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How Does Alcohol Affect the Brain and the Body?

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The effects of alcohol on the human body may be more complicated than we think. Plenty of people are aware – and perhaps familiar with – the immediate, relaxing effects of alcohol consumption and the sometimes less desirable after-effects in the form of a hangover. But alcohol also has complex, unseen and far-reaching effects at the molecular and cellular level, including altering our gut microbiome, accelerating the aging process and even changing the synapses in the brain.

Let’s explore what recent research can tell us about how alcohol affects the brain and the body.

Genetic Evidence That Alcohol Accelerates Biological Aging

Our consumption of alcohol could be accelerating the aging process by damaging our telomeres, according to research from the University of Oxford. The study is published in Molecular Psychiatry.

What are telomeres?

Telomeres are repeated nucleotide sequences that cap the ends of chromosomes to protect the DNA. Every time a cell replicates, its chromosomes can lose between 50-100 bases from its telomeres. The shortening of telomeres can be used as a marker of cell aging.

The research team performed a Mendelian Randomization, where 93 genetic variants that have previously been associated with alcohol consumption and alcohol use disorder (AUD) in genome-wide association studies (GWAS) were used to predict a participant’s exposure to alcohol. The relationship between alcohol exposure and telomere length was then analyzed.

The scientists found that consumption of over 17 units of alcohol per week – approximately 5.5  large glasses of wine or 10 bottles of lager – was associated with shorter telomeres and thus increased cell aging.

They also performed an observational study, which showed an increase in telomere aging by 1-2 years in participants that drank 29 units a week, compared to more moderate drinkers who drank 6 units per week.

The researchers propose that when alcohol is metabolized, it can increase the amount of reactive oxidative species and decrease the levels of antioxidants, which leads to DNA damage and aging.

Alcohol Consumption Can Alter Gut Microbes, but Not How You Might Think

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Alcohol can also influence our gut microbiome – the collection of microbes that inhabit the lower intestines.

In the liver, alcohol is metabolized from ethanol to acetaldehyde to acetate. Acetate is used in cellular metabolism and has important roles in energy expenditure, appetite regulation and immune response. In excess, however, acetate is associated with metabolic changes that precede disease development, including cancer.

In the liver, alcohol is metabolized in a two-step process, from ethanol to acetaldehyde to acetate. Acetate is used in cellular metabolism and has important roles in energy expenditure, appetite regulation and immune response. In excess, however, acetate is associated with metabolic changes that precede disease development, including cancer.

Research from the University of California San Diego suggested that acetate diffuses to the gut, where the microbiota use it as an alternative source of carbon for energy. Some species of bacteria are more suited to using acetate as an energy source than others, so the presence of acetate can drive dysbiosis, the imbalance in bacterial species in the gut.

Excessive Drinking Induces Epigenetic Changes

Credit: Paolo Bendandi/ Unsplash

A team of researchers from Rutgers University identified two genes that are particularly affected by alcohol consumption: PER2, a gene that influences the circadian rhythm and POMC, which is a stress regulator.

Both genes exhibited increased methylation – an epigenetic modification – in groups of people who were either heavy or binge drinkers. The extent to which the genes were methylated increased in correlation with greater alcohol consumption. As a result of methylation, the expression of PER2 and POMC was decreased in binge and heavy drinkers.

The researchers were able to associate the gene expression changes with motivation to drink in response to both seeing and tasting beer and in response to seeing stress-related, neutral or drinking-related images.

"We found that people who drink heavily may be changing their DNA in a way that makes them crave alcohol even more," said Distinguished Professor Dipak K. Sarkar, senior author of the study.

Small Amounts of Alcohol Can Trigger Epigenomic Changes in the Brain

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Epigenetic changes can also happen in the brain in response to alcohol. In a recent rodent study, researchers from the University of Illinois Chicago measured epigenetic and transcriptomic changes in response to small amounts of alcohol. The team also observed changes in the rats’ behavior after alcohol exposure.

The scientists identified that alcohol consumption caused changes to molecular pathways located in the amygdala, the part of the brain that is associated with addictive behaviors.

A specific gene, Hif3a, was particularly affected by epigenetic changes. In response to acute exposure to alcohol, Hif3a expression increased, expression which is associated with feelings of relaxation and euphoria – key to the initiation and maintenance of alcohol use disorder.

After alcohol consumption, the rats’ behavior also indicated decreased levels of anxiety.

“This suggests that when the brain experiences the anti-anxiety effects of alcohol and the mood lift –  the relaxation and the buzz –  it is also being primed for alcohol use disorder,” Professor Subhash Pandey, the study’s senior author, said

A Single Dose of Alcohol Can Permanently Alter the Neuronal Mitochondria

Although many studies have investigated the effect of prolonged alcohol exposure, it’s also important to consider what happens after acute alcohol exposure.

Researchers from the University of Cologne and the Universities of Mannheim and Heidelberg recently found that a single dose of alcohol is enough to alter the dynamics of neuronal mitochondria and the structure of synapses in the brain.

When mouse and Drosophila models were exposed to alcohol for the first time, 72 hippocampal proteins changed in abundance, including mitochondrial proteins and proteins important for neural morphology. Alcohol exposure was also associated with an increase in mitochondrial trafficking, increased synaptic dynamics and changes in the length of the neural axons.

The ethanol-induced changes resulted in altered behaviors in both models, including increased alcohol consumption over time and an increased likelihood of alcohol relapse later in life.

When we learn new things, new synaptic connections are formed, which requires energy from the mitochondria. The researchers propose that the observed mitochondrial and synaptic changes indicate a positive, learned association with alcohol is being formed from the first drink, which then leads to behavioral changes later in life.