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Dihydromyricetin
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DHM, Ampelopsin
- Flavonoid
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Dihydromyricetin (DHM) is a hepatoprotective flavonoid extracted from Hovenia Dulcis, a Japanese raisin tree that's famous in the traditional medicine world. It's been used since the year 659 throughout Japan, China, and Korea as a hangover cure.
But Dihydromyricetin didn't come into the spotlight until 2012, when an associate professor from the UCLA School of Medicine–called Jing Liang performed a study that involved mice getting drunk while using DHM–that it became clear that there was real science behind the ingredient.
The Science of Dihydromyricetin
Liang and her research team first tested whether dihydromyricetin blocks the effect alcohol has on GABA and Glutamate neurotransmitters in the brain. Alcohol binds to GABA receptors and activates them, leading to relaxation, slurred speech and impaired motor function (the feeling of being intoxicated). So they paid close attention to any changes in cognitive skills, clumsiness, and loss of coordination through a series of tests.
1) Dihydromyricetin prevents intoxication
They first examined the effects of DHM on LORR (Loss of righting reflex) or the time it took rats to flip while being placed in a V-shape cradle. When administered alcohol with DHM or a placebo, the DHM dosed rats had a significantly lower LORR.
However, when administered flumazenil a drug that blocks the GABA receptors, all the benefits of DHM were instantly lost. This suggested that DHM works in the same way, by blocking alcohol from activating those receptors and therefore preventing the rats from getting intoxicated, despite the large amounts of alcohol in their blood.
This supports other data that GABA receptors are key in the actions of alcohol and that targeting this interaction is a viable approach to reducing alcohol intake,” says David Nutt of Imperial College London, former head of the British government’s advisory committee on drugs.
2) Dihydromyricetin accelerates the breakdown of alcohol
The researchers tested the rat's blood at intervals after giving them the equivalent of 15-20 drinks. They found that when given DHM with alcohol, the rats regained their composure within just 5 minutes, versus 70 minutes.
But what was happening beneath the surface was even more fascinating. Dihydromyricetin actually increased the activity of liver enzymes ADH and ALDH, which metabolize alcohol and its toxic byproducts faster. We've broken down the basic process involved in the breakdown of alcohol here:
- • Alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) — help your body metabolize alcohol.
- • When you drink, ADH metabolizes alcohol to acetaldehyde — a highly toxic substance known to cause hangover symptoms.
- • ALDH then metabolizes acetaldehyde to a harmless byproduct called acetate, which is safely flushed out of your body.
When you drink more alcohol than your liver can break down, these alcohol-induced toxins build up and put a significant amount of stress on your body. The longer these toxins linger in your body — the worse you feel the next day. Having an ADH or ALDH enzyme deficiency can worsen the severity of this toxin build up. But luckily, DHM helps speed up this entire process so you can wake up feeling clearer and refreshed.
3) Dihydromyricetin reduces alcohol addiction & withdrawal symptoms
Researchers gave the rats a choice between a sweetened solution of alcohol or sweetened water. Normally, rats will develop an addiction to alcohol within several months, but studies found that the group of rats given DHM drank significantly less than the group that didn't. Moreover, the rats that were already addicted to alcohol also significantly reduced their alcohol intake when given DHM.
Lastly, the rats were put into a maze, and when given alcohol with placebo, they behaved erratically, stumbling around and cowering away from the corners of the maze. These were clear signs of anxiety associated with alcohol withdrawal. But those treated with DHM behaved normally and were as inquisitive as rats given no alcohol at all, exploring different corridors of the maze.
How Do You Take Dihydromyricetin?
Suggested Dosage: 300 - 4000 mg
We've optimized the following dosages based on clinical studies, data we've collected from hundreds of thousands of customers and conversions from rat models. To reduce effects of intoxication, we recommend you take DHM before drinking whereas if you want to prevent hangovers, it's recommended to take it during or right after drinking.
Clinically, the Hovenia dosage range used for hangover is 100–650 mg/kg. Total flavonoids purified from Hovenia are 4.53% of the extract, of which DHM accounts for ∼40%, suggesting a 1–15 mg/kg dose for behavioral assays.
To reduce intoxication: 2000 - 4000 mg
To prevent hangovers: 300 mg per "standard" drink
Does Dihydromyricetin Have Any Side Effects?
Dihydromyricetin has been used in Asia for thousands of years as a hangover cure and anti-intoxication medicine and is considered safe for humans even in massive doses.
In a DHM toxicity study, researchers failed to find any side-effects while giving mice massive doses of up to 22 g/kg body weight.
Acute toxicity tests showed that a single dose of oral SHE up to 22 g/kg did not result in any death or toxic side effects in mice during 14 days' observation.
Conversions from rat to human pharmacology can be estimated using the HED ratio of 16%, giving DHM a safe upper limit dosage of 15.68 grams for a 70 kg person.
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Hangover drug shows wider benefits in research
A well-known hangover drug not only helps soothe pounding headaches but also triggers profound changes that protect the liver, USC scientists report in new findings that could help prevent alcohol-related harm.
The study focuses on dihydromyricetin (DHM), also known as ampelopsin, an over-the-counter herbal remedy. When researchers at the USC School of Pharmacy sought to understand how it works, their investigation revealed a sequence of metabolic changes responsible not only for easing headaches but also benefitting the liver.
"We know DHM helps the body to metabolize alcohol faster, but how does it work? We found it activates a cascade of mechanisms that erase alcohol from the body very quickly," said Jing Liang, a research professor of clinical pharmacy and the corresponding author of the study.
The study appears today in Alcoholism: Clinical and Experimental Research.
The findings support the utility of DHM as a dietary supplement to offset acute alcohol-related effects as well as long-term risks. In addition, the authors say the substance likely has wider applications to help people cope with binge drinking, alcoholism and liver damage.
Alcohol use disorders constitute the most common form of substance abuse. About 88,000 people die of alcohol-related deaths annually—the third leading preventable cause of death in the United States, according to the U.S. Centers for Disease Control and Prevention. Globally, alcohol consumption contributes to 3 million deaths each year and is responsible for 5.1% of the global burden of disease, according to the World Health Organization. There is no effective therapeutic agent for the disorder without major side effects.
Meanwhile, excessive alcohol consumption is a significant cause of chronic liver disease, accounting for nearly half of the cirrhosis-associated deaths in the United States, according to the study.
DHM is derived from fruit from the Japanese raisin tree (Hovenia dulcis), which is native to Japan, Korea and Southeast Asia and now commercially grown. It's been used in China for liver ailments for 500 years, but how the substance works is unclear.
To better understand what the drug does inside the body, the scientists fed 36 mice a daily diet of alcohol for two months, gradually increasing doses to 30% of their total food intake for an average of 39.4 g/kg of ethanol per day per mouse. Then, they assessed their livers for injury and markers of stress.
The researchers focused on the liver, Liang said, because when you take a drink, alcohol circulates through the bloodstream. Though the alcohol affects the brain, it is metabolized primarily by the liver, which is significantly harmed by long-term, high levels of alcohol consumption.
"It's like stepping on a tack; your brain says it hurts. During a hangover, the fogginess in your brain is an acute reaction to what's going on in your body," said Daryl Davies, a study co-author and professor of clinical pharmacy in the USC School of Pharmacy.
Among other significant effects, the scientists found that DHM:
- • Triggered the liver to produce more ethanol-gobbling enzymes, including alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH).
- • Boosted the efficiency of ADH and ALDH, enabling the enzymes to convert ethanol into simpler forms the body can eliminate easier.
- • Reduced lipid (fat) accumulation in liver tissue. Heavy doses of alcohol can negatively affect the liver's metabolism, leading to an accumulation of fat, increased stress and the eventual progression to liver diseases such as cirrhosis.
- • Reduced inflammatory agents, called cytokines. Excessive alcohol leads to the release of cytokines in the liver, which contributes to cellular damage to the liver and other organs.
"In total, these findings support the utility of DHM as a dietary supplement to reduce ethanol-induced liver injury via changes in lipid metabolism, enhancement of ethanol metabolism and suppressing inflammation responses to promote liver health," the study said. "This line of research suggests that DHM acts on multiple pathways to promote liver health and counteract ethanol injury."
Davies, who is also director of the Alcohol and Brain Research Laboratory at USC, said the findings also help explain how DHM works as a hangover treatment. The liver converts alcohol into an aldehyde with properties like formaldehyde, which contribute to headache and nausea. Since it takes about one hour for the body to metabolize one drink, a night of heavy drinking causes the liver to keep churning out the chemicals that make people feel woozy for so long.
"We now know what [DHM] is doing and how it's doing it mechanically, activating a cascade of energy-regulating mechanisms that speed metabolism of ethanol and its byproducts," said Joshua Silva, a doctoral student at the USC School of Pharmacy and study co-author.
The findings have important implications for helping prevent liver damage and harm from alcohol abuse.
For example, binge drinkers could use DHM for its liver protection properties, extending the function of the organ long enough for the person to get help and stop their bad drinking habit. "We may not be able to fix their problem overnight, but we can give them step-by-step improvements to help them drink less and gain health protection," Davies said.
Binge drinking is a serious problem for young adults, especially college students. About 37% of students engage in binge drinking—five or more drinks on a single occasion for men or four or more drinks for women—and about 10% engage in heavy alcohol use—binge drinking on 5 or more days in the past month. Those rates are much higher than among non-college peers, according to a recent survey by the National Institutes of Health.
Excessive alcohol consumption significantly contributes to higher rates of alcohol-related liver disease at a younger age.
Excessive drinking has high social and economic costs, leading to heart disease, high blood pressure, unplanned pregnancies, violence and vehicle crashes. The CDC estimates the total economic cost at $249 billion annually.
DHM could potentially help patients who go to the doctor with early warning signs of liver damage. The substance could be used to help restore and prolong their liver function and delay the onset of liver disease while waiting for a transplant. DHM could also prove useful for liver transplant patients to help the new organ perform better so patients could enjoy a better quality of life.
"There's hope here. It could be a new lease on life for a lot of people," Davies said.
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Dihydromyricetin Dose for Preventing Hangovers
- The most common reason people use DHM is to prevent hangovers. The effective dose for preventing hangovers is 300 to 600 mg taken per 3 alcoholic drinks consumed. An alcoholic drink is defined as a single 12oz beer (4.3% alcohol) or 1.5oz of liquor (35% alcohol). This means if you consume 6 shots of rum in a night, the most effective dose ranges from 600 to 1,200 mg.
- Whether you should take the lower end or higher end of the dose depends on the severity of your hangover symptoms. If you experience mild hangover symptoms after 6 drinks, a 600 mg dose of DHM will suffice. If your hangover symptoms are severe after 6 drinks, a 1,2000 mg dose will be most
- The timing of your DHM dose is also very important. DHM is generally NOT effective when taken the morning after drinking. DHM is a preventative supplement, not a treatment or cure. It is best to take DHM while drinking throughout the night. The longer you wait after you have finished drinking, the less effective the DHM will
Dihydromyricetin Dose for Reducing Feelings of Intoxication
The effective dose for Reducing Feelings of Intoxication is 600 to 900 mg taken per 3 alcohol drinks. It is important to note, DHM reduces feelings of intoxication by acting on the brain. It has little effect on one’s blood alcohol content. Do NOT use DHM as an excuse to consume alcohol to excess. Never drink and drive.
Take 900 mg per 3 drinks if you have no tolerance to alcohol and are below average weight. In general, if you are a “light weight” when it comes to drinking, you should take a higher dose of DHM. If you are accustomed to drinking, and less likely to feel drunk after three drinks, a 600 mg dose per three drinks will suffice.
For reducing feelings of intoxication, take your first dose of DHM with your first drink. Take another dose with your fourth drink, seventh drink, etc (every three drinks). DHM is less effective for preventing feelings of intoxication if you wait until you are already drunk and take a large dose.
Dihydromyricetin Dose for Supporting Healthy Liver Function
The effective dose for supporting healthy liver function is a 300 mg dose per three drinks consumed. DHM will NOT completely prevent damage caused to the liver by alcohol, it will only reduce the damage being done. Drinking alcohol to excess on a regular basis will cause liver damage eventually, DHM will only slow down the process.
Even though a dose as small as 300 mg per drinks has been shown to reduce liver damage, the more DHM you take while drinking, the less damage will be caused to your liver. DHM is a completely safe a natural plant extract. You can take as much as 3000 mgs while drinking without experiencing any side effects. *
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Dihydromyricetin has been used in Asia for thousands of years as a hangover cure and anti-intoxication medicine and is considered safe for humans even in massive doses.
In a DHM toxicity study, researchers failed to find any side-effects while giving mice massive doses of up to 22 g/kg body weight.
Acute toxicity tests showed that a single dose of oral SHE up to 22 g/kg did not result in any death or toxic side effects in mice during 14 days' observation.
Conversions from rat to human pharmacology can be estimated using the HED ratio of 16%, giving DHM a safe upper limit dosage of 15.68 grams for a 70 kg person. *
Note 1: Tissue Distribution, Excretion, and Metabolic Profile of Dihydromyricetin, a Flavonoid from Vine Tea (Ampelopsis grossedentata) after Oral Administration in Rats
2024-05-22