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Alcohol

Alcohol featured article

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?

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Episodes

Posted on September 27th 2024 (9 months)

In this clip, Dr. Rhonda Patrick discusses alcohol's effects on fertility, pregnancy, and reproductive health for both men and women.

Posted on September 27th 2024 (9 months)

In this clip, Dr. Rhonda Patrick discusses alcohol's impact on mortality, life expectancy, Blue Zones, and recommended drinking limits for longevity.

Posted on September 27th 2024 (9 months)

In this clip, Dr. Rhonda Patrick discusses alcohol's impact on recovery, exercise benefits, and how exercise may reduce alcohol cravings.

Topic Pages

  • Alcohol

    Alcohols comprise organic compounds featuring a hydroxyl group bonded to sp3 carbon, enabling hydrogen bonding and nucleophilic reactivity.

  • Breast milk and breastfeeding

    Maternal ethanol diffuses passively into breast milk, mirroring blood levels, potentially impairing oxytocin-mediated let-down during breastfeeding.

News & Publications

  • Sunburns are a major contributor to skin cancer risk, yet many people continue to get sunburned, with some experiencing multiple episodes each year. A recent study found that more than 30% of adults reported between one and five sunburns in the past year, and alcohol consumption was linked to an increased risk, with 21% of people who got sunburned having consumed alcohol at the time.

    Researchers analyzed data from the 2022 Health Information National Trends Survey, which included more than 6,200 participants. They used statistical analysis to identify associations between sociodemographic factors, cancer risk perceptions, sun exposure behaviors, and the number of sunburns reported in the previous 12 months.

    They found that 2.1% of participants reported more than six sunburns, 30.3% had between one and five, and 67.6% experienced none. Alcohol consumption was a contributing factor, with 21.5% of those who reported a sunburn also having consumed alcohol. Younger adults (aged 18 to 39) were more likely to experience sunburns than older adults, and men were at higher risk than women. Additionally, higher-income participants were more likely to get sunburned, with people in the highest income bracket more than four times as likely to report at least one sunburn in the past year.

    These findings suggest that public health interventions should focus on groups most at risk for sunburns, including younger adults, men, and higher-income people. Addressing alcohol consumption during sun exposure could also help reduce sunburn incidence. Sunscreens can protect against sunburns, but some carry health risks. Learn more in this Q&A featuring Dr. Rhonda Patrick.

  • Genes play critical roles in determining how long a person lives, but a new study suggests that the secret to longevity may be as simple as “food as medicine.” Centenarians—people who live 100 years or more—typically eat healthy, balanced diets and require fewer medications than their shorter-lived peers.

    Researchers analyzed studies examining the lifestyles, medication use, and overall health of centenarians and near-centenarians aged 95 to 118. Their analysis included 34 studies and involved more than 59,000 participants.

    They identified several healthy lifestyle habits of long-lived adults: Engaging in regular physical activity Avoiding alcohol and tobacco Adhering to a diverse, macronutrient-balanced diet Preferring less salty foods Using few medications—with just over four taken daily, primarily blood pressure medicines or other cardiovascular drugs

    Multiple drug use—known as polypharmacy—is common in older adults. Defined as taking more than five medications daily, polypharmacy is linked with many adverse health effects, especially among older adults, who are at risk of a “prescription cascade”—where the side effects of drugs can be misdiagnosed as symptoms of another disease, creating a vicious cycle of more drug use.

    This analysis suggests that using food as medicine—through healthy, balanced diets—combined with lower drug use contributes to healthy aging and longevity. Learn how other healthy lifestyle behaviors like exercise and dietary supplementation also promote longevity in this episode featuring Dr. Rhonda Patrick.

  • The choices people make in their daily lives—such as whether to smoke, what to eat, and how active they are—can have a profound effect on their cancer risk. These behaviors are not just habits; they are powerful determinants of health. A recent study found that nearly half of cancer deaths among adults in the U.S. are linked to modifiable lifestyle factors.

    The researchers used national data to estimate cancer cases and deaths for 30 types of cancer. They examined the effects of modifiable risk factors such as smoking, obesity, alcohol consumption, diet, physical inactivity, and ultraviolet light exposure on cancer risk.

    They found that 40% of cancer cases and 44% of cancer deaths were linked to modifiable risk factors. Smoking was the leading contributor, accounting for nearly 20% of cases and more than 28% of deaths. Other major risk factors included excess body weight and alcohol use, accounting for more than half of the cases and deaths for 19 out of 30 cancer types.

    These findings suggest that people can reduce their risk of developing cancer by making informed lifestyle choices. Exercise is a powerful lifestyle tool in cancer prevention and survival. During exercise, increased blood flow subjects circulating cancer cells to powerful forces, causing them to self-destruct. Learn more in this clip featuring Dr. Rhonda Patrick.

  • Smoking has numerous harmful effects on health, including increased risks of lung cancer, heart disease, and stroke. Evidence indicates smoking also contributes to cognitive decline, affecting memory and fluency. A recent study found that smoking accelerates cognitive decline by as much as 17% over time.

    Researchers examined data from more than 32,000 cognitively healthy adults aged 50 to 104 from 14 European countries. They grouped participants according to whether they smoked, engaged in regular exercise, were socially active, and drank moderately—defined as less than or equal to two alcoholic drinks per day for men or one drink per day for women. Then, they analyzed the effects of lifestyle on memory and fluency decline over 10 years.

    They found that non-smokers maintained relatively stable memory and fluency scores over the 10 years. However, smokers experienced up to 17 percent greater decline in memory and up to 16 percent greater decline in fluency, even after considering other factors that influence cognitive aging, including age at baseline, gender, country, education, wealth, and chronic conditions. Interestingly, healthy lifestyle behaviors offset some of the risks associated with smoking, with smokers who exercised, socialized, and drank moderately exhibiting cognitive declines comparable to non-smokers.

    These findings suggest that smoking markedly increases cognitive decline, increasing the risk for Alzheimer’s disease and other forms of dementia. Quitting smoking can be challenging, but mindfulness techniques can help. Learn more about mindfulness in this clip featuring Dr. Ashley Mason.

  • Iron is an essential mineral, best known for its critical role in cellular oxygen transport. However, having too much iron in the brain drives cognitive deficits. A 2022 study found that alcohol consumption promotes iron deposition in the brain, compromising cognitive function, even among moderate drinkers.

    The investigation involved nearly 21,000 adults enrolled in the UK Biobank study. Participants provided information about their alcohol intake and completed a battery of cognitive tests. Researchers performed magnetic resonance imaging scans to assess iron levels in the participants' brains and livers.

    They found that, on average, participants consumed about 18 units of alcohol per week, roughly equivalent to ten 12-ounce beers or ten 5-ounce glasses of wine. Participants who consumed as few as 7 units of alcohol per week had higher levels of iron in the brain’s putamen and caudate (in the basal ganglia) and in the substantia nigra (in the midbrain), areas involved in learning, memory, reward processing, and movement. Higher iron levels in the basal ganglia were associated with slower executive function, lower fluid intelligence, and slower reaction times. Those who consumed more than 11 units of alcohol per week had higher iron levels in their livers.

    These findings suggest that moderate alcohol consumption has marked effects on the brain and cognition, likely due to excess iron deposition. Alcohol consumption is associated with a wide range of health problems, including heart disease, stroke, liver dysfunction, and cancer. However, vigorous exercise can help reduce alcohol cravings. Learn more in this video featuring Dr. Rhonda Patrick.

  • Irritable bowel syndrome (IBS) is a digestive disorder characterized by abdominal cramping, gas, diarrhea, and constipation. The condition affects as many as 10 percent of people worldwide and has no cure. A recent study shows that adopting three or more healthy lifestyle behaviors may reduce the risk of IBS by as much as 42 percent.

    The study involved more than 64,000 people enrolled in the UK Biobank database. Researchers collected information about the participants' dietary intake and whether they engaged in any of five healthy lifestyle behaviors: never smoking, getting optimal sleep, engaging in vigorous physical activity, eating a quality diet, and moderating their alcohol intake.

    They found that 11.8 percent of the participants did not practice any of the five critical healthy behaviors; 32.1 percent practiced one, 34.1 percent practiced two, and 21.9 percent practiced three to five healthy behaviors. As participants engaged in more healthy behaviors, their likelihood of developing IBS decreased, with those practicing one healthy behavior having a 21 percent lower risk, those with two healthy behaviors having a 36 percent lower risk, and those engaging in three to five healthy behaviors having a 42 percent lower risk. These findings were consistent across various groups, regardless of age, sex, job status, where they lived, history of gastrointestinal infection, endometriosis, family history of IBS, or other lifestyle habits.

    These findings suggest that adopting multiple healthy lifestyle behaviors, such as not smoking, staying physically active, and getting good sleep, can significantly reduce the risk of developing IBS. Learn more about factors that influence gut health in this episode featuring Dr. Eran Elinav.

  • Alcohol use disorder accounts for approximately 2.8 million deaths worldwide. It’s a chronic condition marked by a strong desire to drink and persistent alcohol use despite its harmful effects. A recent study found that a ketogenic diet reduces alcohol cravings in people with alcohol use disorder.

    The study involved 33 adults with an alcohol use disorder enrolled in a three-week inpatient alcohol detoxification program. Slightly more than half of the patients received a ketogenic diet, while the remainder received a standard American diet. Once a week, using functional magnetic resonance imaging, researchers assessed the participants' brain function and craving responses during exposure to alcohol-related triggers. In addition, the participants reported their perceived alcohol cravings when exposed to the triggers.

    The imaging revealed that participants who ate a ketogenic diet showed reduced neural activity related to alcohol cravings than those who ate the standard American diet across the entire three weeks of treatment. Those who ate a ketogenic diet also reported fewer perceived cravings.

    Following alcohol consumption, the brain uses acetate, a metabolic byproduct of alcohol, for energy instead of glucose. As a result, glucose levels in the brain drop, and acetate levels increase – even after the effects of alcohol wear off. These alterations in fuel can contribute to withdrawal symptoms, cravings for alcohol, and a higher risk of relapse, especially when acetate levels drop. Ketones are structurally similar to acetate and can serve as an alternative energy source for the brain, providing energy in place of glucose.

    This was a small study, but its findings suggest that a ketogenic diet reduces alcohol cravings among people with alcohol use disorders. Other evidence suggests vigorous exercise reduces alcohol cravings, likely due to exercise’s effects on FGF21 – a hormone produced during vigorous activity. Learn more in this short video featuring Dr. Rhonda Patrick.

  • Alcohol has profound, adverse effects on the human body, compromising liver function and cognitive performance and increasing the risk for various cancers. A recent study demonstrates that alcohol impairs mitochondrial function and cellular metabolism and increases inflammation in heart cells.

    Researchers grew human-induced pluripotent stem cells into three-dimensional heart cell structures called cardiac spheroids and exposed them to clinically relevant amounts of ethanol (the type of alcohol found in alcoholic beverages) for five weeks. They then examined various aspects of the heart cells, including mitochondrial function, gene expression patterns, and metabolite production.

    They found that prolonged ethanol exposure reduced the heart cells' mitochondrial function, increased reliance on glycolysis (a less efficient energy production process), hindered fatty acid breakdown, and impaired cardiac structure development. The cells exhibited changes in gene expression related to metabolic processes, heart development, and responses to hypoxia. They also produced more inflammation-associated metabolites.

    Chronic alcohol consumption increases the risk for various heart-related issues, including arrhythmias (irregular heartbeats), cardiomyopathy (heart muscle disease), and heart failure. In addition, chronic heavy alcohol use has adverse effects on bone health, increasing the risk of fractures during weight-bearing activities.

    These findings highlight the harmful effects of chronic alcohol consumption on heart cells at the molecular level. Avoiding alcohol can be challenging, but vigorous aerobic exercise can help reduce alcohol cravings. Learn more in this video featuring Dr. Rhonda Patrick.

  • The effects of alcohol vary between people, largely due to differences in alcohol absorption rates and metabolism in the gut. A new study has found that older women and those with obesity clear alcohol from their systems 52 percent faster than younger women and those with healthy weights.

    Researchers analyzed the findings of three studies that investigated alcohol clearance rates in 143 women. They used a computer-assisted alcohol infusion system to model the self-administration of alcohol. They also measured the women’s body fat via DEXA or bioelectrical impedance.

    They found that women with obesity, particularly those who were older, cleared alcohol 52 percent faster than women with a healthy weight. They also found that age and lean body mass explained 72 percent of the differences in the alcohol elimination rate among women.

    These findings suggest that women with obesity eliminate alcohol faster than leaner women, likely due to the increase in fat-free mass that often accompanies obesity, especially in older women. Drinking alcohol increases a person’s risk for many chronic diseases, but exercise can help reduce alcohol cravings. Learn more in this short video featuring Dr. Rhonda Patrick.

  • Paternal drinking negatively affects pregnancy outcomes, a new study in mice shows. The more alcohol a male mouse drank before conception, the less likely the pregnancy was successful.

    Researchers modeled chronic alcohol consumption in adult mice for six weeks. One group drank no alcohol, one group drank to the legal limit (0.8 percent blood alcohol level), and the other drank to 50 percent above the legal limit. Then, using sperm samples they collected from the mice, they attempted to fertilize eggs taken from female mice.

    They found that any amount of preconception alcohol consumption reduced the fertilization success rate in the mice. However, the highest alcohol consumption – 50 percent above the legal limit – reduced the fertilization success rate by roughly half. They also found that alcohol altered the activity of genes involved in placental development.

    These findings suggest that male alcohol consumption plays a critical role in conception. Evidence suggests that exercise can reduce cravings for alcohol by inducing the production of a hormone called FGF21. Learn more in this video featuring Dr. Rhonda Patrick.

  • From the article:

    When estrogen levels are higher, alcohol is much more rewarding,” said Lasek, who is the corresponding author on the paper and a researcher in the UIC Center for Alcohol Research in Epigenetics. “Women may be more vulnerable to the effects of alcohol or more likely to overindulge during certain stages of their cycle when estrogen levels are higher, or may be more likely to seek out alcohol during those stages.”

    Studies indicate that gender differences in psychiatric disorders, including addiction, are influenced by estrogen, one of the primary female sex hormones. Women are more likely to exhibit greater escalation of abuse of alcohol and other drugs, and are more prone to relapse in response to stress and anxiety.

    […]

    “In mice in diestrus, estrogen levels increase to about 10 times higher than they are in estrus, the phase in which ovulation occurs and estrogen levels drop,” Lasek said.

    VTAs [ventral tegmental area - “reward center”] were taken from mice in both estrus and diestrus and kept alive in special chambers. Electrodes recorded the activity of individual dopamine-sensitive neurons in the VTA. Next, the researchers added alcohol to the chamber. Activity increased twice as much in neurons from mice in diestrus compared to the response of neurons from mice in estrus.

    Lasek and her colleagues then blocked estrogen receptors on dopamine-sensitive neurons in VTA in mice in estrus and diestrus. With the blocker present, the response to alcohol in neurons from mice in diestrus was significantly lower compared with neurons where estrogen receptors remained functional. The estrogen receptor blocker reduced the alcohol response to levels seen in mice in estrus. The responses to alcohol in neurons from mice in estrus were unaffected by the estrogen receptor blocker.

    View full publication

  • More than 20 percent of deaths in the United States are attributable to alcohol.

    Nearly 13 percent of all deaths among young and middle-aged adults in the United States were caused by drinking too much alcohol, a new study finds. Among adults between the ages of 20 and 49 years, excessive alcohol consumption caused more than 20 percent of all deaths.

    Researchers reviewed alcohol consumption data from more than 2 million people living in the United States between 2015 and 2019. Then they looked at the rates and causes of death during the same period.

    They found that 12.9 percent of all deaths among adults aged 20 to 64 years were attributable to excessive alcohol consumption. Men were roughly 50 percent more likely to die from alcohol-related deaths than women. When they limited the age range to 20 to 49 years, they found that 20.3 percent of deaths were attributable to excessive alcohol consumption.

    Alcohol affects multiple organ systems. Drinking too much alcohol is linked with many leading causes of death, including heart disease, cancer, unintentional injury, and liver disease.

    This study shows that alcohol contributed to nearly one in eight deaths among adults living in the United States. However, the researchers noted that the data for this study pre-date the COVID pandemic, during which many people reported drinking more alcohol, so the current number of alcohol-related deaths might now be higher. Learn how exercise can help reduce cravings for alcohol.

  • Heavy drinking in later life increases stroke risk and contributes to a larger waist circumference.

    Heavy drinking into one’s later life could add more than two inches to their waistline, a new study finds. Drinking heavily also contributes to a greater risk of cardiovascular disease and liver dysfunction.

    Researchers asked more than 4,800 people (average age, 69 years) living in the United Kingdom about their alcohol consumption habits. They also took their body measurements and collected information about their overall health.

    They found that people who drank heavily in later life were more likely to have higher blood pressure, higher stroke risk, and worse liver function than non-heavy drinkers. Heavy lifetime drinkers were also more likely to have a larger waist circumference – as much as 5.47 centimeters (~2.15 inches) larger – even if they cut back on their alcohol consumption before the age of 50.

    Other research has shown that heavy drinking contributes to a large waist circumference, which is associated with a greater risk for cardiovascular disease and type 2 diabetes. Cutting back on alcohol consumption may help reduce waist circumference. Learn how exercise can help reduce cravings for alcohol.

  • From the article:

    The average age at which women in both groups had started the menopause was similar, and analysis of the results showed that later menopause and use of hormone replacement therapy (HRT) protected against the risk of a cerebral aneurysm, lessening the risk by 21% and 77%, respectively.

    Premature menopause - before the age of 40 - had occurred in one in four (26%) of the women who had had an aneurysm compared with around one in five (19%) of those in the comparison group.

    And each successive four year increase in the age at which a woman went through the menopause lessened the likelihood of a cerebral aneurysm by around 21%.

    Smoking did not seem to be linked to an increase in risk, while alcohol consumption was of borderline significance.

    View full publication

  • From the article:

    Calculating population attributable risk – the fraction of subarachnoid hemorrhages that can be attributed to a particular trigger factor – the researchers identified the eight factors and their contribution to the risk as:

    -Coffee consumption (10.6 percent)

    -Vigorous physical exercise (7.9 percent)

    -Nose blowing (5.4 percent)

    -Sexual intercourse (4.3 percent)

    -Straining to defecate (3.6 percent)

    -Cola consumption (3.5 percent)

    -Being startled (2.7 percent)

    -Being angry (1.3 percent)

    “All of the triggers induce a sudden and short increase in blood pressure, which seems a possible common cause for aneurysmal rupture,” said Monique H.M. Vlak, M.D., lead author of the study and a neurologist at the University Medical Center in Utrecht, the Netherlands.

    Risk was higher shortly after drinking alcohol, but decreased quickly, researchers said.

    […]

    Although physical activity had triggering potential, researchers don’t advise refraining from it because it’s also an important factor in lowering risk of other cardiovascular diseases.

    “Reducing caffeine consumption or treating constipated patients with unruptured IAs with laxatives may lower the risk of subarachnoid hemorrhage,” Vlak said. “Whether prescribing antihypertensive drugs to patients with unruptured IAs is beneficial in terms of preventing aneurysmal rupture still needs to be further investigated.”

    View publication

  • From the article:

    The upper safe limit of drinking was about 5 drinks per week (100g of pure alcohol, 12.5 units or just over five pints of 4% ABV2 beer or five 175ml glasses of 13% ABV wine).

    However, drinking above this limit was linked with lower life expectancy. For example, having 10 or more drinks per week was linked with 1-2 years shorter life expectancy1. Having 18 drinks or more per week was linked with 4-5 years shorter life expectancy.

    […]

    The researchers also looked at the association between alcohol consumption and different types of cardiovascular disease. Alcohol consumption was associated with a higher risk of stroke, heart failure, fatal aortic aneurysms, fatal hypertensive disease and heart failure and there were no clear thresholds where drinking less did not have a benefit.

    View publication

  • Parental abstention from alcohol reduces an infant’s risk of being born with congenital heart disease.

    Congenital heart disease is an umbrella term for a range of heart conditions that are present at birth. Approximately 1 percent of all children worldwide are born with the conditions. Findings from a 2019 meta-analysis suggest that parental abstention from alcohol reduces an infant’s risk of being born with congenital heart disease.

    Alcohol elicits an array of harmful effects on the human body and is widely considered a toxin. Consuming alcohol is associated with an increased risk of many disorders, including infectious diseases, cancer, neuropsychiatric diseases, cardiovascular disease, liver and pancreas disease, metabolic dysfunction, obesity, and unintentional and intentional injury. Health experts advise women who are pregnant to avoid alcohol to reduce the risk of fetal alcohol spectrum disorder as well as other developmental delays and disorders.

    The investigators searched the scientific literature to identify studies examining links between paternal alcohol consumption and congenital heart disease risk. They filtered their results based on a set of criteria designed to identify studies of high quality. Finally, they combined data from these high-quality studies and reanalyzed it so they could interpret the results on a large scale.

    They identified 55 studies involving nearly 42,000 infants with congenital heart disease and nearly 300,000 without. Infants whose mothers consumed alcohol three months before pregnancy or during the first trimester were 16 percent more likely to develop congenital heart disease. However, if a father consumed alcohol during those timeframes, his infant was 44 percent more likely to develop the condition. Infants whose fathers binge drank were 52 percent more likely to develop congenital heart disease. When the investigators looked at specific diseases, they found that infants whose mothers drank alcohol before or during pregnancy were 20 percent more likely to develop tetralogy of Fallot, a rare condition caused by a combination of four heart defects that are present at birth. Infants with tetralogy of Fallot are often referred to as “blue babies” due to the cyanosis that manifests with the condition.

    These findings suggest that parental consumption of alcohol in the months before or during early pregnancy increases an infant’s risk for developing congenital heart disease. This risk is markedly higher for fathers, whose roles in their offspring’s health are becoming more evident. For example, research suggests that infants of fathers who exercise have better metabolic health later in life.

  • The circadian rhythm aspect of drug rewards: “Our body’s circadian rhythms affect the ‘reward’ signals we receive in the brain from drug-related behavior, and the peak time for this reward typically occurs during the evening, or dark phase. We wanted to test what the role of the brain’s immune system might have on that reward, and whether or not we could switch it off.”

    Using naltrexone to block TLR4 reduces alcohol behavior:

    The researchers focused their attention on the immune receptor Toll-like receptor 4 (TLR4). They administered the drug (+)-Naltrexone (pronounced: PLUS-NAL-TREX-OWN), which is known to block TLR4, to mice.

    “Our studies showed a significant reduction in alcohol drinking behavior by mice that had been given (+)-Naltrexone, specifically at night time when the reward for drug-related behavior is usually at its greatest,” Mr Jacobsen says.

    Interestingly and somewhat paradoxically, chronically activating TLR4 through genetic engineering-associated tricks also seems to reduce alcohol seeking in mice.

  • Genetic activation of TLR4 in the brain reduced binge drinking. What makes this so interesting is that alcohol consumption itself promotes intestinal permeability, which increases systemic activation of TLR4, potentially resulting in negative cardiovascular outcomes, among other things.

    From the article:

    One of the study’s most novel findings concerns TLR4’s important role in binge drinking. Science has traditionally considered TLR4 to be an innate immunity receptor involved with neuroinflammation in the brain. Scientists associated TLR4 with microglia, cells that support inflammatory responses in the brain. “What makes this finding particularly important for the field of neuroscience is that we’re showing that TLR4 plays a significant role in neurons, specifically, the neurons that are connected to the GABA receptor,” says Dr. June.

    To establish the connection between the GABA receptors, TLR4 and alcohol, the scientists manipulated this pathway in the binge drinking rodents. Dr. Aurelian was a pioneer in developing a method to inhibit gene expression, helping scientists to pinpoint the role of individual genes in the body. […] The scientists found that when they artificially stimulated the GABA receptors and TLR4 in order to simulate the good feelings binge drinkers feel when drinking alcohol, the rats lost interest in alcohol for two weeks after the procedure.

  • Liver-derived hormone FGF21 dramatically reduces appetite for alcohol Researchers believe that humans first encountered alcohol long before we learnt how to control the process and make it ourselves – through the consumption of fermented fruit. One plausible result of this long history of alcohol exposure is that we have evolved a suite of biological mechanisms for detoxifying and regulating our appetite for alcohol, which may be useful for developing new treatments for alcohol use disorder. Now, a recent randomized controlled trial suggests that the liver-derived hormone fibroblast growth factor 21 (FGF21) is a candidate treatment capable of altering the reward system of the brain and profoundly reducing alcohol intake in primates.

    The researchers carried out their study in vervet monkeys – a species that parallels human populations in containing a mix of alcohol avoiders, moderate consumers, and heavy consumers who will drink to the point of intoxication. Twenty monkeys were selected based on having at least a slight interest in consuming alcohol. The researchers then quantified each individual’s preferred alcohol intake level by monitoring their behaviours when the animals received four hours of daily access to a bottle of 10% ethanol solution alongside plain tap water.

    After a baseline observation period of nine days, monkeys were randomly selected to receive a daily injection of either a sterile saline solution (placebo) or a pharmacological analog of the liver hormone FGF21 for a total of 16 days.

    The FGF21-mimicking drug was found to produce a 50 percent reduction in alcohol consumption, without influencing the monkeys’ intakes of food or water. Looking into the effects of FGF21 in the brain, the researchers uncovered that both FGF21 and its synthetic analog increased the transmission of signals to a specific group of brain cells in the nucleus accumbens – a hotspot of the brain’s reward system. These cells were distinguished by the presence of specifically D2-type dopamine receptors, which have been strongly implicated in reigning in impulsive and repetitive consumption of other substances like sugar. Human variants in the D2 receptor gene have also been linked to greater risk of alcohol dependence.

    The findings suggest that FGF21 serves as a regulatory message between the liver and the brain’s impulse control circuits, and that boosting this signal may aid in the treatment of substance addictions.

    -Link to full publication.

  • Since the 1980’s, clinicians and researchers have been puzzled by the “French paradox”: the observation that residents of France have a surprisingly low incidence of cardiovascular disease given their high rates of smoking, intakes of saturated fat, and hypercholesterolemia (i.e. abnormally high serum levels of harmful low-density lipoprotein (LDL) cholesterol). A recent study now offers evidence that the negative health impacts of these common risk factors might be effectively mitigated by the French habit of regular red wine consumption.

    The authors of this study examined mice that had been genetically modified to lack LDL receptors – proteins crucial for removing LDLs from the bloodstream and initiating their degradation. This genetic modification, known as a “knock-out”, meant that the mice experienced a virtually life-long state of hypercholesterolemia, which served as the biological backdrop for an experiment on the potential health effects of wine consumption.

    At the age of three months (early mouse adulthood), animals were randomly assigned to receive 60 days of unlimited access to either plain tap water or red wine diluted to yield a 6% ethanol solution. This concentration ensured that the animals consumed the human equivalent of a 5-ounce glass of wine on a daily basis.

    When the researchers tested the mice on a variety of cognitive tasks, they discovered that the water-only group displayed learning and memory impairments characteristic of their poor lipid profiles. Their performance was particularly poor on a short-term memory test, where the animals turned out to be unable to recognize objects they had seen only an hour prior. Long-term memory retention was also compromised. In a test that required the animals to remember the location of an escape platform hidden in a tub of opaque water, the mice swam in the right direction only 20 percent of the time.

    Interestingly, wine-consuming mice were not impaired to the same degree. And while their plasma lipid profiles were no better compared to their water-drinking peers, they had substantially lower levels of several biomarkers of neuroinflammation, such as GFAP and lectin. The findings indicate that red wine compounds might help protect against the negative health outcomes of hypercholesterolemia by interfering with the associated inflammatory processes.

    Link to full study.

  • Alcohol is a group 1 carcinogen, the highest classification of a substance known to cause cancer in humans – and the same classification as asbestos, formaldehyde, and tobacco smoke. Epidemiological data indicate that nearly three-quarters of a million new cancer cases worldwide are directly attributable to alcohol consumption00279-5/fulltext). Findings from a 2015 meta-analysis suggest that alcohol consumption increases the risk of several types of cancer.

    Scientists do not fully understand how alcohol drives cancer, but evidence points to a variety of mechanisms related to how the body metabolizes ethanol, the form of alcohol present in alcoholic beverages. Evidence indicates that the processes and products associated with ethanol metabolism exert genotoxic effects; promote oxidative stress; alter vitamin metabolism (especially folate and vitamin A-related compounds); increase estrogen levels; and drive inflammation.

    The investigators reviewed data from 572 studies involving more than 480,000 cancer cases. They calculated site-specific cancer risk for light, moderate, and heavy drinkers versus non-drinkers.

    They found that cancer risk increased for every category of drinking in a dose-dependent manner. As such, risk was greatest for heavy drinkers (more than four standard drinks per day). For example, compared to non-drinkers, the risk that heavy drinkers would develop cancer oral and pharyngeal cancer was 5.13 times higher; esophageal cancer, 4.95 times higher; laryngeal cancer, 2.65 times higher; breast cancer, 1.61 times higher; and colorectal cancer, 1.44 times higher. Heavy drinkers were also more likely to develop cancers of the stomach, liver, gallbladder, pancreas, and lung.

    These findings suggest that alcohol consumption markedly increases cancer risk in a dose-dependent manner. Alcohol consumption is just one of many lifestyle behaviors that influence cancer risk. Learn how modifying lifestyle behaviors can reduce the risk of breast cancer, for example, as well as other chronic diseases, in this clip featuring Dr. Ruth Patterson.

  • From the article:

    The new study found that giving the drug to newborn mice 15 minutes after “binge” alcohol consumption eliminated the hyperactivity and sleep deficits seen when rodents exposed to alcohol became adults. Moreover, the researchers report, lithium chloride-treated mice were much less likely to show the 25 percent drop in memory and cognitive test scores seen in untreated mice given the same amount of alcohol.

    “Our study showed that lithium chloride prevented many of the damaging neurological effects of alcohol abuse on the still-developing brain, especially the impact on the parts of the brain controlling sleep,” says co-senior study investigator Donald Wilson, PhD.

    Promoting BDNF as one pathway to brain cell survival:

    “Lithium chloride is known to block many pathways that lead to brain cell death, while promoting others that lead to survival, like brain-derived neurotrophic factor, or BDNF,” says Saito, a research assistant professor at NYU Langone. Further experiments are needed, she says, to determine if chemicals that stimulate BDNF production also blunt the effects of alcohol abuse in newborn mammals.

    Note: increased BDNF seems to actually be a natural mechanism by which the brain responds to reduce damage of BDNF

  • From the article:

    The researchers treated rats with alcohol, tobacco smoke or both twice a day for 28 days and then compared their brains with control animals that didn’t receive either substance. They found that the combined alcohol and smoking treatment increased the level of reactive oxygen species in the hippocampus compared with control animals or rats given tobacco smoke alone. In all of the brain areas studied, combined alcohol and smoking increased the levels of specific pro-inflammatory cytokines more than either treatment alone.

    Reduced levels of BDNF, another harbinger of bad news:

    And in the striatum and frontal cortex, rats with both treatments showed lower levels of brain-derived neurotrophic factor, a growth factor that helps existing neurons survive and stimulates the growth of new ones. These results suggest that alcoholics who smoke could be at additional risk for neural damage, the researchers say.

  • Alcohol dependence is a complex disorder that increases a person’s risk of death from all causes. Findings from a 2009 study suggest that variations in certain genes can impact the likelihood of relapsing following treatment.

    BDNF is involved in neuronal growth and survival, as well as influencing neurotransmitters – chemical signals from the nervous system. Low BDNF levels have been linked to the development of depression, anxiety, and alcohol dependence.

    Previous research has demonstrated that alcohol dependence has a genetic component. The current study investigated whether common variations in certain genes would have an effect on post-treatment relapse.

    The prospective study involved 154 participants who met the criteria for alcohol dependence and were admitted to a treatment facility. The patients provided blood samples for genetic analysis and completed self-assessment questionnaires about depression, hopelessness, impulsivity, and the severity of their alcohol use. The authors followed up with participants for approximately one year to assess whether they had relapsed. Relapse was defined as any drinking during the observation period, with heavy drinking considered as more than four drinks per day for more than four consecutive days. During the follow-up period, 59 (48 percent) participants relapsed, with 48 returning to heavy drinking. The average time to relapse was 218 days.

    The authors tested a genetic variant that resides in the BDNF gene, known as Val66Met. They observed that participants with the Val form of this gene were more likely to relapse compared to those with the Met version. Participants with two copies of the Val allele – one from each parent – had higher rates of relapse and shorter times to relapse when compared to carriers of at least one Met allele.

    These findings suggest that BDNF influences a person’s ability to remain abstinent following treatment for alcohol dependence. With further evaluation, these findings may help clinicians to identify people at increased risk for post-treatment relapse and tailor their care plans.

  • How well (and how quickly) we age depends on a confluence of genetic, environmental, and lifestyle factors. Some lifestyle behaviors, such as alcohol consumption and cigarette smoking, elicit harmful effects on multiple body systems that can accumulate over time to modulate aging. A new study demonstrates that alcohol consumption and cigarette smoking accelerate brain aging, in particular.

    Research indicates that smoking cigarettes alters multiple structural aspects of the brain. For example, smokers tend to have less gray matter density and volume in the frontal, occipital, and temporal lobes – areas related to a wide range of brain function. Similarly, heavy alcohol use is associated with reduced gray and white matter volumes in the medial-prefrontal and orbitofrontal cortices.

    The authors of the study assessed relative brain age, a comparative measure of brain aging between people of the same chronological age, to determine if a person’s brain is aging at a different rate relative to their peers. The study was based on analysis of brain-imaging data collected from more than 17,000 UK Biobank participants who were of European ancestry and were cognitively normal. After determining the participants' relative brain age, they studied the association of relative brain age with cigarette smoking, alcohol consumption, and genetic variants.

    They found that regular (daily or nearly daily) cigarette smoking or alcohol consumption increased relative brain aging. Every gram of alcohol (~20 grams in 1 fluid ounce) consumed per day was linked to one week of accelerated brain aging and each year spent smoking one pack of cigarettes per day was linked to 11 days of accelerated brain aging.

    These increases in brain aging were associated with poor cognitive function and declines in fluid intelligence, the ability to creatively solve problems without prior knowledge or learning. They also identified two single nucleotide polymorphisms associated with accelerated brain aging.

    While it is important to note that the effect of alcohol on brain aging was only seen in daily or almost daily drinkers, these findings provide useful insights into how cigarette smoking and alcohol consumption influence brain aging and highlight the need for future research to fully elucidate the factors associated with how the brain ages.

  • FTA:

    The team tested several behavioral models, including a model in which mice escalate alcohol drinking after repeated withdrawal periods, to study the effects of partially deleting Nf1. In this experiment, which simulated the transition to excessive drinking that is associated with alcohol dependence in humans, they found that mice with functional Nf1 genes steadily increased their ethanol intake starting after just one episode of withdrawal. Conversely, mice with a partially deleted Nf1 gene showed no increase in alcohol consumption.

    Looks like the authors of this paper may be looking at epigenetic roles next?

    The team sees the new findings as “pieces to the puzzle.” Sanna believes future research should focus on exactly how Nf1 regulates the GABA system and how gene expression may be altered during early development.