Genetic study provides evidence that alcohol accelerates biological aging

by University of Oxford

Credit: Unsplash/CC0 Public Domain

The short-term effects of excessive drinking are well known, but to date it has been less certain whether alcohol also accelerates the aging process.

31 jul 2022--Traditionally, investigating this has been challenging due to the lack of reliable methods to measure biological aging. In addition, it was not clear from observational studies whether alcohol was the true cause of any effect, or if it was linked to other factors, such as socio-economic status.

Today, researchers from Oxford Population Health have published results from a new genetic-based analysis which suggest that alcohol directly accelerates aging by damaging DNA in telomeres. The findings are published today in Molecular Psychiatry.

Telomeres are repetitive DNA sequences that cap the end of chromosomes, protecting them from damage. Telomere length is considered an indicator of biological aging, since 50-100 DNA bases are lost each time a cell replicates. Once telomeres become too short, cells can no longer divide and may even die. Previous studies have linked shorter telomere lengths with several aging-related diseases including Alzheimer's disease, cancer, and coronary artery disease.

In this analysis, the researchers investigated the association between alcohol intake and telomere length in over 245,000 participants in the UK Biobank. They used a genetic approach called Mendelian Randomisation (MR), the first time this has been applied to investigate the effects of alcohol on aging. This method uses 'genetic proxies' to predict the level of exposure for each participant.

For this study, the researchers used genetic variants that have previously been associated with alcohol consumption and alcohol use disorders in large-scale genome-wide association studies.

To complement the MR analysis, the researchers also performed an observational assessment, based on the participants' self-reported weekly alcohol intake at recruitment.

In the observational analysis, there was a significant association between high alcohol intake and shorter telomere length. Compared with drinking less than 6 units of alcohol a week (about two large 250ml glasses of wine), drinking more than 29 units weekly (about ten 250ml glasses of 14% alcohol by volume wine) was associated with between one and two years of age-related change on telomere length.

Individuals who had been diagnosed with an alcohol-use disorder had significantly shorter telomere lengths compared with controls, equivalent to between 3 and 6 years of age-related change.

Similarly, in the MR analysis, higher genetically-predicted alcohol consumption was associated with shorter telomere length. An increase from 10 units to 32 units per week was associated with the equivalent of 3 years of aging.

However, the association between genetically-predicted alcohol consumption and telomere length was only significant for those drinking more than 17 units per week. This suggests that a minimum amount of alcohol consumption may be required to damage telomeres.

The MR analysis also found a significant association between genetically-predicted alcohol-use disorder and telomere length, equivalent to around 3 years of aging.

Most of the participants were current drinkers, with only 3% being never drinkers and 4% being previous drinkers. 51% were men, 49% were women, and the average age was 57 years.

Study lead, Dr. Anya Topiwala from Oxford Population Health, says that "These findings support the suggestion that alcohol, particularly at excessive levels, directly affects telomere length. Shortened telomeres have been proposed as risk factors which may cause a number of severe age-related diseases, such as Alzheimer's disease. Our results provide another piece of information for clinicians and patients seeking to reduce the harmful effects of excess alcohol. Furthermore, the dose of alcohol is important—even reducing drinking could have benefits."

For both the observational and MR analysis, telomere lengths were measured using leucocytes (immune system cells) from the participants' DNA samples collected when participants were first recruited to the UK Biobank.

In the MR analysis, alcohol intake was estimated by screening DNA samples for 93 genetic variants that have previously been associated with weekly alcohol consumption, besides 24 variants that have previously been linked to a diagnosis of an alcohol use disorder. Because these genetic variants are randomly allocated and fixed before birth, the results give greater confidence that alcohol directly affects telomere length, rather than a different factor being responsible.

Although these results do not conclusively prove that alcohol directly affects telomere length, two findings from the study support this being the case. 1) Effects were only found in current drinkers, and not previous or never-drinkers; 2) The most influential genetic variant in the MR analysis was AD1HB, an alcohol metabolism gene.

According to the research team, a potential biological mechanism to explain alcohol's influence on telomere length is increased oxidative stress and inflammation. The process which breaks down ethanol in the body can both produce reactive oxidative species that damage DNA and reduce levels of antioxidant compounds that protect against oxidative stress.

Dr. Richard Piper, Chief Executive of Alcohol Change UK, says that they "welcome all research into the effects of alcohol on the human body. This particular study shows clear links between consuming alcohol and aging, and points towards a possible link between alcohol and Alzheimer's. The researchers are transparent that this study does not prove a causal link, but they also make a well-argued case about the likely biological mechanism. In general, there is an ever-larger body of science showing how, exactly, alcohol causes so much ill-health and so many early deaths."

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More information: A. Topiwala et al, Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol's effects, Molecular Psychiatry (2022). DOI: 10.1038/s41380-022-01690-9

Journal information: Molecular Psychiatry 

 

More alcohol, less brain: Study finds an association that begins with an average of just one drink a day

by University of Pennsylvania

Credit: Pixabay/CC0 Public Domain

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.

09 mar 2022--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."

In other words, Nave says, "the people who can benefit the most from drinking less are the people who are already drinking the most."

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More information: Associations between alcohol consumption and gray and white matter volumes in the UK Biobank, Nature Communications (2022). DOI: 10.1038/s41467-022-28735-5

Journal information: Nature Communications 

Going for a checkup? You may be screened for alcohol use

Credit: CC0 Public Domain

Here's to your health. Screening and counseling for unhealthy alcohol use could become part of a standard doctor's visit, according to the United States Preventive Services Task Force. The organization, funded and staffed by the U.S. Department of Health and Human Services, published its recommendation in the medical journal JAMA.

16 nov 2018--The United States Preventive Services Task Force "recommends screening for unhealthy alcohol use in primary care settings in adults 18 years or older, including pregnant women, and providing persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce unhealthy alcohol use," according to the report. The organization didn't conclude such a screening was necessary for underage drinkers.
According to the abstract at the start of the report, an estimated 88,000 alcohol-attributed deaths occurred annually between 2006 and 2010 in the U.S. That number includes "acute conditions" such as car accidents and "chronic conditions" such as liver disease.
The report cites statistics from the National Institute on Alcohol Abuse and Alcoholism to define "risky use" of alcohol as exceeding the recommended limits of four drinks per day or 14 drinks per week for healthy adult men aged 21 to 64. For women, "risky" drinking is defined as three drinks per day or seven drinks per week. That standard also applied to men 65 or older.
A standard drink, according to the study, is defined as a 12-ounce beer (5 percent alcohol), a 5-ounce wine (12 percent alcohol) or 1.5 ounces of liquor (40 percent alcohol).

Alcohol drinking in the elderly: Risks and benefits

The Royal College of Psychiatrists of London has published a report related primarily to problems of unrecognized alcohol misuse among the elderly. The report provides guidelines for psychiatrists and family physicians on how to find and how to treat elderly people with misuse of alcohol and drugs. Forum members consider it very important to identify abusive drinking among the elderly and this report provides specific and very reasonable recommendations to assist practitioners in both the identification and treatment of such problems.

04 july 2011--There is no question that, on average, very elderly people may be more sensitive to the effects of alcohol (especially those individuals with chronic diseases, lower muscle mass, a poor diet, etc.) It should be made clear, however, that 65-year-olds are healthier than people of that age a generation ago - age-specific disability rates are decreasing, not increasing.

The report also recommends lower "sensible limits" for older people in comparison with younger people The International Forum on Alcohol Research scientific reviewers point out inherent difficulties in providing guidelines for a very non-homogenous group of individuals whose only criterion for inclusion, in this paper, is being above the age of 65 years Such a group includes individuals varying from marathon runners to very sick, frail people.

The report was conspicuously lacking in a discussion of the important role that moderate drinking can play in reducing the risk of coronary heart disease, ischemic stroke, diabetes, dementia, and osteoporosis. Advising healthy people aged 65 years or older who are moderate, responsible drinkers to stop drinking or to markedly reduce their intake would not be in their best health interests, especially in terms of their risk of cardiovascular diseases. Forum reviewers thought that advice to lower limits of drinking for everyone in this age group is not based on reliable research, and would certainly not apply to all in this age group. Of more importance, the absolute risk for cardiovascular diseases increases markedly with age, and therefore the beneficial or protective effect of light to moderate drinking on cardiovascular diseases is greater in the elderly than in younger people.

Evidence is also accumulating that shows that the risk of Alzheimer's disease and other types of dementia is lower among moderate drinkers than among abstainers. Neurodegenerative disorders are key causes of disability and death among elderly people. Epidemiological studies have suggested that moderate alcohol consumption, may reduce the incidence of certain age-related neurological disorders including Alzheimer's disease. Regular dietary intake of flavonoid-rich foods and/or beverages has been associated with 50% reduction in the risk of dementia, a preservation of cognitive performance with ageing,a delay in the onset of Alzheimer's disease and a reduction in the risk of developing Parkinson's disease.

Further, scientific data are consistent in demonstrating that quality of life is better and total mortality is lower among moderate drinkers than among abstainers. For example, analyses by Simons et al from a large population-based patient population in New South Wales demonstrated clearly that regular moderate alcohol consumption increases life span and quality of life for men up to 80 years of age and for women indefinitely.

In another paper, by Kirchner et al of almost 25,000 American adults over age 65 seen in primary care, those reporting between 8 and 14 drinks/week (A US drink is 14g, against 8g in the UK) did not differ significantly in their characteristics from drinkers consuming 1-7 drinks/week.. Heavier drinkers and binge drinkers did not do as well.

A particular interesting paper by White et al showed a direct dose-response relation between alcohol consumption and risk of death in women aged 16-54 and in men aged 16-34, whereas at older ages the relation is U shaped. These investigators used statistical models relating alcohol consumption to the risk of death from single causes to estimate the all-cause mortality risk for men and women of different ages. The authors state that their data suggest that women should INCREASE their intake to 3 units a day over age 75, and men rise from 3 units a day up to age 54 to 4 units a day up to age 84.

Since the absolute effects of moderate drinking on cardiovascular disease are much greater in older people than in younger adults, the current limitations to intake for the elderly may not be appropriate. Attempting to persuade elderly people who currently drink moderately to decrease their current intake may not be advisable. For healthy moderate and responsible drinkers, advice to reduce or stop all alcoholic beverage intake would not be in the best health interests of such individuals.

More information: Royal College of Psychiatrists, London. Our invisible addicts. First Report of the Older Persons' Substance Misuse Working Group of the Royal College of Psychiatrists, College Report CR165. June 2011. http://www.bu.edu/ … 6-june-2011/

Provided by Boston University Medical Center

Alcohol Use And Cognitive Decline Among The Elderly

Studies of alcohol use and cognition among the elderly are rare and have mixed results. A study of drinking among the elderly in Brazil has found that heavy alcohol use is associated with more memory and cognitive problems than mild-to-moderate alcohol use, especially among women.

10 feb 2010--Results will be published in the April 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"There is a scarcity of information about alcohol use and the elderly," said Marcos Antonio Lopes, corresponding author for the study and currently a visiting lecturer at Newcastle University in the United Kingdom, "which needs to be resolved in order to construct a real diagnosis and promote proper health care for this population."

Jerson Laks, associate professor at the State University of Rio de Janeiro and a researcher with the Brazilian National Committee for Research, agrees. "Alcohol use is frequently an exclusion criterion for any study of cognition and dementia in the elderly, as well as in studies aimed at depression," he said. "Therefore, by simply excluding alcohol use and abuse, most studies cannot reveal the interaction between drinking behaviors and cognition in this age range."

The current study is also important, Laks added, because it did not have any expectations that the elderly would drink less than younger subjects and, furthermore, it asked many difficult questions despite their negative stigmas in order to uncover the facts about drinking among the elderly in Brazil and its association with dementia.

Lopes and his colleagues recruited a sample of 1,145 individuals who were 60 years of age and older (419 men, 726 women), from different socioeconomic levels, and examined them in two phases. The first phase used several instruments, including the CAGE questionnaire, a four-question screening test for alcohol dependence, to identify potential alcohol-related problems, as well as a screening test for dementia to identify cognitive and functional impairment. The second phase used the Cambridge Mental Disorders of the Elderly Examination, as well as the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition, to establish a clinical diagnosis of dementia.

"We found that heavy alcohol use among the elderly people we investigated was high at 8.2 percent and affected principally men from low socioeconomic levels," said Lopes. "However, the effects of heavy alcohol use on memory and other cognitive functions were more evident in women." Lopes added that their finding of 8.2 percent was greater than expected, when compared to previous studies, but that the fundamental lack of information in this area of study makes comparisons difficult.

"This study shows that older people keep drinking along the life span," said Laks. "Taking into consideration that drinking may lead to falls and to cognitive impairment when heavy use is the case, this study creates important awareness about this issue."

Source:

Marcos Antonio Lopes, Ph.D.
University of São Paulo

Jerson Laks, M.D., Ph.D.
State University of Rio de Janeiro

Alcoholism: Clinical & Experimental Research

Study shows 1 in 25 deaths worldwide attributable to alcohol

CAMH researcher sees glass 'as half full'

Toronto, 27 june 2009-- Research from Canada's own Centre for Addiction and Mental Health (CAMH) featured in this week's edition of the Lancet shows that worldwide, 1 in 25 deaths are directly attributable to alcohol consumption. This rise since 2000 is mainly due to increases in the number of women drinking.

CAMH's Dr Jürgen Rehm and his colleagues found that alcohol-attributable disorders are among the most disabling disease categories within the global burden of disease, especially for men. And in contrast to other traditional risk factors for disease, the burden attributable to alcohol lies more with younger people than with the older population.

Dr. Rehm still takes an optimistic 'glass half full' response to this large and increasing alcohol-attributable burden. "Today, we know more than ever about which strategies can effectively and cost-effectively control alcohol-related harms," Dr. Rehm said today. "Provided that our public policy makers act on these practical strategies expeditiously, we could see an enormous impact in reducing damage."

The study showed that Europe had a high proportion of deaths related to alcohol, with 1 in 10 deaths directly attributable (up to 15% in the former Soviet Union). Average alcohol consumption in Europe in the adult population is somewhat higher than in North America: 13 standard drinks per person per week (1 standard drink = 13.6 grams of pure ethanol and corresponds to a can of beer, one glass or wine and one shot of spirits) compared to North America's 10 to 11 standard drinks. The recent Canadian consumption rate is equivalent of almost 9 standard drinks per person per week age 15 plus, and has been going up, as has high risk drinking. Globally, the average is around 7 standard drinks per person per week (despite the fact that most of the adult population worldwide actually abstains from drinking alcohol).

Most of the deaths caused by alcohol were through injuries, cancer, cardiovascular disease, and liver cirrhosis.

"Globally, the effect of alcohol on burden of disease is about the same size as that of smoking in 2000, but it is relatively greatest in emerging economies. Global consumption is increasing, especially in the most populous countries of India and China."

CAMH is known for its pioneering research in the most effective ways of reducing the burden of alcohol. For example, CAMH endorsed the legislative change implemented this year requiring young Ontario drivers to maintain a 0% blood alcohol content; in many jurisdictions this measure has reduced alcohol-related crashes and saved lives.

Other evidence-based policies proven to reduce harms include better controls on access to alcohol through pricing interventions and outlet density restrictions as well as more focused strategies such as violence reduction programs in licensed premises. Within health care, provision of screening and brief interventions for high risk drinkers has enormous potential to reduce the contribution of alcohol to the onset of cancer and other chronic diseases.

"There are significant social, health and economic problems caused by alcohol," said Gail Czukar, CAMH's executive vice-president, Policy, Education and Health Promotion. "But research gives us sound, proven interventions that governments and health providers can use to address these problems."

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To arrange an interview please contact Kirk LeMessurier, CAMH Media Relations, at 416 595 6015 or kirk_lemessurier@camh.net

The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and addiction teaching hospital, as well as one of the world's leading research centres in the area of addiction and mental health. CAMH combines clinical care, research, education, policy development, prevention and health promotion to help transform the lives of people affected by mental health and addiction issues.

Moderate alcohol consumption may help seniors keep disabilities at bay

15 jan 2009--It is well known that moderate drinking can have positive health benefits — for instance, a couple of glasses of red wine a day can be good for the heart. But if you're a senior in good health, light to moderate consumption of alcohol may also help prevent the development of physical disability.

That's the conclusion of a new UCLA study, available in the online edition of the American Journal of Epidemiology, which found that light to moderate drinking among these seniors reduced their odds of developing physical problems that would prevent them from performing common tasks such as walking, dressing and grooming.

"If you start out in good health, alcohol consumption at light to moderate levels can be beneficial," said lead study author Dr. Arun Karlamangla, an associate professor of medicine in the division of geriatrics at the David Geffen School of Medicine at UCLA. "But if you don't start out healthy, alcohol will not give you a benefit."

The researchers based their study on data from three waves of the National Health and Nutrition Examination Survey's Epidemiologic Follow-up Study (1982󈟀, 1987 and 1992). The sample, which included 4,276 people split evenly between male and female, was about 92 percent white, with a mean age of 60.4 years.

Drinkers were classified as light to moderate if they consumed less than 15 drinks per week and less than five drinks per drinking day (less than four per day for women). Heavy drinkers were those who consumed 15 or more drinks per week or five or more per drinking day (four or more for women). Abstainers were those who drank fewer than 12 alcoholic beverages the previous year.

Having a physical disability means having trouble performing, or being unable to perform, routine tasks such as dressing and grooming, personal hygiene, arising, eating, walking, gripping, reaching, and doing daily errands and chores. Participants were asked if they experienced no difficulty, some difficulty, much difficulty or were unable to do these activities at all when alone and without the use of aids.

At the start of the survey, 32 percent of men and 51 percent of women abstained from drinking, 51 percent of men and 45 percent of women were light to moderate drinkers, and 17 percent of men and 4 percent women were heavy drinkers.

No one had any disabilities at the outset, but 7 percent died and 15 percent became disabled over five years.

The researchers found that light to moderate drinkers in good health had a lower risk for developing new disabilities, compared with both abstainers and heavy drinkers.

In unadjusted analyses, light to moderate drinkers had a 17.7 percent chance of becoming disabled or dying in five years, compared with 26.7 percent for abstainers and 21.4 percent for heavy drinkers. Among survivors, the risk for new disability was 12.5 percent for light to moderate drinkers, compared with 20 percent for abstainers and 15.6 percent for heavy drinkers.

However, after controlling for confounding variables such as age, smoking, exercise, heart attacks and strokes, the benefits of alcohol consumption were seen only in seniors who rated their health as good or better: There was a 3 to 8 percent reduction in the odds of developing disability with each additional drink per week in older men and women in good or better health who were not heavy drinkers, but there was no such benefit seen in those who rated their health as fair or poor.

"Light to moderate alcohol consumption appears to have disability prevention benefits only in men and women in relatively good health," the researchers wrote. "It is possible that those who report poor health have progressed too far on the pathway to disability to accrue benefits from alcohol consumption and that alcohol consumption may even be deleterious for them."

Other study authors were Catherine A. Sarkisian, Deborah M. Kado, Howard Dedes, Diana H. Liao, Sungjin Kim, David B. Reuben, Gail A. Greendale and Alison A. Moore, all of the David Geffen School of Medicine. Sarkisian is also affiliated with the Geriatric Research Education and Clinical Center of the Veterans Affairs Greater Los Angeles Healthcare System.

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The study was supported by funding from the John A. Hartford Foundation/American Federation for Aging Research Medical Student Geriatrics Scholars Program; the National Institute on Alcohol Abuse and Alcoholism; and the Claude D. Pepper Older Americans Independence Center of the National Institute on Aging.

UCLA is California's largest university, with an enrollment of nearly 38,000 undergraduate and graduate students. The UCLA College of Letters and Science and the university's 11 professional schools feature renowned faculty and offer more than 323 degree programs and majors. UCLA is a national and international leader in the breadth and quality of its academic, research, health care, cultural, continuing education and athletic programs. Four alumni and five faculty have been awarded the Nobel Prize.

For more news, visit the UCLA Newsroom.

Drinking alcohol associated with smaller brain volume

14 oct 2008--The more alcohol an individual drinks, the smaller his or her total brain volume, according to a report in the October issue of Archives of Neurology, one of the JAMA/Archives journals.
Brain volume decreases with age at an estimated rate of 1.9 percent per decade, accompanied by an increase in white matter lesions, according to background information in the article. Lower brain volumes and larger white matter lesions also occur with the progression of dementia and problems with thinking, learning and memory. Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease; because the brain receives blood from this system, researchers have hypothesized that small amounts of alcohol may also attenuate age-related declines in brain volume.
Carol Ann Paul, M.S., of Wellesley College, Mass., and colleagues studied 1,839 adults (average age 60) who were part of the Framingham Offspring Study, which began in 1971 and includes children of the original Framingham Heart Study participants and their spouses. Between 1999 and 2001, participants underwent magnetic resonance imaging (MRI) and a health examination. They reported the number of alcoholic drinks they consumed per week, along with their age, sex, education, height, body mass index and Framingham Stroke Risk Profile (which calculates stroke risk based on age, sex, blood pressure and other factors).
"Most participants reported low alcohol consumption, and men were more likely than women to be moderate or heavy drinkers," the authors write. "There was a significant negative linear relationship between alcohol consumption and total cerebral brain volume."
Although men were more likely to drink alcohol, the association between drinking and brain volume was stronger in women, they note. This could be due to biological factors, including women's smaller size and greater susceptibility to alcohol's effects.
"The public health effect of this study gives a clear message about the possible dangers of drinking alcohol," the authors write. "Prospective longitudinal studies are needed to confirm these results as well as to determine whether there are any functional consequences associated with increasing alcohol consumption. This study suggests that, unlike the associations with cardiovascular disease, alcohol consumption does not have any protective effect on brain volume."
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(Arch Neurol. 2008; 65[10]:1363-1367. Available pre-embargo to the media at www.jamamedia.org.)

ASH: Excessive Drinking Linked to Structural and Functional Heart Changes

By Peggy Peck
21 may b2008--Use this code to embed video on your website or blog:' name=embed_code>
NEW ORLEANS, May 20 -- The well-known cardiac benefits of red wine aside, too much alcohol can be bad for the heart, according to a study of Irish drinkers.The damage differs by gender, said Azra Mahmud, M.D., Ph.D., of St. James Hospital in Dublin, at the American Society of Hypertension meeting here. For women, consuming more than two stiff drinks daily may lead to big hearts, and for men, more than three drinks a day can lead to stiff ventricles and stiff arteries, she said.
Dr. Mahmud and colleagues studied 200 consecutive patients seen at her hypertension clinic for initial assessment of elevated blood pressure. On the basis of self reports, patients were classified as nondrinkers, moderate drinkers (one to 21 units of alcohol per week for men and one to 14 for women), or excessive drinkers (more than 21 units for men and more than 14 for women).
Approximately 10% of the women in the study and 35% of the men were excessive drinkers and about 20% of men and women were nondrinkers, she said.
The patients were assessed with echocardiography with tissue Doppler imaging, and arterial stiffness was measured with pulse-wave velocity and augmentation index.
Blood pressure was measured with a digital oscillometric monitor after a supine rest of 15 minutes and also by 24-hour ambulatory blood pressure monitoring.
Laboratory measurements included fasting glucose and lipids, serum creatinine, and liver enzymes.
Among men, there was a linear relationship between alcohol intake and increasing aortic systolic and diastolic pressure, augmentation index, pulse-wave velocity, and indices of diastolic function (P <0.05 versus non-drinkers). "There was evidence of this effect even among men who were moderate drinkers," she said.
Women had no evidence of these effects even among heavy drinkers, she said, but there was "evidence of direct cardiac toxicity as there was a dose-response relationship between alcohol intake and thickening of the left ventricular septal (P<0.05) and posterior wall thickness and generally very high levels of left ventricular mass (P<0.01)."
Moreover, there was a tendency toward a slight decrease in left ventricular function -- 58% versus 65% among women who were non-drinkers. So while the ejection fraction was still normal, "it was clearly trending in the wrong direction."
Moreover, Dr. Mahmud said the changes observed in drinkers were "what we would expect to see in older people who have a long history -- 10 years or more -- of hypertension, not what we would expect in a younger population with new onset hypertension."
The mean age of women who were heavy drinkers was 42, and the mean age of the men who were heavy drinkers was 28.
She said she decided to investigate the relationship between alcohol intake and hypertension because there has been a great deal of interest in the "beneficial effect of red wine on coronary artery disease and that message has resonated with the public."
Ireland has been enjoying an economic boon since the 1990s. With prosperity has come "a great interest in wine and wine consumption and I have been observing what appears to be an increase in binge drinking."
The study was investigator initiated and funded. Dr. Mahmud disclosed no financial conflicts.
Primary source: American Society of HypertensionSource reference:Mahmud A, et al "The demon drink, deleterious effects of alcohol on the heart and blood vessels in hypertension" ASH Meeting 2008; Abstract P80.

Adopting Moderate Alcohol Consumption in Middle Age: Subsequent Cardiovascular Events

Dana E. King
11 may 2008--Moderate alcohol use is part of a healthy lifestyle, yet current guidelines caution nondrinkers against starting to drink alcohol in middle age. The purpose of this study was to evaluate whether adopting moderate alcohol consumption in middle age would result in subsequent lower cardiovascular risk.
Methods
This study examined a cohort of adults aged 45-64 years participating in the Atherosclerosis Risk in Communities study over a 10-year period. The primary outcome was fatal or nonfatal cardiovascular events.
Results
Of 7697 participants who had no history of cardiovascular disease and were nondrinkers at baseline, within a 6-year follow-up period, 6.0% began moderate alcohol consumption (2 drinks per day or fewer for men, 1 drink per day or fewer for women) and 0.4% began heavier drinking. After 4 years of follow-up, new moderate drinkers had a 38% lower chance of developing cardiovascular disease than did their persistently nondrinking counterparts. This difference persisted after adjustment for demographic and cardiovascular risk factors (odds ratio 0.62, 95% confidence interval, 0.40-0.95). There was no difference in all-cause mortality between the new drinkers and persistent nondrinkers (odds ratio 0.71, 95% confidence interval, 0.31-1.64).
Conclusion
People who newly begin consuming alcohol in middle age rarely do so beyond recommended amounts. Those who begin drinking moderately experience a relatively prompt benefit of lower rates of cardiovascular disease morbidity with no change in mortality rates after 4 years.

Halting Heavy Drinking Cuts Esophageal and Head-and-Neck Cancer Risks

TORONTO, Sept. 27 -- Stopping heavy drinking can significantly reduce the risk of esophageal and head-and-neck cancers, primarily squamous-cell carcinomas, researchers here said.
In a pooled analysis of 13 studies, those who quit heavy drinking saw their risk of esophageal cancer and head and neck cancer return to normal after 20 years, according to Jürgen Rehm, Ph.D., of the Centre for Addiction and Mental Health and colleagues.
But the first few years after stopping saw a significant rise in development of both types of cancer, he and colleagues reported in the September issue of the International Journal of Cancer.
The researchers postulated that the increase immediately after quitting was the result of what they called the "sick quitter" effect, in which patients stop drinking because they are already suffering symptoms of cancer, although it had not yet been diagnosed.
But after five years in the case of esophageal cancer and 10 years for head and neck cancers, the risk begins to drop, Dr. Rehm and colleagues said.
"Alcohol cessation has very similar effects on risk for head and neck cancers as smoking cessation has on lung cancer. Dr. Rehm said. "It takes about two decades before the risk is back to the risk of those who were never drinkers or never smokers."
The finding comes from 13 case-control studies - five in esophageal cancer and eight in head and neck cancer - that included more than 5,000 cases, the researchers said. Most of the studies involved squamous-cell carcinoma.
Compared with current drinkers, people who have never used alcohol had a risk ratio for esophageal cancer of 0.37 and for head and neck cancers of0.46. Both risk reductions were significant at P<0.001.
For former drinkers (compared with current drinkers) the risk first rose and then fell:
The risk ratio for esophageal cancer in the first two years after stopping was 2.5, with a 95% confidence interval from 2.23 to 2.80, which was significant at P<0.001.
Between five and 10 years after stopping, the risk of esophageal cancer was significantly reduced (at P<0.001) with a risk ratio of 0.85 and a 95% confidence interval from 0.78 to 0.92.
By 15 years, the risk ratio for esophageal cancer was the same as that for a person who had never used alcohol - 0.37.
The risk for head and neck cancers remained high for the first 10 years after going on the wagon. The risk ratio for people between five and 10 years after they quit was 1.26, with a 95% confidence interval from 1.18 to 1.35, which was significant at P<0.001.
But between 10 and 15 years later, the risk ratio was 0.67, with a 95% confidence interval from 0.63 to 0.73, which was significant at P<0.001.
The risks did not change substantially when the researchers adjusted for smoking.
Dr. Rehm and colleagues noted that the study is limited because they treated drinking as an all-or-nothing issue, and were unable to estimate dose-response effects.
They also noted the analysis is entirely based on retrospective studies, which opens the door to various errors, including recall bias.
Nonetheless, they said, the study is comprehensive and provides the most accurate available odds ratios for alcohol cessation. "The risk reductions are quite large, especially for esophageal cancer," they said.
The study was supported by Public Works and Government Services Canada. The authors made no statement regarding potential conflicts. Primary source: International Journal of CancerSource reference: Rehm J et al. "Alcohol drinking cessation and its effect on esophageal and head and neck cancers: A pooled analysis." Int. J. Cancer2007;121:1132-37.

Advantages and Disadvantages of Alcohol Intake on Cardiovascular Health Reviewed

September 4, 2007 — The latest American Heart Association guidelines caution people not to start drinking alcohol if they do not already drink alcohol, according to a review of the advantages and disadvantages of alcohol intake on cardiovascular health published in the August 23 Online First issue of the Journal of the American College of Cardiology.
"Accumulating scientific evidence indicates that light to moderate drinking done on a daily basis may significantly reduce the risks of coronary heart disease (CHD) and all-cause mortality," write James H. O'Keefe, MD, FACC, and colleagues from the Mid America Heart Institute in Kansas City, Missouri. "In contrast, excessive alcohol intake and binge drinking are toxic to both the heart and overall health and are the third leading cause of premature death among Americans. The purpose of the present review is to: 1) outline the specific benefits and risks of alcohol, and the threshold of intake at which drinking becomes a health danger rather than an advantage; 2) detail the mechanisms whereby alcohol confers cardioprotection; and 3) discuss the ideal quantities, drinking patterns, and beverages, and which individuals are most likely to benefit."
Research to date has shown J-shaped relationships between alcohol consumption and several adverse health outcomes, including all-cause mortality, CHD, diabetes, hypertension, congestive heart failure, stroke, dementia, and Raynaud's phenomenon.
Some cardioprotective benefits have been demonstrated for light to moderate alcohol consumption (up to 1 drink daily for women and 1 or 2 drinks daily for men). Most studies have shown that light to moderate drinking is associated with risk reductions for CHD of approximately 30% to 35%.
Alcohol consumed in moderation seems to have an antiatherosclerotic effect, with decreased incidence of peripheral arterial disease and decreased atherosclerotic burden shown by coronary angiography, computerized tomography-detected coronary calcium, and carotid ultrasound.
Like exercise, alcohol consumption seems to be most cardioprotective when done daily and in moderation. However, increasingly excessive consumption is associated with proportional worsening of outcomes.
Because of the beneficial effects on high-density lipoprotein (HDL) cholesterol, insulin action, and inflammation, light to moderate alcohol intake may be particularly helpful for patients with abnormal glucose metabolism and/or insulin resistance. Light to moderate alcohol intake may be associated with reductions in the prevalence and incidence of diabetes, and a large meta-analysis with 12-year follow-up showed a 30% reduction in new diabetes in those who consumed 1 to 2 drinks daily.
The cardiovascular benefits associated with alcohol consumption protection are thought to be mediated by improvements in insulin sensitivity and HDL cholesterol. The major protective component seems to be the ethanol itself, and not the other ingredients found in different types of alcoholic beverages.
In a meta-analysis incorporating data from more than 1 million participants, consumption of 1 drink daily by women and 1 or 2 drinks daily by men was associated with an 18% reduction in total mortality, but daily intakes of more than 2 drinks in women and 3 drinks in men were associated with dose-dependent increased mortality.
Although low-dose, daily alcohol consumption has been linked to better health than less frequent use, binge drinking increases cardiovascular events and mortality, even in otherwise light drinkers.
"Alcohol should not be universally prescribed for health enhancement to nondrinking individuals owing to the lack of randomized outcome data and the potential for problem drinking," the study authors note. "Alcohol (ethanol) consumption is analogous to the proverbial double-edged sword, and perhaps no other factor in cardiovascular (CV) health is capable of cutting so deeply in either direction depending on how it is used."
Guidelines from the United Kingdom suggest that middle-aged or elderly men and postmenopausal women who drink seldom or never might consider the possibility that light drinking would benefit their health. On occasion, the reviewers have made a similar recommendation to patients who do not smoke and who have no personal or family history of substance abuse and no history of depression or bipolar disorder. However, they argue that light to moderate drinking should not be universally recommended to the general public or even to patients with cardiovascular disease.
As an analogy, they point out that observational data and findings from randomized trials using surrogate endpoints suggested that hormone replacement therapy for women and antioxidant vitamins improved cardiovascular outcomes, whereas later randomized trials with larger samples led to the opposite conclusions. They note that no randomized trials of alcohol for improving clinical outcomes have yet been performed. In observational studies, residual unmeasured confounding factors could be contributing to apparent benefits that seem to be associated with light to moderate drinking.
The investigators further note that heavy drinking has caused significant individual and societal problems and morbidity. In the past 15 years, the rates of alcohol abuse and binge drinking have been increasing, according to the findings of some studies. Alcohol abuse causes 100,000 deaths each year in the United States, and it has been deemed the third largest preventable cause of death. Excessive alcohol consumption has been associated with increased risks for all-cause mortality, motor vehicle crashes, stroke, cardiomyopathy, cardiac dysrhythmia, sudden cardiac arrest, suicide, cancer (particularly of the breast and gastrointestinal tract), cirrhosis, fetal alcohol syndrome, and sleep apnea.
"Sobering statistics warn that moderate daily drinking is a slippery slope that many individuals cannot safely navigate," the study authors conclude. "The latest American Heart Association guidelines caution people not to start drinking if they do not already drink alcohol, because it is not possible to predict in which people alcohol abuse will become a problem. Until we have more randomized outcome data, and tools for predicting susceptibility to problem drinking, it would seem prudent to encourage physicians and patients to focus on more innocuous interventions to prevent CHD."
J Am Coll Cardiol. Published online August 23, 2007.
2007;50:1009-1014.

Alcohol linked to bowel cancer, says study

Tue Jul 31, 10:01 AM ET
Drinking wine or beer every day increases the risk of bowel cancer, according to a new study reported Tuesday.
The report, published by the International Journal of Cancer, says that drinking two large glasses of wine or two pints a day increases the risk of this disease by around quarter compared with non-drinkers.
One glass of wine or a pint of beer a day raises the risk by 10 percent.
"The research shows quite clearly that the more alcohol you drink the greater your risk of bowel cancer," said Professor Tim Key, an expert with Cancer Research UK told the Daily Telegraph.
The study was based on questioning of 478,000 people in 10 European countries over six years, of whom over 1,800 developed bowel cancer, which is the third most common form of the disease after lung and breast cancer.
Each year 35,000 people are diagnosed with bowel cancer and it kills 16,100 a year, the British newspaper reported.
The findings will raise question marks for those following widespread scientific advice that regular but modest consumption of red wine can help protect against heart attacks.
"The increase in risk is not large but it is important that people understand they can reduce their risk of a number of different cancers - including bowel cancer - by cutting down on alcohol," said Key.

Americans Drinking More and Seeking Treatment Less

NEW YORK, July 2 -- An alcohol-related disorder -- abuse or dependence--affects three of every 10 adults during their lifetimes, epidemiologists here reported.
But only 24.1% of those who develop alcohol dependence will receive treatment, according to results from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions published in the July issue of Archives of General Psychiatry.
The survey found that 17.8% of adults will abuse alcohol at some point in their lives and 12.5% will become alcohol dependent, said Deborah S. Hasin, Ph.D., of Columbia and the New York State Psychiatric Institute, and colleagues.
The treatment rate was only slightly lower than that reported in a similar survey 10 years ago revealing "a disappointing lack of progress," Dr. Hasin and colleagues wrote.
The survey consisted of face-to-face interviews with 43,093 individuals ages 18 or older. Fifty-two percent of the participants were women, 71% were white, 11% black, 2% Native American, 4% Asian, and 12% Hispanic.
Sixty-two percent were married and about 86% had at least a high school education. Almost half (47%) earned less than $20,000 a year and about 70% had annual incomes of less than $35,000. The investigators relied upon DSM-IV criteria for identification of alcohol-related disorders.
Among the findings:
Men were three times as likely as women to develop an alcohol disorder (OR 3.1, 95% CI 2.81-3.35).
Native Americans had a 40% greater risk for alcohol dependence than whites (OR 1.4, 95% CI 1.03-2.00).
The risk for alcohol dependence was greatest among adults younger than 30 who were almost seven times more likely to develop dependence than those 65 or older (OR 6.7 (95% CI 5.12-8.81)
Income was inversely related to risk of alcohol dependence, so that those earning less than $35,000 had a 60% higher risk than those who earned $70,000 or more annually (OR 1.6, 95% CI 1.28, 1.93) and those who made $35,000 to $69,999 had a 40% increase in risk (OR 1.40, 95% CI 1.15-1.71).
Alcohol disorders are often part of a constellation of disorders including major depressive disorders, bipolar disorder, any personality disorder, as well as dependence on any drug including nicotine, said the investigators.
"Of those with lifetime alcohol dependence, only 24.1% ever received treatment while of those with 12-month alcohol dependence, only 12.1% received alcohol treatment in the past year," they wrote.
Although low income was predictive of alcohol disorders, it was also predictive of the likelihood of getting treatment among those with 12-month alcohol dependence, with an odds ratio of 2.8 for those who earned less than $20,000. For those who reported lifetime abuse and dependence, low income, male gender, low income and lack of a spouse also increased the likelihood of treatment (ORs= 1.5-2.3).
The study was limited by the potential for recall bias especially when assessing comorbidities.
The authors concluded that the survey results suggest "a call to action appears indicated to educate and update the public and policy-makers about alcohol use disorders, to destigmatize the disorders, and to encourage help-seeking among those who cannot stop drinking despite considerable harm to themselves and others."
The survey was funded by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. The authors disclosed no financial conflicts. Primary source: Archives of General PsychiatrySource reference: Hasin D S et al "Prevalence, Correlates, Disability, and Comorbidity of DSM-IV Alcohol Abuse and Dependence in the United States" Arch Gen Psych 2007 64: 830-842