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1.  Alcohol consumption and cognitive decline in early old age 
Neurology  2014;82(4):332-339.
Objective:
To examine the association between alcohol consumption in midlife and subsequent cognitive decline.
Methods:
Data are from 5,054 men and 2,099 women from the Whitehall II cohort study with a mean age of 56 years (range 44–69 years) at first cognitive assessment. Alcohol consumption was assessed 3 times in the 10 years preceding the first cognitive assessment (1997–1999). Cognitive tests were repeated in 2002–2004 and 2007–2009. The cognitive test battery included 4 tests assessing memory and executive function; a global cognitive score summarized performances across these tests. Linear mixed models were used to assess the association between alcohol consumption and cognitive decline, expressed as z scores (mean = 0, SD = 1).
Results:
In men, there were no differences in cognitive decline among alcohol abstainers, quitters, and light or moderate alcohol drinkers (<20 g/d). However, alcohol consumption ≥36 g/d was associated with faster decline in all cognitive domains compared with consumption between 0.1 and 19.9 g/d: mean difference (95% confidence interval) in 10-year decline in the global cognitive score = −0.10 (−0.16, −0.04), executive function = −0.06 (−0.12, 0.00), and memory = −0.16 (−0.26, −0.05). In women, compared with those drinking 0.1 to 9.9 g/d of alcohol, 10-year abstainers showed faster decline in the global cognitive score (−0.21 [−0.37, −0.04]) and executive function (−0.17 [−0.32, −0.01]).
Conclusions:
Excessive alcohol consumption in men (≥36 g/d) was associated with faster cognitive decline compared with light to moderate alcohol consumption.
doi:10.1212/WNL.0000000000000063
PMCID: PMC3929201  PMID: 24431298
2.  Alcohol Consumption in Midlife and Cognitive Performance Assessed 13 Years Later in the SU.VI.MAX 2 Cohort 
PLoS ONE  2012;7(12):e52311.
Background
Associations between alcohol consumption and cognitive function are discordant and data focusing on midlife exposure are scarce.
Objective
To estimate the association between midlife alcohol consumption and cognitive performance assessed 13 y later while accounting for comorbidities and diet.
Methods
3,088 French middle-aged adults included in the SU.VI.MAX (1994) study with available neuropsychological evaluation 13 y later. Data on alcohol consumption were obtained from repeated 24h dietary records collected in 1994–1996. Cognitive performance was assessed in 2007–2009 via a battery of 6 neuropsychological tests. A composite score was built as the mean of the standardized individual test scores (mean = 50, SD = 10). ANCOVA were performed to estimate mean differences in cognitive performance and 95% confidence intervals (CI).
Results
In women, abstainers displayed lower cognitive scores than did low-to-moderate alcohol drinkers (1 to 2 drinks/day) (mean difference = −1.77; 95% CI: −3.29, −0.25). In men, heavy drinkers (>3 drinks/day) had higher cognitive scores than did low-to-moderate (1 to 3 drinks/day) (mean difference = 1.05; 95% CI: 0.10, 1.99). However, a lower composite cognitive score was detected in male drinkers consuming ≥90 g/d (≈8 drinks/d). A higher proportion of alcohol intake from beer was also associated with lower cognitive scores. These associations remained significant after adjustment for diet, comorbidities and sociodemographic factors.
Conclusion
In men, heavy but not extreme drinking was associated with higher global cognitive scores. Given the known harmful effects of alcohol even in low doses regarding risk of cancer, the study does not provide a basis for modifying current public health messages.
Trial Registration
ClinicalTrials.gov NCT00272428
doi:10.1371/journal.pone.0052311
PMCID: PMC3526526  PMID: 23284983
3.  What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels 
BMJ Open  2012;2(3):e000957.
Objective
To estimate the impact of achieving alternative average population alcohol consumption levels on chronic disease mortality in England.
Design
A macro-simulation model was built to simultaneously estimate the number of deaths from coronary heart disease, stroke, hypertensive disease, diabetes, liver cirrhosis, epilepsy and five cancers that would be averted or delayed annually as a result of changes in alcohol consumption among English adults. Counterfactual scenarios assessed the impact on alcohol-related mortalities of changing (1) the median alcohol consumption of drinkers and (2) the percentage of non-drinkers.
Data sources
Risk relationships were drawn from published meta-analyses. Age- and sex-specific distributions of alcohol consumption (grams per day) for the English population in 2006 were drawn from the General Household Survey 2006, and age-, sex- and cause-specific mortality data for 2006 were provided by the Office for National Statistics.
Results
The optimum median consumption level for drinkers in the model was 5 g/day (about half a unit), which would avert or delay 4579 (2544 to 6590) deaths per year. Approximately equal numbers of deaths from cancers and liver disease would be delayed or averted (∼2800 for each), while there was a small increase in cardiovascular mortality. The model showed no benefit in terms of reduced mortality when the proportion of non-drinkers in the population was increased.
Conclusions
Current government recommendations for alcohol consumption are well above the level likely to minimise chronic disease. Public health targets should aim for a reduction in population alcohol consumption in order to reduce chronic disease mortality.
Article summary
Article focus
Alcohol consumption is a risk factor for many chronic diseases, while providing modest protection from others. Assessments of the impact of alcohol on individual chronic diseases can therefore result in contradictory advice about the level of alcohol consumption that is optimal for health.
The UK Government currently recommends that men should consume no more than three to four units per day (24–32 g/day of pure alcohol) and women should drink no more than two to three units per day (16–24 g/day). However the net impact of this level of consumption on chronic disease mortality is unclear.
The aim of this study was to estimate the impact of achieving alternative population alcohol consumption levels on chronic disease mortality in England.
Key messages
Results suggest that the optimum population level of alcohol consumption for minimising chronic disease mortality in England is just 5 g (approximately half a unit) per day.
Current recommendations for alcohol consumption are well above this level and may not be compatible with optimum protection of public health. Substantial reductions in recommendations and in population alcohol consumption levels would be needed to minimise the chronic disease burden associated with alcohol consumption in England.
Community beliefs in the protective role of alcohol in cardiovascular disease are widespread; however, our modelling shows that when multiple conditions are considered simultaneously, the levels of alcohol that would actually be likely to be associated with reduced risk of chronic disease are much lower than is generally accepted or recommended by government.
Strengths and limitations of this study
The study used a detailed modelling approach to synthesise the best available evidence from meta-analysis of prospective cohort studies and provide for the first time an estimate of the level of alcohol associated with theoretical minimum risk of a range of chronic diseases, considering both harmful and protective effects simultaneously.
The model is dependent on the meta-analyses selected to define the parameters. Results may vary significantly in other contexts with varying levels of disease, alcohol consumption and other risk factors. Furthermore, results depend on the quality of the available epidemiological evidence, which remains contested in some areas.
The approach used also relies on chronic (average) consumption of alcohol and is not able to take account of to take account of patterns of drinking (eg, binge drinking). Furthermore, the results are based on the assumption of a steady-state relationship between alcohol consumption patterns and RR of disease and cannot estimate the time required between changes in population alcohol consumption levels occurring and the achievement of changes in mortality rates.
doi:10.1136/bmjopen-2012-000957
PMCID: PMC3367150  PMID: 22649178
4.  A Population-Based Study on Alcohol and High-Risk Sexual Behaviors in Botswana 
PLoS Medicine  2006;3(10):e392.
Background
In Botswana, an estimated 24% of adults ages 15–49 years are infected with HIV. While alcohol use is strongly associated with HIV infection in Africa, few population-based studies have characterized the association of alcohol use with specific high-risk sexual behaviors.
Methods and Findings
We conducted a cross-sectional, population-based study of 1,268 adults from five districts in Botswana using a stratified two-stage probability sample design. Multivariate logistic regression was used to assess correlates of heavy alcohol consumption (>14 drinks/week for women, and >21 drinks/week for men) as a dependent variable. We also assessed gender-specific associations between alcohol use as a primary independent variable (categorized as none, moderate, problem and heavy drinking) and several risky sex outcomes including: (a) having unprotected sex with a nonmonogamous partner; (b) having multiple sexual partners; and (c) paying for or selling sex in exchange for money or other resources. Criteria for heavy drinking were met by 31% of men and 17% of women. Adjusted correlates of heavy alcohol use included male gender, intergenerational relationships (age gap ≥10 y), higher education, and living with a sexual partner. Among men, heavy alcohol use was associated with higher odds of all risky sex outcomes examined, including unprotected sex (AOR = 3.48; 95% confidence interval [CI], 1.65 to 7.32), multiple partners (AOR = 3.08; 95% CI, 1.95 to 4.87), and paying for sex (AOR = 3.65; 95% CI, 2.58 to 12.37). Similarly, among women, heavy alcohol consumption was associated with higher odds of unprotected sex (AOR = 3.28; 95% CI, 1.71 to 6.28), multiple partners (AOR = 3.05; 95% CI, 1.83 to 5.07), and selling sex (AOR = 8.50; 95% CI, 3.41 to 21.18). A dose-response relationship was seen between alcohol use and risky sexual behaviors, with moderate drinkers at lower risk than both problem and heavy drinkers.
Conclusions
Alcohol use is associated with multiple risks for HIV transmission among both men and women. The findings of this study underscore the need to integrate alcohol abuse and HIV prevention efforts in Botswana and elsewhere.
Alcohol use is associated with multiple risks for HIV transmission in men and women. The findings underscore the need to integrate alcohol abuse and HIV prevention efforts in Botswana and elsewhere.
Editors' Summary
Background.
Human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS), is most commonly spread through unprotected sex with an infected partner. HIV enters the body through the lining of the sex organs, rectum, or mouth, and destroys immune system cells, leaving the infected person susceptible to other viruses and bacteria. Although HIV education and prevention campaigns emphasize the importance of safe sex in reducing HIV transmission, people continue to become infected by having unprotected sex (that is, not using a condom) with either a nonmonogamous partner or multiple sexual partners, or in situations where they are paying for or selling sex. Research in different populations suggested that heavy alcohol use is associated with risky sexual behaviors. This is because alcohol relaxes the brain and body, reduces inhibitions, and diminishes risk perception. Drinking alcohol may further increase the risk of becoming infected with HIV through its suppressive effects on the immune system.
Why Was This Study Done?
Alcohol abuse is widespread in sub-Saharan Africa where most HIV infections occur and has been associated with risky sexual behaviors. It may therefore be one of the most common, potentially modifiable HIV risk factors in this region. However, research to date has concentrated on the association between alcohol consumption and risky sex in people attending HIV-treatment clinics or recruited at beer halls, and these populations may not be representative of the general population of sub-Saharan Africa. In this study, the researchers have investigated the potential role of alcohol in perpetuating the HIV epidemic by undertaking a population-based study on alcohol use and high-risk sexual behaviors in Botswana. Nearly a quarter of adults are infected with HIV here, and alcohol abuse is also common, particularly in the townships.
What Did the Researchers Do and Find?
The researchers recruited a random cross-section of people from the five districts of Botswana with the highest number of HIV-infected individuals and interviewed all 1,268 participants using a questionnaire. This included general questions about the participants (for example, their age and marital status) and questions about alcohol use, sexual behavior, and knowledge of HIV. Overall, 31% of the men in the study and 17% of the women were heavy drinkers—more than 21 drinks/week for men, 14 for women; a drink is half a pint of beer or a glass of wine. Heavy alcohol use was associated with being male, being in an intergenerational relationship (at least 10 years age difference between partners; intergenerational sex facilitates the continued spread of HIV in sub-Saharan Africa), having had more education, and living with a sexual partner. Among men, those who drank heavily were three to four times more likely to have unprotected sex or multiple partners or to pay for sex than nondrinkers. Among women, there was a similar association between heavy drinking and having unprotected sex or multiple partners, and heavy drinkers were eight times as likely to sell sex as nondrinkers. For both men and women, the more they drank, the more likely they were to have risky sex. The study did not address behavior among same-sex partnerships.
What Do These Findings Mean?
This study indicates that heavy alcohol consumption is strongly and consistently associated with sexual risk behaviors in both men and women in Botswana. Because of the study design, it does not prove that heavy alcohol use is the cause of such behaviors but provides strong circumstantial evidence that this is the case. It is possible that these results may not apply to neighboring African countries—Botswana is unique in being relatively wealthy and in its government being strongly committed to tackling HIV. Nevertheless, taken together with the results of other studies, this research strongly argues for the need to deal with alcohol abuse within HIV prevention programs in sub-Saharan Africa. Strategies to do this could include education campaigns that target both alcohol use and HIV in schools and in social venues, including beer halls. But, stress the researchers, any strategy that is used must consider the cultural and social significance of alcohol use (in Botswana, alcohol use is a symbol of masculinity and high socioeconomic status) and must simultaneously tackle not only the overlap between alcohol use and risky sexual behavior but also the overlap between alcohol and other risk behaviors such as intergenerational sex.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030392.
US National Institute of Allergy and Infectious Diseases factsheet on HIV infection and AIDS
US Department of Health and Human Services information on AIDS
US Centers for Disease Control and Prevention information on HIV/AIDS
US National Institute on Alcohol Abuse and Alcoholism patient information on alcohol and HIV/AIDS]
Aidsmap, information on HIV and AIDS provided by the charity NAM,which includes some information on HIV infections and alcohol
AVERT information on HIV and AIDS in Botswana
doi:10.1371/journal.pmed.0030392
PMCID: PMC1592342  PMID: 17032060
5.  Alcohol Sales and Risk of Serious Assault 
PLoS Medicine  2008;5(5):e104.
Background
Alcohol is a contributing cause of unintentional injuries, such as motor vehicle crashes. Prior research on the association between alcohol use and violent injury was limited to survey-based data, and the inclusion of cases from a single trauma centre, without adequate controls. Beyond these limitations was the inability of prior researchers to comprehensively capture most alcohol sales. In Ontario, most alcohol is sold through retail outlets run by the provincial government, and hospitals are financed under a provincial health care system. We assessed the risk of being hospitalized due to assault in association with retail alcohol sales across Ontario.
Methods and Findings
We performed a population-based case-crossover analysis of all persons aged 13 years and older hospitalized for assault in Ontario from 1 April 2002 to 1 December 2004. On the day prior to each assault case's hospitalization, the volume of alcohol sold at the store in closest proximity to the victim's home was compared to the volume of alcohol sold at the same store 7 d earlier. Conditional logistic regression analysis was used to determine the associated relative risk (RR) of assault per 1,000 l higher daily sales of alcohol. Of the 3,212 persons admitted to hospital for assault, nearly 25% were between the ages of 13 and 20 y, and 83% were male. A total of 1,150 assaults (36%) involved the use of a sharp or blunt weapon, and 1,532 (48%) arose during an unarmed brawl or fight. For every 1,000 l more of alcohol sold per store per day, the relative risk of being hospitalized for assault was 1.13 (95% confidence interval [CI] 1.02–1.26). The risk was accentuated for males (1.18, 95% CI 1.05–1.33), youth aged 13 to 20 y (1.21, 95% CI 0.99–1.46), and those in urban areas (1.19, 95% CI 1.06–1.35).
Conclusions
The risk of being a victim of serious assault increases with alcohol sales, especially among young urban men. Akin to reducing the risk of driving while impaired, consideration should be given to novel methods of preventing alcohol-related violence.
In a population-based case-crossover analysis, Joel Ray and colleagues find that the risk of being a victim of serious assault increases with retail alcohol sales, especially among young urban men.
Editors' Summary
Background.
Alcohol has been produced and consumed around the world since prehistoric times. In the Western world it is now the most commonly consumed psychoactive drug (a substance that changes mood, behavior, and thought processes). The World Health Organization reports that there are 76.3 million persons with alcohol use disorders worldwide. Alcohol consumption is an important factor in unintentional injuries, such as motor vehicle crashes, and in violent criminal behavior. In the United Kingdom, for example, a higher proportion of heavy drinkers than light drinkers cause violent criminal offenses. Other figures suggest that people (in particular, young men) have an increased risk of committing a criminally violent offense within 24 h of drinking alcohol. There is also some evidence that suggests that the victims as well as the perpetrators of assaults have often been drinking recently, possibly because alcohol impairs the victim's ability to judge potentially explosive situations.
Why Was This Study Done?
The researchers wanted to know more about the relationship between alcohol and intentional violence. The recognition of a clear link between driving when impaired by alcohol and motor vehicle crashes has led many countries to introduce public awareness programs that stigmatize drunk driving. If a clear link between alcohol consumption by the people involved in violent crime could also be established, similar programs might reduce alcohol-related assaults. The researchers tested the hypothesis that the risk of being hospitalized due to a violent assault increases when there are increased alcohol sales in the immediate vicinity of the victim's place of residence.
What Did the Researchers Do and Find?
The researchers did their study in Ontario, Canada for three reasons. First, Ontario is Canada's largest province. Second, the province keeps detailed computerized medical records, including records of people hospitalized from being violently assaulted. Third, most alcohol is sold in government-run shops, and the district has the infrastructure to allow daily alcohol sales to be tracked. The researchers identified more than 3,000 people over the age of 13 y who were hospitalized in the province because of a serious assault during a 32-mo period. They compared the volume of alcohol sold at the liquor store nearest to the victim's home the day before the assault with the volume sold at the same store a week earlier (this type of study is called a “case-crossover” study). For every extra 1,000 l of alcohol sold per store per day (a doubling of alcohol sales), the overall risk of being hospitalized for assault increased by 13%. The risk was highest in three subgroups of people: men (18% increased risk), youths aged 13 to 20 y (21% increased risk), and those living in urban areas (19% increased risk). At peak times of alcohol sales, the risk of assault was 41% higher than at times when alcohol sales were lowest.
What Do These Findings Mean?
These findings indicate that the risk of being seriously assaulted increases with the amount of alcohol sold locally the day before the assault and show that the individuals most at risk are young men living in urban areas. Because the study considers only serious assaults and alcohol sold in shops (i.e., not including alcohol sold in bars), it probably underestimates the association between alcohol and assault. It also does not indicate whether the victim or perpetrator of the assault (or both) had been drinking, and its findings may not apply to countries with different drinking habits. Nevertheless, these findings support the idea that the consumption of alcohol contributes to the occurrence of medical injuries from intentional violence. Increasing the price of alcohol or making alcohol harder to obtain might help to reduce the occurrence of alcohol-related assaults. The researchers suggest that a particularly effective approach may be to stigmatize alcohol-related brawling, analogous to the way that driving under the influence of alcohol has been made socially unacceptable.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050104.
This study is further discussed in a PLoS Medicine Perspective by Bennetts and Seabrook
The US National Institute on Alcohol Abuse and Alcoholism provides information on all aspects of alcohol abuse, including an article on alcohol use and violence among young adults
Alcohol-related assault is examined in the British Crime Survey
Alcohol Concern, the UK national agency on alcohol misuse, provides fact sheets on the health impacts of alcohol, young people's drinking, and alcohol and crime
The Canadian Centre for Addiction and Mental Health in Toronto provides information about alcohol addiction (in English and French)
doi:10.1371/journal.pmed.0050104
PMCID: PMC2375945  PMID: 18479181
6.  Alcohol effects on Cognitive Change in Middle-Aged and Older Adults 
Aging & mental health  2012;17(1):12-23.
Objectives
This study examines cognitive outcomes for alcohol drinking status over time, across cognitive ability and age groups.
Methods
Data (1998-2005) from N=571 Seattle Longitudinal Study participants age 45+years (middle-aged: 45-64, young-old: 65-75, old-old: 75+) were analyzed to examine the alcohol drinking status effect (e.g. abstinent, moderate (≤7 drinks/week), at-risk (≥8 drinks/week)) on cognitive ability (e.g., Memory, Reasoning, Spatial, Verbal Number, Speed abilities).
Results
Findings indicated that alcohol drinking status was associated with change in verbal ability, spatial ability, and perceptual speed. Decline in verbal ability was seen among alcohol abstainers and moderate alcohol consumers, but at-risk drinkers displayed relative stability. At-risk old-old adults and middle-aged adults (regardless of drinking status), displayed relative stability in spatial ability. Decline in spatial ability was however present among young-old adults across drinking status, and among abstaining and moderate drinking old-old adults. At-risk drinkers showed the most positive spatial ability trajectory. A gender effect in perceptual speed was detected, with women who abstained from drinking displaying the most decline in perceptual speed compared with women that regularly consumed alcohol, and men displaying decline in perceptual speed across drinking status.
Discussion
In this study, consuming alcohol is indicative of cognitive stability. This conclusion should be considered cautiously, due to study bias created from survivor effects, analyzing two time points, health/medication change status, and overrepresentation of higher socioeconomic status and white populations in this study. Future research needs to design studies that can make concrete recommendations about the relationship between drinking status and cognition.
doi:10.1080/13607863.2012.717254
PMCID: PMC3561493  PMID: 22934837
alcohol; cognition; aging
7.  The Relationship Between Alcohol Consumption and Glycemic Control Among Patients with Diabetes: The Kaiser Permanente Northern California Diabetes Registry 
BACKGROUND
Alcohol consumption is a common behavior. Little is known about the relationship between alcohol consumption and glycemic control among people with diabetes.
OBJECTIVE
To evaluate the association between alcohol consumption and glycemic control.
DESIGN
Survey follow-up study, 1994–1997, among Kaiser Permanente Northern California members.
PATIENTS
38,564 adult diabetes patients.
MEASUREMENTS
Self-reported alcohol consumption, and hemoglobin A1C (A1C), assessed within 1 year of survey date. Linear regression of A1C by alcohol consumption was performed, adjusted for sociodemographic variables, clinical variables, and diabetes disease severity. Least squares means estimates were derived.
RESULTS
In multivariate-adjusted models, A1C values were 8.88 (lifetime abstainers), 8.79 (former drinkers), 8.90 (<0.1 drink/day), 8.71 (0.1–0.9 drink/day), 8.51 (1–1.9 drinks/day), 8.39 (2–2.9 drinks/day), and 8.47 (≥3 drinks/day). Alcohol consumption was linearly (p < 0.001) and inversely (p = 0.001) associated with A1C among diabetes patients.
CONCLUSIONS
Alcohol consumption is inversely associated with glycemic control among diabetes patients. This supports current clinical guidelines for moderate levels of alcohol consumption among diabetes patients. As glycemic control affects incidence of complications of diabetes, the lower A1C levels associated with moderate alcohol consumption may translate into lower risk for complications.
doi:10.1007/s11606-007-0502-z
PMCID: PMC2359478  PMID: 18183468
diabetes; alcohol consumption; hemoglobin A1C
8.  Fetal Alcohol Exposure and IQ at Age 8: Evidence from a Population-Based Birth-Cohort Study 
PLoS ONE  2012;7(11):e49407.
Background
Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother’s intake but also by genetic variants carried by both the mother and the fetus. Associations between children’s cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development.
Methods
We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child’s cognitive score (measured by the Weschler Intelligence Scale) at age 8.
Findings
We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1–6 units alcohol per week during pregnancy (per allele effect estimates were −1.80 (95% CI = −2.63 to −0.97) p = 0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI = −1.05 to 1.36) p = 0.80), p-value for interaction  = 0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child’s IQ, but again only among mothers who drank during pregnancy.
doi:10.1371/journal.pone.0049407
PMCID: PMC3498109  PMID: 23166662
9.  Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach 
PLoS Medicine  2008;5(3):e52.
Background
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.
Methods and Findings
We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10−6) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10−12) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.
Conclusions
These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Using a mendelian randomization approach Sarah Lewis and colleagues find strong support for the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Editors' Summary
Background.
High blood pressure (hypertension) is a common medical condition that affects nearly a third of US and UK adults. Hypertension has no symptoms but can lead to heart attacks or strokes. It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic pressure) and lowest when it is filling up with blood (diastolic pressure). Normal blood pressure is defined as a systolic pressure of less than 130 millimeters of mercury (mmHg) and a diastolic pressure of less than 85 mmHg (a blood pressure of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat too much salty or fatty foods are at high risk of developing hypertension. Mild hypertension can often be corrected by lifestyle changes, but many people also take antihypertensive drugs to reduce their blood pressure.
Why Was This Study Done?
Another modifiable lifestyle factor thought to affect blood pressure is alcohol intake. Observational studies that ask people about their drinking habits and measure their blood pressure suggest that alcohol intake correlates with blood pressure, but they cannot prove a causal link because of “confounding”—other risk factors associated with alcohol drinking, such as diet, might also affect the study participant's blood pressures. A trial that randomly assigns people to different alcohol intakes could provide this proof of causality, but such a trial is impractical. In this study, therefore, the researchers have used “Mendelian randomization” to investigate whether alcohol intake affects blood pressure. An inactive variant of aldehyde dehydrogenase 2 (ALDH2; the enzyme that removes alcohol from the body) has been identified. People who inherit the variant form of this gene from both parents have an ALDH2 *2*2 genotype (genetic makeup) and become flushed and nauseated after drinking. Consequently, they drink less than people with a *1*2 genotype and much less than those with a *1*1 genotype. Because inheritance of these genetic variants does not affect lifestyle factors other than alcohol intake, an association between ALDH2 genotypes and blood pressure would indicate that alcohol intake has an effect on blood pressure without any confounding.
What Did the Researchers Do and Find?
The researchers identified ten published studies (mainly done in Japan where the ALDH2 gene variant is common) on associations between ALDH2 genotype and blood pressure or hypertension using a detailed search protocol (a “systematic review”). A meta-analysis (a statistical method for combining the results of independent studies) of the studies that had investigated the association between ALDH2 genotype and hypertension showed that men with the *1*1 genotype (highest alcohol intake) and those with the *1*2 genotype (intermediate alcohol intake) were 2.42 and 1.72 times more likely, respectively, to have hypertension than those with the *2*2 genotype (lowest alcohol intake). There was no association between ALDH2 genotype and hypertension among the women in these studies because they drank very little. Systolic and diastolic blood pressures showed a similar relationship to ALDH2 genotype in a second meta-analysis of relevant studies. Finally, the researchers estimated that for men the lifetime effect of drinking 1 g of alcohol a day (one unit of alcohol contains 8 g of alcohol in the UK and 14 g in the US; recommended daily limits in these countries are 3–4 and 1–2 units, respectively) would be an increase in systolic blood pressure of 0.24 mmHg.
What Do These Findings Mean?
These findings support the suggestion that alcohol has a marked effect on blood pressure and hypertension. Consequently, some cases of hypertension could be prevented by encouraging people to reduce their daily alcohol intake. Although the Mendelian randomization approach avoids most of the confounding intrinsic to observational studies, it is possible that a gene near ALDH2 that has no effect on alcohol intake affects blood pressure, since genes are often inherited in blocks. Alternatively, ALDH2 could affect blood pressure independent of alcohol intake. The possibility that ALDH2 could effect blood pressure independently of alcohol is intake made unlikely by the fact that no effect of genotype on blood pressure is seen among women who drink very little. Additional large-scale studies are needed to address these possibilities, to confirm the current finding in more people, and to improve the estimates of the effect that alcohol intake has on blood pressure.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050052.
The MedlinePlus encyclopedia has a page on hypertension (in English and Spanish)
The American Heart Association provides information for patients and health professionals about hypertension
The UK Blood Pressure Association provides information for patients and health professionals on all aspects of hypertension, including information about alcohol affects blood pressure
The Explore@Bristol science center (a UK charity) provides an alcohol unit calculator and information on the effects of alcohol
The International Center for Alcohol Policies provides drinking guidelines for countries around the world
doi:10.1371/journal.pmed.0050052
PMCID: PMC2265305  PMID: 18318597
10.  Moderate alcohol consumption is associated with better endothelial function: a cross sectional study 
Background
Moderate alcohol consumption is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. The effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery in humans.
Methods
In the population-based Northern Manhattan Study (NOMAS), we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 884 stroke-free participants (mean age 66.8 years, women 56.6%, Hispanic 67.4%, black 17.4%, and white 15.2%).
Results
The mean brachial FMD was 5.7% and the median was 5.5%. Compared to non-drinkers, those who drank >1 drink/month to 2 drinks/day were more likely to have FMD above the median FMD (5.5%) (unadjusted OR 1.7, 95% CI 1.2–2.4, p = 0.005). In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease, Framingham risk score, medication use (adjusted OR 1.8, 95%CI 1.1–3.0, p = 0.03). No beneficial effect on FMD was seen for those who drank more than 2 drinks/day.
Conclusion
In conclusion, consumption of up to 2 alcoholic beverages per day was independently associated with better FMD compared to no alcohol consumption in this multiethnic population. This effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.
doi:10.1186/1471-2261-9-8
PMCID: PMC2653471  PMID: 19228434
11.  Associations of alcohol consumption with diabetes mellitus and impaired fasting glycemia among middle-aged and elderly Chinese 
BMC Public Health  2010;10:713.
Background
The U-shaped relationship between alcohol consumption and diabetes mellitus was observed among western populations. However, few studies have systematically evaluated the association in Chinese. We aimed to investigate the associations of alcohol consumption with diabetes mellitus and impaired fasting glycemia (IFG) among middle-aged and elderly Chinese.
Methods
We examined 1,458 men and 1,831 women aged 50 to 70 from Beijing and Shanghai China in a cross-sectional survey. Fasting glucose, adipokines and markers of inflammation were measured. Macronutrients and alcohol consumption were assessed with standardized questionnaires.
Results
Compared with abstainers, alcohol consumption was associated with a decreased risk of having diabetes mellitus in women (OR: 0.41, 95%CI: 0.22-0.78) after controlling for socio-demographic factors, physical activity, smoking, family income, family history of cardiovascular disease or diabetes, macronutrients intake, body mass index, and markers of inflammation and adipokines. In men, both low and high alcohol consumptions were associated with increased risks of having combined diabetes and IFG (ORs 1.36 [95%CI: 1.02-1.82] and 1.50 [95%CI: 1.04-2.15], respectively]. In the multivariable stratified analyses among men, moderate drinkers who had drinking days of ≥ 5 days/week had a deceased likelihood (OR: 0.61, 95%CI: 0.37-0.98) and liquor drinkers had an increased likelihood (OR: 1.47, 95%CI: 1.09-1.98) of having combined diabetes and IFG respectively, compared with the abstainers.
Conclusions
An approximately J-shaped association was observed between alcohol consumption and combined diabetes and IFG among men compared with abstainers in Chinese. Whether moderate alcohol intake could help decrease diabetic risk among Chinese people warrants further investigation.
doi:10.1186/1471-2458-10-713
PMCID: PMC2998495  PMID: 21092093
12.  Inverse associations between light-to-moderate alcohol intake and lipid-related indices in patients with diabetes 
Background
Dyslipidemia is a common complication in patients with diabetes and is involved in being prone to cardiovascular disease. The risk of coronary artery disease is known to be lower in light-to-moderate drinkers than in abstainers. The aim of this study was to clarify whether and how alcohol drinking influences the lipid-related indices, good predictors for cardiovascular disease, such as the ratio of LDL cholesterol to HDL cholesterol (LDL-C/HDL-C ratio), the ratio of triglycerides to HDL cholesterol (TG/HDL-C ratio), and the lipid accumulation product (LAP), in patients with diabetes.
Methods
The subjects were men with diabetes (n = 1477; mean age, 54.0 years) and they were divided into non-, light (< 22 g ethanol/day), moderate (≥ 22 and < 44 g ethanol/day) and heavy (≥ 44 g ethanol/day) drinkers. The relationships between alcohol intake and the lipid-related indices were investigated by the multivariate analyses with adjustment for age, smoking, regular exercise and drug therapy for diabetes.
Results
The odds ratio (OR) vs. nondrinkers for high LDL-C/HDL-C ratio tended to be lower with an increase in alcohol intake (OR with 95% confidence interval (CI): 0.80 [0.50-1.29] in light drinkers; 0.24 [0.15-0.38] in moderate drinkers and 0.10 [0.05-0.19] in heavy drinkers). Alcohol intake showed an inverse association with a high TG/HDL-C ratio (OR with 95% CI vs. nondrinkers for high TG/HDL-C ratio: 0.54 [0.36-0.80] in light drinkers; 0.73 [0.56-0.97] in moderate drinkers and 0.72 [0.53-0.98] in heavy drinkers) and a J-shaped relationship with a high LAP (OR with 95% CI vs. nondrinkers for high LAP: 0.66 [0.43-1.02] in light drinkers; 0.82 [0.61-1.10] in moderate drinkers, and 1.29 [0.95-1.77] in heavy drinkers). Similar associations between alcohol intake and the lipid indices were obtained in a covariance analysis.
Conclusions
In patients with diabetes, light-to-moderate alcohol consumption is inversely associated with lipid-related indices, and this correlates with previous findings of cardiovascular risk reduction by modest drinking in patients with diabetes.
doi:10.1186/1475-2840-12-104
PMCID: PMC3723450  PMID: 23866006
13.  Alcohol and blood pressure: the INTERSALT study. 
BMJ : British Medical Journal  1994;308(6939):1263-1267.
OBJECTIVES--To assess the relation between alcohol intake and blood pressure in men and women and in men at younger and older ages; to examine the influence of amount and pattern of alcohol consumption, as well as of acute effects, taking into account body mass index, smoking, and urinary sodium and potassium excretion. DESIGN--Subjects reported alcohol consumption for each of seven days before standardised blood pressure measurement, and whether they had consumed any alcohol in the 24 hours before measurement. SETTING--50 centres worldwide. SUBJECTS--4844 men and 4837 women aged 20-59. MAIN OUTCOME MEASURES--Effect of alcohol on blood pressure estimated by taking a weighted average of regression coefficients from centres. Acute effect assessed by examining mean differences in blood pressure of non-drinkers and of heavy drinkers who had and had not consumed alcohol in the 24 hours before measurement. Effect of pattern of consumption assessed by examining mean differences in blood pressure of non-drinkers compared with drinkers (i) whose intake was concentrated in fewer days or who were drinking more frequently, and (ii) whose alcohol intake varied little over the seven days or varied more substantially, as indicated by the standard deviation of daily consumption. RESULTS--Of the 48 centres in which some people reported consuming at least 300 ml/week of alcohol, 35 had positive regression coefficients linking heavy alcohol consumption to blood pressure. Overall, alcohol consumption was associated with blood pressure, significantly at the highest intake. After account was taken of key confounders, men who drank 300-499 ml alcohol/week had systolic/diastolic blood pressure on average 2.7/1.6 mmHg higher than non-drinkers, and men who drank > or = 500 ml alcohol/week had pressures of 4.6/3.0 mmHg higher. For women, heavy drinkers (> or = 300 ml/week) had blood pressures higher by 3.9/3.1 mmHg than non-drinkers. Heavy drinking and blood pressure were strongly associated in both sexes, and in men at both younger (20-39 years) and older (40-59 years) ages. In men who were heavy drinkers, episodic drinkers (those with great variation in daily alcohol consumption) had greater differences in blood pressure compared with non-drinkers than did regular drinkers of relatively constant amounts. CONCLUSION--The significant relation of heavy drinking (3-4 or more drinks/day) to blood pressure, observed in both men and women, and in younger and older men, was independent of and added to the effect on blood pressure of body mass index and urinary excretion of sodium and potassium. The findings indicate the usefulness of targeting those at high risk as well as the general population to reduce the adverse effects of alcohol on blood pressure.
PMCID: PMC2540174  PMID: 7802765
14.  Alcohol intake, carotid plaque, and cognition: the Northern Manhattan Study 
Background and purpose: Moderate alcohol intake has been associated with better cognitive performance, implicating vascular and neurodegenerative processes. Few studies to clarify the importance of vascular disease have included direct measures of atherosclerosis or minority populations at higher risk of vascular disease and dementia.
Methods: The Northern Manhattan Study includes stroke-free community based Hispanic (54%), black (25%), and white (22%) participants. We performed a cross-sectional study of alcohol intake and performance on the Mini Mental State Exam (MMSE) in subjects with sonographic measurement of maximal carotid plaque thickness (MCPT) and adjusted for sociodemographic and vascular risk factors.
Results: The median MMSE score was 27 (interquartile range 24-29; N=2,215). Reported alcohol intake was divided into four groups: never (N=509), past (N=494), <1 drink/week (N=300), 1/week to ≤2 drinks/day (N=796), and >2 drinks/day (N=116). Drinking up to 2 drinks/day was associated with better performance on the MMSE (OR=1.19; 95% CI=1.10-1.26) compared to never drinkers in women (P=<0.0001) but not in men, adjusting for sociodemographic and vascular risk factors. MCPT (mean 1.1 mm; SD 1.2 mm) was not associated with alcohol intake and did not mediate the relationship between alcohol and cognition.
Conclusions: Moderate alcohol consumption was independently associated with better cognitive performance in women from this multiethnic sample. Carotid plaque was not a mediator of this association suggesting alcohol may impact cognition through a separate vascular or degenerative pathway.
doi:10.1161/01.STR.0000217439.73041.b4
PMCID: PMC1447604  PMID: 16601215
cognition; carotid diseases; alcohol intake
15.  Alcohol Consumption and Dietary Patterns: The FinDrink Study 
PLoS ONE  2012;7(6):e38607.
The aim of this population-based study was to investigate differences in dietary patterns in relation to the level of alcohol consumption among Finnish adults. This study was part of the FinDrink project, an epidemiologic study on alcohol use among Finnish population. It utilized data from the Kuopio Ischaemic Heart Disease Risk Factor Study. A total of 1720 subjects comprising of 816 men and 904 women aged 53–73 years were included in the study in 1998–2001. Food intake was collected via a 4-day food diary method. Self-reported alcohol consumption was assessed with quantity-frequency method based on the Nordic Alcohol Consumption Inventory. Weekly alcohol consumption was categorized into three groups: non-drinkers (<12 grams), moderate drinkers (12–167.9 grams for men, 12–83.9 grams for women) and heavy drinkers (≥168 grams for men, ≥84 grams for women). Data were analyzed for men and women separately using multiple linear regression models, adjusted for age, occupational status, marital status, smoking, body mass index and leisure time physical activity. In women, moderate/heavy drinkers had lower fibre intake and moderate drinkers had higher vitamin D intake than non-drinkers. Male heavy drinkers had lower fibre, retinol, calcium and iron intake, and moderate/heavy drinkers had higher vitamin D intake than non-drinkers. Fish intake was higher among women moderate drinkers and men moderate/heavy drinkers than non-drinkers. In men, moderate drinkers had lower fruit intake and heavy drinkers had lower milk intake than non-drinkers. Moderate drinkers had higher energy intake from total fats and monosaturated fatty acids than non-drinkers. In contrast, energy intake from carbohydrates was lower among moderate/heavy drinkers than non-drinkers. In conclusion, especially male heavy drinkers had less favorable nutritional intake than moderate and non-drinkers. Further studies on the relationship between alcohol consumption and dietary habits are needed to plan a comprehensive dietary intervention programs in future.
doi:10.1371/journal.pone.0038607
PMCID: PMC3373562  PMID: 22719905
16.  Smoking, drinking, and incident cognitive impairment: a cohort community based study included in the Gospel Oak project 
OBJECTIVES—Recent longitudinal studies have reported that smoking increases risk for cognitive impairment and that moderate alcohol intake could be preventive.The association between both cigarette smoking and alcohol drinking and incident cognitive impairment was studied in a representative population.
METHODS—This is a 1 year prospective population based cohort sudy of all residents aged 65 or over in the electoral ward of Gospel Oak in London, UK (n=889). Cognitive impairment was assessed at baseline and 1 year later using the organic brain syndrome (OBS) cognitive impairment scale from the short CARE structured assessment. Subjects who were cognitively impaired at baseline were excluded from this analysis.
RESULTS—The prevalence of OBS cognitive impairment was 10.4% at index assessment and the 1 year cumulative incidence of cognitive impairment was 5.7%. Cognitive impairment was not associated with use of alcohol, although there was a non-significant association in the direction of a protective effect against onset of cognitive impairment for moderate drinkers compared with non-drinkers and heavy drinkers. Current smoking status predicted cognitive impairment (risk ratio (RR) 3.7; (95% confidence interval (95% CI)=1.1-12.3) independently from sex, age, alcohol, occupational class, education, handicap, depression, and baseline cognitive function.
CONCLUSIONS—Smoking seems to be a prospective risk factor for incident cognitive impairment; thus encouragement of older people to stop smoking could be considered as part of a strategy to reduce the incidence of cognitive impairment.


doi:10.1136/jnnp.68.5.622
PMCID: PMC1736927  PMID: 10766894
17.  Cardiovascular Disease and Cognitive Decline in Postmenopausal Women: Results From the Women's Health Initiative Memory Study 
Background
Data on cardiovascular diseases (CVD) and cognitive decline are conflicting. Our objective was to investigate if CVD is associated with an increased risk for cognitive decline and to examine whether hypertension, diabetes, or adiposity modify the effect of CVD on cognitive functioning.
Methods and Results
Prospective follow‐up of 6455 cognitively intact, postmenopausal women aged 65 to 79 years old enrolled in the Women's Health Initiative Memory Study (WHIMS). CVD was determined by self‐report. For cognitive decline, we assessed the incidence of mild cognitive impairment (MCI) or probable dementia (PD) via modified mini‐mental state examination (3 MS) score, neurocognitive, and neuropsychiatric examinations. The median follow‐up was 8.4 years. Women with CVD tended to be at increased risk for cognitive decline compared with those free of CVD (hazard ratio [HR], 1.29; 95% CI: 1.00, 1.67). Women with myocardial infarction or other vascular disease were at highest risk (HR, 2.10; 95% CI: 1.40, 3.15 or HR, 1.97; 95% CI: 1.34, 2.87). Angina pectoris was moderately associated with cognitive decline (HR 1.45; 95% CI: 1.05, 2.01) whereas no significant relationships were found for atrial fibrillation or heart failure. Hypertension and diabetes increased the risk for cognitive decline in women without CVD. Diabetes tended to elevate the risk for MCI/PD in women with CVD. No significant trend was seen for adiposity.
Conclusions
CVD is associated with cognitive decline in elderly postmenopausal women. Hypertension and diabetes, but not adiposity, are associated with a higher risk for cognitive decline. More research is warranted on the potential of CVD prevention for preserving cognitive functioning.
doi:10.1161/JAHA.113.000369
PMCID: PMC3886762  PMID: 24351701
cardiovascular diseases; cognitive decline; postmenopausal women
18.  Comparative Analysis of Alcohol Control Policies in 30 Countries 
PLoS Medicine  2007;4(4):e151.
Background
Alcohol consumption causes an estimated 4% of the global disease burden, prompting goverments to impose regulations to mitigate the adverse effects of alcohol. To assist public health leaders and policymakers, the authors developed a composite indicator—the Alcohol Policy Index—to gauge the strength of a country's alcohol control policies.
Methods and Findings
The Index generates a score based on policies from five regulatory domains—physical availability of alcohol, drinking context, alcohol prices, alcohol advertising, and operation of motor vehicles. The Index was applied to the 30 countries that compose the Organization for Economic Cooperation and Development and regression analysis was used to examine the relationship between policy score and per capita alcohol consumption. Countries attained a median score of 42.4 of a possible 100 points, ranging from 14.5 (Luxembourg) to 67.3 (Norway). The analysis revealed a strong negative correlation between score and consumption (r = −0.57; p = 0.001): a 10-point increase in the score was associated with a one-liter decrease in absolute alcohol consumption per person per year (95% confidence interval, 0.4–1.5 l). A sensitivity analysis demonstrated the robustness of the Index by showing that countries' scores and ranks remained relatively stable in response to variations in methodological assumptions.
Conclusions
The strength of alcohol control policies, as estimated by the Alcohol Policy Index, varied widely among 30 countries located in Europe, Asia, North America, and Australia. The study revealed a clear inverse relationship between policy strength and alcohol consumption. The Index provides a straightforward tool for facilitating international comparisons. In addition, it can help policymakers review and strengthen existing regulations aimed at minimizing alcohol-related harm and estimate the likely impact of policy changes.
Using an index that gauges the strength of national alcohol policies, a clear inverse relationship was found between policy strength and alcohol consumption.
Editors' Summary
Background.
Alcohol drinking is now recognized as one of the most important risks to human health. Previous research studies (see the research article by Rodgers et al., linked below) have predicted that around 4% of the burden of disease worldwide comes about as a result of drinking alcohol, which can be a factor in a wide range of health problems. These include chronic diseases such as cirrhosis of the liver and certain cancers, as well as poor health resulting from trauma, violence, and accidental injuries. For these reasons, most governments try to control the consumption of alcohol through laws, although very few countries ban alcohol entirely.
Why Was This Study Done?
Although bodies such as the World Health Assembly have recommended that its member countries develop national control policies to prevent excessive alcohol use, there is a huge variation between national policies. It is also very unclear whether there is any link between the strictness of legislation regarding alcohol control in any given country and how much people in that country actually drink.
What Did the Researchers Do and Find?
The researchers carrying out this study had two broad goals. First, they wanted to develop an index (or scoring system) that would allow them and others to rate the strength of any given country's alcohol control policy. Second, they wanted to see whether there is any link between the strength of control policies on this index and the amount of alcohol that is drunk by people on average in each country. In order to develop the alcohol control index, the researchers chose five main areas relating to alcohol control. These five areas related to the availability of alcohol, the “drinking context,” pricing, advertising, and vehicles. Within each policy area, specific policy topics relating to prevention of alcohol consumption and harm were identified. Then, each of 30 countries within the OECD (Organization for Economic Cooperation and Development) were rated on this index using recent data from public reports and databases. The researchers also collected data on alcohol consumption within each country from the World Health Organization and used this to estimate the average amount drunk per person in a year. When the researchers plotted scores on their index against the average amount drunk per person per year, they saw a negative correlation. That is, the stronger the alcohol control policy in any given country, the less people seemed to drink. This worked out at around roughly a 10-point increase on the index equating to a one-liter drop in alcohol consumption per person per year. However, some countries did not seem to fit these predictions very well.
What Do These Findings Mean?
The finding that there is a link between the strength of alcohol control policies and amount of alcohol drinking does not necessarily mean that greater government control causes lower drinking rates. The relationship might just mean that some other variable (e.g., some cultural factor) plays a role in determining the amount that people drink as well as affecting national policies for alcohol control. However, the index developed here is a useful method for researchers and policy makers to measure changes in alcohol controls and therefore understand more clearly the factors that affect drinking rates. This study looked only at the connection between control measures and extent of alcohol consumption, and did not examine alcohol-related harm. Future research might focus on the links between controls and the harms caused by alcohol.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040151.
A Perspective in PLoS Medicine by Alison Ritter accompanies this article: “Comparing alcohol policies between countries: Science or silliness?”
Facts and figures on alcohol are available from the World Health Organization, including information about the burden of disease worldwide as a result of alcohol
Information from the US Centers for Disease Control and Prevention is available about alcohol and public health
A 2004 PLoS Medicine research article includes discussion of the health burdens of alcohol: Rodgers A, Ezzati M, Vander Hoorn S, Lopez AD, Lin RB, et al. (2004) Distribution of major health risks: Findings from the global burden of disease study. PLoS Medicine 1(1): e27. doi:10.1371/journal.pmed.0010027
Current information about research on alcohol and alcoholism is available from the National Institute on Alcohol Abuse and Alcoholism
doi:10.1371/journal.pmed.0040151
PMCID: PMC1876414  PMID: 17455992
19.  Alcohol Marketing Receptivity, Marketing-specific Cognitions and Underage Binge Drinking 
Background
Exposure to alcohol marketing is prevalent and is associated with both initiation and progression of alcohol use in underage youth. The mechanism of influence is not well understood, however. This study tests a model that proposes alcohol-specific cognitions as mediators of the relation between alcohol marketing and problematic drinking among experimental underage drinkers.
Methods
This paper describes a cross-sectional analysis of 1734 U.S. 15–20 year old underage drinkers, recruited for a national study of media and substance use. Subjects were queried about a number of alcohol marketing variables including television time, internet time, favorite alcohol ad, ownership of alcohol branded merchandise (ABM), and exposure to alcohol brands in movies. The relation between these exposures and current (30 day) binge drinking was assessed, as were proposed mediators of this relation, including marketing-specific cognitions (drinker identity and favorite brand to drink), favorable alcohol expectancies and alcohol norms. Paths were tested in a structural equation model that controlled for socio-demographics, personality and peer drinking.
Results
Almost one-third of this sample of ever drinkers had engaged in 30 day binge drinking. Correlations among mediators were all statistically significant (range 0.16 – 0.47) and all were significantly associated with binge drinking. Statistically significant mediation was found for the association between ABM ownership and binge drinking through both drinker identity and having a favorite brand, which also mediated the path between movie brand exposure and binge drinking. Peer drinking and sensation seeking were associated with binge drinking in paths through all mediators.
Conclusions
Associations between alcohol marketing and binge drinking were mediated through marketing-specific cognitions that assess drinker identity and brand allegiance, cognitions that marketers aim to cultivate in the consumer.
doi:10.1111/j.1530-0277.2012.01932.x
PMCID: PMC3548023  PMID: 23256927
Adolescent; young adult; alcohol; advertising; marketing; binge drinking
20.  Alcohol consumption and the risk of morbidity and mortality for different stroke types - a systematic review and meta-analysis 
BMC Public Health  2010;10:258.
Background
Observational studies have suggested a complex relationship between alcohol consumption and stroke, dependent on sex, type of stroke and outcome (morbidity vs. mortality). We undertook a systematic review and a meta-analysis of studies assessing the association between levels of average alcohol consumption and relative risks of ischemic and hemorrhagic strokes separately by sex and outcome. This meta-analysis is the first to explicitly separate morbidity and mortality of alcohol-attributable stroke and thus has implications for public health and prevention.
Methods
Using Medical Subject Headings (alcohol drinking, ethanol, cerebrovascular accident, cerebrovascular disorders, and intracranial embolism and thrombosis and the key word stroke), a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science databases between 1980 to June 2009 was performed followed by manual searches of bibliographies of key retrieved articles. From twenty-six observational studies (cohort or case-control) with ischemic or hemorrhagic strokes the relative risk or odds ratios or hazard ratios of stroke associated with alcohol consumption were reported; alcohol consumption was quantified; and life time abstention (manually estimated where data for current abstainers were given) was used as the reference group. Two reviewers independently extracted the information on study design, participant characteristics, level of alcohol consumption, stroke outcome, control for potential confounding factors, risk estimates and key criteria of study quality using a standardized protocol.
Results
The dose-response relationship for hemorrhagic stroke had monotonically increasing risk for increasing consumption, whereas ischemic stroke showed a curvilinear relationship, with a protective effect of alcohol for low to moderate consumption, and increased risk for higher exposure. For more than 3 drinks on average/day, in general women had higher risks than men, and the risks for mortality were higher compared to the risks for morbidity.
Conclusions
These results indicate that heavy alcohol consumption increases the relative risk of any stroke while light or moderate alcohol consumption may be protective against ischemic stroke. Preventive measures that should be initiated are discussed.
doi:10.1186/1471-2458-10-258
PMCID: PMC2888740  PMID: 20482788
21.  Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME) 
Objective To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France.
Design Cohort data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol <50 g if on only one occasion), volume of alcohol intake, frequency of consumption, and types of beverage consumed were assessed once at inclusion. All coronary events that occurred during the 10 year follow-up were prospectively registered. The relation between baseline characteristics and incidence of hard coronary events and angina events was assessed by Cox’s proportional hazards regression analysis.
Setting One centre in Northern Ireland (Belfast) and three centres in France (Lille, Strasbourg, and Toulouse).
Participants 9778 men aged 50-59 free of ischaemic heart disease at baseline, who were recruited between 1991 and 1994.
Main outcome measures Incident myocardial infarction and coronary death (“hard” coronary events), and incident angina pectoris.
Results A total of 2405 men from Belfast and 7373 men from the French centres were included in the analyses, 1456 (60.5%) and 6679 (90.6%) of whom reported drinking alcohol at least once a week, respectively. Among drinkers, 12% (173/1456) of men in Belfast drank alcohol every day compared with 75% (5008/6679) of men in France. Mean alcohol consumption was 22.1 g/day in Belfast and 32.8 g/day in France. Binge drinkers comprised 9.4% (227/2405) and 0.5% (33/7373) of the Belfast and France samples, respectively. A total of 683 (7.0%) of the 9778 participants experienced ischaemic heart disease events during the 10 year follow-up: 322 (3.3%) hard coronary events and 361 (3.7%) angina events. Annual incidence of hard coronary events per 1000 person years was 5.63 (95% confidence interval 4.69 to 6.69) in Belfast and 2.78 (95% CI 2.41 to 3.20) in France. After multivariate adjustment for classic cardiovascular risk factors and centre, the hazard ratio for hard coronary events compared with regular drinkers was 1.97 (95% CI 1.21 to 3.22) for binge drinkers, 2.03 (95% CI 1.41 to 2.94) for never drinkers, and 1.57 (95% CI 1.11 to 2.21) for former drinkers for the entire cohort. The hazard ratio for hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to 2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for alcohol patterns and wine drinking. Only wine drinking was associated with a lower risk of hard coronary events, irrespective of the country.
Conclusions Regular and moderate alcohol intake throughout the week, the typical pattern in middle aged men in France, is associated with a low risk of ischaemic heart disease, whereas the binge drinking pattern more prevalent in Belfast confers a higher risk.
doi:10.1136/bmj.c6077
PMCID: PMC2990863  PMID: 21098615
22.  Dietary Fat Intake and Cognitive Decline in Women With Type 2 Diabetes 
Diabetes Care  2009;32(4):635-640.
OBJECTIVE
Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications—both associated with cognitive decline—may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes.
RESEARCH DESIGN AND METHODS
Beginning in 1995–1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged ≥70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake.
RESULTS
Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI −0.24 to −0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis.
CONCLUSIONS
These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.
doi:10.2337/dc08-1741
PMCID: PMC2660474  PMID: 19336640
23.  Alcohol intake over the life course and breast cancer survival in Western New York Exposures and Breast Cancer (WEB) study: Quantity and intensity of intake 
Alcohol intake is a risk factor for breast cancer, but the association between alcohol and mortality among breast cancer survivors is poorly understood. We examined the association between alcohol intake from all sources, assessed by cognitive lifetime drinking history, and all-cause and breast cancer mortality among women with breast cancer (N=1097) who participated in a population-based case-control study. Vital status was ascertained through 2006 using the National Death Index. Using Cox Proportional Hazards models, we computed hazard ratios for all-cause and breast cancer mortality in association with alcohol intake. We examined lifetime volume and intensity (drinks per drinking day) of alcohol consumption as well as drinking status during various life periods. Analyses were stratified by menopausal status. After adjustment for total intake, postmenopausal women with consumption of four or more drinks per drinking day over their lifetimes were nearly three times more likely to die from any cause compared to abstainers (HR2.94, 95%CI 1.31,6.62). There was a similar but non-significant association with breast cancer mortality (HR2.68, 95%CI 0.94,7.67). Postmenopausal women who drank one drink or fewer per drinking day between menarche and first birth had a significantly decreased hazard of all-cause (HR0.54, 95%CI 0.31,0.95) and breast cancer mortality (HR0.27, 95%CI 0.09,0.77). Premenopausal breast cancer survival was not associated with drinking intensity. We observed no associations between drinking status or total volume of alcohol intake and breast cancer or all-cause mortality. High-intensity alcohol consumption may be associated with decreased survival in postmenopausal women with breast cancer. Low-intensity alcohol consumption between menarche and first birth may be inversely associated with all-cause and breast cancer mortality; this period may be critical for development of and survival from breast cancer. Intensity of alcohol intake may be a more important factor than absolute volume of intake on survival in women with breast cancer.
doi:10.1007/s10549-013-2533-y
PMCID: PMC3667502  PMID: 23605086
breast cancer; alcohol; survival; population-based study
24.  Muscle-Strengthening and Conditioning Activities and Risk of Type 2 Diabetes: A Prospective Study in Two Cohorts of US Women 
PLoS Medicine  2014;11(1):e1001587.
Anders Grøntved and colleagues examined whether women who perform muscle-strengthening and conditioning activities have an associated reduced risk of type 2 diabetes mellitus.
Please see later in the article for the Editors' Summary
Background
It is well established that aerobic physical activity can lower the risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are beneficial for the prevention of T2D is unclear. This study examined the association of muscle-strengthening activities with the risk of T2D in women.
Methods and Findings
We prospectively followed up 99,316 middle-aged and older women for 8 years from the Nurses' Health Study ([NHS] aged 53–81 years, 2000–2008) and Nurses' Health Study II ([NHSII] aged 36–55 years, 2001–2009), who were free of diabetes, cancer, and cardiovascular diseases at baseline. Participants reported weekly time spent on resistance exercise, lower intensity muscular conditioning exercises (yoga, stretching, toning), and aerobic moderate and vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression with adjustment for major determinants for T2D was carried out to examine the influence of these types of activities on T2D risk. During 705,869 person years of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted models including aerobic MVPA, the pooled relative risk (RR) for T2D for women performing 1–29, 30–59, 60–150, and >150 min/week of total muscle-strengthening and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women reporting no muscle-strengthening and conditioning activities (p<0.001 for trend). Furthermore, resistance exercise and lower intensity muscular conditioning exercises were each independently associated with lower risk of T2D in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening activities had substantial risk reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29–0.38]). Limitations to the study include that muscle-strengthening and conditioning activity and other types of physical activity were assessed by a self-administered questionnaire and that the study population consisted of registered nurses with mostly European ancestry.
Conclusions
Our study suggests that engagement in muscle-strengthening and conditioning activities (resistance exercise, yoga, stretching, toning) is associated with a lower risk of T2D. Engagement in both aerobic MVPA and muscle-strengthening type activity is associated with a substantial reduction in the risk of T2D in middle-aged and older women.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 370 million people have diabetes mellitus, a disorder characterized by poor glycemic control—dangerously high amounts of glucose (sugar) in the blood. Blood sugar levels are normally controlled by insulin, a hormone released by the pancreas. In people with type 2 diabetes (the commonest form of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing excess sugar from the blood become less responsive to insulin. Type 2 diabetes, which was previously known as adult-onset diabetes, can often initially be controlled with diet and exercise, and with antidiabetic drugs such as metformin and sulfonylureas. However, as the disease progresses, the pancreatic beta cells, which make insulin, become impaired and patients may eventually need insulin injections. Long-term complications of diabetes, which include an increased risk of cardiovascular problems such as heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes.
Why Was This Study Done?
Type 2 diabetes is becoming increasingly common worldwide so better preventative strategies are essential. It is well-established that regular aerobic exercise—physical activity in which the breathing and heart rate increase noticeably such as jogging, brisk walking, and swimming—lowers the risk of type 2 diabetes. The World Health Organization currently recommends that adults should do at least 150 min/week of moderate-to-vigorous aerobic physical activity to reduce the risk of diabetes and other non-communicable diseases. It also recommends that adults should undertake muscle-strengthening and conditioning activities such as weight training and yoga on two or more days a week. However, although studies have shown that muscle-strengthening activity improves glycemic control in people who already have diabetes, it is unclear whether this form of exercise prevents diabetes. In this prospective cohort study (a study in which disease development is followed up over time in a group of people whose characteristics are recorded at baseline), the researchers investigated the association of muscle-strengthening activities with the risk of type 2 diabetes in women.
What Did the Researchers Do and Find?
The researchers followed up nearly 100,000 women enrolled in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII), two prospective US investigations into risk factors for chronic diseases in women, for 8 years. The women provided information on weekly participation in muscle-strengthening exercise (for example, weight training), lower intensity muscle-conditioning exercises (for example, yoga and toning), and aerobic moderate and vigorous physical activity (aerobic MVPA) at baseline and 4 years later. During the study 3,491 women developed diabetes. After allowing for major risk factors for type 2 diabetes (for example, diet and a family history of diabetes) and for aerobic MVPA, compared to women who did no muscle-strengthening or conditioning exercise, the risk of developing type 2 diabetes among women declined with increasing participation in muscle-strengthening and conditioning activity. Notably, women who did more than 150 min/week of these types of exercise had 40% lower risk of developing diabetes as women who did not exercise in this way at all. Muscle-strengthening and muscle-conditioning exercise were both independently associated with reduced diabetes risk, and women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening exercise were a third as likely to develop diabetes as inactive women.
What Do These Findings Mean?
These findings show that, among the women enrolled in NHS and NHSII, engagement in muscle-strengthening and conditioning activities lowered the risk of type 2 diabetes independent of aerobic MVPA. That is, non-aerobic exercise provided protection against diabetes in women who did no aerobic exercise. Importantly, they also show that doing both aerobic exercise and muscle-strengthening exercise substantially reduced the risk of type 2 diabetes. Because nearly all the participants in NHS and NHSII were of European ancestry, these results may not be generalizable to women of other ethnic backgrounds. Moreover, the accuracy of these findings may be limited by the use of self-administered questionnaires to determine how much exercise the women undertook. Nevertheless, these findings support the inclusion of muscle-strengthening and conditioning exercises in strategies designed to prevent type 2 diabetes in women, a conclusion that is consistent with current guidelines for physical activity among adults.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001587.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals and the general public, including information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes and explains the benefits of regular physical activity
The World Health Organization provides information about diabetes and about physical activity and health (in several languages); its 2010 Global Recommendations on Physical Activity for Health are available in several languages
The US Centers for Disease Control and Prevention provides information on physical activity for different age groups; its Physical Activity for Everyone web pages include guidelines, instructional videos and personal success stories
More information about the Nurses Health Study and the Nurses Health Study II is available
The UK charity Healthtalkonline has interviews with people about their experiences of diabetes
MedlinePlus provides links to further resources and advice about diabetes and about physical exercise and fitness (in English and Spanish)
doi:10.1371/journal.pmed.1001587
PMCID: PMC3891575  PMID: 24453948
25.  Prenatal alcohol exposure and offspring cognition and school performance. A ‘Mendelian randomization’ natural experiment 
Background There is substantial debate as to whether moderate alcohol use during pregnancy could have subtle but important effects on offspring, by impairing later cognitive function and thus school performance. The authors aimed to investigate the unconfounded effect of moderately increased prenatal alcohol exposure on cognitive/educational performance.
Methods We used mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) and performed both conventional observational analyses and Mendelian randomization using an ADH1B variant (rs1229984) associated with reduced alcohol consumption. Women of White European origin with genotype and self-reported prenatal alcohol consumption, whose offspring’s IQ score had been assessed in clinic (N = 4061 pairs) or Key Stage 2 (KS2) academic achievement score was available through linkage to the National Pupil Database (N = 6268), contributed to the analyses.
Results Women reporting moderate drinking before and during early pregnancy were relatively affluent compared with women reporting lighter drinking, and their children had higher KS2 and IQ scores. In contrast, children whose mothers’ genotype predisposes to lower consumption or abstinence during early pregnancy had higher KS2 scores (mean difference +1.7, 95% confidence interval +0.4, +3.0) than children of mothers whose genotype predisposed to heavier drinking, after adjustment for population stratification.
Conclusions Better offspring cognitive/educational outcomes observed in association with prenatal alcohol exposure presumably reflected residual confounding by factors associated with social position and maternal education. The unconfounded Mendelian randomization estimates suggest a small but potentially important detrimental effect of small increases in prenatal alcohol exposure, at least on educational outcomes.
doi:10.1093/ije/dyt172
PMCID: PMC3807618  PMID: 24065783
Alcohol dehydrogenase; causality; cognition; confounding factors; educational measurement; ethanol; Mendelian randomization analysis; pregnancy

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