Connecting the Dots: Alcohol Hangover, Inflammation, and Aging

One of the coolest things about living in 2023 is that increasingly, thought leaders are connecting unexpected dots that elevate our knowledge of pertinent therapeutic areas. Alcohol hangover is one such example.

Credit: freshidea - stock.adobe.com

Alcohol hangover (AH) is defined as the combination of negative mental and physical symptoms that can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero. Note in this illustration from a recent study linked here and covered, in part, by this article.

Biomarkers of alcohol metabolism, the inflammatory response to alcohol consumption and their relation to hangover severity. Credit: van de Loo AJAE, Mackus M, Kwon O, Krishnakumar IM, Garssen J, Kraneveld AD, Scholey A, Verster JC. The Inflammatory Response to Alcohol Consumption and Its Role in the Pathology of Alcohol Hangover. J Clin Med. 2020 Jul 2;9(7):2081. doi: 10.3390/jcm9072081. PMID: 32630717; PMCID: PMC7408936.

But for years, because some AH symptoms resemble dehydration (dry mouth, headache) and because alcohol is a diuretic, it has been commonly believed that AH can be treated with hydration and electrolyte supplementation. Whether this approach is effective has not been proven in clinical trials; however, the hangover cure marketplace is anticipated to grow to $4.67 billion over the next 5 years.

Relationship of hangover severity with blood ethanol concentration and the inflammatory response to alcohol. Credit: van de Loo AJAE, Mackus M, Kwon O, Krishnakumar IM, Garssen J, Kraneveld AD, Scholey A, Verster JC. The Inflammatory Response to Alcohol Consumption and Its Role in the Pathology of Alcohol Hangover. J Clin Med. 2020 Jul 2;9(7):2081. doi: 10.3390/jcm9072081. PMID: 32630717; PMCID: PMC7408936.

That’s a lot of snake oil being sold, folks. Meanwhile, new evidence supports alcohol consumption causing an inflammatory response that leads to those pesky hangover symptoms. Immediately after alcohol consumption, inflammatory mediators, specifically interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP), and biomarkers of oxidative stress begin to rise.

Makes sense when you think about it. Alcohol is a toxin and your body’s intelligent response to external toxins is an inflammatory one, right? Yet, with alcohol consumption, these inflammatory mediators increase up to 40%-60% above baseline and remain elevated for greater than 12 hours.

Oxidative stress and the inflammatory response during alcohol hangover. Credit: van de Loo AJAE, Mackus M, Kwon O, Krishnakumar IM, Garssen J, Kraneveld AD, Scholey A, Verster JC. The Inflammatory Response to Alcohol Consumption and Its Role in the Pathology of Alcohol Hangover. J Clin Med. 2020 Jul 2;9(7):2081. doi: 10.3390/jcm9072081. PMID: 32630717; PMCID: PMC7408936.

In addition, alcohol hangover severity is correlated with higher levels of inflammatory biomarkers. These elevated inflammatory biomarkers have been associated with symptoms that mimic hangover (headache, apathy, fatigue, runny nose, watery eyes, dry mouth, brain fog).

Inflammatory biomarkers (IL-6, TNF-α and CRP) have been shown to be elevated in other diseases in which a chronic inflammatory process is present. These chronic diseases include arthritis, irritable bowel, asthma, atopic dermatitis, eczema, type 2 diabetes, atherosclerosis, heart disease, and dementia. Click here for more information

It’s interesting to think of AH in the same way, but the truth is that inflammatory cascade connects these diseases. Inflammation is at the core of so many diseases, including AH, which the World Health Organization just recently acknowledged by providing an ICD-11 (or International Classification of Diseases 11th Revision) listing alcohol hangover as a separate entity.

This is in line with the FDA, which considers alcohol hangover as a disease, requiring treatments to be registered as drugs. Although we have OTC products that are recognized by the FDA (i.e., blowfish for hangovers), we don’t yet have any FDA-approved treatments.

An effective agent would be impactful because the cost of hangover on workplace productivity and absenteeism is enormous, costing approximately $77 billion per year in the United States alone. In fact, with all inflammation-related diseases, the resulting health costs and externalities have doubled in the past decade. But not only is it costly, it is deadly.

Fifty percent of the population dies prematurely due to a chronic inflammatory disease. The progression of inflammation leads to irreversible tissue damage, with no currently available therapeutic agents that can reverse this damage.

This therapeutic conundrum makes prevention the best modality to reduce inflammation and prolong longevity. Imagine if we had agents that worked upstream in the immune system’s inflammatory cascade. What might that do for disease mitigation, health care costs, and the Holy Grail of health—preventing aging?

Preventing alcohol hangover, as well as the inevitable increase in proinflammatory biomarkers and subsequent next day symptoms, is a smart strategy to reduce overall inflammation circulating within your body. Clinical trials are underway to prevent the inflammation associated with alcohol hangovers, using safe pharmaceutical agents sold OTC.

These new products will provide the pharmacist with an opportunity to educate patients about the effects of alcohol and offer a preventative solution, creating a more productive and healthier tomorrow. And with runaway inflammation’s connection to tissue damage, premature aging, and even death, I think a proactively preventative anti-inflammatory could be incredible, giving new meaning to the age-old cheers, “To life!”

About the Author

Jackie Iversen, RPh, MS, founder and chief clinical officer at Sen-Jam Pharmaceutical.