Alcohol is one of the most heavily used and abused drugs. It's also a very controversial topic, in part because alcohol plays such a large role in societies and cultures around the world. For many, it's a normal part of daily life.

There is also a lot of confusion about alcohol. There's no doubt that alcohol can have a personal and public health impact. On the other hand, research in the last few decades suggests that not only may a moderate intake of alcohol not be harmful, but it might also be protective against certain diseases. This idea is heavily debated, and conflicting evidence has led to a divide among scientists, public health professionals, and government organizations over what the guidelines should be around alcohol consumption.

The literature on alcohol's effects on healthspan and lifespan is vast — and that's an understatement. We might know more about how this drug affects the body than any other substance.

How much is a drink?

It's important to note that what defines a "standard drink" differs around the world.

In the United States, 1 standard drink is 14 grams of alcohol (ethanol), the equivalent of:

• A 12-ounce can of beer.
• 8–10 ounces of malt liquor or malt beverage like hard seltzer.
• 5 ounces of wine.
• One shot (1.5 ounces) of 80-proof distilled spirits like gin, rum, tequila, vodka, or whiskey.

Although the volume of these drinks is different, they each contain the same amount of alcohol (ethanol) because they differ in their percent alcohol by volume.

In the United States, the Centers for Disease Control and Prevention (CDC) uses the following categories of drinking behavior:

• Current infrequent drinker: someone who consumed one to 11 drinks in the last year.
• Current light drinker: someone who consumed at least 12 drinks in the last year but on average consumed three or fewer drinks per week.
• Current moderate drinker: women who consume three to less than seven drinks per week and men who consume seven to less than 14 drinks per week.
• Current heavier drinker: women who consume more than seven and men who consume more than 14 drinks per week.

Alcohol use disorder is a medical condition where someone has an impaired ability to stop or control their alcohol use despite experiencing severe social, work-related, or health-related consequences. The condition can be classified as mild, moderate, or severe depending on the number of symptoms experienced.

When heavy drinking occurs in a single session:

• The World Health Organization defines heavy episodic drinking as consuming 60 grams of alcohol or more on at least one occasion in the last 30 days.
• Binge drinking is defined as having four or more drinks for women or five or more drinks for men on at least one occasion in the last 30 days — enough alcohol to raise one's blood alcohol content to 0.08% or higher.

Now that we understand how the literature defines a drink and different drinking categories, it's time to talk about how the body metabolizes alcohol after we drink it and how it then affects the brain and body.

Alcohol metabolism

Alcohol metabolism is generally influenced by four main factors:

• How much alcohol is consumed.
• The presence (and quantity) of food in the stomach.
• Factors that affect the rate of gastric emptying.
• The rate that the body oxidizes alcohol.

It's a three-step process:

• Step 1: Alcohol dehydrogenase (ADH) catalyzes the oxidation of ethanol into acetaldehyde.
• Step 2: Aldehyde dehydrogenase (ALDH) oxidizes acetaldehyde into acetate.
• Step 3: Acetate leaves the liver, enters the circulation, and converts into acetyl coenzyme A to generate energy in the citric acid cycle.

Ethanol and acetaldehyde are both responsible for the neurotoxic and behavioral effects of alcohol consumption. Acetaldehyde is often considered the main toxic byproduct, and current evidence suggests that it likely modulates rather than mediates ethanol's effect.

It turns out that not everyone metabolizes alcohol at the same rate.

Genetic differences in alcohol metabolism

• Variants of the genes for ALDH 2 and ADH 1B can cause the accumulation of excess acetaldehyde after alcohol consumption, increasing levels of oxidative stress in the body. These variations are common in people of East Asian ancestry (prevalence of low-alcohol-tolerability alleles between 21% and 69%) but rare in people of European descent (prevalence of 0.01% to 4%). People with these genetic variations experience facial redness/flushing, nausea, and a rapid heart beat when they drink.^[1]
• A variation in the ADH1B gene (encoding for the ADH1B enzyme) is associated with a faster rate of ethanol elimination and an intense initial response to alcohol consumption — but it's also associated with a protection against alcohol-related birth defects and alcohol use disorder. This allele is found in about one-fourth of people of African descent.^[1]

Can alcoholism/alcohol use disorder be inherited?

"While there is not an"alcoholism gene,"several gene variants have been associated with this condition. For example, people with one variant of the mu-opioid receptor (which is involved in the reward circuitry of the brain) experience a large dopamine increase when they consume alcohol. These people are at a greater risk of developing alcohol use disorder due to the euphoric effects they feel when drinking."- Dr. Rhonda Patrick Click To Tweet

The short answer: yes.

While there's no "alcoholism gene," several gene variants have been associated with this condition. For example, people with one variant of the mu-opioid receptor (which is involved in the brain's reward circuitry) experience a large dopamine increase when they consume alcohol. These people are at a greater risk of developing alcohol use disorder due to the euphoric effects they feel when drinking.^[2]

People with a family history of alcohol use disorder have a larger dopamine response to the expectation of alcohol even when their dopamine response to alcohol consumption is similar to those with no family history of alcohol use disorder.^[3]

Genetics aren't the only factors that affect alcohol metabolism.

The effects of food on alcohol metabolism

Food in the stomach slows the rate of gastric emptying and delays the absorption of alcohol, hence the common advice to never drink on an empty stomach. High-fat, high-carbohydrate, and high-protein meals appear to be equally effective at slowing gastric emptying.^[4]

Being in the fed state elevates levels of ADH and increases the body's ability to transport reducing equivalents (such as NADH) into the mitochondria. Food also increases liver blood flow. Certain sugars like fructose actually increase alcohol metabolism by aiding in the conversation of NADH to NAD and enhancing mitochondrial oxygen uptake. Participants who consumed fructose with alcohol experienced a 30% reduction in the time they were intoxicated and a 45% increase in the rate of alcohol elimination but had worse blood glucose and triglycerides compared to those who consumed alcohol or fructose alone.^[5]

Aging and alcohol metabolism

The rate of alcohol metabolism and elimination appears to be similar between younger and older adults. However, older adults may experience fewer hangover symptoms for a few reasons:

• They consume less alcohol.
• They have a longer drinking experience and a greater alcohol tolerance.
• They have a lower pain sensitivity.
• They tend to drink more "expensive" types of alcohol that are lower in congeners (more on congeners later).

Alcohol biochemistry

"Unlike the major macronutrients, alcohol cannot be stored in the body for use as energy. Alcohol provides what are considered to be"empty calories"because it does not contain beneficial nutrients that contribute to our health."- Dr. Rhonda Patrick Click To Tweet

Alcohol is a nutrient just like protein, carbohydrates, and fat, providing approximately 7 calories per gram, which is higher than protein and carbohydrates (at 4 calories per gram each) but lower than fat (at 9 calories per gram).

Unlike the major macronutrients, alcohol can't be stored in the body for use as energy. Alcohol provides what are considered to be "empty calories" because it doesn't contain beneficial nutrients that contribute to our health. In fact, alcohol interferes with our body's ability to absorb crucial micronutrients.

Heavy drinking may negatively affect the absorption of:^[6]

• Glucose
• Glutamine
• Vitamin B1
• Vitamin B2
• Vitamin B9
• Vitamin C
• Iron
• Zinc
• Selenium

Alcohol interferes with nutrient absorption in several ways:

• It causes structural changes to the intestinal mucosa.
• It alters microbiome composition.
• It disrupts the gastric mucosal barrier.
• It modifies cellular junction protein and membrane dynamics.
• It increases intestinal permeability (aka "leaky gut").

These changes all contribute to a reduction in the enzymatic digestion of nutrients and their absorption in the small intestine at a crucial area known as the brush border membrane.

Heavy chronic drinking can elevate the risk for several nutrient deficiencies. Adults with alcohol use disorder have a 20%–50% greater prevalence of calcium deficiency, a 25%–50% greater prevalence of magnesium deficiency, a 6%–80% greater prevalence of deficiencies in many B vitamins, and a 14%–58% greater prevalence of deficiencies in vitamins C, D, E, and K.

Zinc and magnesium are two crucial micronutrients that alcohol affects. Alcohol causes less zinc absorption in the intestine and more zinc excretion in the urine. Between 30% and 50% of people with alcohol use disorder have low zinc status. Alcohol consumption can also [increase magnesium excretion up to two- to threefold in chronic heavy drinkers.]^[7]

Alcohol and gut health

"Just 20 grams of alcohol (about 1.5 standard drinks) can disrupt two key tight junction proteins known as zonula occludins-1 and occludin. These proteins are crucial for forming tight junctions that maintain intestinal barrier integrity."- Dr. Rhonda Patrick Click To Tweet

Alcohol, its metabolites, and reactive oxygen species produced during alcohol metabolism cause damage to intestinal barrier cells and weaken cell membranes, leading to leaky gut through transepithelial and paracellular mechanisms.

• Transepithelial: Materials can pass directly through epithelial cell membranes in the intestine and enter the circulation.
• Paracellular: Materials can pass through junctions or small gaps between intestinal epithelial cells because alcohol disrupts tight junction proteins.

Importantly, a heavy dose of alcohol may not be required to cause these changes. Just 20 grams of alcohol (about 1.5 standard drinks) can disrupt two key tight junction proteins known as zonula occludins-1 and occludin. These proteins are crucial for forming tight junctions that maintain intestinal barrier integrity.

Leaky gut has consequences: Inflammatory cytokines produced in the intestine along with bacteria and toxins can migrate from the gut to the circulation and other organs throughout the body.

A bacterial toxin known as lipopolysaccharide (LPS) or endotoxin is particularly harmful in this regard — it normally provides a structural barrier to bacterial cells and is only present on the inner side of the intestinal membrane where it doesn't cause damage. But LPS has toxic effects when it leaves the intestine and enters the circulation, where it induces an inflammatory response, explaining why it has been linked to type 2 diabetes, heart disease, and liver disease.

• A single binge drinking occasion elevates LPS levels in the bloodstream for up to three hours.^[8]
• Chronic heavier drinking is associated with higher circulating levels of LPS compared to non-heavy drinking and correlates with higher levels of gut permeability.^[9]
• Short-term alcohol abstinence (19 days) reduces gut permeability levels in adults with alcohol dependence to levels observed in adults who consume just one drink per day.^[10]

The gut-brain axis

"Somewhere between 30% and 40% of all alcohol use disorders may have a gut-related component, and targeting the gut microbiome could provide an alternative and effective treatment for these conditions."- Dr. Rhonda Patrick Click To Tweet

Gut bacteria can communicate with the brain to modulate brain function, behavior, cognition, mood, anxiety, and pain. This gut-brain interaction is mediated by the immune system, enteric nervous system, neuroendocrine system, circulatory system, and vagus nerve, all of which can receive information indicating alterations in gut microbiota that can either promote or prevent the development of certain behaviors or disease. Neurotransmitters and neurohormones are produced not only in the brain, but also in the gut. For example, the gut bacteria known as Lactobacillus produces the neurotransmitter GABA, the gut bacteria known as Enterococcus can produce serotonin, and the gut bacteria Bacillus can produce dopamine.

Some gut-derived compounds may influence alcohol consumption and may explain how the gut gives rise to alcohol use disorders. Injecting mice with LPS increases their alcohol consumption and prevents alcohol-conditioned taste aversion, an effect that lasts for almost three months!

Somewhere between 30% and 40% of all alcohol use disorders may have a gut-related component, and targeting the gut microbiome could provide an alternative and effective treatment for these conditions. Here are a few promising options to improve gut health, though they've not been studied for alcohol use disorder per se:

Probiotics and prebiotics to improve gut microbiota composition, gut barrier integrity, and inflammation. Increased consumption of dietary fiber, omega-3 fatty acids, and polyphenols. Engaging in regular exercise.

Alcohol and disease risk: The "sick quitter effect" and the "healthy user bias"

"The"healthy user effect"refers to a bias in observational studies where individuals who engage in a particular healthy behavior (such as moderate drinking) also tend to have other health-promoting habits (like exercising and eating well), which can confound the results."- Dr. Rhonda Patrick Click To Tweet

The sick quitter effect and the healthy user bias are often used to explain why moderate drinkers appear to be healthier than non-drinkers or abstainers in observational studies. These studies are often criticized for being influenced by confounding variables — characteristics of the participants that aren't accounted for but influence the results significantly.

The sick quitter effect refers to a bias in observational studies on alcohol consumption and disease risk, where former drinkers who have quit due to health problems are grouped with lifetime abstainers, potentially inflating the perceived health benefits of moderate drinking. This misclassification can make moderate drinkers appear healthier by comparison, as the abstainer group may include individuals who quit drinking due to existing health issues. The better health of the moderate drinkers isn't due to their moderate alcohol consumption per se.

To correctly control for the sick quitter effect, studies should include a group of never drinkers and a group of current non-drinkers (including both never and former drinkers).

The "healthy user effect" refers to a bias in observational studies where individuals who engage in a particular healthy behavior (such as moderate drinking) also tend to have other health-promoting habits (like exercising and eating well), which can confound the results. This effect can lead to an overestimation of the health benefits of the behavior being studied, as the observed benefits may actually be due to these other healthy lifestyle choices rather than the behavior itself. For example, light and moderate drinkers have better dental hygiene, exercise routines, weight, diet quality, and income than abstainers.

When these confounding factors are adequately controlled for, most or all of the protective effects of alcohol on disease risk are abolished. With that in mind, let's explore the effects of alcohol on disease risk, starting with the brain.^[11]

Alcohol and brain health

"The anxiety-reducing effects of alcohol are due to its interaction with gamma-aminobutyric acid or GABA — an inhibitory neurotransmitter in the brain. Alcohol is a GABA receptor agonist."- Dr. Rhonda Patrick Click To Tweet

Alcohol is water- and fat-soluble and can cross the blood-brain barrier. When social drinkers (people without an alcohol use disorder) first consume alcohol, there's an activity spike in parts of the brain called the ventral striatum and the nucleus accumbens — both of which are key components of the brain's reward system.

• Alcohol triggers dopamine release in these areas, contributing to feelings of pleasure and satisfaction and encouraging repeated behavior.
• In people with alcohol use disorder, the dopamine release is blunted — for the same amount of alcohol, they get less of a dopamine release (possibly due to a lower dopamine receptor/transporter density) and need more alcohol for a similar level of dopamine.^[12]
• Alcohol causes serotonin release in the median and dorsal raphe, which are involved in impulses, motivation and reward, and stress and anxiety responses. Initially, this serotonin contributes to the "feel good" sensations some people experience when drinking.

The anxiety-reducing effects of alcohol are due to its interaction with gamma-aminobutyric acid or GABA — an inhibitory neurotransmitter in the brain. Alcohol is a GABA receptor agonist. Alcohol also reduces levels of the excitatory neurotransmitter glutamate and may even influence how we perceive and respond to threats. When under the influence of alcohol, there's less activity in the brain's visual and limbic regions.^[13]

Highly anxious people may experience potent anxiety-reducing effects in response to alcohol, especially in social situations. But after alcohol's effects wear off, they may experience worse anxiety, a phenomenon often referred to as hangxiety. The mechanisms that drive hangxiety may include:^[14]

• Disrupted sleep patterns.
• A down-regulation of GABA receptors and an up-regulation of glutamate receptors.
• Nausea and fatigue as a result of alcohol's metabolism into acetaldehyde. ###Alcohol, Alzheimer's disease, and dementia

One of the most heavily referenced studies in the area of alcohol and brain health, "Associations between alcohol consumption and gray and white matter volumes in the UK biobank," was published in 2022. Using data from over 36,000 participants, the research revealed that consuming just one to two drinks per day was associated with less gray matter and white matter volume in the brain.^[14]

This study supports existing evidence that alcohol can contribute to cerebral volume loss in areas crucial for memory processing and visuospatial function, while heavy alcohol use can lead to the loss of neurons in the hypothalamus, cerebellum, hippocampus, and amygdala.

Alcohol may affect the brain directly through its effects on nutrient absorption, direct toxicity, and inflammation.

• Thiamin deficiency: Alcohol consumption can lead to a deficiency in thiamin, or vitamin B1, which is essential for nerve function and brain health, by impairing its absorption or the body's ability to utilize it. The resultant thiamin deficiency can lead to decreased cellular defense against oxidative stress, contributing to brain damage. Some of this damage may be related to iron toxicity. Thiamin maintains the integrity of the blood-brain barrier. A thiamin deficiency could impair blood-brain barrier function, allowing more iron to deposit in the brain. This is known as the brain iron overload and thiamin hypothesis. Consuming more than seven units of alcohol per week was associated with higher iron levels and worse cognitive function among a cohort of more than 20,000 participants from the United Kingdom, lending some support to this hypothesis.^{[15] [16]}
• Acetaldehyde toxicity: The body metabolizes ethanol into acetaldehyde, a substance that's toxic to brain cells. This compound can damage DNA and proteins within brain cells, leading to cellular dysfunction and cell death.
• Neuroinflammation: Alcohol also affects the gut-brain axis, which is a direct communication pathway linking your gastrointestinal tract and your brain. Heavy drinking can increase gut permeability, often referred to as "leaky gut," leading to the release of pro-inflammatory cytokines into the bloodstream. Additionally, alcohol can increase glutamate — a neurotransmitter linked to stress and excitotoxicity — and activate the stress response system, further promoting brain inflammation that's mediated by the activation of microglia and astrocytes, the brain's resident immune cells.^[15]

Alcohol and cognitive function

Research indicates that light to moderate alcohol consumption in middle to late adulthood is associated with a reduced risk of cognitive impairment and dementia, while heavy alcohol use and alcohol use disorder increase the risk for these diseases.^[17]

• The risk reduction associated with light to moderate drinking may be as high as 26%–28% for dementia and Alzheimer's disease.
• A more modest 10% reduction in the risk of dementia may occur at four drinks per week.^[18]
• Consuming one to 14 drinks per week is associated with a 47% lower risk of dementia compared to abstinence, but above 14 units per week, each seven-unit increase elevates dementia risk by 17%.^[19]
• Once alcohol intake surpasses 23 drinks per week (about three standard drinks per day), there's a significant increase in the risk for dementia.

These observations hold up in populations of adults older than 60: Occasional and light drinking (one drink per week) reduces the risk of dementia by 22% and moderate to heavy drinking (up to three drinks per day) reduces the risk by 38%. Drinking three or more drinks per day was associated with an equal risk of dementia compared to abstaining.^[20]

Alcohol, APOE e4, and Alzheimer's

"Some evidence suggests that the risk of dementia increases along with increasing alcohol consumption in people with one or more copies of the APOE e4 allele but not in people without this allele."- Dr. Rhonda Patrick Click To Tweet

APOE is a gene that instructs our body to make apolipoprotein E, which combines with lipids (cholesterol and triglycerides) to form lipoproteins. There are three variants or alleles of the APOE gene: APOE e2, APOE e3, and APOE e4.

• The APOE e4 allele is associated with an increased risk of dementia and Alzheimer's disease and an earlier age of onset of these diseases in some populations.
• Around 15%–25% of people have one copy of the APOE e4 allele and 2%–5% carry two copies.
• Having one copy elevates Alzheimer's risk two- to threefold compared to having no copies, and two copies can increase the risk of Alzheimer's disease as much as 15-fold.^[21]

Some evidence suggests that the risk of dementia increases along with increasing alcohol consumption in people with one or more copies of the APOE e4 allele but not in people without this allele.

• Carriers who consumed alcohol less than once a month still had a 2.3 times greater risk of dementia than carriers who never drank, and carriers who drank several times per month had a 3.6 times greater risk.^[22]
• For adults with one or more copies of the APOE e4 allele, any alcohol was associated with a greater risk of cognitive decline, with 90% greater risk for two or fewer drinks per day, a 170% increase for two to five drinks per day, and a 730% increase for five or more drinks per day.^[23]

Not all studies support a lower threshold for the negative effects of alcohol on dementia. One meta-analysis published in 2017 found a protective effect of alcohol consumption up to 14 drinks per week among APOE e4 carriers, while protection was only observed up to seven drinks per week among non-carriers.^[18]

Alcohol and brain health mechanisms

"While resveratrol has shown potential in laboratory studies, the [actual amount of resveratrol in red wine is quite small — ranging from about 0.03 milligrams to 1 milligram per glass."- Dr. Rhonda Patrick Click To Tweet

What might explain the association between low to moderate alcohol consumption and better brain health? A few mechanisms have been proposed:

• Glucose metabolism: One of the hallmarks of Alzheimer's disease and other forms of dementia is impaired glucose metabolism in the brain. The brain's ability to utilize glucose effectively is crucial for maintaining cognitive functions. Alcohol, interestingly, might help improve the brain's glucose tolerance. This is potentially due to alcohol's ability to increase the presence of insulin-sensitive glucose transporters, which help cells absorb glucose more effectively, thus supporting better brain function.
• Cardiovascular health: A healthy heart and blood vessels are essential for maintaining adequate blood flow to the brain, and a lack of brain blood flow is implicated as one of the main causes of Alzheimer's disease and dementia.^[24] Moderate alcohol consumption has been shown to increase levels of HDL cholesterol. HDL plays a protective role in the cardiovascular system by helping to remove other forms of cholesterol from the blood and preventing them from forming plaque in the arteries.
• Blood coagulation and platelet activity: Alzheimer's disease and dementia are also associated with abnormal platelet activity and other thrombotic factors that can affect blood flow. Alcohol can reduce platelet aggregation — essentially, it can make platelets less sticky and less likely to form clots. This reduction in coagulation and improvement in blood flow can be beneficial for brain health by ensuring that the brain receives adequate blood supply, which is essential for its function and maintenance.
• Glymphatic clearance: The glymphatic system is our brain's highly organized system for cerebrospinal and interstitial fluid exchange, which is most active during sleep. It serves a few purposes. For one, it clears waste products and metabolites from the intracellular space of the brain via lymphatic drainage vessels in the head and neck. In mice, acute and chronic exposure for 30 days to a low dose of alcohol (0.5 grams per kilogram of body weight), corresponding to about two standard drinks per day for a human, improved glymphatic activity, whereas intermediate and high doses, corresponding to about eight and 21 drinks per day for a human, impaired glymphatic activity.^[24]
• Resveratrol: Resveratrol is a polyphenol found in red wine, among other plant sources, and is known for its antioxidant and anti-inflammatory properties. It has been studied for its ability to protect neurons by neutralizing free radicals, reducing inflammation, and enhancing neuronal energy metabolism. Some research has also suggested that resveratrol can improve cerebral blood flow and even aid in the clearance of beta-amyloid proteins, which are implicated in Alzheimer's disease.^[25]

While resveratrol has shown potential in laboratory studies, the actual amount of resveratrol in red wine is quite small — ranging from about 0.03 milligrams to 1 milligram per glass. To achieve the levels used in pharmacological studies, which are often between 50 to 500 milligrams, one would need to consume an impractical amount of wine—literally thousands of glasses.

Alcohol and sleep

A brief overview of the sleep stages:

• NREM Stage 1 (N1): The lightest sleep stage, marking the transition from wakefulness to sleep, with slow eye movements and theta brain waves.
• NREM Stage 2 (N2): A deeper sleep stage with sleep spindles and K-complexes, where heart rate and body temperature decrease. This stage is the largest portion of the sleep cycle.
• NREM Stage 3 (N3): Known as deep sleep or slow-wave sleep, characterized by delta brain waves. It is the most restorative stage, essential for physical recovery and immune function.
• REM Sleep: The stage where most dreaming occurs, marked by rapid eye movements and increased brain activity. REM sleep is crucial for emotional regulation and memory consolidation.

How does alcohol affect sleep quality and sleep stages?

• Alcohol reduces the time it takes to fall asleep, also known as sleep onset latency.
• Alcohol increases nighttime awakenings, also known as wake after sleep onset.
• Alcohol increases slow-wave sleep at a dose of three or more standard drinks, an effect that is most prominent in the first half of the night.
• Alcohol suppresses REM sleep during the first half of the night and delays the onset of the first REM sleep period.^[26]

Timing matters

"The effects of alcohol on REM sleep are minimized when it is consumed four or more hours before sleep compared to consuming the same amount of alcohol 90 minutes or less before sleep."- Dr. Rhonda Patrick Click To Tweet

Alcohol's effects on REM sleep are minimized when it's consumed four or more hours before sleep compared to consuming the same amount of alcohol 90 minutes or less before sleep. However, even if breath or blood alcohol levels are zero at bedtime and alcohol is consumed late in the afternoon there are lingering effects on sleep including:^[27]

• Reduced efficiency.
• Less total sleep time.
• Less stage 1 sleep.
• Less REM sleep.
• More wakefulness in the second half of the night.

People with sleep apnea should especially avoid alcohol close to bedtime. Alcohol can worsen sleep apnea by relaxing the genioglossus muscle (the muscle that prevents the tongue from blocking the airway). The risk of sleep apnea is 25% higher in people who consume alcohol compared to those who don't; consuming higher levels of alcohol appears to be worse than consuming less.^[28]

Want to have a night out, enjoy a few drinks, and still sleep well? These tips may help:

• Consume your last drink at least three to four hours before bedtime.
• Consume a meal before or while you drink to slow the absorption of alcohol and buffer some of the impact on sleep. But keep in mind that eating a heavy meal close to bedtime can also disrupt sleep.
• Stay hydrated and supplement with electrolytes (sodium, potassium, and magnesium) to counterbalance alcohol's diuretic effect and the micronutrient excretion that happens when you drink.
• Do not mix melatonin and alcohol — together they have a potent sedating effect.

Consuming alcohol close to bedtime — but really at all times — is likely to cause next-day effects that are known as a hangover.

Hangover

"...recent evidence suggests that a hangover can occur at much lower levels of consumption. Some people appear to be"hangover resistant"— they do not experience hangover symptoms after drinking."- Dr. Rhonda Patrick Click To Tweet

An alcohol hangover refers to the mental and physical symptoms that occur after a single episode of alcohol consumption that begin when blood alcohol concentration approaches zero. Hangover symptoms are not due to alcohol intoxication, nor are they due to alcohol withdrawal, which occurs when someone who is a regular heavy drinker stops drinking.

The thinking is that someone can only experience a hangover if their alcohol concentration reaches 0.11% or more (which is higher than the legal limit of 0.08% in most places). But recent evidence suggests that a hangover can occur at much lower levels of consumption. Some people appear to be "hangover resistant" — they don't experience hangover symptoms after drinking. Genetic factors may account for up to 43% of this attribute.^[29]

Common hangover symptoms include:

• Fatigue
• Thirst
• Drowsiness
• Headache
• Problems with concentration and memory
• Elevated heart rate
• Light and noise sensitivity
• Muscle cramps

What causes a hangover?

There are several theories about what causes a hangover and not a lot of evidence. Here are a few proposed mechanisms:

• Dehydration and electrolyte imbalances: Many people attribute hangovers to dehydration or electrolyte imbalances due to alcohol's diuretic effects, but recent studies suggest these aren't the primary culprits. While it's true that alcohol suppresses antidiuretic hormone (ADH), leading to increased urine production, the volume of fluids typically consumed with alcohol often compensates for this increase. Alcohol only somewhat disrupts overall electrolyte imbalance, but does cause metabolic acidosis — a potentially life threatening decrease in blood pH.^[30]

• Ethanol metabolism: Ethanol metabolism produces reactive oxygen species that cause oxidative stress in the mitochondria and central nervous system. Reactive oxygen species also initiate an inflammatory response, causing nausea, vomiting, headaches, and cognitive impairment. Higher levels of inflammatory markers (e.g., interleukin 6, TNF-alpha, and C-reactive protein) are associated with a worse severity of hangover symptoms.^[31]

• Alterations in hormones and neurotransmitters: Alcohol disrupts GABA, glutamate, dopamine, and serotonin. It also impairs sleep quality, likely contributing to hangover symptoms including drowsiness, confusion, and trouble concentrating.

• Congeners: Congeners are naturally occurring compounds in alcohol beverages that are produced during the distillation and fermentation process. They can enhance the inflammatory response in the body and compete with the metabolism of ethanol. This prolongs the processing of alcohol in the system, leading to longer and more intense hangover symptoms. Inflammation can affect the brain and other systems, exacerbating the typical symptoms of a hangover such as headaches, nausea, and overall malaise.^[32]

Potential strategies for reducing hangover symptom severity

"In humans, the simple sugar fructose accelerates alcohol metabolism in the body by up to 45% and reduces the duration of intoxication by as much as 30%. Studies performed in vitro (in a dish) and in vivo (in living organisms) have shown that pear, sweet lime, and coconut water enhance the activity of ADH and ALDH — the enzymes that metabolize alcohol — by 20%–90%."- Dr. Rhonda Patrick Click To Tweet

One of the most frequently asked questions about alcohol is what one can do (if anything) to reduce its negative after effects. In other words, can you prevent a hangover? The short answer is no, but there are a few things that might help.

Fructose

In humans, the simple sugar fructose accelerates alcohol metabolism in the body by up to 45% and reduces the duration of intoxication by as much as 30%. Studies performed in vitro (in a dish) and in vivo (in living organisms) have shown that pear, sweet lime, and coconut water enhance the activity of ADH and ALDH — the enzymes that metabolize alcohol — by 20%–90%. Carambola (starfruit), Chinese quince, yellow lemon, pear, Java apple, melon, and banana reduce ethanol levels in the blood and/or reduce levels of the liver enzymes AST and ALT, suggesting protection against acute alcohol-induced liver stress.^{[5] [33] [34]}

Vitamins & minerals

Zinc is crucial for the function of several enzymes involved in alcohol metabolism (remember that alcohol consumption can increase zinc excretion up to twofold). Vitamin B3 plays a role in the enzymatic process that converts alcohol into less harmful substances before they're cleared from the body. Social drinkers who have a higher dietary intake of zinc and vitamin B3 report significantly less severe hangovers compared to people with lower intakes.

NSAIDS and other drugs

Taking nonsteroidal anti-inflammatory drugs (NSAIDS) to prevent hangovers is not advised and could be harmful. These medications slow down the enzymes that metabolize alcohol and its byproducts. Acetaminophen (e.g., Tylenol), can lead to increased liver toxicity when consumed alongside alcohol. It's probably safe to take these medications the day after consuming alcohol to ease hangover symptoms once the alcohol has left your body.^[35]

Glutathione

Glutathione is a potent antioxidant that helps neutralize free radicals, thereby protecting cells from damage.

Alcohol consumption has a well-documented impact on reducing glutathione levels in various organs, including the liver, which is crucial for detoxifying harmful substances in the body.^[36]

Some animal studies and preliminary research have suggested that boosting glutathione levels, either through direct supplementation or via precursors like N-acetylcysteine (NAC), could help mitigate these effects. For example, studies in rats have shown that glutathione supplementation can reduce blood concentrations of alcohol and acetaldehyde, potentially easing hangover symptoms by enhancing the activity of alcohol-metabolizing enzymes and exerting antioxidant effects.^[37] A placebo-controlled study that tested NAC supplementation in humans found mixed results: Overall, NAC did not significantly reduce hangover symptoms, though some subgroup analyses suggested potential benefits for women in terms of reducing symptoms like nausea and weakness. You can boost glutathione levels by supplementing with liposomal glutathione, NAC, or sulforaphane.^[37]

ZBiotics

ZBiotics is a genetically engineered probiotic bacteria that, once consumed, produces the enzyme ALDH in the gut. With more of the ALDH enzyme, more acetaldehyde can be metabolized. Although a faster metabolism of ethanol into acetaldehyde is associated with having less severe hangover symptoms, there's no evidence that a faster elimination of acetaldehyde — which hangover products like ZBiotics claim to promote — is effective for reducing hangover severity.

Dihydromyricetin (DHM)

DHM is a flavonoid compound that's derived from the Chinese herbal medicine Hovenia dulcis and has been used as an anti-hangover remedy for centuries. It's a very common ingredient in commercial hangover remedies. DHM reduces alcohol intoxication, decreases signs of alcohol withdrawal, and reduces voluntary alcohol consumption. The mechanism seems to involve the ability of DHM to counteract the effects of alcohol on GABA receptors, which play a role in the development of alcohol tolerance and alcohol use disorder.^[38]

Exercise and sauna

Though you might not feel like exerting yourself after a night of drinking, breaking a sweat may lift your mood by increasing endorphins, enhancing blood flow and metabolism, and promoting relaxation and reducing anxiety that you might be experiencing during a hangover. Hydration and electrolyte replenishment are important here as you lose water and electrolytes via sweat.

These hangover-mitigation strategies may provide some relief from hangover symptoms and may ease the harms of alcohol, potentially altering alcohol's effects on processes that contribute to aging.

Alcohol, longevity, and aging

"Overall, it seems that consuming around one standard drink per day does not increase mortality risk, but it does not appear to decrease it either. In other words, there is no level of alcohol consumption at which lifespan improves."- Dr. Rhonda Patrick Click To Tweet

Does a low-risk drinking habit impact healthspan and lifespan?

One meta-analysis of more than 4.8 million people failed to find an association between consuming less than one to up to three drinks per day and all-cause mortality compared to lifetime nondrinkers.^[39]

• High-volume (three to five drinks per day) and the highest-volume consumption (five drinks per day) had a 19%–35% greater mortality risk than lifetime nondrinkers.
• In women, mortality risk increased at two or more drinks per day while in men, it increased at three or more drinks per day.

An important advancement from this study was the finding that while low- to medium-volume drinking didn't increase mortality risk compared to abstaining, it didn't provide protection either, as had been suggested by previous large-scale studies.

Other studies suggest even moderate drinking may reduce life expectancy.^[40]

• Consuming around eight drinks per week is associated with a reduction in life expectancy of about six months by the age of 40 (vs. people consuming 4 or fewer drinks per week).
• Life expectancy (at age 40) decreases by one to two years with 15 drinks per week and four to five years with 26 drinks per week.

Overall, it seems that consuming around one standard drink per day does not increase mortality risk, but it doesn't appear to decrease it either. In other words, there's not a level of alcohol consumption at which lifespan improves. This is interesting in light of the observation that, in certain areas of the world, people live exceptionally long while also practicing light to moderate drinking habits.

What about the "blue zones"?

"People in the blue zones seem to drink regularly but lightly — about one glass of wine per day with meals."- Dr. Rhonda Patrick Click To Tweet

The "blue zones" are areas of the world that have an unusually high number of people who live to be 90 to 100 years old. They include places like Okinawa, Japan; Sardinia; Ikaria, Greece; and Loma Linda, California.

People in the blue zones seem to drink regularly but lightly — about one glass of wine per day with meals.

• Ikarian men and women report drinking one to two glasses of red wine daily.^[41]
• Among residents of Okinawa, more men and women report moderate daily drinking than the general Japanese population. ^[42]

Is it all due to "longevity genes"?

One gene known as Forkhead box O3A or FOXO3a has consistently been associated with human longevity. FOXO3a has a protective role against oxidative stress and is involved in apoptosis, DNA repair, immune cell regulation, carcinogenesis, and stem cell maintenance. However, some studies fail to find differences in the prevalence of the protective allele of the FOXO3a gene among blue zone populations like Sardinia compared to other Italians and Greeks.^[43]

There's not much evidence to conclude whether alcohol promotes or subtracts from longevity, but it appears that a glass of wine per day may not be harmful for lifespan for those who enjoy light drinking on occasion.

Alcohol and cancer

"Alcohol consumption is associated with a higher risk for oropharyngeal, laryngeal, esophageal, liver, colon, rectal, and breast cancer. Importantly, risk increases in a dose-response fashion, and there is no apparent evidence of a threshold effect."- Dr. Rhonda Patrick Click To Tweet

Alcohol has been implicated as a cause of cancer. Alcohol consumption is associated with a higher risk for oropharyngeal, laryngeal, esophageal, liver, colon, rectal, and breast cancer. Importantly, risk increases in a dose-response fashion, and there's no apparent evidence of a threshold effect. In other words, the more alcohol you drink, the greater your risk for these cancers.^[44]

Here's how different levels of drinking have been shown to impact cancer risk:

Light drinking (~seven drinks per week or one drink per day)

• 4%–9% increase in the risk of breast and colorectal cancer.
• 13%–17% increase in the risk of oral and pharyngeal cancer.
• 26%–44% greater risk of esophageal cancer and malignant melanoma.

Moderate drinking (one to three drinks per day)^[45]

• 12%–123% increase in the risk of oropharyngeal, laryngeal, colorectal, breast, and liver cancer.

Heavy drinking (three or more drinks per day)^[45]

• 15%–21% increase in the risk of stomach cancer.
• 300%–400% increase in the risk of esophageal, pharyngeal, and oral cancers.

Is alcohol as bad as cigarette smoking?

"...consuming five standard drinks per week (about one bottle of wine) was roughly equivalent to smoking four to five cigarettes per week for men and 10 cigarettes per week for women in terms of the absolute impact on lifetime cancer risk."- Dr. Rhonda Patrick Click To Tweet

One study estimated that consuming five standard drinks per week (about one bottle of wine) was roughly equivalent to smoking four to five cigarettes per week for men and 10 cigarettes per week for women in terms of the absolute impact on lifetime cancer risk. Hazardous drinking (equivalent to three bottles of wine per week) was equivalent to a man smoking eight cigarettes per week and a woman smoking nearly a pack per week.^[46]

Drinking patterns matter: Consuming 14 drinks per week on fewer days (one to three days) carries a greater breast cancer risk compared to the same number of drinks spread out over four to seven days. This pattern isn't observed for other types of cancer, including colorectal, lung, and prostate cancer.^[47]

The role of genetics

There's some evidence that certain genetic factors influence alcohol-associated cancer risk. For example:

• Cancer risk is higher in Asian adults who carry genetic variants associated with low alcohol tolerability (variants in the ALDH and ADH enzymes) and who are also heavy drinkers^[48]
• Interactions have been reported for the TT genotype of the MTHFR enzyme and certain cancers, including head and neck, esophageal, and colorectal cancer.^{[49] [50] [51]}
• Carriers of the peroxisome proliferator-activated receptor gamma or PPARG2 had a 20% increase in their risk of breast cancer for every 10-gram increase in daily alcohol consumption, or just under one standard drink per day.^[52]

Does quitting alcohol reverse the effects on cancer risk?

The short answer is "yes," but it might take a while. For example, the risk of laryngeal and pharyngeal cancers doesn't return to levels of never drinkers until 36 and 39 years, respectively, after quitting. The good news is that the risk eventually does fall slightly each year without alcohol.^[53]

Mechanisms by which alcohol increases cancer risk

Alcohol (ethanol) is recognized as a Group 1 carcinogen by the International Agency for Research on Cancer. Group 1 is the highest risk group and includes other known carcinogens like asbestos, radiation, and tobacco.^[54]

• Acetaldehyde toxicity: Acetaldehyde can directly cause DNA damage and prevent DNA repair processes from happening. It binds to DNA to cause mutations, double-strand breaks, and chromosomal changes.
• Ethanol toxicity: Ethanol increases reactive oxygen species that cause oxidative stress and DNA damage.
• Inflammation: Alcohol causes inflammation by recruiting immune cells called monocytes and macrophages to the tumor microenvironment and increasing pro-inflammatory markers like TNF-alpha and the interleukins IL-1, IL-6, and IL-8.
• Immune function: Alcohol weakens the function and release of natural killer cells and T cells, which are immune cells with anti-cancer properties.
• Hormones: Alcohol increases estrogen levels and enhances the activity of estrogen receptors that play a role in breast cancer development.
• Leaky gut: Ethanol can lead to bacterial overgrowth in the intestine and cause gut dysbiosis and leaky gut. A compromised gut barrier allows endotoxins to enter the bloodstream and reach the liver.
• Nutrient absorption: Alcohol interferes with our ability to break down and absorb key micronutrients, including vitamin A, vitamin B1, vitamin C, vitamin D, folate, selenium, zinc, and magnesium, all of which have been identified as having anti-cancer properties.

Alcohol and cardiovascular disease

"There appears to be a U- or J-shaped relationship between alcohol and cardiovascular disease — very low and very high levels of consumption are associated with a greater risk when compared to light to moderate consumption. But a lot of this research was shown to be confounded by the so-called sick quitter effect and as a result, the protective effects of alcohol were likely overestimated."- Dr. Rhonda Patrick Click To Tweet

Early research indicated that a moderate intake of alcohol — about seven drinks per week — had a protective effect against cardiovascular diseases when compared to not drinking.^[55]

There appears to be a U- or J-shaped relationship between alcohol and cardiovascular disease — very low and very high levels of consumption are associated with a greater risk when compared to light to moderate consumption. But a lot of this research was shown to be confounded by the so-called sick quitter effect and as a result, the protective effects of alcohol were likely overestimated.

Removing former drinkers from the non-drinker category reveals a different story:

• One study observed that the lowest risk for cardiovascular disease (i.e., ischemic heart disease) was right below one standard U.S. drink per week — men and women at this level of consumption had an ~18% lower risk compared to nondrinkers.

Other studies note a dose-response relationship between alcohol intake and cardiovascular diseases: For every 100-gram increase in alcohol consumption (above 100 grams per week or less):^[40]

• The risk for stroke, coronary heart disease, heart failure, hypertension, and aortic aneurysm increased by 6%–24%.
• The risk of myocardial infarction decreased by 6% for every 100-gram increase in alcohol consumption.
• The lowest risk for all-cause mortality and cardiovascular diseases occurred around seven drinks per week — no protective effects were observed beyond this level.

These findings debunk the simplistic view of a J-shaped curve commonly described in earlier studies, where moderate alcohol consumption was thought to universally benefit cardiovascular health. Instead, the effects of alcohol are specific to the type of cardiovascular disease. This study is particularly robust because it only included current drinkers, thus eliminating potential bias from sick quitters.

Let's look at one final meta-analysis from 2020 which had some interesting findings regarding the dose of alcohol that leads to cardiovascular protection and harm:^[56]

• Up to 40 grams of alcohol per day (about three U.S. standard drinks) was protective against coronary heart disease and stroke, but only among men.
• No protective effects were observed in adults with three or more comorbid conditions (e.g., high blood pressure, diabetes, dyslipidemia) or among participants younger than 40.
• For women, adults under 40, and adults with comorbidities, any amount of alcohol raised the risk of cardiovascular disease.
• Among men with three or more comorbid conditions, consuming four to six standard drinks per day nearly doubled the risk of developing a cardiovascular disease.

Cardiovascular mechanisms

There are several mechanisms that might link alcohol consumption to an increased or decreased risk of cardiovascular disease, some of which are discussed below.^[57]

• Microvascular damage: Chronic alcohol can damage the microvasculature — small blood vessels that supply blood and oxygen to the heart — by causing inflammation, fibrosis, swelling, and tissue scarring.
• Endothelial dysfunction: Alcohol can cause endothelial dysfunction, elevate blood pressure, and activate the sympathetic nervous system.
• Blood lipids: Low to moderate alcohol consumption increases HDL cholesterol and decreases LDL cholesterol and triglycerides, improves insulin sensitivity, and reduces blood clotting factors; heavy alcohol consumption has the opposite effects.
• Atrial fibrillation: Acutely, alcohol elevates the risk of developing a heart arrhythmia known as atrial fibrillation (Afib) — binge drinking appears to be the most risky.
• Oxidative stress: Alcohol metabolism generates free radicals and impacts the activity of antioxidant protein and enzymes. Ultimately, this leads to oxidative stress, which can damage the heart and blood vessels.
• Cardiac changes: Heavy chronic drinking leads to a condition known as alcoholic cardiomyopathy — a dangerously large heart with dilated ventricles and a poor ability to pump blood.

Has industry funding influenced alcohol research findings?

"Among the studies with no ties to industry, only about 50% of them concluded that alcohol had health-protective effects."- Dr. Rhonda Patrick Click To Tweet

An analysis published in 2021 that investigated the role of industry funding in alcohol research noted that almost 25% of systematic reviews (14 of 60 studies) had a known connection to alcohol industry funding. All of these reviews identified a cardioprotective or beneficial effect of alcohol. Among the studies with no ties to industry, only about 50% of them concluded that alcohol had health-protective effects. Another notable finding was that the studies with industry funding were more likely to study broader outcomes like "cardiovascular disease" instead of more specific cardiovascular disease outcomes like stroke or hypertension.

Does this mean that alcohol doesn't have protective effects? No. But it does mean we should read the research with a healthy dose of skepticism.

Alcohol and metabolic health

The connection between alcohol and diabetes risk presents an intriguing and inconsistent picture, but most studies suggest a U- or J-shaped relationship between the two. However, some of the studies are confounded because they did not account for the sick quitter effect. Here's a brief summary of the literature:^{[58] [59]}

• Men who consume about one and a half standard drinks per day have a 13% lower risk of developing type 2 diabetes compared to never-drinkers. After four drinks per day, there's a greater risk of type 2 diabetes.
• In women, consuming one and a half drinks per day increases type 2 diabetes risk by 40%, and beyond about three and a half drinks per day, the risk of diabetes increases.
• One meta-analysis suggests that there is a lower risk of diabetes among adults consuming up to 63 grams of alcohol per day (about four standard drinks), but the most significant risk reduction occurs around 10–14 grams per day (about one standard drink).

Diabetes mechanisms

"Mechanistic studies — that is, studies looking at how alcohol affects the body on a biochemical level — also support the notion that alcohol can beneficially influence blood glucose regulation. However, other aspects of metabolic health seem to be negatively affected by alcohol consumption."- Dr. Rhonda Patrick Click To Tweet

Acutely, alcohol has a hypoglycemic effect — it lowers blood glucose. This occurs due to a few mechanisms:

• When alcohol is consumed, pancreatic blood flow is redistributed from the exocrine portion to the endocrine portion, which is the part that produces insulin. Insulin secretion elicits a drop in blood glucose.
• Alcohol improves insulin sensitivity via anti-inflammatory mechanisms or by increasing levels of adiponectin.^[60]
• Some intervention studies report lower fasting insulin and improved HbA1c with moderate alcohol consumption.^[61]

The overall evidence suggests that consuming about one to two drinks per day may offer the most significant protective effect against developing type 2 diabetes. This protective effect may extend up to about four drinks per day for both men and women. Mechanistic studies — that is, studies looking at how alcohol affects the body on a biochemical level — also support the notion that alcohol can beneficially influence blood glucose regulation. However, other aspects of metabolic health seem to be negatively affected by alcohol consumption.

Alcohol and visceral fat

Visceral fat is fat that wraps around organs and has pro-inflammatory properties. It's commonly indicated by an elevated waist circumference and is an independent marker of cardiometabolic risk. Alcohol (ethanol) may be particularly dangerous for visceral fat, in part because the "empty calories" in alcohol promote excess energy intake and promote fat gain. Indeed, chronic heavy alcohol consumption is associated with an elevated waist circumference and a redistribution of fat to central regions (i.e., visceral fat accumulation). Another mechanism may involve ethanol's ability to suppress fat oxidation.^[62]

Hazardous drinking at any point in life leads to a larger waistline. Research found that:[ ref doi ='10.1111/add.15013']

• Adults who reported consuming hazardous levels of alcohol (three or more drinks on four or more occasions during the week) had a 2.4 centimeter larger waistline than adults who report never hazardous drinking.
• Former hazardous drinkers who stopped before age 50 had a 1.2 centimeter larger waistline.
• Former hazardous drinkers who stopped after age 50 had a 1.8 centimeter larger waistline.
• Being a hazardous drinker at every decade of life carried the risk of a nearly 4 centimeter larger waistline.

Does the type of alcohol matter? Maybe. Consuming mostly beer or spirits is associated with greater visceral fat mass, while consuming mostly red wine is associated with less visceral fat mass.

Alcohol and fertility

"Chronically, alcohol consumption reduces GnRH, LH, testosterone, and progesterone and increases estrogen/estradiol and FSH. These changes are associated with reproductive disorders like menstrual cycle irregularity, reduced fertility, and hypogonadism."- Dr. Rhonda Patrick Click To Tweet

Alcohol impacts the hypothalamic-pituitary-gonadal, or HPG, axis, which plays a major role in hormone production and fertility. For example:

• Alcohol can disrupt luteinizing hormone (LH) production and alter its potency to stimulate the production of testosterone and estrogen.
• Alcohol affects the sensitivity of gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and therefore, reduces LH production and secretion.

Alcohol's effects on the HPG axis influence reproductive hormone levels. Acute alcohol consumption increases levels of GnRH, LH, follicle-stimulating hormone (FSH), and estrogen/estradiol, and decreases testosterone and progesterone.

Regarding testosterone, low to moderate intake may elevate testosterone levels while heavier consumption decreases it in men. Chronically, alcohol consumption reduces GnRH, LH, testosterone, and progesterone and increases estrogen/estradiol and FSH. These changes are associated with reproductive disorders like menstrual cycle irregularity, reduced fertility, and hypogonadism.^[63]

Female reproduction and fertility

• Sexual function: Women who drink alcohol are 74% more likely to experience pain during intercourse, a lack of sexual desire, and disturbances in sexual arousal and orgasm than women who don't drink. They're also 45% more likely to experience premenstrual syndrome.^[64]
• Premenstrual syndrome: Heavy drinking (one or more standard drinks per day increases the risk of premenstrual syndrome by 79%).
• Pregnancy: Light drinking is associated with an 11% lower chance of achieving a pregnancy, while moderate drinking is associated with a 23% lower risk. For each additional drink per day, the chance of experiencing a pregnancy drops by 2%.^[64]
• Embryo quality: There is a dose-response relationship between alcohol intake and embryo quality. Women who report consuming any alcohol have fewer high-quality embryos and more low-quality embryos than women who don't drink. The risk of having any embryo abnormalities increases in a linear fashion from no drinking to light drinking to moderate drinking to heavy drinking.
• IVF/ICSI outcomes: Above a weekly alcohol intake of 84 grams (about six standard drinks), there is a negative impact on the chances of achieving a pregnancy during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Paternal alcohol consumption is also associated with a 9% lower risk of achieving a pregnancy with alcohol intake of six or more drinks per week.^[65]
• Reproductive hormones: Acute alcohol intake increases plasma estradiol levels by 55%–56% above baseline. Consuming one to two drinks per day for a week increases testosterone levels and increases plasma DHEAS (in the follicular phase), estrone/estradiol (in the peri-ovulatory phase), and estrone, estradiol, and estriol (in the luteal phase).^[66]

Alcohol's effect on male reproduction and fertility

• Light to moderate alcohol consumption (up to 14 drinks per week) has been associated with a lower risk for erectile dysfunction (ED).
• Consuming more than seven drinks per week reduces semen quality and volume, sperm antioxidant capacity, and levels of testosterone, FSH, and LH. Alcohol doesn't appear to impact sperm density, motility, morphology, or DNA fragmentation.^[67]
• Consuming lower levels of alcohol (one to seven drinks per week) is associated with better fertility in some studies, but heavy alcohol definitely leads to drastic reduction in sperm count and quality.^[68]
• Chronic heavy alcohol consumption is associated with lower testosterone levels, while low to moderate alcohol consumption does not appear to reduce testosterone and may even increase testosterone levels somewhat.^[63]

Epigenetic effects of alcohol and tips for future parents

"Expecting parents or those trying to conceive should think about cutting out their alcohol consumption at least three months before they start trying. Furthermore, there is no safe level of alcohol consumption during pregnancy."- Dr. Rhonda Patrick Click To Tweet

Parental alcohol intake can have a profound impact on the health and development of a newborn. Expecting parents or those trying to conceive should think about cutting out their alcohol consumption at least three months before they start trying. Furthermore, there is no safe level of alcohol consumption during pregnancy. Fetal alcohol spectrum disorders and related abnormalities are completely preventable if you avoid exposing yourself and your baby to alcohol.

Drugs, cigarette smoke, dietary micronutrients, and alcohol in utero can have effects on the developing embryo that manifest during childhood and can even last until adulthood. But even before conception when a mother's eggs are maturing, environmental and dietary exposures can impact characteristics of eggs and the health of the child after birth. Here's some evidence on alcohol's epigenetic effects:^[69]

• In animal studies, mothers who consumed the equivalent of five drinks around the time of conception gave birth to offspring with impaired glucose tolerance, a risk factor for type 2 diabetes.^[70]
• Binge drinking levels of alcohol consumed prior to conception causes smaller offspring body weights and reduced pubertal and behavioral development, regardless of which parent was exposed to alcohol.^[71]
• Paternal alcohol intake has been linked to deficits in skull, and facial growth and development, reduced organ growth in the heart, lungs, liver, and kidney, and impaired development in brain regions responsible for complex cognitive functions and behavior, several of which are characteristic of fetal alcohol spectrum disorders.^{[72] [73]}
• Offspring from alcohol-treated fathers have lower birth weights, lower individual organ weights, smaller brains, and impaired cognitive and motor abilities compared to non-alcohol-treated fathers.^[74]

Do the health effects of alcohol vary according to the type of alcohol consumed?

"Ultimately, you should not view wine consumption as a way to achieve positive health benefits, but rather, an alternative alcoholic option that carries a lower risk than beer or other spirits."- Dr. Rhonda Patrick Click To Tweet

Is red wine a definitely better option than beer or hard liquor? Some people believe this to be true, but let's take a look at what the research indicates.

• The World Alzheimer Report from 2022 concluded that when it comes to Alzheimer's disease, a protective effect may only exist for red wine consumption up to four glasses per day, but not other types of alcohol.
• Beer and spirit drinkers have a greater cardiovascular disease risk compared to wine drinkers.^[40]
• Wine consumption, all-cause, and cardiovascular disease mortality have a U-shaped relationship — two standard glasses per day is associated with the lowest risk — while non-wine intake is associated with a higher all-cause mortality risk at any dose above zero.^[75]
• Wine intake is not associated with cancer mortality at any dose, but non-wine intake at any dose is.^[75]
• Drinking red wine is associated with more favorable cardiometabolic health outcomes: less visceral fat, lower levels of inflammation, and higher levels of high-density lipoproteins. Drinking white wine is associated with greater bone density.^[76]

Ultimately, you shouldn't view wine consumption as a way to achieve positive health benefits, but rather, an alternative alcoholic option that carries a lower risk than beer or other spirits.

Alcohol and exercise

Alcohol is sometimes used to socialize after exercise or celebrate a big individual or team achievement. Research has investigated the effects of alcohol on the following three areas related to exercise:^[77]

• Physical performance.
• Recovery from exercise.
• Training adaptations.

Alcohol and performance

• Alcohol acutely reduces endurance exercise performance.
• Alcohol may not have a major impact on strength performance, even at higher doses.

Alcohol and recovery

• Alcohol negatively impacts hydration status at a dose of 1 gram per kilogram of body weight (e.g., five or more standard drinks).
• At a dose of less than 0.5 grams per kilogram of body weight, alcohol doesn't impair hydration/rehydration.
• As long as it's consumed along with a post-exercise meal, alcohol does not affect muscle glycogen resynthesis.
• Post-exercise alcohol reduces muscle protein synthesis for as long as 24 hours.
• Consuming alcohol after exercise worsens the damaging effects of muscle-damaging exercise and impairs the recovery of muscle damage.
• Combining alcohol with protein after combined aerobic and resistance exercise reduces muscle protein synthesis compared to protein alone by 24%.^[78]

Furthermore, chronic heavy alcohol consumption is associated with muscle abnormalities, including inflammation, mitochondrial dysfunction, oxidative stress, reduced muscle mass, enhanced protein degradation, and increased autophagy.^[79]

The BEER-HIIT Study: How moderate alcohol affects fitness improvements

For 10 weeks, participants performed high-intensity interval training twice per week while consuming beer, sparkling water with vodka, water, or non-alcoholic beer. Men in the alcohol group consumed one standard drink with lunch and dinner on Monday through Friday, and the women consumed one standard drink at dinner. All of the groups increased their VO2 max at the end of the study and there were no differences between the groups, indicating that low to moderate alcohol consumption may not get in the way of cardiorespiratory fitness improvements during HIIT.^[80]

Exercise for alcohol use disorders

"... regular exercise is beneficial for the brain among regular consumers of alcohol and may help people feel a greater sense of control over alcohol consumption."- Dr. Rhonda Patrick Click To Tweet

Many of the ways in which exercise benefits brain health overlap with some of the ways alcohol harms it. In fact, regular exercise may counteract some of the damage related to heavy alcohol consumption.

A study published in 2013 titled "Aerobic Exercise Moderates the Effect of Heavy Alcohol Consumption on White Matter Damage" illustrates this idea:^[81]

• Alcohol consumption was associated with white matter damage in several brain regions among adults who did not exercise regularly.
• Alcohol consumption was not associated with white matter damage among regular exercisers.
• Among the adults who did not exercise regularly, alcohol consumption was more strongly associated with a loss of control over drinking compared to adults who exercised regularly.

This study provides some evidence that regular exercise is beneficial for the brain among regular consumers of alcohol and may help people feel a greater sense of control over alcohol consumption.

There is some evidence that exercise is effective for reducing alcohol intake in people with alcohol use disorders. Why might this be the case?^[82]

• Exercise activates brain reward circuitry and may reduce cravings for alcohol.
• Exercise enhances self efficacy, reduces stress, promotes social interaction, improves mood, and mitigates symptoms of depression and anxiety — all of which are reasons why people drink alcohol.
• Exercise triggers the release of beta-endorphins and modulates the endogenous opioid system.
• Exercise elevates dopamine levels and may substitute for the dopamine achieved through alcohol consumption.

FGF21: A potent exercise-induced signaling molecule

"While exercise increases FGF21, one of the most potent triggers for FGF21 release is alcohol intoxication. FGF21 acts as a negative feedback mechanism to decrease subsequent alcohol intake through a liver-brain signaling axis. FGF21 also protects against alcohol intoxication."- Dr. Rhonda Patrick Click To Tweet

During exercise, fibroblast growth factor 21 (FGF21) is released by our liver and muscles, and it can cross the blood-brain barrier and bind to receptors in the hypothalamus. FGF21 plays a role in many of the beneficial responses to exercise like improved glucose uptake and insulin sensitivity, lower blood cholesterol levels, and reductions in body weight. It also alters dopamine signaling. While exercise increases FGF21, one of the most potent triggers for FGF21 release is alcohol intoxication. FGF21 acts as a negative feedback mechanism to decrease subsequent alcohol intake through a liver-brain signaling axis. FGF21 also protects against alcohol intoxication.^[83]

Is there any evidence that FGF21 could help people with alcohol use disorder?

• Humans with a genetic polymorphism that reduces FGF21 signaling consume more alcohol.^[84]
• Mice who can't release FGF21 drink more alcohol.
• Giving alcohol-addicted animals (mice and monkeys) an FGF21 analog reduces their alcohol consumption by 50%.

Where does exercise come into the picture? Well, exercise is one of the most potent ways to elevate FGF21: Cycling at 70% of VO2 peak increases FGF21 levels almost fourfold above baseline for up to an hour after exercise.^[85]

Exercise summary and recommendations

• Alcohol (1 gram per kilogram of body weight) impairs recovery from exercise — avoid high-volume alcohol consumption after exercise if your goal is to optimize recovery and adaptation.
• If you are going to consume alcohol after exercise, be sure to consume it with protein (25–30 grams or more) and carbohydrates to minimize its effects on glycogen replenishment and muscle protein synthesis.
• Abstain from alcohol if you're recovering from an illness or injury.
• Exercise reduces alcohol cravings through several mechanisms.
• Exercise may reverse or prevent some of the brain damage associated with heavier alcohol consumption.

So far, we've explored the wide-ranging effects of alcohol on the brain and body. In this final section, we'll delve into some strategies that may help lessen the negative effects of alcohol. None of these should be thought of as ways to justify consuming alcohol, but rather, "damage control" strategies.

Damage control

Alcohol is a part of many social occasions. Acknowledging that people may consume alcohol from time to time, it makes sense to think about the lowest risk ways to have alcohol and strategies to reduce some of the adverse effects of consuming it. But let's be clear: The safest amount of alcohol is still zero.

What is the safest level of alcohol consumption for disease mitigation?

"The ideal amount of alcohol is zero, but from a disease reduction standpoint, the literature suggests that one to two drinks per week is associated with the lowest risk among alcohol consumers (e.g., current drinkers)."- Dr. Rhonda Patrick Click To Tweet

The ideal amount of alcohol is zero, but from a disease reduction standpoint, the literature suggests that one to two drinks per week is associated with the lowest risk among alcohol consumers (e.g., current drinkers).

• One to two drinks per day is associated with the lowest risk for cardiovascular disease and diabetes.
• One to two drinks per week is associated with the lowest risk for most cancers.
• Binge drinking (four to five drinks in a single occasion) is associated with adverse health effects even when weekly alcohol intake falls below the low-risk or cardioprotective range.^[86]

In short: The cardioprotective or glucose-lowering effects of alcohol that occur with one to two drinks per day don't outweigh the cancer or dementia risk associated with this level of intake.

For sleep

• Consume your final drink four hours or more before bedtime.
• Eat a meal, consume fruit, and stay hydrated with water and electrolytes.
• Supplement with magnesium glycinate to promote sleep and counteract magnesium losses from alcohol consumption.

For reducing hangover severity

• Eat a meal before or while consuming alcohol.
• Supplement with electrolytes and stay hydrated.

Supplements for reducing hangover severity

• Liposomal glutathione, NAC, and sulforaphane: These increase glutathione levels and help with liver detoxification processes.
• Zinc, magnesium, and B vitamins: These micronutrients aid in the metabolism of alcohol and their excretion is elevated due to alcohol consumption.
• Electrolytes (sodium, potassium, and magnesium): These help maintain hydration, and their excretion is elevated due to alcohol consumption.

Tracking alcohol's effects

To understand how alcohol affects your body and your sleep, you can use a health or fitness wearable such as a smart ring or a smart watch. Data like sleep metrics, resting heart rate, respiratory rate, and heart rate variability can lend important insights into how your body responds on a day when you consume alcohol compared to a day when you didn't.

The importance of exercise

The number one thing you can do if you want to consume alcohol occasionally without experiencing adverse health outcomes is exercise. Being physically active lessens the all-cause mortality risk associated with drinking and almost completely nullifies the association between cancer mortality and drinking. That's powerful stuff.^[87]