Routinely drinking alcohol may raise blood pressure even in adults without hypertension

Even in adults without hypertension, blood pressure readings may climb more steeply over the years as the number of daily alcoholic drinks rise, according to an analysis of seven international research studies published today in Hypertension, an American Heart Association journal.

With the statistical power of seven international research studies, this analysis confirms for the first time there was a continuous increase in blood pressure measures in both participants with low and high alcohol intake. Even low levels of alcohol consumption were associated with detectable increases in blood pressure levels that may lead to a higher risk of cardiovascular events.

"We found no beneficial effects in adults who drank a low level of alcohol compared to those who did not drink alcohol," said senior study author Marco Vinceti, M.D., Ph.D., a professor of epidemiology and public health in the Medical School of the University of Modena and Reggio Emilia University in Italy and an adjunct professor in the department of epidemiology at Boston University's School of Public Health. "We were somewhat surprised to see that consuming an already-low level of alcohol was also linked to higher blood pressure changes over time compared to no consumption -- although far less than the blood pressure increase seen in heavy drinkers."

"Our analysis was based on grams of alcohol consumed and not just on the number of drinks to avoid the bias that might arise from the different amount of alcohol contained in 'standard drinks' across countries and/or types of beverages," said study co-author Tommaso Filippini, M.D., Ph.D., an associate professor of epidemiology and public health in the Medical School of the University of Modena and Reggio Emilia in Italy, and affiliate researcher at the University of California Berkeley School of Public Health.

Researchers reviewed the health data for all participants across the seven studies for more than five years. They compared adults who drank alcohol regularly with non-drinkers and found:
 

• Systolic (top number) blood pressure rose 1.25 millimeters of mercury (mm Hg) in people who consumed an average of 12 grams of alcohol per day, rising to 4.9 mm Hg in people consuming an average of 48 grams of alcohol per day. (In the U.S., 12 ounces of regular beer, 5 ounces of wine or a 1.5 ounce shot of distilled spirits contains about 14 grams of alcohol. Usual alcohol content differs in alcohol available in other countries.)
• Diastolic (bottom number) blood pressure rose 1.14 mm Hg in people consuming an average of 12 grams of alcohol per day, rising to 3.1 mm Hg in people consuming an average of 48 grams of alcohol per day. These associations were seen in males but not in females. Diastolic blood pressure measures the force against artery walls between heartbeats and is not as strong a predictor of heart disease risk in comparison to systolic.

"Alcohol is certainly not the sole driver of increases in blood pressure; however, our findings confirm it contributes in a meaningful way. Limiting alcohol intake is advised, and avoiding it is even better," Vinceti said.

Although none of the participants had high blood pressure when they enrolled in the studies, their blood pressure measurements at the beginning did have an impact on the alcohol findings.

"We found participants with higher starting blood pressure readings, had a stronger link between alcohol intake and blood pressure changes over time. This suggests that people with a trend towards increased (although still not "high") blood pressure may benefit the most from low to no alcohol consumption," said study co-author Paul K. Whelton, M.D., M.Sc., the Show Chwan Chair in Global Public Health in the department of epidemiology at Tulane University's School of Public Health and Tropical Medicine in New Orleans and president of the World Hypertension League. Whelton is also the chair of the American Heart Association's 2017 Hypertension Practice Guidelines and a member of the writing committee for the Association's 2021 Scientific Statement on Management of Stage 1 Hypertension in Adults.

According to American Heart Association recommendations, if you don't drink already, don't start. If you do drink, talk with your doctor about the benefits and risks of consuming alcohol in moderation. The Association also does not recommend drinking any form of alcohol to gain potential health benefits. Instead, follow the Association's lifestyle and health metrics for optimal cardiovascular health called Life's Essential 8: eat healthy food, be physically active, don't smoke, get enough sleep, maintain a healthy weight, and control cholesterol, blood sugar and blood pressure levels.

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Light or moderate alcohol consumption does not guard against diabetes, obesity

People who have just one or two drinks per day are not protected against endocrine conditions such as obesity and type 2 diabetes, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Alcohol consumption is a significant public health concern because it is related to many medical conditions such as diabetes, obesity, liver conditions and heart disease. While it is widely accepted that excessive alcohol consumption causes a wide range of health issues, whether modest alcohol consumption has beneficial health effects remains controversial.

"Some research has indicated that moderate drinkers may be less likely to develop obesity or diabetes compared to non-drinkers and heavy drinkers. However, our study shows that even light-to-moderate alcohol consumption (no more than one standard drink per day) does not protect against obesity and type 2 diabetes in the general population," said Tianyuan Lu, Ph.D., from McGill University in Québec, Canada. "We confirmed that heavy drinking could lead to increased measures of obesity (body mass index, waist-to-hip ratio, fat mass, etc.) as well as increased risk of type 2 diabetes."

The researchers assessed self-reported alcohol intake data from 408,540 participants in the U.K. Biobank and found people who had more than 14 drinks per week had higher fat mass and a higher risk of obesity and type 2 diabetes.

These associations were stronger in women than in men. No data supported the association between moderate drinking and improved health outcomes in people drinking less than or equal to seven alcoholic beverages per week.

"We hope our research helps people understand the risks associated with drinking alcohol and that it informs future public health guidelines and recommendations related to alcohol use," Lu said. "We want our work to encourage the general population to choose alternative healthier behaviors over drinking."

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Researchers uncover why light-to-moderate drinking is tied to better heart health

A new study led by investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, offers an explanation for why light-to-moderate alcohol consumption may be associated with lower risk of heart disease. For the first time, researchers found that alcohol, in light to moderate quantities, was associated with long-term reductions in stress signaling in the brain. This impact on the brain's stress systems appeared to significantly account for the reductions in cardiovascular events seen in light to moderate drinkers participating in the study. Findings are published in the Journal of the American College of Cardiology.

"We are not advocating the use of alcohol to reduce the risk of heart attacks or strokes because of other concerning effects of alcohol on health," says senior author and cardiologist Ahmed Tawakol, MD, co-director of the Cardiovascular Imaging Research Center at Massachusetts General Hospital. "We wanted to understand how light to moderate drinking reduces cardiovascular disease, as demonstrated by multiple other studies. And if we could find the mechanism, the goal would be to find other approaches that could replicate or induce alcohol's protective cardiac effects without the adverse impacts of alcohol."

Previous epidemiological studies have suggested that light to moderate alcohol consumption (1 drink per day for women and 1 to 2 drinks per day for men) is associated with a lower risk of cardiovascular disease. But it was unknown whether alcohol was inducing cardiovascular benefits, or whether light/moderate drinkers' health behaviors, socioeconomic status, or other factors protected their hearts.

The study, led by K Mezue and M Osborne, included more than 50,000 individuals enrolled in the Mass General Brigham Biobank. The first part of the study evaluated the relationship between light/moderate alcohol consumption and major adverse cardiovascular events after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic confounders. The researchers found that light/moderate alcohol consumption was associated with a substantial reduction in the risk of cardiovascular disease events, even after accounting for those other factors.

Next, they studied a subset of 754 individuals who had undergone previous PET/CT brain imaging (primarily for cancer surveillance) to determine the effect of light/moderate alcohol consumption on resting stress-related neural network activity.

The brain imaging showed reduced stress signaling in the amygdala, the brain region associated with stress responses, in individuals who were light to moderate drinkers compared to those who abstained from alcohol or who drank little. And when the investigators looked at these individuals' history of cardiovascular events, they found fewer heart attacks and strokes in light to moderate drinkers. "We found that the brain changes in light to moderate drinkers explained a significant portion of the protective cardiac effects," says Tawakol.

It's long been known that alcohol reduces the amygdala's reactivity to threatening stimuli while individuals are drinking. The current study is the first to indicate that light to moderate alcohol consumption has longer-term neurobiological effects in dampening activity in the amygdala, which may have a significant downstream impact on the cardiovascular system.

"When the amygdala is too alert and vigilant, the sympathetic nervous system is heightened, which drives up blood pressure and increases heart rate, and triggers the release of inflammatory cells," explains Tawakol. "If the stress is chronic, the result is hypertension, increased inflammation, and a substantial risk of obesity, diabetes, and cardiovascular disease."

Finally, the investigators examined whether light/moderate alcohol would be even more effective at reducing heart attacks and strokes in people who are prone to a chronically higher stress response, such as those with a history of significant anxiety. They found that, within the 50,000-patient sample, light to moderate drinking was associated with nearly double the cardiac-protective effect in individuals with a history of anxiety compared with others.

Yet while light/moderate drinkers lowered their risk for cardiovascular disease, the study also showed that any amount of alcohol increases the risk of cancer. And at higher amounts of alcohol consumption -- more than 14 drinks a week -- heart attack risk started to increase while overall brain activity started to decrease (which may be associated with adverse cognitive health).

The authors concluded that research should focus on finding new interventions that reduce the brain's stress activity without the deleterious effects of alcohol. The research team is currently studying the effect of exercise, stress-reduction interventions such as meditation, and pharmacological therapies on stress-associated neural networks and how they might induce cardiovascular benefits.

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How alcohol consumption contributes to chronic pain

Chronic alcohol consumption may make people more sensitive to pain through two different molecular mechanisms -- one driven by alcohol intake and one by alcohol withdrawal. That is one new conclusion by scientists at Scripps Research on the complex links between alcohol and pain.

The research, published in the British Journal of Pharmacology on April 12, 2023, also suggests potential new drug targets for treating alcohol-associated chronic pain and hypersensitivity.

"There is an urgent need to better understand the two-way street between chronic pain and alcohol dependence," says senior author Marisa Roberto, PhD, the Schimmel Family Chair of Molecular Medicine, and a professor of neuroscience at Scripps Research. "Pain is both a widespread symptom in patients suffering from alcohol dependence, as well as a reason why people are driven to drink again."

Alcohol use disorder (AUD), which encompasses the conditions commonly called alcohol abuse, alcohol dependence and alcohol addiction, affects 29.5 million people in the U.S. according to the 2021 National Survey on Drug Use and Health. Over time, AUD can trigger the development of numerous chronic diseases, including heart disease, stroke, liver disease and some cancers.

Among the many impacts of long-term alcohol consumption is pain: more than half of people with AUD experience persistent pain of some type. This includes alcoholic neuropathy, which is nerve damage that causes chronic pain and other symptoms. Studies have also found that AUD is associated with changes in how the brain processes pain signals, as well as changes to how immune system activation occurs. In turn, this pain can lead to increased alcohol consumption. Moreover, during withdrawal, people with AUD can experience allodynia, in which a harmless stimulus is perceived as painful.

Roberto and her colleagues were interested in learning the underlying causes of these different types of alcohol-related pain. In the new study, they compared three groups of adult mice: animals that were dependent on alcohol (excessive drinkers), animals that had limited access to alcohol and were not considered dependent (moderate drinkers), and those that had never been given alcohol.

In dependent mice, allodynia developed during alcohol withdrawal, and subsequent alcohol access significantly decreased pain sensitivity. Separately, about half of the mice that were not dependent on alcohol also showed signs of increased pain sensitivity during alcohol withdrawal but, unlike the dependent mice, this neuropathy was not reversed by re-exposure to alcohol.

When Roberto's group then measured levels of inflammatory proteins in the animals, they discovered that while inflammation pathways were elevated in both dependent and non-dependent animals, specific molecules were only increased in dependent mice. This indicates that different molecular mechanisms may drive the two types of pain. It also suggests which inflammatory proteins may be useful as drug targets to combat alcohol-related pain.

"These two types of pain vary greatly, which is why it is important to be able to distinguish between them and develop different ways to treat each type," says first author Vittoria Borgonetti, PhD, a postdoctoral associate at Scripps Research.

Roberto's group is continuing studies on how these molecules might be used to diagnose or treat alcohol-related chronic pain conditions.

"Our goal is to unveil new potential molecular targets that can be used to distinguish these types of pain and potentially be used in the future for the development of therapies," says co-senior author Nicoletta Galeotti, PhD, associate professor of preclinical pharmacology at the University of Florence.

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Sugar is processed differently in the brains of obesity-prone vs. obesity-resistant rats

On a diet? Perhaps you're avoiding sweets or carbs altogether or curbing late-night munchies. These are examples of behavior modifications and when it comes to food, avoiding those diet triggers can be pretty hard to do.

To understand what drives people to overeat, scientists are looking more closely at a brain structure involved in motivation, called the nucleus accumbens. This small region drives reward-seeking behaviors underlying the pursuit of sex, recreational drugs like nicotine and alcohol, and food.

"These brain motivation centers evolved to help us survive; finding food and having sex are essential to the survival of an individual and of a species," said Carrie Ferrario, Ph.D., associate professor in the Department of Pharmacology at U-M Medical School.

"What was advantageous when food was hard to find has become a disadvantage and unhealthy in the current food dense environment. This is compounded by the over-abundance of over-processed, low nutrition foods that may satisfy our taste but leave our bodies unnourished. People don't tend to find it difficult to turn down an extra serving of broccoli, but just one more french-fry or making room for a bit of chocolate dessert...that's a different story. The real challenge is overcoming these urges and changing our behavior when it comes to food," Ferrario added.

Given the immense toll obesity takes on virtually all body systems, Ferrario, Peter Vollbrecht, Ph.D., of Western Michigan University, and their colleagues are using rat models to understand potential brain differences between animals who are prone to over-eating and obesity and those who are not.

Previous research from Ferrario's lab pinpointed differences in the nucleus accumbens in obesity-prone and obesity-resistant rats. Their latest study, published in the Journal of Neurochemistry, tracked what was happening in real time in the brain when these animals were presented with glucose, a type of sugar, labeled with a tracer. The tracer allowed the researchers to measure this new sugar in the brain.

Sugar is the brain's main fuel source and once there, the molecule is broken down and used to create new molecules such as glutamine, glutamate, and GABA, each with an important role in influencing the activation of neurons in the brain and nervous system.

"Glucose that is consumed gets broken down and then its carbons get incorporated into neurotransmitters. We see those labelled carbons showing up in those molecules -- glutamate, glutamine, and GABA -- over time," explained Vollbrecht.

They found that glucose was taking longer to get into the nucleus accumbens of obesity-prone animals.

Furthermore, when measuring the concentration of the glutamate, glutamine, and GABA, they discovered excess levels of glutamate, an excitatory neurotransmitter. This, said the team, implied a defect in a neurotransmitter recycling process, typically maintained in the nervous system by star-shaped cells called astrocytes.

Normally, astrocytes will pull glutamate out of the space between neurons, called the synapse, convert it into glutamine, and then shuttle it back to cells that produce GABA or glutamate. This sequence is crucial for turning neurons off and on. "The findings suggest that we're getting too much glutamate and it's not being taken out of the synapse," said Vollbrecht.

Ferrario added, "The balance between glutamate and GABA (the main inhibitory transmitter) is really important for brain function and will influence activity of the neurons in the nucleus accumbens."

This balance, and therefore brain activity, is different in obesity-prone vs. obesity-resistant rats.

The fact that these rats are either prone to obesity or not is important for disentangling cause and effect, says Vollbrecht. "It allows us to remove diet as one of the variables."

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Lager beer, whether it contains alcohol or not, could help men's gut microbes

Like wine, beer can have health benefits when consumed in moderation. Non-alcoholic beers have become wildly popular recently, but are these drinks also healthful? In a pilot study, researchers in ACS' Journal of Agricultural and Food Chemistry report that compared to their pre-trial microbiome, men who drank either one alcoholic or non-alcoholic lager daily had a more diverse set of gut microbes, which can reduce the risk for some diseases.

Trillions of microorganisms line human gastrointestinal tracts, directly impacting their host's well-being. Studies have shown that when more types of bacteria are present, people tend to have a lower chance of developing chronic diseases, such as heart disease and diabetes. And beer contains compounds, such as polyphenols, as well as microorganisms from its fermentation, that could impact the variety of microbes in the human gut. A previously published "cross-over" study showed that when both men and women consumed non-alcoholic lager beer for 30 days, their gut microbiome diversity increased. Many of those same people were also in a second group that drank an alcoholic version of the beer, and it didn't have the same effect. Few other clinical trials have tested this issue, so Ana Faria and colleagues wanted to see if they would find similar results with men in a different type of study -- a parallel, randomized trial design -- with two separate groups of participants.

In this double-blind study, 19 healthy men were randomly divided into two groups who drank 11 fluid ounces of either alcoholic or non-alcoholic lager with dinner for 4 weeks. The researchers found that the participants' weight, body mass index and serum markers for heart health and metabolism didn't change during the study. But at the end of the 4-week period, both groups had greater bacterial diversity in their gut microbiome and higher levels of fecal alkaline phosphatase, indicating an improvement in intestinal health. The researchers suggest that these results could differ from those of the prior study because of the different designs of the trials, and because the participants were living in different communities. But based on this pilot study, the researchers say that consuming one bottle of beer, regardless of its alcohol content, may be beneficial to the gut microbiome and intestinal health of men. However, they add that because the safest level of alcohol consumption is none, non-alcoholic beer may be the more healthful choice.

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Alcohol may be more risky to the heart than previously thought

Levels of alcohol consumption currently considered safe by some countries are linked with development of heart failure, according to research presented at Heart Failure 2022, a scientific congress of the European Society of Cardiology (ESC).1

"This study adds to the body of evidence that a more cautious approach to alcohol consumption is needed," said study author Dr. Bethany Wong of St. Vincent's University Hospital, Dublin, Ireland. "To minimise the risk of alcohol causing harm to the heart, if you don't drink, don't start. If you do drink, limit your weekly consumption to less than one bottle of wine or less than three-and-a-half 500 ml cans of 4.5% beer."

According to the World Health Organization, the European Union is the heaviest-drinking region in the world.2 While it is well recognised that long-term heavy alcohol use can cause a type of heart failure called alcoholic cardiomyopathy,3 evidence from Asian populations suggests that lower amounts may also be detrimental.4,5 "As there are genetic and environmental differences between Asian and European populations this study investigated if there was a similar relationship between alcohol and cardiac changes in Europeans at risk of heart failure or with pre-heart failure," said Dr. Wong. "The mainstay of treatment for this group is management of risk factors such as alcohol, so knowledge about safe levels is crucial."

This was a secondary analysis of the STOP-HF trial.6 The study included 744 adults over 40 years of age either at risk of developing heart failure due to risk factors (e.g. high blood pressure, diabetes, obesity) or with pre-heart failure (risk factors and heart abnormalities but no symptoms).7 The average age was 66.5 years and 53% were women. The study excluded former drinkers and heart failure patients with symptoms (e.g. shortness of breath, tiredness, reduced ability to exercise, swollen ankles). Heart function was measured with echocardiography at baseline and follow up.

The study used the Irish definition of one standard drink (i.e. one unit), which is 10 grams of alcohol.8 Participants were categorised according to their weekly alcohol intake: none; low (less than seven units; up to one 750 ml bottle of 12.5% wine or three-and-a-half 500 ml cans of 4.5% beer); moderate (7-14 units; up to two bottles of 12.5% wine or seven 500 mL cans of 4.5% beer); high (above 14 units; more than two bottles of 12.5% wine or seven 500 ml cans of 4.5% beer).

The researchers analysed the association between alcohol use and heart health over a median of 5.4 years. The results were reported separately for the at-risk and pre-heart failure groups. In the at-risk group, worsening heart health was defined as progression to pre-heart failure or to symptomatic heart failure. For the pre-heart failure group, worsening heart health was defined as deterioration in the squeezing or relaxation functions of the heart or progression to symptomatic heart failure. The analyses were adjusted for factors that can affect heart structure including age, gender, obesity, high blood pressure, diabetes, and vascular disease.

A total of 201 (27%) patients reported no alcohol usage, while 356 (48%) were low users and 187 (25%) had moderate or high intake. Compared to the low intake group, those with moderate or high use were younger, more likely to be male, and had a higher body mass index.

In the pre-heart failure group, compared with no alcohol use, moderate or high intake was associated with a 4.5-fold increased risk of worsening heart health. The relationship was also observed when moderate and high levels were analysed separately. In the at-risk group, there was no association between moderate or high alcohol use with progression to pre-heart failure or to symptomatic heart failure. No protective associations were found for low alcohol intake.

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Multi-tasking wearable continuously monitors glucose, alcohol, and lactate

Imagine being able to measure your blood sugar levels, know if you've had too much to drink, and track your muscle fatigue during a workout, all in one small device worn on your skin. Engineers at the University of California San Diego have developed a prototype of such a wearable that can continuously monitor several health stats -- glucose, alcohol, and lactate levels -- simultaneously in real-time.

The device is about the size of a stack of six quarters. It is applied to the skin through a Velcro-like patch of microscopic needles, or microneedles, that are each about one-fifth the width of a human hair. Wearing the device is not painful -- the microneedles barely penetrate the surface of the skin to sense biomolecules in interstitial fluid, which is the fluid surrounding the cells beneath the skin. The device can be worn on the upper arm and sends data wirelessly to a custom smartphone app.

Researchers at the UC San Diego Center for Wearable Sensors describe their device in a paper published May 9 in Nature Biomedical Engineering.

"This is like a complete lab on the skin," said center director Joseph Wang, a professor of nanoengineering at UC San Diego and co-corresponding author of the paper. "It is capable of continuously measuring multiple biomarkers at the same time, allowing users to monitor their health and wellness as they perform their daily activities."

Most commercial health monitors, such as continuous glucose monitors for patients with diabetes, only measure one signal. The problem with that, the researchers said, is that it leaves out information that could help people with diabetes, for example, manage their disease more effectively. Monitoring alcohol levels is useful because drinking alcohol can lower glucose levels. Knowing both levels can help people with diabetes prevent their blood sugar from dropping too low after having a drink. Combining information about lactate, which can be monitored during exercise as a biomarker for muscle fatigue, is also useful because physical activity influences the body's ability to regulate glucose.

"With our wearable, people can see the interplay between their glucose spikes or dips with their diet, exercise and drinking of alcoholic beverages. That could add to their quality of life as well," said Farshad Tehrani, a nanoengineering Ph.D. student in Wang's lab and one of the co-first authors of the study.

Microneedles merged with electronics

The wearable consists of a microneedle patch connected to a case of electronics. Different enzymes on the tips of the microneedles react with glucose, alcohol and lactate in interstitial fluid. These reactions generate small electric currents, which are analyzed by electronic sensors and communicated wirelessly to an app that the researchers developed. The results are displayed in real time on a smartphone.

An advantage of using microneedles is that they directly sample the interstitial fluid, and research has shown that biochemical levels measured in that fluid correlate well with levels in blood.

"We're starting at a really good place with this technology in terms of clinical validity and relevance," said Patrick Mercier, a professor of electrical and computer engineering at UC San Diego and co-corresponding author of the paper. "That lowers the barriers to clinical translation."

The microneedle patch, which is disposable, can be detached from the electronic case for easy replacement. The electronic case, which is reusable, houses the battery, electronic sensors, wireless transmitter and other electronic components. The device can be recharged on any wireless charging pad used for phones and smartwatches.

Integrating all these components together into one small, wireless wearable was one of the team's biggest challenges. It also required some clever design and engineering to combine the reusable electronics, which must stay dry, with the microneedle patch, which gets exposed to biological fluid.

"The beauty of this is that it is a fully integrated system that someone can wear without being tethered to benchtop equipment," said Mercier, who is also the co-director of the UC San Diego Center for Wearable Sensors.

Testing

The wearable was tested on five volunteers, who wore the device on their upper arm, while exercising, eating a meal, and drinking a glass of wine. The device was used to continuously monitor the volunteers' glucose levels simultaneously with either their alcohol or lactate levels. The glucose, alcohol and lactate measurements taken by the device closely matched the measurements taken respectively by a commercial blood glucose monitor, Breathalyzer, and blood lactate measurements performed in the lab.

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Large study challenges the theory that light alcohol consumption benefits heart health

Observational research has suggested that light alcohol consumption may provide heart-related health benefits, but in a large study published in JAMA Network Open, alcohol intake at all levels was linked with higher risks of cardiovascular disease. The findings, which are published by a team led by researchers at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard, suggest that the supposed benefits of alcohol consumption may actually be attributed to other lifestyle factors that are common among light to moderate drinkers.

The study included 371,463 adults -- with an average age of 57 years and an average alcohol consumption of 9.2 drinks per week -- who were participants in the UK Biobank, a large-scale biomedical database and research resource containing in-depth genetic and health information. Consistent with earlier studies, investigators found that light to moderate drinkers had the lowest heart disease risk, followed by people who abstained from drinking. People who drank heavily had the highest risk. However, the team also found that light to moderate drinkers tended to have healthier lifestyles than abstainers -- such as more physical activity and vegetable intake, and less smoking. Taking just a few lifestyle factors into account significantly lowered any benefit associated with alcohol consumption.

The study also applied the latest techniques in a method called Mendelian randomization, which uses genetic variants to determine whether an observed link between an exposure and an outcome is consistent with a causal effect -- in this case, whether light alcohol consumption causes a person to be protected against cardiovascular disease. "Newer and more advanced techniques in 'non-linear Mendelian randomization' now permit the use of human genetic data to evaluate the direction and magnitude of disease risk associated with different levels of an exposure," says senior author Krishna G. Aragam, MD, MS, a cardiologist at MGH and an associate scientist at the Broad Institute. "We therefore leveraged these new techniques and expansive genetic and phenotypic data from biobank populations to better understand the association between habitual alcohol intake and cardiovascular disease."

When the scientists conducted such genetic analyses of samples taken from participants, they found that individuals with genetic variants that predicted higher alcohol consumption were indeed more likely to consume greater amounts of alcohol, and more likely to have hypertension and coronary artery disease. The analyses also revealed substantial differences in cardiovascular risk across the spectrum of alcohol consumption among both men and women, with minimal increases in risk when going from zero to seven drinks per week, much higher risk increases when progressing from seven to 14 drinks per week, and especially high risk when consuming 21 or more drinks per week. Notably, the findings suggest a rise in cardiovascular risk even at levels deemed "low risk" by national guidelines from the U.S. Department of Agriculture (i.e. below two drinks per day for men and one drink per day for women).

The discovery that the relationship between alcohol intake and cardiovascular risk is not a linear one but rather an exponential one was supported by an additional analysis of data on 30,716 participants in the Mass General Brigham Biobank. Therefore, while cutting back on consumption can benefit even people who drink one alcoholic beverage per day, the health gains of cutting back may be more substantial -- and, perhaps, more clinically meaningful -- in those who consume more.

"The findings affirm that alcohol intake should not be recommended to improve cardiovascular health; rather, that reducing alcohol intake will likely reduce cardiovascular risk in all individuals, albeit to different extents based on one's current level of consumption," says Aragam.

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More alcohol, less brain: Association begins with an average of just one drink a day

 Even light-to-moderate drinking is associated with harm to the brain, according to a new study. Researchers analyzed data from more than 36,000 adults that found a link between drinking and reduced brain volume that begins at an average consumption level of less than one alcohol unit a day -- the equivalent of about half a beer -- and rises with each additional drink.

The research, using a dataset of more than 36,000 adults, revealed that going from one to two drinks a day was linked with changes in the brain equivalent to aging two years. Heavier drinking was associated with an even greater toll. The science on heavy drinking and the brain is clear: The two don't have a healthy relationship. People who drink heavily have alterations in brain structure and size that are associated with cognitive impairments.

But according to a new study, alcohol consumption even at levels most would consider modest -- a few beers or glasses of wine a week -- may also carry risks to the brain. An analysis of data from more than 36,000 adults, led by a team from the University of Pennsylvania, found that light-to-moderate alcohol consumption was associated with reductions in overall brain volume.

The link grew stronger the greater the level of alcohol consumption, the researchers showed. As an example, in 50-year-olds, as average drinking among individuals increases from one alcohol unit (about half a beer) a day to two units (a pint of beer or a glass of wine) there are associated changes in the brain equivalent to aging two years. Going from two to three alcohol units at the same age was like aging three and a half years. The team reported their findings in the journal Nature Communications.

"The fact that we have such a large sample size allows us to find subtle patterns, even between drinking the equivalent of half a beer and one beer a day," says Gideon Nave, a corresponding author on the study and faculty member at Penn's Wharton School. He collaborated with former postdoc and co-corresponding author Remi Daviet, now at the University of Wisconsin-Madison, and Perelman School of Medicine colleagues Reagan Wetherill -- also a corresponding author on the study -- and Henry Kranzler, as well as other researchers.

"These findings contrast with scientific and governmental guidelines on safe drinking limits," says Kranzler, who directs the Penn Center for Studies of Addiction. "For example, although the National Institute on Alcohol Abuse and Alcoholism recommends that women consume an average of no more than one drink per day, recommended limits for men are twice that, an amount that exceeds the consumption level associated in the study with decreased brain volume,"

Ample research has examined the link between drinking and brain health, with ambiguous results. While strong evidence exists that heavy drinking causes changes in brain structure, including strong reductions in gray and white matter across the brain, other studies have suggested that moderate levels of alcohol consumption may not have an impact, or even that light drinking could benefit the brain in older adults.

These earlier investigations, however, lacked the power of large datasets. Probing massive quantities of data for patterns is the specialty of Nave, Daviet, and colleagues, who have conducted previous studies using the UK Biobank, a dataset with genetic and medical information from half a million British middle-aged and older adults. They employed biomedical data from this resource in the current study, specifically looking at brain MRIs from more than 36,000 adults in the Biobank, which can be used to calculate white and gray matter volume in different regions of the brain.

"Having this dataset is like having a microscope or a telescope with a more powerful lens," Nave says. "You get a better resolution and start seeing patterns and associations you couldn't before."

To gain an understanding of possible connections between drinking and the brain, it was critical to control for confounding variables that could cloud the relationship. The team controlled for age, height, handedness, sex, smoking status, socioeconomic status, genetic ancestry, and county of residence. They also corrected the brain-volume data for overall head size.

The volunteer participants in the Biobank had responded to survey questions about their alcohol consumption levels, from complete abstention to an average of four or more alcohol units a day. When the researchers grouped the participants by average-consumption levels, a small but apparent pattern emerged: The gray and white matter volume that might otherwise be predicted by the individual's other characteristics was reduced.

Going from zero to one alcohol units didn't make much of a difference in brain volume, but going from one to two or two to three units a day was associated with reductions in both gray and white matter.

"It's not linear," says Daviet. "It gets worse the more you drink."

Even removing the heavy drinkers from the analyses, the associations remained. The lower brain volume was not localized to any one brain region, the scientists found.

To give a sense of the impact, the researchers compared the reductions in brain size linked with drinking to those that occur with aging. Based on their modeling, each additional alcohol unit consumed per day was reflected in a greater aging effect in the brain. While going from zero to a daily average of one alcohol unit was associated with the equivalent of a half a year of aging, the difference between zero and four drinks was more than 10 years of aging.

In future work, the authors hope to tap the UK Biobank and other large datasets to help answer additional questions related to alcohol use. "This study looked at average consumption, but we're curious whether drinking one beer a day is better than drinking none during the week and then seven on the weekend," Nave says. "There's some evidence that binge drinking is worse for the brain, but we haven't looked closely at that yet."

They'd also like to be able to more definitively pin down causation rather than correlation, which may be possible with new longitudinal biomedical datasets that are following young people as they age.

"We may be able to look at these effects over time and, along with genetics, tease apart causal relationships," Nave says.

And while the researchers underscore that their study looked only at correlations, they say the findings may prompt drinkers to reconsider how much they imbibe.

"There is some evidence that the effect of drinking on the brain is exponential," says Daviet. "So, one additional drink in a day could have more of an impact than any of the previous drinks that day. That means that cutting back on that final drink of the night might have a big effect in terms of brain aging."

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Even light drinking can be harmful to health

Drinking less than the UK's recommended limit of 14 units of alcohol per week still increases the risk of cardiovascular issues such as heart and cerebrovascular disease, according to new research published in the journal Clinical Nutrition.

Academics from Anglia Ruskin University (ARU) examined hospitalisations related to cardiovascular events among more than 350,000 UK residents aged between 40 and 69 from data obtained from the UK Biobank study.

The sample included 333,259 people who drank alcohol. Participants had been asked about their overall weekly alcohol intake and their intake of specific types of alcohol including beer, wine and spirits. Those participants were followed up for a median of approximately seven years, capturing all incidents where patients had been hospitalised through cardiovascular events.

Anyone who had suffered a previous cardiovascular event was excluded from the analysis, as were former drinkers or those who had not completed information on alcohol intake.

The analysis found that, for those participants that drank less than 14 units of alcohol per week -- the limit recommended by the UK's Chief Medical Officers -- each additional 1.5 pints of beer at 4% strength (alcohol by volume) is associated with a 23% increased risk of suffering a cardiovascular event.

The authors argue that biases in existing epidemiological evidence have resulted in the widespread acceptance of the "J-shaped curve" that wrongly suggests low to moderate alcohol consumption can be beneficial to cardiovascular health.

These biases include using non-drinkers as a reference group when many do not drink for reasons of existing poor health, pooling of all drink types when determining the alcohol intake of a study population, and embedding the lower risk observed of coronary artery disease among wine drinkers, potentially distorting the overall cardiovascular risk from the drink.

Lead author Dr Rudolph Schutte, course leader for the BSc Hons Medical Science programme and Associate Professor at ARU, said:

"The so-called J-shaped curve of the cardiovascular disease-alcohol consumption relationship suggesting health benefit from low to moderate alcohol consumption is the biggest myth since we were told smoking was good for us.

"Among drinkers of beer, cider and spirits in particular, even those consuming under 14 units a week had an increased risk of ending up in hospital through a cardiovascular event involving the heart or the blood vessels. While we hear much about wine drinkers having lower risk of coronary artery disease, our data shows their risk of other cardiovascular events is not reduced.

"Biases embedded in epidemiological evidence mask or underestimate the hazards associated with alcohol consumption. When these biases are accounted for, the adverse effects of even low-level alcohol consumption are revealed.

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Redefining alcohol use disorder

Researchers at the University of Missouri have developed a new framework that they believe will help identify people previously overlooked for alcohol use disorder (AUD). This framework focuses on 13 risk factors, such as impulsive behavior, reward sensitivity, and punishment sensitivity, that could lead to someone developing an AUD.

"We know from decades of research that there are a lot of different pathways to alcohol use disorder," said Cassie Boness, a former graduate student at MU in the Department of Psychological Sciences. "So, we want to make sure that we are targeting people's specific pathways as accurately as possible in order to be most effective in identifying and treating AUD."

Throughout her career, Boness has been interested in the causes, diagnosis and assessment of substance use disorders, including AUD, a chronic medical condition characterized by ongoing alcohol use despite adverse consequences. For Boness, it's personal -- after seeing her loved ones stigmatized for their addiction to alcohol, and then watching them struggle to get connected with treatment, she wanted to help reduce the amount of suffering people may experience with AUD.

While today's assessment tools, such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) can help health care professionals diagnose someone with AUD, Boness believes the current methods are too narrowly focused on the consequences of someone's actions, rather than incorporating a broad list of potential risk factors that may lead to an AUD diagnosis.

Boness, who is now a research assistant professor at the University of New Mexico, hopes their framework can be a step forward toward a comprehensive diagnosis of AUD throughout the health care community. However, she stresses that this tool is not meant to be the only solution, but rather a way for other researchers like her to build upon and enhance the existing research on the subject.

"Eventually, we'd like to see assessment tools that more comprehensively capture the factors articulated in our framework so that we can identify individual profiles of risk and potentially intervene during earlier stages of addiction," Boness said.

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Only alcohol -- not caffeine, diet or lack of sleep -- might trigger heart rhythm condition

New research from UC San Francisco that tested possible triggers of a common heart condition, including caffeine, sleep deprivation and sleeping on the left side, found that only alcohol use was consistently associated with more episodes of the heart arrhythmia.

The authors conclude that people might be able to reduce their risk of atrial fibrillation (AF) by avoiding certain triggers.

The study is published in JAMA Cardiology and was presented November 14, 2021, at the annual Scientific Sessions of the American Heart Association.

Researchers were surprised to find that although most of the things that participants thought would be related to their AF were not, those in the intervention group still experienced less arrhythmia than the people in a comparison group that was not self-monitoring.

"This suggests that those personalized assessments revealed actionable results," said lead author Gregory Marcus, MD, professor of medicine in the Division of Cardiology at UCSF. "Although caffeine was the most commonly selected trigger for testing, we found no evidence of a near-term relationship between caffeine consumption and atrial fibrillation. In contrast, alcohol consumption most consistently exhibited heightened risks of atrial fibrillation."

Atrial fibrillation contributes to more than 150,000 deaths in the United States each year, reports the federal Centers for Disease Control and Prevention, with the death rate on the rise for more than 20 years.

To learn more about what patients felt was especially important to study about the disease, researchers held a brainstorming session in 2014. Patients said researching individual triggers for AF was their top priority, giving rise to the I-STOP-AFib study, which enabled individuals to test any presumed AF trigger. About 450 people participated, more than half of whom (58 percent) were men, and the overwhelming majority of whom were white (92 percent).

Participants in the randomized clinical trial utilized a mobile electrocardiogram recording device along with a phone app to log potential triggers like drinking alcohol and caffeine, sleeping on the left side or not getting enough sleep, eating a large meal, a cold drink, or sticking to a particular diet, engaging in exercise, or anything else they thought was relevant to their AF. Although participants were most likely to select caffeine as a trigger, there was no association with AF. Recent research from UCSF has similarly failed to demonstrate a relationship between caffeine and arrhythmias -- on the contrary, investigators found it may have a protective effect.

The new study demonstrated that consumption of alcohol was the only trigger that consistently resulted in significantly more self-reported AF episodes.

The individualized testing method, known as n-of-1, did not validate participant-selected triggers for AF. But trial participants did report fewer AF episodes than those in the control group, and the data suggest that behaviors like avoiding alcohol could lessen the chances of having an AF episode.

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Study of 18000+ US and Australian older people reveals moderate drinking protective against heart disease, more than for tea totalers

A landmark study by Monash University researchers has found that moderate drinking of alcohol is associated with a reduced risk of cardiovascular disease and a lowering of mortality from all causes -- when compared to zero alcohol consumption. The study in more than 18,000 people in the US and Australia over the age of 70 is the first to look at the heart health implications of alcohol intake.

Excess alcohol consumption is a leading contributor to the global burden of disease and a major risk factor for mortality. Yet, prior studies suggested that moderate alcohol consumption may be associated with a lower risk of cardiovascular disease (CVD) events.

This Monash University study, published in the European Journal of Preventive Cardiology is the first to investigate the risk of CVD events and mortality, from all causes, associated with alcohol consumption in initially healthy, older individuals.

Populations around the world are ageing. The Monash University- led ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial was a large-scale, long-term multi-centre, bi-national study of aspirin and health in older adults, with the purpose to discover ways to maintain health, quality of life and independence as we age.

This study, led by Dr Johannes Neumann, from the Monash University School of Public Health and Preventive Medicine, analysed data from almost 18,000 ASPREE participants -- Australians and Americans mostly aged 70 years and older.

Participants in the study did not have prior CVD events, diagnosed dementia or independence-limiting physical disability. CVD events included coronary heart disease death, non-fatal myocardial infarction, fatal and non-fatal stroke, non-coronary cardiac or vascular death, and hospitalisation for heart failure. Information on alcohol consumption (days of drinking per week and average standard drinks per day) was assessed by self-reported questionnaire at baseline. The study excluded former alcohol consumers who may have stopped alcohol consumption for various health reasons, possibly introducing bias from reverse causality.

Based on this information, the alcohol intake was calculated as grams per week -- for US participants a standard drink was equivalent to 14 g and 10 g for Australian participants.

In the study, alcohol consumption was categorised as 0 (never drinks) and those who drink 1-50; 51-100; 101-150, and >150g/week. For Australians that is up to 5; 5-10; 10-14 and over 15 standard drinks per week. For Americans -- that is up to 3.5; 3.5-7; 7-10 and over 10 standard drinks per week. Of the almost 18,000 eligible participants with median age 74 years:
 

• 57% were female
• 43.3% were current or former smokers and
• mean BMI was 28.1 kg/m2

The participants reported that
 

• 18.6% ingested no alcohol every week
• 37.3% reported 1-50 g/week
• 19.7%reported 51-100 g/week
• 15.6% reported 101-150 g/week
• 8.9% reported >150 g/week

The participants were followed for an average of 4.7 years and the study found that there was a reduced risk of CVD events for individuals consuming alcohol of 51-100, 101-150, and >150 g/week, compared to never consuming alcohol, regardless of gender.

Consumption of 51-100 g/week was also associated with a reduced risk of all-cause mortality.

Lead author, Dr Neumann, says the findings need to be interpreted with caution, as study participants were all initially healthy without prior CVD or other severe diseases, and may have been more physically and socially active than the wider ageing population.

Furthermore, prior evidence showed that excess alcohol consumption increases the risk of other chronic diseases, such as cancer, liver disease or pancreatitis.

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Brain-circuit discovery may help explain sex differences in binge drinking

A brain circuit that works as a "brake" on binge alcohol drinking may help explain male-female differences invulnerability to alcohol use disorders, according to a preclinical study led by scientists at Weill Cornell Medicine.

In the study, which appeared August 23 in Nature Communications, the researchers examined a brain region in mice called the bed nucleus of the stria terminalis (BNST) -- a major node in a stress-response network whose activity in humans has been linked to binge drinking behaviors. The researchers found that one important population of BNST neurons is more excitable in female mice than in males, helping to account for female mice's greater susceptibility to binge drinking.

The researchers also found that a distant cluster of neurons called the paraventricular nucleus of the thalamus (PVT), which is wired into the BNST, acts as a brake on its activity and has a stronger influence on the female BNST compared with the male BNST. Thus, the PVT is able to curb excessive alcohol consumption through this circuit brake in female mice but not males. While females may be offered more protection through this mechanism, they may also be more vulnerable to disease when this brake is disrupted.

"This study highlights that there are sex differences in the brain biology that controls alcohol drinking behaviors, and we really need to understand those differences if we're going to develop optimal treatments for alcohol use disorder," said senior author Dr. Kristen Pleil, assistant professor of pharmacology at Weill Cornell Medicine.

Women tend to consume less alcohol than men do, but researchers believe that is due mostly to cultural factors, and in recent decades that gender gap has narrowed significantly, especially among younger women. Women may in fact have an inherently greater vulnerability to alcohol use disorders, for reasons that lie deep within mammalian biology.

"Females across mammalian species, compared to males, display greater binge drinking and progress from first alcohol use to disease states more quickly," Dr. Pleil said. "But there has been hardly any research on the neural details that underlie this sex difference."

For the study, she and her team showed that BNST neurons, whose activity enhances binge-drinking behavior in mice, are more excitable and likely to fire spontaneously in female mice compared to males, apparently due to greater stimulation from other brain regions wired into the BNST. This higher excitability in females means that more inhibition of the female BNST is needed to prevent or reduce binge-drinking behavior.

The researchers found that the brain region with the densest projection to the BNST is the PVT -- which works as a natural inhibitor of BNST activity, more so in female mice. They found that reducing the strength of this PVT projection promotes binge alcohol drinking behavior in female mice, but not in male mice, whose BNST activity is lower to begin with.

The results, Dr. Pleil said, indicate that although this BNST-driven stress response circuit is tuned to be more excitable in females, it is also more heavily regulated in females, perhaps as an adaptation for more female-specific behaviors.

What behaviors? That is still unclear, although the researchers found that altering BNST activity via the PVT had no effect on the mice's intake of sweet-tasting sucrose -- suggesting that the PVT-BNST circuit, with its greater sensitivity and tighter regulation in females, evolved for something more specific than guiding general reward-seeking behaviors.

"Female mammals have a different set of goals compared to males, and may need to be more sensitive to different types of reward," Dr. Pleil said.

She added that sex differences in the PVT-BNST circuit may be relevant to sex differences not only in alcohol-use disorders but also in anxiety disorders -- which are much more common in women and frequently co-occur with binge drinking. The researchers found that enhancing PVT inhibition of the BNST led to reduced avoidance behaviors -- a proxy for reduced anxiety in humans -- in both male and female mice.

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New study links moderate alcohol use with higher cancer risk

A new study from the World Health Organization's (WHO) International Agency for Research on Cancer (IARC), published in the journal Lancet Oncology, has found an association between alcohol and a substantially higher risk of several forms of cancer, including breast, colon, and oral cancers. Increased risk was evident even among light to moderate drinkers (up to two drinks a day), who represented 1 in 7 of all new cancers in 2020 and more than 100,000 cases worldwide.

In Canada, alcohol use was linked to 7,000 new cases of cancer in 2020, including 24 per cent of breast cancer cases, 20 per cent of colon cancers, 15 per cent of rectal cancers, and 13 per cent of oral and liver cancers.

"All drinking involves risk," said study co-author Dr. Jürgen Rehm, Senior Scientist, Institute for Mental Health Policy Research and Campbell Family Mental Health Research Institute at CAMH. "And with alcohol-related cancers, all levels of consumption are associated with some risk. For example, each standard sized glass of wine per day is associated with a 6 per cent higher risk for developing female breast cancer."

"Alcohol consumption causes a substantial burden of cancer globally," said Dr. Isabelle Soerjomataram, Deputy Branch Head, Cancer Surveillance Branch at IARC. "Yet the impact on cancers is often unknown or overlooked, highlighting the need for implementation of effective policy and interventions to increase public awareness of the link between alcohol use and cancer risk, and decrease overall alcohol consumption to prevent the burden of alcohol-attributable cancers."

Dr. Leslie Buckley, CAMH Chief of Addictions, added: "In our clinic we are seeing many people who report increased alcohol use since the onset of the pandemic. Although this may be related to temporary stressors, there is a potential for new habits to become more permanent. The consequences with alcohol use are often subtle harms initially that take time to show themselves, while long-term consequences such as cancer, liver disease and substance use disorder can be devastating."

The modelling study was based on data on alcohol exposure from almost all countries of the world, both surveys and sales figures, which were combined with the latest relative risk estimates for cancer based on level of consumption.

"Alcohol causes cancer in numerous ways," explained Dr. Kevin Shield, Independent Scientist, Institute for Mental Health Policy Research, and study co-author. "The main mechanism of how alcohol causes cancer is through impairing DNA repair. Additional pathways include chronic alcohol consumption resulting in liver cirrhosis, and alcohol leading to a dysregulation of sex hormones, leading to breast cancer. Alcohol also increases the risk of head and neck cancer for smokers as it increases the absorption of carcinogens from tobacco."

Dr. Rehm says research into the link between light to moderate drinking and cancer is relatively new and that public policy does not yet reflect the degree of cancer risk. He added, "As an epidemiologist, I would recommend higher taxes to fully reflect the burden of disease from alcohol. Along with limiting the physical availability and marketing of alcohol, price controls are recognized as high-impact, cost-effective measures to reduce alcohol-related harm." Governments can also consider requiring manufacturers to include information about health and safety risks associated with alcohol consumption, including cancer risk, on alcoholic beverage labels.

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Revealing the mystery behind the threat of non-alcoholic liver disease

Researchers revealed how non-alcoholic fatty liver disease can develop into a life-threatening complication. Their discovery will accelerate the search for therapeutic solutions. The study was led by Helmholtz Zentrum München in collaboration with the Heidelberg University Hospital and the German Center for Diabetes Research.

Non-alcoholic fatty liver disease is the most common liver disorder worldwide and is present in approximately 25 percent of the world's population. Over 90 percent of obese, 60 percent of diabetic, and up to 20 percent of normal-weight people develop it. A key feature of the condition is the accumulation of fat in the liver. A liver can remain fatty without disturbing normal function; however, fat accumulations may progress into a so-called non-alcoholic steatohepatitis -- an aggressive form of the non-alcoholic fatty liver disease combined with inflammation and sometimes fibrosis. Non-alcoholic steatohepatitis can lead to further complications such as liver cirrhosis, primary liver cancer and eventually death.

Liver fibrosis is a strong predictor of long-term mortality in patients with non-alcoholic fatty liver disease. The mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis and liver fibrosis are incompletely understood. "Understanding the mechanism by which this condition becomes life threatening is key in our quest for the discovery of therapeutic solutions and preventative measures," said Stephan Herzig.

Loss of identity results in dysfunction

The researchers used comparative genomics to analyze mechanisms that control the development and specialized functions of the most abundant cell type in the liver, the hepatocyte. "Our results demonstrated that during progression to non-alcoholic steatohepatitis, hepatocytes suffer from partial identity loss, they are re-programmed," explained Anne Loft, first co-author of the article.

The hepatocyte reprogramming is tightly controlled by a network of proteins acting as molecular switches, so-called 'transcription factors'. Their activity results in the dysfunction of hepatocytes. The network of transcription factors that controls this process also plays a role in fibrosis progression. "These findings are important because they unravel the cellular mechanisms underlying non-alcoholic steatohepatitis. Knowing about the role of the protein networks and the identity loss of hepatocytes gives us potential intervention targets for the development of effective therapies" says Ana Alfaro, first co-author of the article.

Future work

Based on these findings, it will now be possible to develop novel approaches to effectively target certain nodes in the protein network to prevent disease progression or even revert existing fibrosis, something that is still not possible to-date.

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Brain regions responsible for intoxicating effects of alcohol

The slurred speech, poor coordination, and sedative effects of drinking too much alcohol may actually be caused by the breakdown of alcohol products produced in the brain, not in the liver as scientists currently think. That is the finding of a new study led by researchers from the University of Maryland School of Medicine (UMSOM) and the National Institute on Alcohol Abuse and Alcoholism. It was published recently in the journal Nature Metabolism and provides new insights into how alcohol may affect the brain and the potential for new treatments to treat alcohol misuse.

It is well known that the liver is the major organ that metabolizes alcohol, using the enzyme alcohol dehydrogenase to convert alcohol into a compound called acetaldehyde. Acetaldehyde, which has toxic effects, is quickly broken down into a more benign substance called acetate. This occurs through a different enzyme called acetaldehyde dehydrogenase 2 (ALDH2). Until now, alcohol and acetaldehyde, produced by the liver, have been considered important players in triggering the cognitive impairment associated with imbibing. Acetate, on the other hand, was considered relatively unimportant in producing effects like motor impairment, confusion, and slurred speech. Researchers also did not know which brain region or particular brain cells were most important for alcohol metabolism.

To learn more about the role played by the brain in alcohol metabolism, the researchers measured the distribution of ALDH2 enzyme in the cerebellum, using magnetic resonance (MR) scanners in both mice and in human tissue. They observed that ALDH2 was expressed in the cerebellum, in a type of nerve cell called an astrocyte, in both human brain tissue and in living mice.

The researchers found that this enzyme controlled the conversion of acetaldehyde into acetate in the brain. They also found alcohol-induced cellular and behavioral effects in specific regions of the brain where this enzyme was expressed. Acetate was found to interact with the brain messenger chemical called GABA, which is known to decrease activity in the nervous system. This decreased activity can lead to drowsiness, impair coordination, and lower normal feelings of inhibition.

"We found ALDH2 was expressed in cells known as astrocytes in the cerebellum, a brain region that controls balance and motor coordination," said Qi Cao, PhD, Assistant Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine. "We also found that when ALDH2 was removed from these cells, the mice were resistant to motor impairment inducted by alcohol consumption."

Su Xu, PhDHe and his team also found the enzyme ALDH2 in other brain regions responsible for emotional regulation and decision-making (both impaired by excess alcohol consumption), including in the hippocampus, amydala, and prefrontal cortex.

These findings suggest that certain brain regions are important for alcohol metabolism and that abnormalities in the enzyme production in these brain regions can lead to detrimental effects associated with alcohol misuse. They also suggest that acetate produced in the brain and in the liver differ in their ability to affect motor and cognitive function.

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Health declining in Gen X and Gen Y, US study shows

 Recent generations show a worrying decline in health compared to their parents and grandparents when they were the same age, a new national study reveals.

Researchers found that, compared to previous generations, members of Generation X and Generation Y showed poorer physical health, higher levels of unhealthy behaviors such as alcohol use and smoking, and more depression and anxiety.

The results suggest the likelihood of higher levels of diseases and more deaths in younger generations than we have seen in the past, said Hui Zheng, lead author of the study and professor of sociology at The Ohio State University.

"The worsening health profiles we found in Gen X and Gen Y is alarming," Zheng said.

"If we don't find a way to slow this trend, we are potentially going to see an expansion of morbidity and mortality rates in the United States as these generations get older."

Zheng conducted the study with Paola Echave, a graduate student in sociology at Ohio State. The results were published yesterday (March 18, 2021) in the American Journal of Epidemiology.

The researchers used data from the National Health and Nutrition Examination Survey 1988-2016 (62,833 respondents) and the National Health Interview Survey 1997-2018 (625,221 respondents), both conducted by the National Center for Health Statistics.

To measure physical health, the researchers used eight markers of a condition called metabolic syndrome, a constellation of risk factors for heart disease, stroke, kidney disease and diabetes. Some of the markers include waist circumference, blood pressure, cholesterol level and body mass index (BMI). They also used one marker of chronic inflammation, low urinary albumin, and one additional marker of renal function, creatinine clearance.

The researchers found that the measures of physical health have worsened from the Baby Boomer generation through Gen X (born 1965-80) and Gen Y (born 1981-99). For whites, increases in metabolic syndrome were the main culprit, while increases in chronic inflammation were seen most in Black Americans, particularly men.

"The declining health trends in recent generations is a shocking finding," Zheng said. "It suggests we may have a challenging health prospect in the United State in coming years."

Zheng said it is beyond the scope of the study to comprehensively explain the reasons behind the health decline. But the researchers did check two factors. They found smoking couldn't explain the decline. Obesity could help explain the increase in metabolic syndrome, but not the increases seen in chronic inflammation.

It wasn't just the overall health markers that were concerning for some members of the younger generations, Zheng said.

Results showed that levels of anxiety and depression have increased for each generation of whites from the War Babies generation (born 1943-45) through Gen Y.

While levels of these two mental health indicators did increase for Blacks up through the early Baby Boomers, the rate has been generally flat since then.

Health behaviors also show worrying trends.

The probability of heavy drinking has continuously increased across generations for whites and Black males, especially after late-Gen X (born 1973-80).

For whites and Blacks, the probability of using street drugs peaked at late-Boomers (born 1956-64), decreased afterward, then rose again for late-Gen X. For Hispanics, it has continuously increased since early-Baby Boomers.

Surprisingly, results suggest the probability of having ever smoked has continuously increased across generations for all groups.

How can this be true with other research showing a decline in overall cigarette consumption since the 1970s?

"One possibility is that people in older generations are quitting smoking in larger numbers while younger generations are more likely to start smoking," Zheng said. "But we need further research to see if that is correct."

Zheng said these results may be just an early warning of what is to come.

"People in Gen X and Gen Y are still relatively young, so we may be underestimating their health problems," he said. "When they get older and chronic diseases become more prevalent, we'll have a better view of their health status."

Zheng noted that the United States has already seen recent decreases in life expectancy and increases in disability and morbidity.

Read more at Science Daily

Like wine, environmental conditions impact flavor of whiskey, study finds

 Flavor differences in whiskey can be discerned based solely on the environment in which the barley used to make the whiskey is grown, a new study co-authored by an Oregon State University researcher found.

This is first scientific study that found the environmental conditions, or terroir, of where the barley is grown impacts the flavor of whiskey, said Dustin Herb, an author of the study and a courtesy faculty member in the Department of Crop and Soil Science at Oregon State University.

"Terroir is increasingly being used to differentiate and market agricultural products, most commonly wine, as consumers grow more interested in the origins of their food," Herb said. "Understanding terroir is something that involves a lot of research, a lot of time and a lot of dedication. Our research shows that environmental conditions in which the barley is grown have a significant impact."

Herb, who is originally from Lebanon, Oregon, and earned his undergraduate and doctoral degrees from Oregon State, is the only American author of the study, which was published in the journal Foods. The other authors are all from Ireland, where the study was conducted.

Herb's doctoral research at Oregon State with Pat Hayes, a barley breeder in the College of Agricultural Sciences, focused on the contributions of barley to beer flavor. Their research found notable differences in the taste of beers malted from barley varieties reputed to have flavor qualities.

That research caught the attention of Waterford Distillery. The Irish distillery reached out to Herb, flew him to Ireland and asked him if he could design a study that would attempt to answer the question of whether terroir exists in whiskey. They dubbed it The Whisky Terroir Project. (Whiskey can be spelled with and without an "e.")

Herb designed a study that involved planting two common commercial varieties of barley in Ireland -- Olympus and Laureate -- in two distinct environments: Athy, Co. Kildare and Buncloudy, Co. Wexford in 2017 and 2018. Athy is an inland site and Buncloudy is a coastal site. They were selected in part because they have different soil types and different temperature ranges and rainfall levels during the barley growing season.

The crops of each barley variety at each site in each year were harvested, stored, malted and distilled in a standardized way. Once distilled, the product is called "new make spirit." (It isn't called whiskey until it is matured in a wooden cask for at least three years.)

The researchers used gas chromatography mass spectrometry and the noses of a six-person trained sensory panel to determine which compounds in the barley most contributed to the aroma of the new make spirit.

That analysis, along with further mathematical and statistical analysis, found that the environment in which the barley was grown had a greater contribution to the aroma of the whiskey than the variety of the barley. That was the clear indication of the impact terroir has on the new make spirit.

Furthermore, the sensory analysis found distinct differences in the aroma characteristics of the new make spirit from the barley grown in each location. In Athy, it was more positively associated with sweet, cereal/grainy, feinty/earthy, oily finish, soapy, sour, stale and mouldy sensory attributes and in Bunclody it was more associated with dried fruit and solventy attributes.

"What this does is actually make the farmer and the producer come to the forefront of the product," Herb said. "It gets to the point where we might have more choices and it might provide an opportunity for a smaller brewer or a smaller distiller or a smaller baker to capitalize on their terroir, like we see in the wine industry with a Napa Valley wine, or Willamette Valley wine or a French Bordeaux."

The sensory analysis also found differences in the aromatic profiles between the 2017 and 2018 seasons that were studied.

"This makes us think there might be a vintage aspect to the whiskey like wine, where you buy a 2019 or a 2020 or a 2016," Herb said. "Could the whiskey industry operate in a similar way, where someone is going to seek out a certain vintage of a certain year?"

To answer that question, more research needs to be done, Herb said. That is a project the Whisky Terroir Project plans to tackle: examining flavor changes in the spirits as they mature in casks and to see what happens with the terroir impact.

The team is also scaling up the research to study terroir in commercial-scale barley fields over a five-year period.

In addition to Herb, who also works full-time as a plant breeder at Albany, Oregon-based OreGro, which develops turf and forage products, other authors of the paper are: Maria Kyraleou and Kieran Kilcawley of the Teagasc Food Research Park; Grace O'Reilly and Neil Conway of Waterford Distillery; and Tom Bryan of Boormalt.

Read more at Science Daily