Bi om ed ic al Alcoholism — a deep insight in to its role in various diseases : A critical review

Abstract Introduction The article critically reviews about some emerging problems due to alcoholism. In the present decade, various diseases caused by chronic alcoholism are immensely important. Alcohol is a water-soluble molecule that is rapidly absorbed into the bloodstream from the stomach, small intestine and colon and metabolized primarily in the liver by the actions of alcohol dehydrogenase and mixed function enzymes. Alcohol dehydrogenase converts alcohol to acetaldehyde, which is subsequently converted to acetate by the actions of acetaldehyde dehydrogenase. Four percent of the global burden of disease can be attributed to alcohol, which is linked to more than 60 different specific diseases that have fatal outcome in human society. The most common are cancer, neuropsychiatric disorders, diabetes and cardiovascular diseases. The article reports the results of some of our studies about the role of alcoholism in various diseases and the need to improve experimental research to minimize such outcomes support by evidence-based scientific research regarding harnessing the alcohol policies of today and tomorrow globally for the betterment of mankind. Conclusion Lack of widespread screening and brief interventions, however, has meant that alcoholism is treated more often as an acute illness than chronic disease worldwide. Despite important evidence collected thus far, more research on effective strategies is needed in developing countries to stop this menace.


Introduction
Alcoholic beverages, and the problems they engender, have been familiar in human societies since the beginning of recorded history.Accompanying the near ubiquity of alcoholic beverages in human history has been an appreciation of the social and health problems caused by drinking.Whether in Greece, Palestine or China, ancient texts speak eloquently of such problems.Scientific attention to problems of alcohol consumption has increased during the past 30 years.Every major world religion has at least some strands that counsel abstinence from alcoholic beverages.Alcohol is no longer viewed as a threat to all, but rather to a small subclass of 'alcoholics', or in today's technical terms, people who are 'alcohol dependent'.Alcohol is causally related to more than 60 medical conditions 1 .Overall, 3.5% of the global burden of disease is attributable to alcohol, which accounts for as much death and disability as tobacco and hypertension 2 .
For most people, alcohol use is enjoyable, unassociated with problems and socially accepted.However, for about 10% of people, alcohol use progresses to alcohol abuse or alcohol dependency (alcoholism).This latter group suffers from a primary illness (a brain disease) with terrible morbidity and underreported mortality.When both drugs and alcohol among the estimated 10% of the population with addictive illness are considered, the cost to society is a staggering half a trillion dollars a year 3,4 .The World Health Organization estimates that alcohol causes nearly 1.8 million deaths each year, with 76.3 million persons worldwide having diagnosable alcohol use disorders 5 .Alcoholism is a family disease and results in untold suffering for the entire family.The aim of this review was to discuss the role alcoholism plays in various diseases.

Metabolism of alcohol
Drinking heavily puts people at risk for many adverse health consequences, including alcoholism, liver damage and various cancers.But some people appear to be at greater risk than others for developing these problems.
In this aspect, over viewing the metabolism of alcohol is very important.
Alcohol is metabolized by several processes or pathways.The most common of these pathways involves two enzymes-alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).These enzymes help break apart the alcohol molecule, making it possible to eliminate it from the body.First, ADH metabolizes alcohol to acetaldehyde, a highly toxic substance and known carcinogen.Then, in a second step, acetaldehyde is further metabolized down to another, less active by-product called acetate, which then is broken down into water and carbon dioxide for easy elimination.
The enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down alcohol to acetaldehyde.Small amounts of alcohol also are removed by interacting with fatty acids to form compounds called fatty acid ethyl esters (FAEEs).These compounds have been shown to contribute to damage to the liver and pancreas 3 .

The genetics behind metabolism of alcohol
Regardless of how much a person consumes, the body can only metabolize a certain amount of alcohol every hour.That amount of alcohol varies widely among individuals and depends on a range of factors, including liver size and body mass 5 .
In addition, research shows that different people carry different variations of the ADH and ALDH enzymes.These different versions can be traced to variations in the same gene.Some of these enzyme variants work more or less efficiently than others; this means that some people can break down alcohol to acetaldehyde, or acetaldehyde to acetate, more quickly than others.A fast ADH enzyme or a slow ALDH enzyme can cause toxic acetaldehyde to build up in the body, creating dangerous and unpleasant effects that also may affect an individual's risk for various alcohol-related problems-such as developing alcoholism and causing various diseases 6,7 .

Alcohol-related diseases
Excessive consumption of alcohol may lead to a variety of gastrointestinal, neurologic, cardiovascular and malignant diseases 8 .The percentages of different complications due to alcoholism in both the genders are given in Table 1 10 .Even moderate drinking by the pregnant mother can affect the IQ of the foetus after birth.Alcohol inhibits glucose formation from lactate and from other glucogenic amino acids in the liver.Chronic alcoholism is associated with derangement in sulphur containing amino acid metabolism, producing ethanol-induced hyperhomocysteinemia. Homocysteine induces neuronal cell death.Alcohol after short-term binge drinking and is the hallmark of acute ingestion.It is rare to actually diagnose alcoholic fatty liver as patients are usually asymptomatic and have normal to mildly abnormal liver tests.Physical examination may reveal mild liver enlargement, and stigmata of chronic liver disease are rarely seen 26 .Once alcohol ingestion ceases, the steatosis usually resolves.

Alcoholic hepatitis
The clinical presentation of alcoholic hepatitis is reflective of the inflammatory features characteristic of this disorder.Classically, alcoholic hepatitis presents with fever, jaundice, hepatomegaly and occasionally signs of decompensated liver disease, such as ascites, portal hypertensive bleeding and hepatic encephalopathy 27 .However, patients with alcoholic hepatitis may be entirely asymptomatic.

Alcoholic cirrhosis
Patients with alcoholic cirrhosis have clinical features similar to those of other causes of cirrhosis.The diagnosis of cirrhosis may be suspected in patients with stigmata of chronic liver disease found on examination or laboratory abnormalities suggestive of liver synthetic dysfunction, such as coagulopathy, hypoalbuminemia and hyperbilirubinemia.Ultrasound imaging of the liver may show features of cirrhosis such as irregular enlarged or shrunken liver, dilated torturous portal vein with collaterals and ascites 28 .Splenomegaly may be present.Upper gastrointestinal endoscopy may reveal oesophageal and gastric varices and portal gastropathy.

Alcohol and liver cancer
Alcoholic liver disease can lead to hepatocellular cancer.Infection with hepatitis C or B viruses enhances the risk.

Coronary heart disease
A meta-analysis on the average volume of alcohol consumption and CHD yielded a J-shaped curve 19 .Compared with non-drinking, lowto-moderate consumption of alcohol is associated with lower CHD incidence and mortality.For higher average volumes of alcohol consumption, the risk reverses 20 .Several studies confirming the cardioprotective effect of regular light-to-moderate drinking found an increased risk for major coronary events in drinkers with an episodic heavy drinking pattern compared with abstainers, even when the overall volume of alcohol consumption was low 21 .In addition to its effect on CHD, an irregular pattern of heavy drinking appears to be related to other types of cardiovascular problems such as stroke or sudden cardiac death 22 .

Intentional injury (violence)
Alcohol has been consistently associated with violent crime, although the association might not always be causal 23 .

Liver disease
Worldwide alcohol is one of the main causes of end-stage liver disease.For many decades, alcohol was considered the primary cause of cirrhosis.Alcoholic liver disease occurs in patients who consume excessive amounts of alcohol.Alcoholic cirrhosis occurs in the setting of alcoholism; mortality from alcoholic liver disease closely follows the per capita alcohol consumption 24 .

Fatty liver
Up to 90% of alcoholics have fatty liver, a disorder that is seldom fatal and usually resolves within 2 weeks, if alcohol consumption is discontinued.In the past, it was assumed that alcoholic fatty liver was a benign process and did not lead to fibrosis or cirrhosis.However, 5% to 15% of patients with alcoholic fatty liver develop cirrhosis 25 .Fatty liver typically occurs in high doses induces DNA damage and impairs the DNA repair system.These mechanisms induce apoptosis and early aging 11 .
The volume of consumption as well as the patterns of drinking, especially irregular heavy drinking, has been shown to determine the burden of disease 12 .In other words, the impact of average volume of consumption on mortality or morbidity is partly moderated by the way alcohol is consumed by the individual, which in turn is influenced by the cultural context 13 .Patterns of drinking have been linked not only to acute health outcomes such as injuries, but also to chronic diseases such as coronary heart disease (CHD) and sudden cardiac death 14 .The other potential factors are age, gender, genetic background, nutritional status, intestinal microflora, reactions with xenobiotics, occupational hazards and viral diseases 15 .
There is general agreement that excessive alcohol consumption is associated with an increased risk of cirrhosis.However, there is no consensus on the exact dose or a specific dose-response relationship for cirrhosis 16 .Evidence suggest that there is an increased risk with ingestion of >60 to 80 g/d of alcohol in men and >20g/d in women.In men, cut-off risk level of alcohol consumption to cause chronic liver disease has been suggested to be >40g/day.However, only 6% to 41% of those drinking these amounts will develop cirrhosis 17 .Bellentani et al. (1997)  showed that even in patients with an extremely high daily alcohol intake (>120 g/d), only 13.5% developed alcohol-induced liver damage.It is believed that other factors such as genetic susceptibility and dietary intolerance may be cofactors in alcohol-induced liver damage.

Breast cancer
Meta-analyses have shown a linear increase in the risk of breast cancer with increasing average volumes of consumption of alcohol 18 .levels of toxic by-products such as acetaldehyde and FAEEs.Still, less than 10% of heavy alcohol users develop alcoholic pancreatitis-a disease that irreversibly destroys the pancreas-suggesting that alcohol consumption alone is not enough to cause the disease 29 .
Alcohol is the leading cause of chronic pancreatitis in all the affluent countries such as Europe, North America and Japan.Alcoholic pancreatitis can lead to pancreatic cancer.There is rising prevalence of alcoholrelated pancreatitis even in developing countries.
The other physical complications associated with alcoholism are discussed in Table 2.

Conclusion
Lack of widespread screening and brief interventions, however, has meant that alcoholism is treated more often as an acute illness than chronic disease worldwide.Despite important evidence collected thus far, more research on effective strategies is needed in developing countries to stop this menace.Detoxification helps patients overcome their physiological and psychological dependence on alcohol and save the curse of various diseases.Brief hospitalization may be required for some severely addicted individuals; for others, treatment can be completed on an outpatient basis.The most urgent focus should be on evaluation of the outcome of various policy and program interventions to stop the curse and reduce the burden.Moreover, a stronger epidemiological database is needed in developing countries on levels and patterns of drinking and on the health and social consequences of drink for showing the pathway of future research in alcoholism.

Table 1 Major disease and injury conditions attributable to alcoholism world- wide (WHO, 2002) Men Women Both Malignant neoplasms
. Alcohol abuse can lead to different types of disorders like gastritis, fatty liver, liver cirrhosis and alcoholic hepatitis.Alcohol is one of the commonest causes of pancreatitis.Alcohol in heavy doses causes muscular weakness and acute alcoholic myopathy.It can lead to elevation of blood pressure.It can change the membrane fluidity.In binge drinkers,