Glutathione found to significantly reduce acetaldehyde levels and help relieve hangovers

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.Sep 29 2024

New clinical research shows that glutathione can effectively reduce acetaldehyde levels in the bloodstream, offering a promising solution for hangover relief.

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In a recent study published in the journal Nutrients, researchers in the Republic of Korea evaluated the effects of glutathione (GSH) on alcohol metabolism and hangover relief by reducing serum acetaldehyde levels.

Background 

Alcohol consumption is widespread globally, but the resulting hangovers can lead to discomfort, such as headaches, dizziness, and fatigue, significantly impacting daily activities like work performance and driving.  Managing hangovers is crucial due to its medical, social, and economic impact. Alcohol is primarily metabolized in the liver, where it is converted to acetaldehyde, a toxic compound. Significantly, acetaldehyde plays a central role in causing hangover symptoms. Excessive alcohol use activates cytochrome P450 2E1 (CYP2E1), producing harmful reactive oxygen species (ROS) and reducing glutathione, a vital antioxidant. GSH (glutathione-rich yeast extract) helps detoxify acetaldehyde, potentially relieving hangover symptoms. Further research is needed to better understand the long-term effects, optimal dosage, and mechanisms of GSH in reducing hangover symptoms and improving alcohol metabolism.

About the study 

The clinical trial involved healthy adults aged 19 to 40, with a Body mass index (BMI) between 18.5 and 25 kg/m², who had consumed alcohol at least once a month and experienced hangover symptoms. Participants were excluded if they had significant medical histories, abnormal lab results, or conditions affecting alcohol metabolism or absorption of the investigational product. Those with alcohol dependence or excessive recent alcohol consumption were also excluded. A total of 40 participants were selected and randomized into two sequences in a double-blind, placebo-controlled crossover design, with a one-week washout period between treatments to eliminate carryover effects. They were randomly assigned to Sequence A or Sequence B, where Sequence A started with the GSH intervention followed by the placebo and Sequence B followed the opposite order. 

The intervention involved administering GSH (yeast extract containing 50 mg of glutathione) or a placebo. Participants consumed the capsules two hours after a standard meal, followed by whiskey (0.78 g/kg body weight) and snacks. Water intake was restricted before and after capsule administration. Hangover symptoms were assessed using the Acute Hangover Scale (AHS) and Alcohol Hangover Severity Scale (AHSS) at various intervals post-alcohol consumption. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, and 15 hours after alcohol consumption to measure both alcohol and acetaldehyde levels using validated assay kits, capturing key pharmacokinetic parameters such as maximum serum concentration (Cmax) and area under the curve (AUC). Statistical analyses were performed using IBM SPSS software, with significance set at p < 0.05.

Study results 

A total of 45 participants were initially enrolled in the study, following the exclusion of 5 individuals during the screening process, which involved questionnaires, physical examinations, and laboratory tests. This led to 20 participants being assigned to Sequence A and 20 to Sequence B. The enrollment took place over four weeks, and informed consent was obtained from all participants before the trial began. During the trial, four participants were excluded from the final analysis: one from Sequence A and three from Sequence B. The safety analysis was performed on 40 participants who received treatment at least once, while the pharmacodynamic analysis was conducted on 36 participants- 19 in Sequence A and 17 in Sequence B.

An analysis of the participants' general characteristics showed no statistically significant differences between Sequence A and Sequence B regarding sex, height, age, fertility (for women), exercise, smoking, or BMI. This suggests that the randomization was successful, ensuring that these demographic factors did not influence the study outcomes or act as confounding variables.

Twelve hours after alcohol consumption, the participants' vital signs and laboratory test results were measured. These tests included blood pressure, pulse rate, and biochemical markers such as Alanine Transaminase (ALT), Aspartate Transaminase (AST), bilirubin, and glucose levels. There were no significant differences in these parameters between the GSH and placebo groups, indicating that GSH treatment was safe and did not produce any adverse effects in the participants.

To assess the efficacy of GSH in reducing hangover symptoms, the pharmacokinetic data revealed that while the alcohol levels in the GSH group were lower than in the placebo group, this reduction was not statistically significant (p > 0.05). However, the acetaldehyde levels were significantly lower in the GSH group at all time points—with marked reductions seen at 0.25, 0.5, 1, 2, 4, 6, and 15 hours post-consumption (p < 0.01 at most time points). This indicates that GSH effectively reduced acetaldehyde, a pivotal contributor to hangover symptoms.

Pharmacokinetic analysis showed a significant reduction in both the maximum serum concentration (Cmax) and area under the curve (AUC) for acetaldehyde in the GSH group, further confirming the efficacy of GSH in accelerating acetaldehyde clearance from the bloodstream. Conversely, although the alcohol levels decreased, the difference was not statistically significant.

Lastly, although the hangover symptom surveys (AHS and AHSS) showed no significant differences between the GSH and placebo groups overall, the subjective nature of these surveys may have influenced the results. Some improvements were noted in specific symptoms for female participants, particularly in reducing thirst and fatigue, but these effects were not significant across the broader participant group.

Conclusions 

To summarize, GSH, a potent antioxidant, aids in detoxifying acetaldehyde, a toxic byproduct of alcohol metabolism linked to hangovers. Although serum alcohol levels were not significantly reduced, acetaldehyde levels were substantially lower in the GSH group compared to the placebo group. The pharmacokinetic data highlight the objective reduction in acetaldehyde levels, which is a more reliable indicator than subjective survey results. The reduction in acetaldehyde suggests that GSH may help relieve hangover symptoms.