Alcohol

88-100,000 Americans die annually from alcohol.

Globally ethanol is the most widely used psychoactive substance.

In 2019, 44% of the global population of age 15 years or older, had consumed alcohol in the previous year.

The CDC reports that alcohol consumption accounts for more than 140,000 deaths per year in the US, more than 380 deaths per day.

The prevalence of alcohol consumption varies according to geographic region: ranging from 4% in the Eastern Mediterranean region to at least 60% in the European, American, and Western Pacific regions, and his higher among men, than among women.

Unhealthy alcohol uses the third leading preventable cause of death in the United States, accounting for 145,000 deaths annually.

An estimated 3.2% of cancer deaths in United States were attributed to alcohol consumption. 

Worlwide 2 billion people consume alocohol, and 76.3 million have alcohol misuse problems (WHO).

Risk is greater in younger people due to binge drinking which may result in violence or accidents.

About 3.3 million deaths (5.9% of all deaths) annually are due to ethanol use.

NHANES 2013–2014 survey: women ages 20 and up consume on average 6.8 grams of alcohol per day and men consume on average 15.5 grams per day.

Globally alcohol associated cancers contributed 6.3 million cases and 3.3 million deaths in 2020 (GLOBCAN 2020).

In 2020 an estimated 741,302 cancer cases or 4.1% of all new cancer cases worlwide were attributed to alcohol consumption with 6.1% among men and 2% and among women.

For cancer prevention it is best not to drink alcohol.

Alcohol use is third leading risk factor for preventable and premature diseases (WHO).

Use contributes to around 4% of the global disease burden.

It is estimated that alcohol related deaths increased by 25% during the first year of the Covid-19 pandemic as compared with the previous year.

WHO-alcohol responsible for more than 5% of all deaths worldwide, or around 3 million a year.

Alcohol consumption has the highest prevalence among White individuals, the highest prevalence of abuse/dependence in Native Americans, and the highest vulnerability to alcohol related health consequences in Black individuals and Native Americans.

It is estimated that alcohol related deaths increased by 25% during the first year of the Covid-19 pandemic as compared with the previous year.

Alcohol consumption has decreased in many European countries, particularly Eastern Europe, whereas alcohol use is on the rise in Asia and many countries in sub Saharan Africa.

The data, part of a report from the World Health Organization, shows that about 2.3 million of those deaths in 2016 were of men, and that almost 29% of all alcohol-caused deaths were due to injuries: including traffic accidents and suicide.

There are more than 10,000 alcohol related motor vehicle accident fatalities annually in the US.

There is an average of 30 years of potential life lost for each life lost from alcohol.

Excess alcohol is the third leading cause of lifestyle related mortality.

An analysis of approximately 600,000 alcohol consumers and 83 prospective studies, alcohol consumption was associated with an increased risk of stroke, heart failure, fatal hypertensive disease, fatal aortic, and coronary disease, excluding myocardial infarction.

An estimated 15 million people in the U.S. have alcoholism.

136.9 million people 12 years or older self report consuming alcohol and of those

60.1 million report binging and 16.5 million report heavy binging.

57% of American adults drink regularly.

Accounts for approximately 2 1/2 million deaths worldwide annually, and the United States estimated economic costs exceed $200 billion a year.

Europe has highest level of ETOH consumption in world and, highest burden of ill health and premature death linked directly to alcohol.

Patients who consume 3-4 drinks per day may have up to 50% higher complication rates, including bleeding, cardiac arrhythmias, impaired wound healing, and intensive care unit admissions when compared with patients who consume 0-2 drinks per day.

The 2011 National Survey on Drug Used Health 52% of Americans age 12 years or older reported alcohol use, and nearly 25% reported binge ing and 6% heavy ing over the past 30 days.

Harmful effects of alcohol involve nearly every organ system as well as psychiatric and social comorbidity.

Common manifestations of alcohol abuse on examination include: mental state of intoxification and withdrawal delirium, depression, anxiety, psychosis, motivation and insight impairment, cognitive decline, cerebellar degeneration, peripheral neuropathy, myopathy, hypertension, cardiomyopathy, malnutrition, liver disease, pancreatic disease,aspiration pneumonia, pneumonia, tuberculosis, tobacco related disorders, and hypogonadism.

Harms caused by use related to the average volume of alcohol consumed per day.

An average liver can process 7 grams of ethanol per hour.

For example, it takes 12 hours to eliminate the ethanol in a bottle of wine, giving 12 hours or more of acetaldehyde exposure.

Risk of harm with alcohol use rises steeply when more than 10-20 g consumed each day.

A standard drink contains 14 g of alcohol and is defined as 12 ounces of beer with 5% alcohol, 5 ounces of wine with 12% alcohol, or 15 ounces of liquor with 40% alcohol.

Use causes harm that is far outweighed by possible modest benefits if cardiovascular disease in middle-aged men.

The Acetaldehyde motif can bind DNA to alter its physical shape or block repair and synthesis mechanisms to induce mutations, breaks and exchanges 

Binging increases risks of accidents, injuries, violence and heart disease.

Approximately 9% of US adults meet the criteria for alcohol use disorder, and this makes up approximately 13% of those who .

 Alcohol excess (>21 standard drinks/week for men and >14 for women in the USA.

Alcohol use disorders most prevalent in young adulthood, ages 18-29.

Mild alcohol abuse disorders frequently remit when individuals enter the labor force, marry and have children.

Less than 15% of patients with alcohol use disorders recieve mental health treatment.

Hazardous use of alcohol increases the risk of future negative consequences.

Individuals with alcohol use disorders account for approximately half of alcohol-related harm, with the remainder due to accidents, assaults and suicide in young adults, especially in men engaging in episodic ing to intoxication.

DSM-5 refers to alcohol use disorder.

Alcohol consumption causally related to approximately 60 illnesses.

Alcohol consumption occurs by more than half of US adults.

Contributes to greater than $223 billion in societal costs annually.

Consumption may result in adverse social, legal, occupational, medical, and psychological consequences.

The risk of harmful consequences and disability is on a continuum.

Risk is defined as a average of 15 or more standard drinks per week or five or more on an occasion for men and eight or more drinks per week or four or more on occasion for women and individuals over the age of 65 years (National Institute on Alcohol Abuse and Alcoholism).

A standard contains 14 g of ethanol and and that would be equivalent to 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80 proof liquor.

Persistent alcohol intake despite adverse consequences is referred to as an alcohol use disorder.

Caloric value of alcohol is 7.1 kcal/g.

Ethanol does supply approximately 29 kilojoules (7 kilocalories) of food energy per gram.

For spirits (vodka, gin, rum, etc.) a standard serving in the United States is 44 millilitres (1+1⁄2 US fluid ounces), which at 40% ethanol (80 proof) would be 14 grams and 410 kJ (98 kcal). (At 50% alcohol, 17.5 g and 513 kJ (122.5 kcal).).

Wine and beer contain a similar amount of ethanol in servings of 150 and 350 mL (5 and 12 US fl oz), respectively, but these beverages also contribute to food energy intake from components other than ethanol. 

A 150 mL (5 US fl oz) serving of wine contains 420 to 540 kJ (100 to 130 kcal). A 350 mL (12 US fl oz) serving of beer contains 400 to 840 kJ (95 to 200 kcal).

Alcoholic beverages are considered empty calorie foods because, while providing energy, they contribute no essential nutrients.

May contribute to positive energy balance and weight gain and development of obesity.

Associated with numerous diseases and injuries.

Alcohol consumption causes premature death: injury, liver disease, heart disease,stroke, GI disease and cancers.

Ethanol consumption increases the risk of heart disease, high blood pressure, atrial fibrillation, and stroke. 

5-6% of new cancers and deaths globally are directly linked to alcohol.

Approximately 87,000 cancers each year in the US are associated with alcohol include cancers of the oral cavity, pharynx, larynx, liver, esophagus, female breast, and colorectal.

All types of alcohol increased levels of acid aldehyde and in turn promotes DNA damage.

Heavy alcohol consumption can cause a decrease in folic acid availability which can decrease the availability of nucleotides for DNA repair, ethanol can decrease the conversion of homocysteine to methionine which is an essential amino acid that is part of the formation of SAMe (S-adenosyl-L-methionine), increased inflammation due to alcohol consumption can increase various cytokine formations especially NF-κB which is a transcription factor, lowers Vitamin A levels which causes a reduction in retinoid conversion and signaling.

Serum alcohol levels are determined by the rate of alcohol absorption from the gastrointestinal (GI) tract, the volume of distribution in the body, and the rate of elimination.

Alcohol is absorbed throughout the GI tract, the majority of which occurs in the small intestine. 

Following absorption it travels to the liver and then is distributed throughout the body water.

First-pass metabolism of alcohol occurs through the liver, which serves as the primary metabolizer.

Alcohol is eliminated from the body primarily through oxidation via the enzyme alcohol dehydrogenase (ADH).

The rate of elimination in the average person is commonly estimated at 0.015 to 0.020 grams per deciliter per hour (g/dL/h), which can vary from person to person and in a given person from one moment to another. 

The rate of alcohol detoxification can be slowed by certain drugs which interfere with the action of alcohol dehydrogenases, notably aspirin, fumes of certain solvents, many heavy metals, and some pyrazole compounds. 

Cimetidine, ranitidine, and acetaminophen are also suspected of slowing alcohol detoxification.

The only known substance that can increase the rate of alcohol metabolism is fructose:  a 100 g dose of fructose has been shown to increase alcohol metabolism by an average of 80%. 

Women have decreased gastric ADH.

The metabolism of alcohol by gastric ADH decreases its systemic bioavailability. 

The stomach protects against systemic absorption of alcohol via ADH activity.

Alcoholic and nonalcoholic women had significantly higher blood alcohol concentrations compared with their male counterparts when the alcohol was ingested; but no significant difference between the sexes when the alcohol was administered intravenously. 

Alcohol dehydrogenase (ADH) enzymes are located throughout the GI tract and the liver as well as in other tissues including adipose, breast, brain, and whole blood.

A protective association for some cancers with alcohol includes: kidney, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma.

As alcohol consumption decreases the risk of cancer also decreases.

Even moderate alcohol consumption is a risk factor for hepatic steatosis development in obese a individuals..

Heavy alcohol consumption is associated with faster progression of chronic kidney disease.

A risk factor for mesenteric ischemia.

Cardiovascular protection by ethanol is observed at approximately 26 g per day.

Increased alcohol intake is associated with risk of cardiovascular events including atrial fibrillation, heart failure and cerebrovascular accidents.

There is a dose independent relationship between alcohol intake and incident atrial fibrillation, left atrial dilatation, atrial fibrosis, and recurrence of arrhythmia after ablation.

Causally linked with risk factors other than atrial fibrillation and include hypertension, obesity, obstructive sleep apnea, and left ventricular dysfunction.

Even moderate alcohol consumption is a risk factor for hepatic steatosis development in obese individuals,

Abstinence from alcohol reduces arrhythmia recurrence in regular drinkers with atrial fibrillation.

Moderate intake is inversely associated with the risk of cardiovascular disease and diabetes, with the benefits being greater for persons with existing cardiovascular risk disease than for those without such risk factors.

In a longitudinal study of 24,029 individuals moderate alcohol consumption was

not associated with a reduced all-cause mortality in older adults (Robert Goulden).

Heavy episodic, or binge ing raises the risk of injuries can increase the risk or exacerbate cardiovascular disease and liver disease.

Repeated episodes of intoxication and withdrawal of alcohol with binge drinking can damage  the amygdala.

Light to moderate alcohol consumption in normal weight women is associated with less weight gain and lower risk of becoming overweight and or obese during 12.9 years of follow-up (Wang L).

Study suggests that regular light-moderate alcohol intake is inversely associated with cardiovascular disease and all cause mortality in a healthy population.

Patients with hypertension benefit from low levels of alcohol intake, although hypertensive guidelines advise that alcohol intake should not exceed two s per day among men and one per day among women.

Daily alcohol consumption is linked with higher systolic blood pressure in people without hypertension.

At low levels is anxiolytic, and socially facilitating.

With increasing dose levels reduces cognitive and psychomotor impairment along with the risks of injury, and disrupts emotional regulation contributing to assaults.

Provides pleasurable effects explaining initiation and persistence of use, and partly explains the development of alcohol use disorders.

The repetition of the pairing of environmental cues and rewards enhances subjective and physiological effects by conditioning and social and cognitive learning about the expectation of alcohol use.

The belief in the benefits of alcohol use, with increased self-confidence allows individuals to believe in their ability to refrain from ing contributes to the development of alcohol use disorders.

In the Framingham study men and women who increased their alcohol consumption during 20 years of follow-up experienced weight gains more than average (Gordon T).

Light to moderate alcohol consumption in normal weight women is associated with less weight gain and lower risk of becoming overweight and or obese during 12.9 years of follow-up (Wang L).

In the Framingham study men and women who increased their alcohol consumption during 20 years of follow-up experienced weight gains more than average (Gordon T).

Use of alcohol responsible for 4% of the global burden of disease, only slight less than that imposed by tobacco and hypertension.

Causes more premature deaths in young adults than does tobacco smoking.

Tobacco smoking is an established cause of most alcohol related cancers – oral cavity, pharynx, larynx, esophagus, liver, and colorectal, and modest associations for female breast cancer.

Involved in 86% of homicides, 60% of sexual assaults, 57% of marital violence, 37% of assaults, 64% of fires and burns, 40-50% of traffic fatalities, 25-35% of nonfatal motor vehicle injuries and 20% of successful suicides.

Involvement in motor vehicle accidents directly correlates with crash severity.

Consumption associated with alcoholic hepatitis, fatty infiltration of the liver, accelerated progression of liver disease, a higher frequency of cirrhosis, a higher incidence of hepatocellular cancer, and death.

The burden of alcohol use is greatest in developed countries where more people to intoxication and other causes of mortality are low.

Alcohol is a carcinogen and even light increases risks of oral, esophageal, liver, colorectal and breast cancers (Bagnardi V et al).

Alcohol intake associated with increased for developing breast cancer, as alcohol intake increases estrogen levels among postmenopausal women.

Alcohol is a risk factor for breast cancer, particularly estrogen receptor positive cancer and it increases mammographic breast density in pre-menopausal and post menopausal women.

A comprehensive analysis of 119 studies has found that it takes only 1 glass of wine or any other kind of alcoholic drink a day to increase risk of breast cancer.

Worldwide research on how breast cancer risk included data from 12 million women and approximately 260,000 breast cancer cases: strong evidence found that risk of pre-menopausal breast cancer is increased by 5% and risk of post-menopausal breast cancer is increased by 9% with drinking the equivalent of a beer or a small glass of wine a day.

Alcohol is a known risk factor for breast cancer, particularly estrogen receptor positive cancers and alcohol increases mammographic breast density in premenopausal and post menopausal women.

One or two daily drinks associated with a low incidence of heart disease in the French.

Excessive alcohol intake associated with cardiomyopathy.

In a study of 4466 patients with moderate alcohol intake undergoing transthoracic echocardiographyfound that heightened alcohol consumption was linked to a larger left ventricular diastolic and systolic diameters and a bigger left atrial diameter in both men and women (Goncalves A et al.).

In the above study increased alcohol use in women was associated with modestly lowered left ventricular ejection fraction.

While observational studies suggest that it lowers cardiovascular risk, there are no significant data to prove the benefits of alcohol.

Daily consumption of more than four s of alcohol (48 g) increases the risk of cirrhosis, as well as death from other causes. The standard varies between 8 gm in the UK and 19.75 gm in Japan.

Low risk alcohol intake varies between countries, but generally ranges from 20-40 gm per day for men or less than 200 gm per week, and 10-30 gm per day or less than 140 gm per week for women.

Low risk alcohol intake equates to 2-3 s per day for men and 1-2 s per day for women.

Thresholds for alcohol related mortality from chronic illness is 2 s per day and for acute injury is 3-4 driks per day.

12-ounce can of beer has between 10 and 20 gm of alcohol.

A 4-ounce glass of wine has about 10-20 gm of alcohol.

A 1.5 ounce shot of alcohol spirits contains about 10-20 gm of alcohol.

Beers contains 4 to 8% alcohol by volume whereas wine is about 13% and liquors 40 to 50%.

Risk of cirrhosis increases proportionately with consumption of more than 30 gm of alcohol per day.

120 gm per day of alcohol intake associated with the highest risk of the development of alcoholic cirrhosis.

Prevalence of cirrhosis is 1% in persons ing 30-60 gm of alcohol a day and up to 5.7% of individuals ing 120 gm a day.

The regular consumption of alcohol can cause fatty liver with hepatocytes containing macrovesicular droplets of triglycerides.

Moderate alcohol intake decreases the risk of myocardial infarction.

Consumption of moderate amounts associated with reduced risks of coronary heart disease, stroke and congestive heart failure.

Excessive intake on a regular basis increases the risk from alcoholic cardiomyopathy and congestive heart failure.

Surgical complication rates increase to 200-400% for those who have five or more drinks per day.

Binging associated with increased risks of myocardial infarction, stroke and atrial fibrillation.

Consumption reduces the risk of non-Hodgkin’s lymphoma and especially Burkitt’s lymphoma.

The adverse affect of alcohol in patients with hepatitis C to promote the development and progression of liver damage is synergistic.

Exacerbates the progression of hepatic fibrosis in chronic hepatitis C.

Ingestion of large amounts of alcohol causes secondary hyperlipidemia usually Fredrickson type IV, or rarely, type V.

When used in excessive amounts no change or a slight decrease in LDL levels.

Excess alcohol intake has an adverse effect of cognitive function.

Causes ataxia by inducing a peripheral polyneuropathy, with predominantly sensory and autonomic deficits and usually with a loss of deep-tendon reflexes.

Consumption can adversely affect vestibular function.

Consumption in association with thiamine deficiency causes Wernicke’s encephalopathy.

Risk of injury increases with the amount of alcohol consumed.

Usage associated with worse outcome in head and neck cancer, liver and stomach cancers.

In a cross-over study there was a 9 fold increase in the odds of an injury when one consumes 5-6 s during a 6 hour period and a 17 fold increase in the odds of injury if 7 or more s are consumed in the same period of time.

Affects a wide range of brain neurotransmitter systems implicating cognition, motion, and motivation.

Detoxified in two enzymatic steps: firstly it is oxidized to acetaldehyde by alcohol dehydrogenase and secondly the enzyme aldehyde dehydrogenase oxidizes acetaldehyde to acetate.

The accumulation of acetaldehyde, the first metabolite of alcohol, accounts for alcoholic’s flush reaction.

Acetaldehyde, the first by-product of ethanol, is between 10 and 30 times more toxic than alcohol itself.

Interacts with many neurotransmitter systems.

Increases GABA, glycine, nicotinic acetylcholine, and serotonin activity.

Indirectly increases dopamine, opioids, and endocannabinoid activity and inhibits glutamate transmission.

The above chemical alterations contribute to intoxication

Pleasurable effects mediated by increased dopaminergic transmission in the mesolimbic rewards system.

Both alcohol enzyme oxidizers use cofactor nicotinamide adenine dinculeotide (NAD) to provide oxidizing power needed.

Liver cells contain limited supply of nicotinamide adenine dinculeotide (NAD), so that these enzymes act as fast as recycled limiting detoxification rate to about one per hour with the remaining alcohol staying in the circulation until metabolized.

Six genes for alcohol dehydrogenase are found in the human genome, with several of these having multiple alleles.

There is a wide range of metabolic activities because active complexes may form in cells resulting in great variation in individuals ability to break down alcohol.

Increases susceptibility to cardiomyopathy, atrial fibrillation, alcoholic hepatitis, renal failure from rhabdomyolysis, hypomagnesemia, hypokalemia, hypophosphatemia, lactic acidosis, alcoholic ketoacidosis, Wernicke-Korsakoff syndrome, pneumonia, acute respiratory distress syndrome, pancreatitis and myopathy.

Strongest link to cancer and alcohol ingestion are cancers of the mouth, pharynx, larynx and esophagus.

Alcohol consumption, specifically liquor consumption of three or more s per day is associated with increased pancreatic cancer mortality (Gapstur SM et al).

Alcohol intake associated with increased for developing breast cancer, as alcohol intake increases estrogen levels among postmenopausal women.

A linear increase in the risk of developing risk cancer with increasing alcohol intake has been noted for up to 60 g per day ( Smith-Warner et al).

For each 10 g increment of alcohol consumed each day ( approximately 0.5-1 ) the risk of breast cancer increases approximately 9%.

American Cancer Society suggests that for those who consume alcoholic beverages, intake should be no more than 1 drink per day for women or 2 per day for men.

Nurses’ Health Study, prospective observational study of 105,986 women: increasing alcohol consumption increased breast cancer risk as low levels of 5.0-9.9 g per day, equivalent to 3-6 s per week, and increased risk related to cumulative alcohol intake throughout adult life.

Consumption of up to 2 s per day not associated with increased risk of atrial fibrillation among initially healthy, middle aged women (Conen), however in women with a greater consumption of 2 or more alcoholic beverages per day has a 1.6 fold greater risk relative to non-ing women.

Factors such as gender, genetics, environmental factors have a role in the development of alcoholic liver disease.

There is an increase use and misuse of alcohol by the LGBTQ community.

Long-term consumption increases intestinal permeability, worsens endotoxemia, stimulates Kupffer cell activity, and increases pro-inflammatory cytokines.

Atherosclerosis Risk in Communities study found that men and women who consumed 7 drinks a week had a 20% and 16% low risk of developing heart failure compared to abstainers.

In the above study former drinker is a found to have greatest risk of developing heart failure at 19% in men and 17% in women.

Individuals who consumed the most alcohol during the study did not have significantly different risk of heart failure than abstainers (Goncalves A et al).

Alcohol dependence features include tolerance and withdrawal.

Repeated alcohol dosing causes neurotransmitter responses to be reduced and increase doses of alcohol are needed to produce the same effect.