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Acetaldehyde and Hangovers: The Role of Phenolic Compounds

Updated on March 24, 2023

Article Summary:

  • Acetaldehyde buildup caused by alcohol consumption is believed to play a critical role in hangovers.
  • The mechanisms of action of phenolic compounds, including resveratrol, quercetin, and curcumin, can enhance alcohol metabolism, thereby minimizing acetaldehyde accumulation and alleviating hangover symptoms.
  • Advanced phenolic-based supplements are well-tolerated and readily available for individuals seeking to protect themselves against the discomforts associated with alcohol consumption.*

There’s nothing wrong with having a glass of wine to relax after dinner or occasionally letting loose on a Saturday night. For some individuals, however, the consequences of even a small amount of alcohol consumption can be intense. A hangover can leave you feeling terrible whether it’s the result of one too many bellinis or a night of heavy partying. Regardless of your drinking habits, the reality is that alcohol plays an essential role in our culture today—and that can present a major challenge for individuals who struggle with hangover symptoms. As a result, there is growing interest in the science behind hangover symptoms, including the effects of the byproducts of the body’s metabolism of alcohol, like acetaldehyde.

Acetaldehyde’s role in causing the characteristic pharmacological and behavioral effects of alcohol consumption has long been controversial. Acetaldehyde is the first breakdown product in the multi-step process of alcohol metabolism, and the buildup of this toxic compound in the liver is associated with some of the most common hangover symptoms, including headache and nausea. Although the evidence remains mixed, a number of studies have highlighted statistically significant correlations between acetaldehyde levels in the blood and hangover severity. Based on the available data, some researchers hypothesize that therapies targeting acetaldehyde-related pathways could be effective in improving symptoms. In particular, preliminary studies suggest that supplements derived from phenolic compounds, such as resveratrol, quercetin, curcumin, and other antioxidants are effective therapeutics for reducing hangover symptoms.*

Why Acetaldehyde Buildup Worsens Hangovers

To understand why acetaldehyde buildup worsens a hangover, it is essential to consider the initial steps of alcohol metabolism in the liver. The first step is the breakdown of ethanol to acetaldehyde, a toxic compound that promotes cell and tissue damage. From there, acetaldehyde is metabolized by the enzyme alcohol dehydrogenase, leading to the production of glutathione, an antioxidant. However, when ethanol intake is excessive, the normal activity of alcohol dehydrogenase is insufficient to process the amount of acetaldehyde that is accumulating, which can lead to acetaldehyde buildup in the liver. It is the subsequent acetaldehyde accumulation that is believed to account for hangover symptoms like headache and nausea.

As the level of acetaldehyde rises, the level of glutathione falls. This is partially because less acetaldehyde is being broken down by the acetaldehyde dehydrogenase enzyme. Additionally, glutathione is further depleted in the presence of excessive acetaldehyde because it conjugates with acetaldehyde. The rise in these glutathione-acetaldehyde conjugates has the potential to lower glutathione antioxidant activity, which can further contribute to oxidative stress that produces more severe hangover symptoms.

Although questions remain within the scientific community regarding the connections between hangover symptoms, acetaldehyde levels, and glutathione levels, their intertwined relationships are supported by recent genetic data on acetaldehyde dehydrogenase enzyme activity in ethnic Asian populations. There are three genes that encode acetaldehyde dehydrogenase, and several variants are associated with a higher risk of alcohol dependence among certain ethnic populations, suggesting that gene-based reductions in acetaldehyde dehydrogenase activity might be the source of problems with alcohol metabolism, leading to more severe hangover symptoms. Indeed, the populations studied reveal that certain gene variants are associated with limited acetaldehyde dehydrogenase activity, increased acetaldehyde buildup, and more severe reactions to alcohol consumption. Therefore, this study has served as a foundation for research on therapeutic strategies for hangover relief that seeks to target the chemical pathways involved in acetaldehyde buildup during the alcohol metabolism process.

Using Phenolic Compounds to Address the Effects of Acetaldehyde Accumulation on Hangovers

Preliminary research suggests that dietary supplementation with phenolic compounds can effectively address acetaldehyde-mediated symptoms of hangovers.* One of the most enlightening studies was conducted by researchers from Kyungpook National University in South Korea. Recognizing the connection between acetaldehyde buildup and inhibited antioxidant activity, the researchers conducted a study to determine whether supplementation with sprouted peanut extract could mediate ethanol-induced hangover symptoms in rat models. Sprouted peanut extract is high in resveratrol, a phenolic compound with known antioxidant properties and the ability to support the body’s natural inflammatory response. Upon treatment with 100 mg, 200 mg, or 400 mg of sprouted peanut extract, the rat models exhibited higher levels of alcohol dehydrogenase activities. Based on their findings, the researchers propose that phenolic compounds, such as resveratrol, quercetin, and curcumin can effectively limit acetaldehyde accumulation by improving alcohol metabolism, making supplementation a possible option for addressing symptoms.*

Another relevant study by researchers at Sun Yat-Sen University in China produced mixed evidence, although the overall implications are consistent with those of the above-described study. These researchers simultaneously treated mouse models with ethanol and various non-alcoholic beverages, including two types of tea that are high in phenolic compounds: green tea and honey chrysanthemum tea. Although intake of these beverages did not lower acetaldehyde levels to a statistically significant degree, they did significantly increase acetaldehyde dehydrogenase activity in the liver, suggesting they might still enhance the alcohol metabolism process. The researchers also suggest that the antioxidant activity of the phenolic compounds in these teas further contributes to reductions in hangover symptoms by reversing the toxic oxidative effects of acetaldehyde buildup. Therefore, they propose the development of nutritional supplements formulated with the active phenolic compounds in green tea and honey chrysanthemum tea for minimizing hangover symptoms, as well as other harmful impacts of alcohol consumption.

A related preliminary study out of Suwon Women’s University in South Korea generated similar results and recommendations. This 2016 study stands out because it was conducted on humans. Again, the research was premised on the notion that these compounds can enhance alcohol metabolism and lower oxidative stress, thereby reducing hangover symptoms. For this study, 20 healthy adult males were recruited to participate. The treatment group was directed to ingest a supplement containing three botanical extracts with antioxidant activity that have traditionally been used to address hangover symptoms—Viscum album L. (40 percent), Lycium chinesense L. (30 percent), Inonotus obliquus (20 percent), and Acathopanax senticosus H. (10 percent)—contemporaneous with consuming a bottle of commercially available liquor. The control group ingested a placebo along with the liquor. In the participants in the treatment group, although the researchers observed a non-significant decline in acetaldehyde levels, they also noted a significant rise in antioxidant activity levels two hours after drinking. Not only does the study provide additional evidence that acetaldehyde levels are directly related to hangover symptoms, but the results also suggest that supplements with antioxidant activity help resist the oxidative stress that leads to hangover symptoms.

Opportunities for More Comprehensive Research in the Future

Research on acetaldehyde and hangovers is still in its preliminary stages. The scientific community has yet to come to a consensus on the mechanisms of action by which hangovers can be mediated and the roles that acetaldehyde and other reaction products play in the process. Although early animal studies suggest that polyphenolic compounds and other antioxidants are promising candidates for the development of nutritional supplements in the future, the evidence is not definitive. Similarly, the results in small-scale human studies suggest that reducing acetaldehyde levels can address hangover symptoms, but an ideal strategy is not yet clear.What is clear is that researchers need to build on the existing research, through a combination of in vitro and in vivo studies, to establish stronger connections between acetaldehyde levels and hangovers, as well as to explore the efficacy of various nutritional supplements—especially polyphenolic compounds that have antioxidant properties. However, practitioners and consumers can consider trying polyphenol-based nutritional supplements to address the usual headaches and nausea caused by a hangover, before such large-scale research gets underway.* Because anecdotal evidence often serves as a driver of comprehensive, randomized controlled trials, the research community can benefit from input from the clinical community. Plant-derived compounds like resveratrol, quercetin, and curcumin are considered to be safe for otherwise healthy individuals, so they are worthy of consideration by those who are seeking hangover relief.

The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your hepatic health.*

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Al Czap, Founder | Tesseract

Al Czap has more than four decades of professional experience in preventative medicine. He founded Thorne Research in 1984 (sold in 2010) and he published Alternative Medicine Review for 17 years beginning in 1996. AMR was a highly acclaimed, peer-reviewed, and indexed medical journal. Al was the first to recognize the need for hypoallergenic ingredients and to devise methods of manufacture for and delivery of hypoallergenic products to underserved patient populations. His work has greatly impacted those with impaired immune and digestive systems and compromised health due to environmental exposures.

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