TheSide Effects from Drinking Alcohol

What does alcohol do?

Alcohol is the most widely used mind-altering drug in New Zealand. It is legal, it is readily available and it is generally socially acceptable. Alcohol has stimulating, depressing and mood-altering functions that leave practically no circuit or system of the brain untouched.
This range of effects is what sets alcohol apart from many other drugs.

Stimulant and depressant

Alcohol acts as a stimulant when it directly stimulates those brain cells which lead to feelings of pleasure and euphoria.

Alcohol is a depressant when it slows the brain down and reduces tensions and worries. It can affect our judgement and make us do things we would not usually do when sober.
 

Alcohol acts as an anaesthetic when it slows down our reflexes and coordination. Alcohol can put us to sleep, it can induce a coma and it can kill.

Alcohol's effects are dose related - the more alcohol you drink, the greater the effects that may occur. The effect alcohol has on you can also be related to your mood and your expectations. If we get the dose of alcohol right, it can be a pleasant and sometimes useful drug.


If the dose is wrong, then alcohol can cause a wide range of harmful effects. Some of these are discussed below.

Defining alcohol problems

A number of different terms are used to describe alcohol problems. Sometimes the terms can be confusing.

• Hazardous drinking means drinking at levels or in situations that are likely to cause harmful consequences.
• Alcohol abuse refers to the idea that alcohol causes harmful consequences for a person, and the person continues to drink alcohol despite these consequences. 
• 
• Alcohol dependence is a more technical term indicating that either the body or the mind has become hooked or addicted to alcohol.
• Psychological dependence occurs when the mind seems to take over the control of a person's drinking. The person feels they have to drink to feel good or normal. Psychologically dependent people start to act in ways to ensure their addiction is satisfied - they think a lot about alcohol, they always ensure they have enough alcohol to drink and they plan their activities around alcohol. 
• 
• Physical dependence occurs when the body adapts to the high use of alcohol and requires this level of use to feel right or maintain its balance. There are two main signs of physical dependence.
  - Tolerance, which means a person has to progressively drink more alcohol to achieve the same effect that was previously achieved with smaller amounts.
  - Withdrawal, which is a state people can experience if they go without alcohol. Here the body reacts against the absence of alcohol by going through a period of shaking and sweating. If this progresses to a more severe stage, delirium tremens (DTs) may occur, with people becoming confused and experiencing hallucinations (seeing things or hearing things when there is nothing to be seen or heard).

Alcoholism or alcoholic are descriptions that mean different things to different people. Usually alcoholism relates to a state of alcohol dependence, but many people can have severe alcohol-related problems without having signs and symptoms of dependence.
 

Alcohol use common

Alcohol use is very common. Estimates are that over 90% of New Zealanders drink alcohol. Studies suggest over 20% of the population drinks excessively and that, at any one time, 7-10% of us have a problem with dependence on alcohol.

It is further estimated that about 30% of people who are admitted to a general medical hospital have an alcohol-related health problem. Around 40% of people in contact with the mental health services drink in a hazardous way.

Many people drink heavily for brief periods at different times and are then able to reduce or control their drinking. Severe drinking problems can become long-term ones if they are left unchecked or untreated.

People who continually drink heavily can expect to have a disruptive life with more social problems than moderate and non-drinkers. They can expect more health problems and they can expect to die earlier.

Signs of an alcohol problem

How much a person drinks, or whether or not they are hooked on alcohol is perhaps less important than looking at the whole picture of a person's drinking and whether the way in which a person drinks causes problems both to themselves and to others. If this is the case, managing the drinking will need to be part of the solution.

Reducing risk from alcohol

To help reduce the risks from drinking alcohol - start by measuring your drinks, keeping track of how much you are having, and sticking to recommended guidelines on alcohol consumption for men and women (see below).

What is a 'standard drink' measure?

The amount of alcohol we drink can be measured in a number of ways. The most commonly used method is to refer to a standard drink. A standard drink equals 10g of pure alcohol.

The standard drink refers to the amount of alcohol in the drink, not the amount of liquid, so cans or bottles of the same size can have different numbers of standard drinks if they have different alcohol volumes.

The number of standard drinks is listed on the label of each bottle or can of alcoholic beverage you buy.

Some examples of standard drinks:

• 330ml can of beer (@ 4% alcohol volume) is approx 1 standard drink
• 100ml glass of table wine (@12.5% alcohol volume) is approx 1 standard drink
• 30ml of straight spirits is approx 1 standard drink.

Examples of higher amounts:

• 750ml bottle of beer (@ 4% alcohol volume) is aprox 2.4 standard drinks
• 750ml bottle of wine (@ 13% alcohol volume) is aprox 7.7 standard drinks
• 275ml bottle of RTD [ready-to-drink] spirits (@ 5% alcohol) is approx 1.1 standard drinks
• 335ml bottle of RTD spirits (@ 8% alcohol) is approx 2.1 standard drinks.

The long term effects of alcohol (ethanol)

Consumption range from cardioprotective health benefits for low to moderate alcohol consumption in industrialized societies with higher rates of cardiovascular disease to severe detrimental effects in cases of chronic alcohol abuse.

High levels of alcohol consumption are associated with an increased risk of alcoholism, malnutrition, chronic pancreatitis, alcoholic liver disease, and cancer. In addition damage to the central nervous system and peripheral nervous system can occur from chronic alcohol abuse.

Long-term use of alcohol in excessive quantities is capable of damaging nearly every organ and system in the body. The developing adolescent brain is particularly vulnerable to the toxic effects of alcohol.

In addition, the developing fetal brain is also vulnerable, and fetal alcohol syndrome (FAS) may result if pregnant mothers consume alcohol.
The inverse relation in Western cultures between alcohol consumption and cardiovascular disease has been known for over 100 years. There has been reluctance by many physicians, however, to promote alcohol consumption given the many concerns associated with chronic alcohol abuse. Some even suggest that alcohol should be regarded as a recreational drug, and prefer exercise and good nutrition to combat cardiovascular disease. Others have argued that the benefits of moderate alcohol consumption may be outweighed by other increased risks, including those of injuries, violence, fatal damage, liver disease, and certain forms of cancer.

Background

The adverse effects of long-term excessive use of alcohol are close to those seen with other sedative-hypnotics (apart from organ toxicity which is much more problematic with alcohol). Withdrawal effects and dependence are also almost identical.

Alcohol at moderate levels has some positive and negative effects on health. The negative effects include increased risk of liver diseases, oropharyngeal cancer, esophageal cancer and pancreatitis. Conversely moderate intake of alcohol may have some beneficial effects on gastritis and cholelithiasis.

Chronic alcohol misuse and abuse has serious effects on physical and mental health. Chronic excess alcohol intake, or alcohol dependence, can lead to a wide range of neuropsychiatric or neurological impairment, cardiovascular disease, liver disease, and malignant neoplasms.

The psychiatric disorders which are associated with alcoholism include major depression, dysthymia, mania, hypomania, panic disorder, phobias, generalized anxiety disorder, personality disorders, schizophrenia, suicide, neurologic deficits (e.g. impairments of working memory, emotions, executive functions, visuospatial abilities and gait and balance) and brain damage.

Alcohol dependence is associated with hypertension, coronary heart disease, and ischemic stroke, cancer of the respiratory system, and also cancers of the digestive system, liver, breast and ovaries. Heavy drinking is associated with liver disease, such as cirrhosis. Excessive alcohol consumption can have a negative impact on aging.


Recent studies have focused on understanding the mechanisms by which moderate alcohol consumption confers cardiovascular benefit. One study has suggested a beneficial effect of alcohol on patients with hypertension.

Russia

One study claims that "excessive alcohol consumption in Russia, particularly by men, has in recent years caused more than half of all the deaths at ages 15-54 years."^[22]

However, there are some difficulties with this study. For instance the same study also found a protective effect of heavy drinking on breast cancer mortality. This contradicts the well established scientific view that alcohol increases breast cancer risk.^[23]

On this account in further correspondence it was advised that "careful interpretation of mortality statistics in relation to alcohol use is needed, taking into account other relevant risk factors, incidence, and survival."

The authors replied that "whether or not the apparent shortfall in breast cancer mortality among heavy drinkers is real, it accounts for only about 0·1% of adult deaths in Russia. Careful interpretation of it is therefore of little relevance to the findings for alcohol and overall mortality".

United Kingdom

Alcohol-related deaths in the United Kingdom are coded using the Tenth Revision of the International Classification of Diseases (ICD-10).^[25] ICD-10 comprises:

• Mental and behavioural disorders due to use of alcohol – ICD-10 F10
• Degeneration of nervous system due to alcohol – ICD-10 G31.2
• Alcoholic polyneuropathy – ICD-10 G62.1
• Alcoholic cardiomyopathy – ICD-10 I42.6
• Alcoholic gastritis – ICD-10 K29.2
• Alcoholic liver disease – ICD-10 K70
• Chronic hepatitis, not elsewhere classified – ICD-10 K73
• Fibrosis and cirrhosis of liver – ICD-10 K74 (Excluding K74.3-K74.5 – Biliary cirrhosis)
• Alcohol induced chronic pancreatitis – ICD-10 K86.0
• Accidental poisoning by and exposure to alcohol – ICD-10 X45
• Intentional self-poisoning by and exposure to alcohol – ICD-10 X65
• Poisoning by and exposure to alcohol, undetermined intent – ICD-10 Y15

UK statistical bodies report that "There were 8,724 alcohol-related deaths in 2007, lower than 2006, but more than double the 4,144 recorded in 1991. The alcohol-related death rate was 13.3 per 100,000 population in 2007, compared with 6.9 per 100,000 population in 1991."^[26]
In Scotland, the NHS estimate that in 2003 one in every 20 deaths could be attributed to alcohol.^[27]
A 2009 study found that 9,000 people are dying from alcohol-related diseases every year, three times the number 25 years previously.^[28]

United States

The Centers for Disease Control and Prevention report, "From 2001–2005, there were approximately 79,000 deaths annually attributable to excessive alcohol use. In fact, excessive alcohol use is the 3rd leading lifestyle-related cause of death for people in the United States each year."^[29] A 1993 study estimated US deaths through alcohol at 100,000.^[30]

Overall mortality

Extensive research of Western cultures has consistently shown increased survival associated with light to moderate alcohol consumption.^[31]

A 23-year prospective study of 12,000 male British physicians aged 48–78, found that overall mortality was significantly lower in current drinkers compared to non-drinkers even after correction for ex-drinkers. This benefit was strongest for ischemic heart disease, but was also noted for other vascular disease and respiratory disease.

Death rate amongst current drinkers was higher for 'alcohol augmentable' disease such as liver disease and oral cancers, but these deaths were much less common than cardiovascular and respiratory deaths.

The lowest mortality rate was found for consumption of 8 to 14 'units' per week. In the UK a unit is defined as 10ml or 8g of pure alcohol.^[32] Higher consumption increased overall mortality rate, but not above that of non-drinkers.

This is consistent with other research that found a J-curve dependency between alcohol consumption and total mortality among middle aged and older men. While the mortality rates of ex-drinkers and heavy drinkers are significantly elevated, the all-cause mortality rates may be 15-18% lower among moderate drinkers.

Although the definition of a drink varies between studies and countries, this meta-analysis found that low levels of alcohol intake, defined as 1-2 drinks per day for women and 2-4 drinks per day for men, was associated with lower mortality than abstainers.^[34]

This claim was challenged by another study^[35][36] that found that in certain low quality studies occasional drinkers or ex-drinkers were included as abstainers, resulting in the increased mortality in that group. However, the J-curve for total and CHD mortality was reconfirmed by studies that took the mentioned confounders into account.

It has been suggested that the observed decrease in mortality of light-to-moderate drinkers compared to never drinkers might be partially explained by superior health and social status of the drinking group;^[41] however, the protective effect of alcohol in light to moderate drinkers remains significant even after adjusting for these confounders.^[38][40]

Additionally, confounders such as underreporting of alcohol intake might lead to the underestimation of how much mortality is reduced in light-to-moderate drinkers.^[37][42]

A 2010 study confirmed the beneficial effect of moderate alcohol consumption on mortality.^[40] Subjects were grouped into abstainers, light, moderate, and heavy drinkers.

The order of mortality rates from lowest to highest were moderate, light, heavy, and abstainers. The increased risk for abstainers was twice the mortality rate as for moderate drinkers. This study specifically sought to control for confounding factors including the problem of ex-drinkers considered as non-drinkers.^[40]

According to another study, drinkers with heavy drinking occasions (six or more drinks at a time) have a 57% higher all-cause mortality than drinkers without heavy drinking occasions.^[43]
In contrast to studies of Western cultures, research in other cultures has yielded some opposite findings.

The landmark INTERHEART Study has revealed that alcohol consumption in South Asians was not protective against CAD in sharp contrast to other populations who benefit from it.^[44] In fact Asian Indians who consume alcohol had a 60% higher risk of heart attack which was greater with local spirits (80%) than branded spirits (50%).^[45]

The harm was observed in alcohol users classified as occasional as well as regular light, moderate, and heavy consumers.^[45]

Another large study of 4465 subjects in India also confirmed the possible harm of alcohol consumption on coronary risk in men. Compared to lifetime abstainers, alcohol users had higher blood sugar (2 mg/dl), blood pressure (2 mm Hg) levels, and the HDL-C levels (2 mg/dl) and significantly higher tobacco use (63% vs. 21%).^[45]

Cardiovascular system

A meta-analysis of 34 studies found a reduced risk of mortality from coronary heart disease in men who drank 2 - 4 drinks per day and women who drank 1 - 2 drinks per day.^[34] Alcohol has been found to have anticoagulant properties.^[46][47]

Thrombosis is lower among moderate drinkers than abstainers.^[48] A meta-analysis of randomized trials found that alcohol consumption in moderation decreases serum levels of fibrinogen, a protein that promotes clot formation, while it increases levels of tissue type plasminogen activator, an enzyme that helps dissolve clots.^[49]

These changes were estimated to reduce coronary heart disese risk by about 24%.
Serum levels of C-reactive protein (CRP), a marker of inflammation and predictor of CHD (coronary heart disease) risk, are lower in moderate drinkers than in those who abstain from alcohol, suggesting that alcohol consumption in moderation might have anti-inflammatory effects.

Despite epidemiological evidence, many have cautioned against recommendations for the use of alcohol for health benefits. A physician from the World Health Organisation labeled such alcohol promotion as "ridiculous and dangerous".

One reviewer has noted, "Despite the wealth of observational data, it is not absolutely clear that alcohol reduces cardiovascular risk, because no randomized controlled trials have been performed.

Alcohol should never be recommended to patients to reduce cardiovascular risk as a substitute for the well-proven alternatives of appropriate diet, exercise, and drugs."^[55]

It has been argued that the health benefits from alcohol are at best debatable and may have been exaggerated by the alcohol industry.

Some investigators hold that alcohol should be regarded as a recreational drug with potentially serious adverse effects on health and should not be promoted for cardio-protection.^[10]

Nevertheless, a large prospective non-randomized study has shown that moderate alcohol intake in individuals already at low risk based on body mass index, physical activity, smoking, and diet, yields further improvement in cardiovascular risk.^[56]

Peripheral arterial disease

"Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men."^[57] "In this large population-based study, moderatable alcohol consumption was inversely associated with peripheral arterial disease in women but not in men. Residual confounding by smoking may have influenced the results.

Among nonsmokers an inverse association was found between alcohol consumption and peripheral arterial disease in both men and women."^[58][59]

Intermittent claudication (IC)

A study found that moderate consumption of alcohol had a protective effect against intermittent claudication. The lowest risk was seen in men who drank 1 to 2 drinks per day and in women who drank half to 1 drink per day.^[60]

Heart attack and stroke

Drinking in moderation has been found to help those who have suffered a heart attack survive it.^[61][62][63] However, excessive alcohol consumption leads to an increased risk of heart failure.^[64]

A review of the literature found that half a drink of alcohol offered the best level of protection. However, they noted that at present there have been no randomised trials to confirm the evidence which suggests a protective role of low doses of alcohol against heart attacks.^[65] However, moderate alcohol consumption is associated with hypertension.^[12]

There is an increased risk of hypertriglyceridemia, cardiomyopathy, hypertension, and stroke if 3 or more standard drinks of alcohol are taken per day.^[66]

Cardiomyopathy

Large amount of alcohol over the long term can lead to alcoholic cardiomyopathy. Alcoholic cardiomyopathy presents in a manner clinically identical to idiopathic dilated cardiomyopathy, involving hypertrophy of the musculature of the heart that can lead to congestive heart failure.^[67]

Hematologic diseases

Alcoholics may have anemia from several causes;^[68] they may also develop thrombocytopenia from direct toxic effect on megakaryocytes, or from hypersplenism.

Nervous system

Results of the ISCD 2010 study ranking the levels of damage caused by drugs, in the opinion of drug-harm experts. When harm to self and others is summed, alcohol was the most harmful of all drugs considered, scoring 72%.

Chronic heavy alcohol consumption impairs brain development, causes brain shrinkage, dementia, physical dependence, increases neuropsychiatric and cognitive disorders and causes distortion of the brain chemistry.

Some studies however have shown that moderate alcohol consumption may decrease risk of dementia, including Alzheimer disease, although there are studies which find the opposite. At present, due to poor study design and methodology, the literature is inconclusive on whether moderate alcohol consumption increases the risk of dementia or decreases it.^[69]

Evidence for a protective effect of low to moderate alcohol consumption on age related cognitive decline and dementia has been suggested by some research, however, other research has not found a protective effect of low to moderate alcohol consumption.^[70]

Some evidence suggests that low to moderate alcohol consumption may speed up brain volume loss.^[71] Chronic consumption of alcohol may result in increased plasma levels of the toxic amino acid homocysteine;^[72][73] which may explain alcohol withdrawal seizures,^[74] alcohol-induced brain atrophy^[75] and alcohol-related cognitive disturbances.^[76]

Alcohol's impact on the nervous system can also include disruptions of memory and learning (see Effects of alcohol on memory), such as resulting in a blackout phenomenon.

Strokes

Epidemiological studies of middle-aged populations generally find the relationship between alcohol intake and the risk of stroke to be either U- or J-shaped.

There may be very different effects of alcohol based on the type of stroke studied. The predominate form of stroke in Western cultures is ischemic, whereas non-western cultures have more hemorrhagic stroke. In contrast to the beneficial effect of alcohol on ischemic stroke, consumption of more than 2 drinks per day increases the risk of hemorrhagic stroke.

The National Stroke Association estimates this higher amount of alcohol increases stroke risk by 50%.^[81] "For stroke, the observed relationship between alcohol consumption and risk in a given population depends on the proportion of strokes that are hemorrhagic.

Light-to-moderate alcohol intake is associated with a lower risk of ischemic stroke which is likely to be, in part, causal. Hemorrhagic stroke, on the other hand, displays a loglinear relationship with alcohol intake."^[82]

Brain

Alcohol abuse is associated with widespread and significant brain lesions. Alcohol related brain damage is not only due to the direct toxic effects of alcohol; alcohol withdrawal, nutritional deficiency, electrolyte disturbances, and liver damage are also believed to contribute to alcohol-related brain damage.^[83] The long-term effects of alcohol on brain chemistry is an important cause of chronic fatigue.^[84]

Adolescent brain development

Consuming large amounts of alcohol over a period of time can impair normal brain development in humans.^[85] Deficits in retrieval of verbal and nonverbal information and in visuospatial functioning were evident in youths with histories of heavy drinking during early and middle adolescence.^[86][87]

During adolescence critical stages of neurodevelopment occur, including remodeling and functional changes in synaptic plasticity and neuronal connectivity in different brain regions. These changes may make adolescents especially susceptible to the harmful effects of alcohol.

Compared to adults, adolescents exposed to alcohol are more likely to exhibit cognitive deficits (including learning and memory dysfunction). Some of these cognitive effects, such as learning impairments, may persist into adulthood.^[88]

Mechanisms of action

Neuroinflammation

Ethanol can trigger the activation of astroglial cells which can produce a proinflammatory response in the brain. Ethanol interacts with the TLR4 and IL-1RI receptors on these cells to activate intracellular signal transduction pathways. Specifically, ethanol induces the phosphorylation of IL-1R-associated kinase (IRAK), ERK1/2, stress-activated protein kinase (SAPK)/JNK, and p38 mitogen-activated protein kinase (p38 MAPK). Activation of the IRAK/MAPK pathway leads to the stimulation of the transcription factors NF-kappaB and AP-1. These transcription factors cause the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression.^[89] The upregulation of these inflammatory mediators by ethanol is also associated with an increase in caspase 3 activity and a corresponding increase in cell apoptosis.^[89][90] The exact mechanism by which various concentrations of ethanol either activates or inhibits TLR4/IL-1RI signaling is not currently known, though it may involve alterations in lipid raft clustering ^[91] or cell adhesion complexes and actin cytoskeleton organization.^[92]

Changes in dopaminergic and glutamatergic signaling pathways

Intermittent ethanol treatment causes a decrease in expression of the dopamine receptor type 2 (D2R) and a decrease in phosphorylation of 2B subunit of the NMDA receptor (NMDAR2B) in the prefrontal cortex, hippocampus, nucleus accumbens, and for only D2R the striatum.

It also causes changes in the acetylation of histones H3 and H4 in the prefrontal cortex, nucleus accumbens, and striatum, suggesting chromatin remodeling changes which may mediate long-term alterations.

Additionally, adolescent rats pre-exposed to ethanol have higher basal levels of dopamine in the nucleus accumbens, along with a prolonged dopamine response in this area in response to a challenge dose of ethanol.

Together, these results suggest that alcohol exposure during adolescence can sensitize the mesolimbic and mesocortical dopamine pathways to cause changes in dopaminergic and glutamatergic signaling, which may affect the remodeling and functions of the adolescent brain.^[93]

These changes are significant as alcohol’s effect on NMDARs could contribute to learning and memory dysfunction.

Inhibition of hippocampal neurogenesis

Excessive alcohol intake (binge drinking) causes a decrease in hippocampal neurogenesis, via decreases in neural stem cell proliferation and newborn cell survival.

Alcohol decreases the number of cells in S-phase of the cell cycle, and may arrest cells in the G1 phase, thus inhibiting their proliferation.^[94]

 Ethanol has different effects on different types of actively dividing hippocampal progenitors during their initial phases of neuronal development. Chronic alcohol exposure decreases the number of proliferating cells that are radial glia-like, preneuronal, and intermediate types, while not affecting early neuronal type cells; suggesting ethanol treatment alters the precursor cell pool.

Furthermore, there is a greater decrease in differentiation and immature neurons than there is in proliferating progenitors, suggesting that the abnormal decrease in the percentage of actively dividing preneuronal progenitors results in a greater reduction in the maturation and survival of postmitotic cells.^[95]
Additionally, alcohol exposure increased several markers of cell death. In these studies neural degeneration seems to be mediated by non-apoptotic pathways.^[94][95] One of the proposed mechanisms for alcohol’s neurotoxicity is the production of nitric oxide (NO), yet other studies have found alcohol-induced NO production to lead to apoptosis (see Neuroinflammation section).

Cognition and dementia

Excessive alcohol intake is associated with impaired prospective memory. This impaired cognitive ability leads to increased failure to carry out an intended task at a later date, for example, forgetting to lock the door or to post a letter on time.

The higher the volume of alcohol consumed and the longer consumed, the more severe the impairments.^[96] One of the organs most sensitive to the toxic effects of chronic alcohol consumption is the brain.

In France approximately 20% of admissions to mental health facilities are related to alcohol-related cognitive impairment, most notably alcohol-related dementia. Chronic excessive alcohol intake is also associated with serious cognitive decline and a range of neuropsychiatric complications.

The elderly are the most sensitive to the toxic effects of alcohol on the brain.^[97] There is some inconclusive evidence that small amounts of alcohol taken in earlier adult life is protective in later life against cognitive decline and dementia.^[98]

However, a study concluded, "Our findings suggest that, despite previous suggestions, moderate alcohol consumption does not protect older people from cognitive decline."^[99]

 Acetaldehyde is produced from ethanol metabolism by the liver. The acetaldehyde is further metabolized by the enzyme acetaldehyde dehydrognease.

A deficency of this enzyme is not uncommon in individuals from Northeastern Asia as pointed out in a study from Japan.^[100]

This study has suggested these individuals may be more susceptible to late-onset Alzheimer's disease, however this higher risk is associated with the enzyme deficiency not with alcohol consumption. Individuals with this defect generally do not drink alcohol.

Wernicke-Korsakoff syndrome is a manifestation of thiamine deficiency, usually as a secondary effect of alcohol abuse.^[101] The syndrome is a combined manifestation of two eponymous disorders, Korsakoff's Psychosis and Wernicke's encephalopathy, named after Drs. Sergei Korsakoff and Carl Wernicke.

Wernicke's encephalopathy is the acute presentation of the syndrome and is characterised by a confusional state while Korsakoff's psychosis main symptoms are amnesia and executive dysfunction.^[102]

Essential tremor

Essential tremors can be temporarily relieved in up to two-thirds of patients by drinking small amounts of alcohol.^[103]

Ethanol is known to activate aminobutyric acid type A (GABAA) and inhibit N-methyl-D-aspartate (NMDA) glutamate receptors, which are both implicated in essential tremor pathology ^[104] and could underlie the ameliorative effects.^[105][106]

Chronic use of alcohol used to induce sleep can lead to insomnia. Frequent moving between sleep stages occurs, with awakenings due to headaches and diaphoresis. Stopping chronic alcohol abuse can also lead to profound disturbances of sleep with vivid dreams.

Chronic alcohol abuse is associated with NREM stage 3 and 4 sleep as well as suppression of REM sleep and REM sleep fragmentation. During withdrawal REM sleep is typically exaggerated as part of a rebound effect.^[107]

Mental health effects

High rates of major depressive disorder occur in heavy drinkers and those who abuse alcohol. Whether it is more true that major depressive disorder causes self-medicating alcohol abuse, or the increased incidence of the disorder in alcohol abusers is caused by the drinking, is not known though some evidence suggests drinking causes the disorder.^[108]

Alcohol misuse is associated with a number of mental health disorders and alcoholics have a very high suicide rate.^[109] A study of people hospitalised for suicide attempts found that those who were alcoholics were 75 times more likely to go on to successfully commit suicide than non-alcoholic suicide attempters.^[110]

 In the general alcoholic population the increased risk of suicide compared to the general public is 5-20 times greater. About 15 percent of alcoholics commit suicide. Abuse of other drugs is also associated with an increased risk of suicide. About 33 percent of suicides in the under 35s are due to alcohol or other substance misuse.^[111]

Social skills are significantly impaired in people suffering from alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain.

The social skills that are impaired by alcohol abuse include impairments in perceiving facial emotions, prosody perception problems and theory of mind deficits; the ability to understand humour is also impaired in alcohol abusers.^[112]

Studies have shown that alcohol dependence relates directly to cravings and irritability.^[113] Another study has shown that alcohol use is a significant predisposing factor towards antisocial behavior in children.^[114]

 Depression, anxiety and panic disorder are disorders commonly reported by alcohol dependent people. Alcoholism is associated with dampened activation in brain networks responsible for emotional processing (e.g. the amygdala and hippocampus).^[115]

Evidence that the mental health disorders are often induced by alcohol misuse via distortion of brain neurochemistry is indicated by the improvement or disappearance of symptoms that occurs after prolonged abstinence, although problems may worsen in early withdrawal and recovery periods.^{[116][117][118]}

Psychosis is secondary to several alcohol-related conditions including acute intoxication and withdrawal after significant exposure.^[119] Chronic alcohol misuse can cause psychotic type symptoms to develop, more so than with other drugs of abuse.

Alcohol abuse has been shown to cause an 800% increased risk of psychotic disorders in men and a 300% increased risk of psychotic disorders in women which are not related to pre-existing psychiatric disorders.

This is significantly higher than the increased risk of psychotic disorders seen from cannabis use making alcohol abuse a very significant cause of psychotic disorders.^[120] Approximately 3 percent of people who are alcohol dependent experience psychosis during acute intoxication or withdrawal.

Alcohol-related psychosis may manifest itself through a kindling mechanism. The mechanism of alcohol-related psychosis is due to distortions to neuronal membranes, gene expression, as well as thiamin deficiency.

It is possible in some cases that alcohol abuse via a kindling mechanism can cause the development of a chronic substance-induced psychotic disorder, i.e. schizophrenia.

The effects of an alcohol-related psychosis include an increased risk of depression and suicide as well as psychosocial impairments.^[119]

While alcohol initially helps social phobia or panic symptoms, with longer term alcohol misuse can often worsen social phobia symptoms and can cause panic disorder to develop or worsen, during alcohol intoxication and especially during the alcohol withdrawal syndrome.

This effect is not unique to alcohol but can also occur with long term use of drugs which have a similar mechanism of action to alcohol such as the benzodiazepines which are sometimes prescribed as tranquillisers to people with alcohol problems.^[121]

Approximately half of patients attending mental health services for conditions including anxiety disorders such as panic disorder or social phobia suffer from alcohol or benzodiazepine dependence.

It was noted that every individual has an individual sensitivity level to alcohol or sedative hypnotic drugs and what one person can tolerate without ill health another will suffer very ill health and that even moderate drinking can cause rebound anxiety syndromes and sleep disorders.

A person who is suffering the toxic effects of alcohol will not benefit from other therapies or medications as they do not address the root cause of the symptoms.^[122]

Digestive system and weight gain

See also: Alcohol and weight, Alcoholic liver disease, Alcoholic hepatitis, Fatty liver, and Cirrhosis

The impact of alcohol on weight-gain is contentious: some studies find no effect,^[123] others find decreased^[124] or increased effect on weight gain.
Alcohol use increases the risk of chronic gastritis (stomach inflammation);^[125][126] it is one cause of cirrhosis, hepatitis, and pancreatitis in both its chronic and acute forms.

Metabolic syndrome

A study concluded, "Mild to moderate alcohol consumption is associated with a lower prevalence of the metabolic syndrome, with a favorable influence on lipids, waist circumference, and fasting insulin. This association was strongest among whites and among beer and wine drinkers."^[127] This is also true for Asians. A J-curve association between alcohol intake and metabolic syndrome was found: "The results of the present study suggest that the metabolic syndrome is negatively associated with light alcohol consumption (1–15 g alcohol/d) in Korean adults". However, "odds ratios for the metabolic syndrome and its components tended to increase with increasing alcohol consumption."^[128]

Gallbladder effects

Research has found that drinking reduces the risk of developing gallstones.

Compared with alcohol abstainers, the relative risk of gallstone disease, controlling for age, sex, education, smoking, and body mass index, is 0.83 for occasional and regular moderate drinkers (< 25 ml of ethanol per day), 0.67 for intermediate drinkers (25-50 ml per day), and 0.58 for heavy drinkers.

This inverse association was consistent across strata of age, sex, and body mass index."^[129] Frequency of drinking also appears to be a factor. "An increase in frequency of alcohol consumption also was related to decreased risk.

Combining the reports of quantity and frequency of alcohol intake, a consumption pattern that reflected frequent intake (5-7 days/week) of any given amount of alcohol was associated with a decreased risk, as compared with nondrinkers. In contrast, infrequent alcohol intake (1-2 days/week) showed no significant association with risk."^[130]

Consumption of alcohol is unrelated to gallbladder disease.^[131] However one study suggested that drinkers who take vitamin C (ascorbic acid) might reduce their risk of gallbladder disease.^[132]

Liver disease

Alcoholic liver disease is a major public health problem. For example in the United States up to two million people have alcohol-related liver disorders.^[133] Chronic alcohol abuse can cause fatty liver, cirrhosis and alcoholic hepatitis.

Treatment options are limited and consist of most importantly discontinuing alcohol consumption. In cases of severe liver disease, the only treatment option may be a liver transplant in alcohol abstinent patients.

Research is being conducted into the effectiveness of anti-TNFs. Certain complementary medications, e.g., milk thistle and silymarin, appear to offer some benefit.^[133][134] Alcohol is a leading cause of liver cancer in the Western world, accounting for 32-45% of hepatic cancers. Up to half a million people in the United States develop alcohol-related liver cancer.^[135][136] Moderate alcohol consumption also increases the risk of liver disease.^[12]

Pancreatitis

Alcohol misuse is a leading cause of both acute pancreatitis and chronic pancreatitis.^[137][138] Chronic excessive intake of alcohol can cause destruction of the pancreas resulting in severe chronic pain, which may progress to pancreatic cancer.^[139] Chronic pancreatitis often results in malabsorption problems and diabetes.^[140]

Other systems

Respiratory system

Chronic alcohol ingestion can impair multiple critical cellular functions in the lung.^{[citation needed]} These cellular impairments can lead to increased susceptibility to serious complications from lung disease. Recent research cites alcoholic lung disease as comparable to liver disease in alcohol-related mortality.

Alcoholics have a higher risk of developing acute respiratory distress syndrome (ARDS) and experience higher rates of mortality from ARDS when compared to non-alcoholics.^{[citation needed]} Despite these effects, a large prospective study has shown a protective effect of moderate alcohol consumption on respiratory mortality.^[33]

Kidney stones

Research indicates that drinking alcohol is associated with a lower risk of developing kidney stones. One study concludes, "Since beer seemed to be protective against kidney stones, the physiologic effects of other substances besides ethanol, especially those of hops, should also be examined."^[141] "...consumption of coffee, alcohol, and vitamin C supplements were negatively associated with stones.

"After mutually adjusting for the intake of other beverages, the risk of stone formation decreased by the following amount for each 240-ml (8-oz) serving consumed daily: caffeinated coffee, 10%; decaffeinated coffee, 10%; tea, 14%; beer, 21%; and wine, 39%."^[143] "...stone formation decreased by the following amount for each 240-mL (8-oz) serving consumed daily: 10% for caffeinated coffee, 9% for decaffeinated coffee, 8% for tea, and 59% for wine." (CI data excised from last two quotes.).^[144]

Sexual dysfunction

Long term excessive intake of alcohol can lead to damage to the central nervous system and the peripheral nervous system resulting in loss of sexual desire and impotence in men.^[145] This can result due to a reduction of testosterone from ethanol-induced testicular atrophy, resulting in increased feminisation of males and is a clinical feature of alcohol abusing males who have cirrhosis of the liver.^[146]

Hormonal Imbalance

Excessive alcohol intake can result in hyperoestrogenisation.^[147] It has been speculated that alcohol beverages may contain estrogen like compounds. In men, high levels of estrogen can lead to testicular failure and the development of feminine traits including development of male breasts, called gynecomastia.^[148][149] In women, increased levels of estrogen due to excessive alcohol intake have been related to an increased risk of breast cancer.^[149][150]

Diabetes mellitus

A twenty year twin study from Finland has shown that moderate alcohol consumption may reduce the risk of type 2 diabetes in men and women. However, binge drinking and high alcohol consumption was found to increase the risk of type 2 diabetes in women. ^[151] A study in mice has suggested a beneficial effect of alcohol in promoting insulin sensitivity.^[152]

Rheumatoid arthritis

Regular consumption of alcohol is associated with an increased risk of gouty arthritis^[153][154] and a decreased risk of rheumatoid arthritis.^{[155][156][157][158][159]} Two recent studies report that the more alcohol consumed, the lower the risk of developing rheumatoid arthritis. Among those who drank regularly, the one-quarter who drank the most were up to 50% less likely to develop the disease compared to the half who drank the least.^[160]

The researchers noted that moderate alcohol consumption also reduces the risk of other inflammatory processes such as cardiovascualar disease. Some of the biological mechanisms by which ethanol reduces the risk of destructive arthritis and prevents the loss of bone mineral density (BMD), which is part of the disease process.^[161]

A study concluded, "Alcohol either protects from RA or, subjects with RA curtail their drinking after the manifestation of RA".^[162] Another study found, "Postmenopausal women who averaged more than 14 alcoholic drinks per week had a reduced risk of rheumatoid arthritis..."^[163]

Osteoporosis

Moderate alcohol consumption is associated with higher bone mineral density in postmenopausal women. "...Alcohol consumption significantly decreased the likelihood [of osteoporosis]."^[164] "Moderate alcohol intake was associated with higher BMD in postmenopausal elderly women."^[165] "Social drinking is associated with higher bone mineral density in men and women [over 45]."^[166] However, alcohol abuse is associated with bone loss.^[167][168]

Skin

Chronic excessive alcohol abuse is associated with a wide range of skin disorders including urticaria, porphyria cutanea tarda, flushing, cutaneous stigmata of cirrhosis, psoriasis, pruritus, seborrheic dermatitis and rosacea.^[169]
A 2010 study concluded, "Nonlight beer intake is associated with an increased risk of developing psoriasis among women. Other alcoholic beverages did not increase the risk of psoriasis in this study."^[170]

Immune system

Bacterial infection

There is a protective effect of alcohol consumption against active infection with H. pylori^[171] In contrast, alcohol intake (comparing those who drink > 30g of alcohol per day to non-drinkers) is not associated with higher risk of duodenal ulcer.^[172] Excessive alcohol consumption seen in alcoholics is a known risk factor for pneumonia.

Common cold

A study on the common cold found that "Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness following infection.

However, the benefits of drinking occurred only among nonsmokers. [...] Although alcohol consumption did not influence risk of clinical illness for smokers, moderate alcohol consumption was associated with decreased risk for nonsmokers."^[173]

Another study concluded, "Findings suggest that wine intake, especially red wine, may have a protective effect against common cold. Beer, spirits, and total alcohol intakes do not seem to affect the incidence of common cold."^[174]

Cancer

In 1988 the International Agency for Research on Cancer (Centre International de Recherche sur le Cancer) of the World Health Organization classified alcohol as a Group 1 carcinogen, stating "There is sufficient evidence for the carcinogenicity of alcoholic beverages in humans.... Alcoholic beverages are carcinogenic to humans (Group 1)."^[175]

The U.S. Department of Health & Human Services’ National Toxicology Program in 2000 listed alcohol as a known carcinogen.^[176]
It was estimated in 2006 that "3.6% of all cancer cases worldwide are related to alcohol drinking, resulting in 3.5% of all cancer deaths."^[177] A European study from 2011 found that one in 10 of all cancers in men and one in 33 in women were caused by past or current alcohol intake.^[178][179] The World Cancer Research Fund panel report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective finds the evidence "convincing" that alcoholic drinks increase the risk of the following cancers: mouth, pharynx and larynx, oesophagus, colorectum (men), breast (pre- and postmenopause).^[180]

Acetaldehyde, a metabolic product of alcohol, is suspected to promote cancer. Typically the liver eliminates 99% of acetaldehyde produced.

However, liver disease and certain genetic enzyme deficiencies result in high acetaldehyde levels. Heavy drinkers who are exposed to high acetaldehyde levels due to a genetic defect in alcohol dehydrogenase have been found to be at greater risk of developing cancers of the upper gastrointestinal tract and liver.^[181]

A review in 2007 found "convincing evidence that acetaldehyde... is responsible for the carcinogenic effect of ethanol... owing to its multiple mutagenic effects on DNA."^[182]

Acetaldehyde can react with DNA to create DNA adducts including the Cr-Pdg adduct. This Cr-PdG adduct "is likely to play a central role in the mechanism of alcoholic beverage related carcinogenesis." ^[183] Some have pointed out that even moderate levels of alcohol consumption are associated with an increased risk of certain forms of cancer.^[12]

Alcohol's effect on the foetus

Main articles: Foetal alcohol syndrome and Fetal Alcohol Spectrum Disorder

Foetal alcohol syndrome or FAS is a disorder of permanent birth defects that occurs in the offspring of women who drink alcohol during pregnancy.

 

Drinking heavily or during the early stages of prenatal development has been conclusively linked to FAS; moderate consumption is associated with fetal damage.^[12]

Alcohol crosses the placental barrier and can stunt fetal growth or weight, create distinctive facial stigmata, damaged neurons and brain structures, and cause other physical, mental, or behavioural problems.

Fetal alcohol exposure is the leading known cause of mental retardation in the Western world.^[185] Alcohol consumption during pregnancy is associated with brain insulin and insulin-like growth factor resistance.^[167]