A well-known hangover drug not only relieves throbbing headaches, but also triggers profound changes that protect the liver. Founded in 1880, the University of Southern California is one of the world’s leading private research universities. It is located in the heart of Los Angeles.“Class =” glossaryLink “> USC scientists report 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 tried to understand how it works, their investigation revealed a sequence of metabolic changes that are responsible not only for headache relief but also for the liver.
“We know that DHM helps the body metabolize alcohol faster, but how does it work? We have found that it activates a cascade of mechanisms that remove alcohol from the body very quickly, ”said Jing Liang, clinical pharmacy research professor and author of the study.
The study appears today (April 7, 2020) in Alcoholism: clinical and experimental research.
The results support the benefits of DHM as a dietary supplement to offset acute alcohol-related effects and long-term risks. In addition, the authors say the substance is likely to have wider uses to help people with alcohol abuse, alcoholism, and liver damage.
Alcohol use disorders are the most common form of drug abuse. About 88,000 people die each year from alcohol-related deaths – the third leading preventable cause of death in the United States, according to the U.S. Centers for Disease Control and Prevention. Worldwide, alcohol consumption contributes to 3 million deaths each year and, according to the World Health Organization, is responsible for 5.1% of the global disease burden. There is no effective therapeutic for the disorder without major side effects.
In the meantime, excessive alcohol consumption is a major cause of chronic liver disease, which, according to the study, accounts for almost half of the deaths associated with cirrhosis in the United States.
DHM is made from fruits of the Japanese raisin tree (Hovenia dulcis), which is native to Japan, Korea and Southeast Asia and is now being grown commercially. It has been used in China for liver disease for 500 years, but how the substance works is unclear.
To better understand what the drug does in the body, the scientists fed 36 mice daily for two months with alcohol and gradually increased the doses to 30% of their total food intake, which was an average of 39.4 g / kg ethanol per day per mouse corresponds. Then they examined their livers for injuries and stress markers.
The researchers focused on the liver, Liang said, because when you drink something, alcohol circulates through the bloodstream. Although alcohol affects the brain, it is mainly metabolized by the liver, which is severely damaged by long-term alcohol consumption.
“It’s like stepping on a turn. Your brain says it hurts. During a hangover, the fog in your brain is an acute reaction to what’s going on in your body, ”said Daryl Davies, co-author and professor of clinical pharmacy at the USC School of Pharmacy.
Among other things, the scientists found that DHM:
- The liver has been stimulated to produce more ethanol-eating enzymes, including alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH).
- Increased the efficiency of ADH and ALDH and allowed the enzymes to convert ethanol to simpler forms that the body can more easily eliminate.
- Reduced accumulation of lipids (fat) in the liver tissue. Heavy doses of alcohol can negatively affect the liver’s metabolism and lead to the accumulation of fat, increased stress and ultimately to the progression of liver diseases such as cirrhosis.
- Reduced inflammation pathogens, so-called cytokines. Excessive alcohol leads to the release of cytokines in the liver, which contributes to cell damage to the liver and other organs.
“Overall, these results support the usefulness of DHM as a dietary supplement to reduce ethanol-induced liver damage by altering lipid metabolism, improving ethanol metabolism, and suppressing inflammatory responses to promote liver health,” the study said. “This line of research suggests that DHM works in several ways to promote liver health and counter ethanol injuries.”
Davies, who is also director of the USC’s Alcohol and Brain Research Laboratory, said the results also help explain how DHM works as a hangover treatment. The liver converts alcohol to an aldehyde with properties like formaldehyde that lead to headaches and nausea. Since it takes about an hour for the body to metabolize a drink, a night of heavy alcohol consumption causes the liver to keep producing the chemicals that make people feel so dazed for so long.
“We now know what [DHM] and how it works mechanically and activates a cascade of energy regulation mechanisms that accelerate the metabolism of ethanol and its by-products, ”said Joshua Silva, a PhD student at the USC School of Pharmacy and co-author of the study.
The results have important implications for preventing liver damage and alcohol abuse.
For example, binge drinkers could use DHM because of its liver protection properties and prolong the function of the organ so long that the person receives help and ends their bad drinking habit. “We may not be able to fix your problem overnight, but we can improve it step by step so that you drink less and get health protection,” said Davies.
Excess alcohol is a serious problem for young adults, especially students. About 37% of students are concerned with alcohol excess – five or more drinks on one occasion for men or four or more drinks for women – and about 10% with heavy alcohol consumption – alcohol excess on 5 or more days in the last month. These rates are much higher than those of non-college colleagues, according to a recent survey by the National Institutes of Health.
Excessive alcohol consumption significantly contributes to a higher rate of alcohol-related liver disease in younger years.
Excessive drinking has high social and economic costs that lead to heart disease, high blood pressure, unplanned pregnancies, violence and vehicle accidents. The CDC estimates the total economic cost at $ 249 billion a year.
DHM could potentially help patients who go to the doctor with early warning signs of liver damage. The substance could be used to restore and prolong liver function and delay the onset of liver disease while waiting for a transplant. DHM could also prove useful for liver transplant patients to improve the performance of the new organ and to provide patients with a better quality of life.
“There is hope here. This could be a new life for many people, ”said Davies.
Reference: April 7, 2020, Alcoholism: clinical and experimental research.
DOI: 10.1111 / acer.14326
The authors of the study are Joshua Silva, Xin Yu, Renita Moradian, Carson Folk, Maximilian H. Spatz, Phoebe Kim, Adil A. Bhatti, Daryl L. Davies and Jing Liang from the USC School of Pharmacy.
The work was supported by grants and grants from the National Institutes of Health – National Institute for Alcohol Abuse and Alcoholism (R01AA022448), the USC Good Neighbors Campaign, the USC School of Pharmacy, the American Foundation for Pharmaceutical Education, and More Labs.