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Effects of Alcohol

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[2][3] to severe detrimental effects in cases of chronic alcohol abuse.[4] 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.[5][6] Long-term use of alcohol in excessive quantities is capable of damaging nearly every organ and system in the body.[7] The developing adolescent brain is particularly vulnerable to the toxic effects of alcohol.[8] 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.[9] Many physicians do not promote alcohol consumption, however, given the many health concerns associated with it. Some suggest that alcohol should be regarded as a recreational drug, and prefer exercise and good nutrition to combat cardiovascular disease.[10][11] Others have argued that the benefits of moderate alcohol consumption may be outweighed by other increased risks, including those of injuries, violence, fetal damage, liver disease, and certain forms of cancer.[12]
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.[13] 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.[14] Of the total number of deaths and diseases caused by alcohol, most happen to the majority of the population who are moderate drinkers, rather than the heavy drinker minority.[15] 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.[16] Excessive alcohol consumption can have a negative impact on aging.[17]
Recent studies have focused on understanding the mechanisms by which moderate alcohol consumption confers cardiovascular benefit.[18] One study has suggested a beneficial effect of alcohol on patients with hypertension.[19]

Peripheral arterial disease

"Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men."[61] "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."[62][63]

Intermittent claudication

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.[64]

Heart attack and stroke

Drinking in moderation has been found to help those who have suffered a heart attack survive it.[65][66][67] However, excessive alcohol consumption leads to an increased risk of heart failure.[68] 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.[69] 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.[70]

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.[71]

Hematologic diseases

Alcoholics may have anemia from several causes;[72] 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. 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.[73] 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.[74] Some evidence suggests that low to moderate alcohol consumption may speed up brain volume loss.[75] Chronic consumption of alcohol may result in increased plasma levels of the toxic amino acid homocysteine;[76][77] which may explain alcohol withdrawal seizures,[78] alcohol-induced brain atrophy[79] and alcohol-related cognitive disturbances.[80] 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.[81][82][83][84] 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%.[85] "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."[86]

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.[87] The long-term effects of alcohol on brain chemistry is an important cause of chronic fatigue.[88]

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.[89] 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.[90] 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.[91] However, a study concluded, "Our findings suggest that, despite previous suggestions, moderate alcohol consumption does not protect older people from cognitive decline."[92]
Acetaldehyde is produced from ethanol metabolism by the liver. The acetaldehyde is further metabolized by the enzyme acetaldehyde dehydrogenase. A deficiency of this enzyme is not uncommon in individuals from Northeastern Asia as pointed out in a study from Japan.[93] 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.[94] 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.[95]

Essential tremor

Essential tremors can be temporarily relieved in up to two-thirds of patients by drinking small amounts of alcohol.[96]
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 [97] and could underlie the ameliorative effects.[98][99] Additionally, the effects of ethanol have been studied in different animal essential tremor models.
For more details on this topic, see Essential tremor

Sleep

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.[100]

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.[101] Alcohol misuse is associated with a number of mental health disorders and alcoholics have a very high suicide rate.[102] 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.[103] 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.[104]
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.[105]
Studies have shown that alcohol dependence relates directly to cravings and irritability.[106] Another study has shown that alcohol use is a significant predisposing factor towards antisocial behavior in children.[107] 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).[108] 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.[109][110][111] Psychosis is secondary to several alcohol-related conditions including acute intoxication and withdrawal after significant exposure.[112] 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.[113] 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.[112] However, moderate wine drinking has been shown to lower the risk for depression.[114]
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.[115] 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.[116]

Digestive system and weight gain

The impact of alcohol on weight-gain is contentious: some studies find no effect,[117] others find decreased[118] or increased effect on weight gain.
Alcohol use increases the risk of chronic gastritis (stomach inflammation);[119][120] 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."[121] 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."[122]

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."[123] 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."[124]

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.[127] 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.[127][128] 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.[129][130] Moderate alcohol consumption also increases the risk of liver disease.[12]

Pancreatitis

Alcohol abuse is a leading cause of both acute pancreatitis and chronic pancreatitis.[131][132] Alcoholic pancreatitis can result in severe abdominal pain and may progress to pancreatic cancer.[133] Chronic pancreatitis often results in intestinal malabsorption, and can result in diabetes.[134]

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