Gastrointestinal

Acetaldehyde and Hangovers: Understanding the Role of Phenolic Compounds in Treatment

acetaldehyde and hangovers

There’s nothing wrong with having a glass of wine to relax after a dinner or occasionally letting loose on a Saturday night. For some people, however, the consequences of even a small amount of alcohol consumption can be intense. Hangovers leave you feeling terrible whether they’re 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 people who struggle with severe hangover symptoms. As a result, there is growing interest in the science behind hangover symptoms, including the effects of alcohol breakdown products like acetaldehyde.

The role of acetaldehyde in mediating 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 buildup of this toxic compound in the liver has been associated with some of the most common hangover symptoms, including headache and nausea. A number of studies have also highlighted statistically significant correlations between acetaldehyde levels in the blood and hangover severity, although the evidence remains mixed. Based on the available data, some researchers hypothesize that treatments targeting acetaldehyde-related pathways may be effective for improving symptoms in patients. In particular, preliminary studies suggest that supplements derived from phenolic compounds, such as quercetin and curcumin, and other antioxidants may serve as effective therapeutics for reducing hangover symptoms.

Understanding Why Acetaldehyde Buildup May Worsen Hangovers

In order to understand why acetaldehyde buildup may worsen hangovers, it is essential to consider the first few steps of alcohol metabolism in the liver. The first step is the breakdown of ethanol to acetaldehyde, a toxic compound that can promote 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 high, alcohol dehydrogenase activity is insufficient to process the amount of acetaldehyde that accumulates, which can lead to acetaldehyde buildup in the liver. The subsequent acetaldehyde accumulation is believed to mediate acute hangover symptoms like headache and nausea.

As levels of acetaldehyde rise, levels of glutathione decrease. This is partially because a lower amount of acetaldehyde is being broken down by the acetaldehyde dehydrogenase enzyme. Additionally, glutathione may be depleted in the presence of excessive acetaldehyde because it forms conjugates with acetaldehyde. The increase in these glutathione-acetaldehyde conjugates has the potential to reduce glutathione antioxidant activity, which could further contribute to oxidative stress that produces more severe hangover symptoms.

While there are still questions within the scientific community regarding the connections between hangover symptoms, acetaldehyde levels, and glutathione levels, the 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 have been associated with an increased risk of alcohol dependence among certain ethnic populations, suggesting that gene-based reductions in acetaldehyde dehydrogenase activity may be the source of problems with alcohol metabolism, leading to more severe hangover symptoms. Indeed, the populations revealed that certain gene variants were associated with reduced acetaldehyde dehydrogenase activity, increased acetaldehyde buildup, and more severe reactions to alcohol intake. Therefore, this study has served as a foundation for research on therapeutic strategies for hangovers that seek 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 may be an effective way to reduce the acetaldehyde-mediated symptoms of hangovers. One of the most promising studies was conducted by a group of researchers from Kyungpook National University in South Korea. Recognizing the connection between acetaldehyde buildup and reduced 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 and anti-inflammatory properties. Upon treatment with 100mg, 200mg, or 400mg  of sprouted peanut extract, the rat models exhibited higher levels of alcohol dehydrogenase activities. Based on their findings, the researchers proposed that phenolic compounds such as resveratrol, quercetin, and curcumin may effectively reduce acetaldehyde accumulation by improving alcohol metabolism, making supplementation a possible option for treatment.

Another relevant study by a group of researchers at Sun Yat-Sen University in China produced mixed evidence, but the overall implications were consistent with those of the above-described research 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 reduce acetaldehyde levels to a statistically significant degree, they did significantly increase acetaldehyde dehydrogenase activity in the liver, suggesting that they may still improve the alcohol metabolism process. The researchers also proposed that the antioxidant activity of the phenolic compounds in these teas may further contribute to reductions in hangover symptoms by reversing the toxic oxidative effects of acetaldehyde buildup. Therefore, the researchers proposed the development of dietary supplements based on the compounds in green tea and honey chrysanthemum tea for minimizing hangover symptoms and 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 human subjects. Again, the research was premised on the notion that antioxidant and anti-inflammatory compounds may improve alcohol metabolism and reduce 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 antioxidant herbs that have traditionally been used to reduce hangover symptoms—Viscum album L. (40%), Lycium chinesense L. (30%), Inonotus obliquus (20%), and Acathopanax senticosus H. (10%)—alongside a bottle of commercially available liquor. The control group ingested a placebo alongside the liquor. In the participants in the treatment group, the researchers observed a non-significant decline in acetaldehyde levels, but they also noted a significant increase 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 it also suggests that supplements with antioxidant activity may help combat the oxidative stress that leads to severe hangover symptoms.

Opportunities for More Comprehensive Research in the Future

It is clear that the research on acetaldehyde and hangovers is still in its most preliminary stages. The scientific community has yet to come to a consensus on the mechanisms through which hangovers are mediated and the roles that acetaldehyde and other reaction products play in the process. While early animal studies suggest that polyphenolic compounds and other antioxidants may be promising candidates for the development of dietary supplements in the future, the evidence is not definitive. Similarly, the results in small-scale human studies suggest that reducing acetaldehyde levels may help ameliorate hangover symptoms, but the ideal treatment 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 and hangovers, as well as to explore the efficacy of various dietary supplements—especially polyphenolic compounds with antioxidant properties. Practitioners and patients may also consider trying polyphenol-based supplements to reduce headaches and nausea caused by hangovers, even before large-scale research gets underway. After all, anecdotal evidence often serves as a driver of comprehensive, randomized controlled trials, so the research community may benefit from input from the clinical community. Plant-derived compounds like resveratrol, quercetin, and curcumin are considered to be safe for otherwise-healthy patients, so they may be worthy of consideration by patients who are seeking hangover relief.

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Works Cited

Eng MY, Luczak SE, Wall TL. 2007. ALDH2, ADH1B, and ADH1C genotypes in Asians: A literature review. Alcohol Research Current Reviews. 30(1): 22-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860439/

Hong YH. 2016. Effects of the herb mixture, DTS20, on oxidative stress and plasma alcoholic metabolites after alcohol consumption in healthy young men. Integrative Medicine Research. 5(4): 309-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390758/

Seo JY, Kim SS, Kim HJ, Liu KH, Lee Hy, Kim JS. 2013. Laxative effect of peanut sprout extract. Nutrition Research and Practice. 7(4): 262-6. https://www.ncbi.nlm.nih.gov/pubmed/23964312/

Penning R, van Nuland M, Fliervoet LA, Olivier B, Verster JC. 2010. The pathology of alcohol hangover. Current Drug Abuse Reviews. 3(2): 68-75. https://www.ncbi.nlm.nih.gov/pubmed/20712596

Piasecki TM, Robertson BM, Epler AJ. 2010. Hangover and risk for alcohol use disorders: Existing evidence and potential mechanisms. Current Drug Abuse Reviews. 3(2): 92-102. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264051/

Quertemont E, Didone V. Role of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol. National Institute on Alcohol Abuse and Alcoholism. https://pubs.niaaa.nih.gov/publications/arh294/258-265.htm

Seo JY, Kim SS, Kim JS. 2014. Enhancement of alcohol metabolism by sprouted peanut extract in SD rats. Preventive Nutrition and Food Science. 19(1): 1-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999802/

Verster JC, Alford C, Bervoets AC, de Klerk S, Grange JA et al. 2013. Hangover research needs: Proceedings of the 5th alcohol hangover research group meeting. Current Drug Abuse Reviews. 6(3): 245-51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013289/

Vogt BL, Richie JP. 2007. Glutathione depletion and recovery after acute ethanol administration in the aging mouse. Biochemical Pharmacology. 73(10): 1613-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1930162/

Wang F, Zhang Y, Zhou Y, Li Y, Zhou T et al. 2016. Effects of beverages on alcohol metabolism: Potential health benefits and harmful impacts. International Journal of Molecular Sciences. 17(3): 354. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813215/

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