Alcohol consumption is responsible for 2.8 million deaths per year across the globe, with cancer the leading cause of alcohol-related death among people aged 50 years and older, warn researchers, who also emphasize that there is no safe level of alcohol consumption.

The findings come from the latest version of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which analyzed data on 28 million people from 195 countries to estimate the prevalence of alcohol consumption, the amounts consumed, and the associated harms.

The report was published online in the Lancet on August 23.

The analysis found that among individuals aged 15 to 49 years, alcohol accounted for around 4% of deaths in women and 12% in men. Tuberculosis and road injuries were the leading causes of death related to alcohol.

For those aged 50 years and older, alcohol was linked to 27% of deaths in women and 19% of deaths in men, with cancer the leading cause of alcohol-related death.

Overall, consuming just one drink a day increased the risk of developing alcohol-related health problems by 0.5% vs abstaining; drinking five drinks a day led to 37% increase in risk.

Lead author Max G. Griswold, MA, Institute for Health Metrics and Evaluation, University of Washington, Seattle, said in a release that although previous studies have suggested that alcohol is protective against some conditions, "we found that the combined health risks associated with alcohol increase with any amount of alcohol.

"In particular, the strong association between alcohol consumption and the risk of cancer, injuries, and infectious diseases offset the protective effects for ischemic heart disease in women in our study," he said.

"Although the health risks associated with alcohol starts off being small with one drink a day, they then rise rapidly as people drink more," he added.

The new findings echo those from in the 2014 World Cancer Report, which found a dose/response relationship between alcohol consumption and certain cancers.

Griswold calls for public health policies to focus on "reducing alcohol consumption to the lowest level" and to revise the "widely held view of the benefits of alcohol."

Coauthor Emmanuela Gakidou, PhD, also from Institute for Health Metrics and Evaluation, went further, declaring: "Alcohol poses dire ramifications for future population health in the absence of policy action today.

"Our results indicate that alcohol use and its harmful effects on health could become a growing challenge as countries become more developed, and enacting or maintaining strong alcohol control policies will be vital," she said.

She suggested that countries look at measures such as excise taxes and controlling the availability and advertising of alcohol.

"Any of these policy actions would contribute to reductions in population-level consumption, a vital step toward decreasing the health loss associated with alcohol use."

In an accompanying comment, Robyn Burton, PhD, Institute of Psychiatry, Psychology and Neuroscience, King's College London, and Nick Sheron, MD, Division of Infection, Inflammation and Immunity, University of Southampton, United Kingdom, say that the results are "clear and unambiguous."

Alcohol is a colossal global health problem. Dr Robyn Burton and Dr Nick Sheron

"Alcohol is a colossal global health problem and small reductions in health-related harms at low levels of alcohol intake are outweighed by the increased risk of other health-related harms, including cancer," they write.

Echoing the conclusion that "there is no safe level of alcohol," they call for public health policies to reduce population-level consumption to be "prioritised."

Burton and Sheron say: "These diseases of unhealthy behaviours, facilitated by unhealthy environments and fuelled by commercial interests putting shareholder value ahead of the tragic human consequences, are the dominant health issue of the 21st century.

"The solutions are straightforward: increasing taxation creates income for hard-pressed health ministries, and reducing the exposure of children to alcohol marketing has no downsides."

The claim that commercial interests are being placed ahead of the human consequences follows from a recent study that showed that the websites and literature of 26 organizations related to the alcohol industry contained significant omissions or misrepresentations of the evidence linking alcohol to increased risk for many cancers.

Despite all this, Griswold told Medscape Medical News that a ban on alcohol would be "a little step too far."

"There is a lot of cultural relevancy to alcohol, and there's a long history in human society," he said.

"From a policy standpoint on a population level, we should work on reducing the amount of consumption, but I don't think taking a step of a ban would necessarily be the right direction, right away at least," he said. "I think that's a little severe."

Long Recognized as a Health Risk

Alcohol has long been recognized as a leading risk factor for disease burden and has been linked to 60 acute and chronic diseases via a multitude of mechanisms, both through cumulative consumption and acute intoxication.

Studies have suggested that low-level alcohol consumption may be protective against ischemic heart disease and diabetes, among other conditions. However, such findings have been challenged by recent analyses.

Previous iterations of the GBD study examined alcohol consumption and its associated effects, but those studies were hampered by methodologic limitations, including limitations related to risk estimation and the use of alcohol sales to determine consumption.

To address these limitations for GBD 2016, the current researchers conducted systematic searches of the Global Health Data Exchange and PubMed.

From this, they identified 121,029 data points from 694 sources for the alcohol exposure calculations and 3992 relative risk estimates from 592 studies to assess the harms of alcohol exposure. These estimates corresponded to a combined population of 28 million individuals and 649,000 registered cases.

Exposure was calculated by gathering data on sales in liters per capita, the prevalence of alcohol consumers and abstainers, and amount of alcohol consumption per day. The researchers controlled for tourism and estimates of unrecorded consumption.

The team then conducted a meta-analysis of the relative risks of 23 health outcomes associated with alcohol use to determine alcohol-attributable deaths for people in 195 countries from 1990 to 2016.

Health outcomes included colorectal and esophageal cancer and cancers of the breast, larynx, liver, and nasal and oral cavities, as well as cardiovascular diseases, other noncommunicable diseases, communicable diseases such as lower respiratory infections and tuberculosis, and intentional and unintentional injuries.

The team calculated that 33% of people worldwide drink alcohol, which equates to 2.4 billion people. Twenty-five percent of women drink alcohol, consuming an average of 0.73 alcoholic drinks per day. Thirty-nine percent of men drink alcohol, consuming 1.7 alcoholic drinks per day.

The highest proportion of alcohol drinkers was in Denmark, where 95.3% of women and 97.1% of men consumer alcohol. The lowest proportion for men was in Pakistan, at 0.8%. The lowest proportion for women was Bangladesh, at 0.3%.

For men, the highest daily consumption was found in Romania, at 8.2 drinks per day. For women, the highest daily consumption was in Ukraine, at 4.2 drinks per day. The lowest consumption among men was in Pakistan, at 0.0007 drinks per day; for women, the lowest consumption was in Iran, at 0.0003 drinks per day.

Overall, alcohol was the seventh highest risk factor for premature death and disease in 2016 and accounted for 2.2% of deaths among women and 6.8% among men.

Among individuals aged 15 to 49 years, the proportion of deaths attributable to alcohol rose to 3.8% of deaths in women and 12.2% in men. The primary causes of alcohol-related death were tuberculosis (1.4%), road injuries (1.2%), and self-harm (1.1%).

The leading cause of alcohol-related deaths among individuals aged 50 years and older was cancer, which caused 27.1% of deaths in women and 18.9% of deaths in men.

This was particularly notable in high-income countries. In low-income countries, tuberculosis was the leading cause of alcohol-related death among persons aged 50 years and older.

This analysis found no protective effect of low-level alcohol consumption against the development of diabetes and ischemic stroke. The only benefit was seen for ischemic heart disease, with a relative risk of 0.82 for women at a consumption of 0.92 standard drinks per day, and a relative risk of 0.86 for men, at a consumption of 0.83 standard drinks per day.

Because this did not offset the health risks associated with alcohol consumption, the researchers conclude that the only safe level of consumption was zero.

Despite attempts to minimize the limitations in previous studies, the researchers concede that it is difficult to estimate unrecorded alcohol consumption, that they did not include data for people younger than 15 years, and that they did not include health problems such as dementia and psoriasis.

If anything, these limitations suggest that they have probably underestimated the number of people who drink alcohol and the associated risks, especially when one considers that there were few reliable data on alcohol-related interpersonal violence.

Another area that was not examined in the study was patterns of drinking, specifically, consistent daily drinking vs binge drinking, in which individuals do not consume alcohol for several days of the week and then consume to excess on the others days.

Griswold said that there has been relatively little examination of the cultural factors regarding the initiation of alcohol consumption and patterns of consumption, and that it "would be a fruitful area of research and one that needs to be pursued further."

He noted that the "pattern of consumption can have implications for coronary heart disease and for injuries, and our current study, by taking the assumption that it's probably consistent throughout the year, tends to underestimate the harm related to these outcomes."

He explained that they did not find enough evidence in the literature to estimate how people typically consume alcohol, especially with regard to the associated risks.

"A lot of these studies are not estimating in tandem the relationship between your pattern of consumption, if you're drinking a lot on one day vs throughout the week, with the risk associated with the amount you're drinking," he said.

Griswold added that future areas of research by the team include cataloging current policies associated with alcohol use and "trying to look at the efficacy of those policies, given the trends in the data about alcohol consumption."

The research was funded by the Bill and Melinda Gates Foundation. The authors' relevant financial relationships are described in the published article. Dr Burton is employed at Public Health England (PHE) and is a visiting researcher at King's College London. Dr Sheron is employed part time at PHE, has received research grants from the British Liver Trust, the Alcohol Education Research Council, and various other funding bodies, has undertaken paid consultancy work and has received traveling expenses from Gilead, and has been paid for medicolegal work regarding hepatitis C and alcohol-related liver disease.

Lancet. Published online August 23, 2018. Full text, Comment

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc