscopic examination.
How DHM Works in the Body
DHM is a flavonoid found naturally in the Japanese raisin tree and in vine tea, a plant used in traditional Chinese medicine for centuries. Most people take it for its effects on alcohol metabolism or hangover symptoms. It works through two main pathways.
First, it boosts the activity of enzymes in your liver that break down alcohol. In mouse studies, DHM increased the activity of alcohol dehydrogenase (the enzyme that processes alcohol) and acetaldehyde dehydrogenase (the enzyme that clears the toxic byproduct acetaldehyde). One study found ALDH activity in the liver increased by 87.4% compared to untreated animals.
Second, DHM acts on GABA receptors in the brain, the same receptors that alcohol and anti-anxiety medications like benzodiazepines target. It works as a positive modulator at the benzodiazepine binding site, enhancing GABA signaling. But it also counteracts alcohol’s own effects on those receptors, which is why researchers at USC’s School of Pharmacy have studied it as a potential anti-intoxication compound. Unlike traditional benzodiazepines, DHM appears to block the receptor changes that alcohol causes while still supporting normal GABA function.
Potential Drug Interactions
This is where caution matters most. Lab studies using human liver tissue found that DHM inhibits three of the liver’s key drug-processing enzymes: CYP3A4, CYP2E1, and CYP2D6. It did not affect five other major enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, and CYP2C8), even at high concentrations.
CYP3A4 is the big one. It metabolizes roughly half of all prescription drugs, including many statins, blood pressure medications, certain antidepressants, and immunosuppressants. DHM is not just a simple inhibitor of CYP3A4 but a time-dependent one, meaning its inhibitory effect builds with continued exposure. CYP2D6 processes many antidepressants, antipsychotics, and some pain medications. CYP2E1 is involved in metabolizing acetaminophen (Tylenol) and certain anesthetics.
If you take prescription medications processed by any of these enzymes, DHM could theoretically slow their breakdown and increase their blood levels. This is the same type of interaction that grapefruit juice is famous for. These findings come from lab studies on isolated liver tissue, not from human interaction studies, so the real-world significance is unclear. But the potential is real enough to warrant a conversation with your pharmacist if you’re on regular medications.
Doses Used in Research
Human trials have used doses ranging from 300 mg per day (150 mg twice daily) to 760 mg per day. Most DHM supplements sold for hangover prevention contain between 300 and 600 mg per serving. Both the low and high ends of this range produced no reported side effects in clinical trials, though the 760 mg dose was only tested for one month and the 300 mg dose for three months.
Gaps in the Evidence
No human studies have tested DHM during pregnancy or breastfeeding, and no safety data exists for these populations. There is also no published research on DHM use in children or adolescents.
The compound has poor bioavailability, meaning your body absorbs only a fraction of what you swallow. Some supplement companies use special formulations to improve absorption, but enhanced bioavailability could also amplify any drug interactions or side effects. The safety data from clinical trials applies to standard DHM powder in capsule form, not necessarily to novel delivery systems.
Perhaps the most important limitation is simply the scale of the evidence. The largest human trial involved just 80 people for one month. Compare that to well-studied supplements like fish oil or vitamin D, which have been tested in trials of thousands of people over years. DHM’s safety profile looks clean so far, but the picture is drawn from a small number of data points.