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2010, 7(4), 1285-1301;

Alcohol and Acetaldehyde in Public Health: From Marvel to Menace
by Rui Guo and Jun Ren *
Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, College of Health Sciences, WY 82071, USA
Author to whom correspondence should be addressed.
Received: 11 January 2010; in revised form: 23 February 2010 / Accepted: 12 March 2010 / Published: 25 March 2010


Alcohol abuse is a serious medical and social problem. Although light to moderate alcohol consumption is beneficial to cardiovascular health, heavy drinking often results in organ damage and social problems. In addition, genetic susceptibility to the effect of alcohol on cancer and coronary heart disease differs across the population. A number of mechanisms including direct the toxicity of ethanol, its metabolites [e.g., acetaldehyde and fatty acid ethyl esters (FAEEs)] and oxidative stress may mediate alcoholic complications. Acetaldehyde, the primary metabolic product of ethanol, is an important candidate toxin in developing alcoholic diseases. Meanwhile, free radicals produced during ethanol metabolism and FAEEs are also important triggers for alcoholic damages.
alcohol; acetaldehyde; metabolism; human health

1. Introduction

The alcohol family is comprised of three different members namely methyl alcohol (methanol), isopropyl alcohol and ethyl alcohol (ethanol, EtOH or CH3CH2OH). The first two forms of alcohol are toxic and prohibited to consume. However, ethanol, or alcohol as commonly called, is an intoxicating ingredient in beer, wine and other forms of liquor. Over centuries, alcohol has become the most socially-accepted addictive drug worldwide. Alcohol beverages have long been known for their rather important role in social activities. Drinking alcoholic beverages is a common feature of social gatherings. Although light to moderate drinkers tend to display an overall better cardiovascular health and longevity compared with abstainers or heavy drinkers [14], long-term alcohol misuse or binge drinking can result in life-threatening health hazards both physically and mentally. Moreover, genetic susceptibility to alcohol-associated risk prevalence of cancer and coronary heart disease differs across the population. Therefore, it is recommended that moderate drinking must be individualized to reflect the potentially confounding effects of alcohol on several chronic diseases [5]. For example, individuals with a high risk of carcinogenesis should abstain from alcohol use [6]. Certain devastating chronic diseases such as heart disease [79], Alzheimer’s disease [10], stroke [11,12], liver disease [1315], cancer [1618], chronic respiratory disease [19,20], diabetes mellitus [2123] and bone disease [24,25] may develop following chronic alcohol ingestion and contribute to the alcoholism-related high morbidity and mortality. In addition to chronic diseases, alcohol abuse may also trigger a cascade of acute health problems such as traffic accident-related injuries. Furthermore, social problem can also be a consequence of alcohol abuse including domestic violence, loss of work-place productivity, economic burden on society, crime and public disorders [2629]. With the increased alcohol consumption in women and adolescences [30], alcohol-related social and health problems are attracting more and more attention.
To-date, a number of theories have been postulated for the pathogenesis of alcohol-induced complications including direct toxicity of ethanol and its metabolites [31], oxidative stress, accumulation of fatty acid ethyl esters [32] as well as modifications of lipoprotein and apolipoprotein particles [33]. In particular, acetaldehyde, the primary metabolic product of ethanol, is thought to be a candidate toxin and plays a pivotal role in priming and developing alcoholism [34]. Genetic polymorphism in alcohol dehydrogenase (ADH) [35] and aldehyde dehydrogenase (ALDH) [36,37], the two key enzymes responsible for ethanol/acetaldehyde metabolism, is involved in the susceptibility to alcoholism and alcohol-related organ damage and diseases. Ethanol elimination occurs through oxidation to acetaldehyde and acetate by way of ADH and ALDH, respectively. Different levels of blood acetaldehyde are shown in different genotypic verifications in the ADH or ALDH gene following alcohol intake [37], thus predisposing these individuals to alcohol damage, and the degrees of polymorphism differs depending on racial and ethnic groups [38].

2. Alcohol and Human Health

Since the beginning of last century, a number of studies have demonstrated that light to moderate alcohol consumption is associated with better cardiovascular health and longevity outcome compared with either abstainers or heavy drinkers [34,39]. One of the earliest scientific studies on the subject appeared in the Journal of the American Medical Association in 1904. In addition to reducing the risk of heart attacks, e.g., coronary heart disease (CHD), ischemic heart disease, atherosclerosis, angina pectoris [4044], light to moderate drinking is also generally beneficial in minimizing the risk of stroke [45], peripheral artery disease [46], hypertension [35,47], liver disease [48], Alzheimer’s disease, Parkinson’s disease, diabetes [4951], rheumatoid arthritis [52], bone fractures and osteoporosis [53,54], digestive ailments [55], stress and depression [56], renal cell carcinoma [57], pancreatic cancer [58], duodenal ulcer [59], macular degeneration [60], hearing loss [61], gallstones [62], poor physical condition in the elderly [63] and common cold [64]. Although the benefits and risks associated with light to moderate drinking have gained increasing attention in recent years from both researchers and the general public [39], no universal definition of moderate drinking has been established. The currently accepted definition for moderate drinking employs pure ethanol contained in “one drink” as a unit quantity to evaluate the amount consumed in a specific time period (e.g., USA and Canada, 12 or 14 g; Australia, 10 g; UK and Ireland, 8 g; Italy and Spain, 10 g; Denmark and France, 12 g; Japan, 20 g) [65]. There is also an indication to use 24 g ethanol, or two US standard drinks or less in a day, as the moderate alcohol intake [66].
Despite the beneficial effects of light to moderate alcohol intake, an ample of clinical and experimental evidence has demonstrated the concordant J or U-shaped associations between alcohol intake and a variety of adverse health outcomes [1]. Long-term alcohol misuse or heavy drinking not only failed to improve the health outcome but also enhanced the risk of various human diseases such as those mentioned previously. Binge drinking may cause detrimental damage to human organs including brain, liver, heart, lung, skeletal muscle and bones. For example, the brain may be affected resulting in confusion and memory loss [6769]. The liver, the main site of ethanol oxidation, is extremely vulnerable to alcoholic damage [70,71], leading to cirrhosis, a severe form of liver disease and a major cause of death in the United States [72,73]. Excessive ethanol consumption also results in cardiovascular disease (the number one cause of death in the US), including ventricular dysfunction [74,75], dilated cardiomyopathy [74], ventricular arrhythmias [76], myocardial fibrosis [77] as well as enhanced risk of stroke and hypertension [78,79]. These morphological and functional defects of myocardium will eventually result in heart failure.
It should be emphasized that moderate drinking is recommended to be individualized to reflect the potentially competing or confounding effects of alcohol on certain chronic diseases [5]. It was indicated that moderate drinking had no beneficial effect on mortality in young adults (premenopausal women and men <40 years of age). Nonetheless, it is speculated that moderate drinking in young adulthood may dampen the risk of heart diseases later on in life. In certain populations, such as pregnant women, heavy drinkers and those on medication that may interact adversely with alcohol, the risk of alcohol consumption, even in the form of moderate ingestion, outweighs potential benefits [80]. Somewhat along this line, Sun and colleagues found that light to moderate alcohol use may provide the optimal benefit in older adults with poor health condition [81]. Evidence from the 2007 World Cancer Research Fund and American Institute for Cancer Research summary report recommended individuals with high risk of cancer are not recommended to drink alcoholic drinks despite the fact that modest amounts of alcoholic drinks are likely to reduce the risk of coronary heart disease [6]. Evidence from Allen and colleagues revealed that moderate alcohol use may particularly increase the risk of certain cancers such as breast and liver cancers while reducing the risk of some other cancers in women. Moreover, the alcohol-associated risk for upper aerodigestive tract cancer (oral cavity, esophagus, larynx and pharynx) was confined in active smokers, with little effect of alcohol use in never and past smokers [82]. Nonetheless, it is rather difficult to conclude whether the increased risk of cancer was due to alcohol intake or smoking since the two behaviors tend to be concurrent quite often. Although further work is still needed to fully consolidate the correlation between cancer prevalence and moderate alcohol intake, the American Cancer Society recommends limited alcohol use in both men (<2 drinks per day) and women (<1 drink per day). Taken together, whether moderate alcohol use plays a protective, unrelated or adverse role in human health is still controversial, depending heavily on age, gender and type of alcoholic beverage.

3. Mechanisms of Alcoholic Diseases

A number of mechanisms have been postulated for the pathogenesis of alcoholic injuries and diseases, including toxicity of ethanol and its metabolite acetaldehyde, the primary metabolic product of ethanol. In addition, oxidative stress, accumulation of fatty acid ethyl esters and modification of lipoprotein and apolipoprotein particles [33] also contribute to alcohol-associated complications. Although alcohol exposure is associated with multiple toxic effects on various organs through different mechanisms, two main categories are worth considering: acetaldehyde-related and non-acetaldehyde-related mechanisms.

3.1. Mechanism of Alcohol Metabolism

Ethanol metabolites and oxidative stress (through accumulation of reactive oxygen species—ROS) are thought to be the main causes of alcohol-induced organ damage. A majority of ethanol is metabolized in the cytoplasm of the liver by the enzyme ADH to produce acetaldehyde, which is then further metabolized to another less active byproduct, acetate, by ALDH [83]. The two enzymatic steps both require NAD as the hydrogen acceptor. The enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down alcohol to acetaldehyde. However, CYP2E1, the enzyme in the E subfamily of the second family P450s, becomes active only after a person has consumed large amount of alcohol. Under normal conditions, CYP2E1 accounts for less than 10% of ethanol metabolism. Catalase also metabolizes only a small fraction of alcohol without requiring NAD as a cofactor [83]. All these ways of metabolizing ethanol result in acetaldehyde, a primary metabolic product of alcohol. Acetaldehyde is a key generator of free radicals and a known carcinogen. Moreover, high levels of NADH in mitochondria can cause an increase in the number of superoxide (O2) free radicals leading to the formation of hydroxyl radicals (OH), lipid peroxidation and damage to mitochondria DNA [84]. High levels of free radicals diminish or impair the antioxidant homeostasis, leading to tissue damage. In addition, ethanol may induce up to a 10-fold up-regulation of CYP2E1 in the liver, which may be responsible for alcoholism-triggered oxidative damage [8587]. Evidence has indicated that small amounts of alcohol may be removed via interaction with fatty acids to form fatty acid ethyl esters (FAEEs), the latter has been shown to contribute to damage to the heart, liver and pancreas [88,89].

3.2. Acetaldehyde-Related Mechanism in Alcohol-Induced Damages

Acetaldehyde, an organic chemical compound (CH3CHO or MeCHO), is an active metabolite that induces a range of toxic, pharmacological and behavioral responses. Although acetaldehyde is only short-lived prior to its breakdown into acetate, it possesses the ability to elicit overt cellular and tissue damage. The liver is often considered the primary site of oxidation [90], although other organs including the heart, pancreas, gastrointestinal tract and the brain, may also participate in the ethanol metabolism to form acetaldehyde [16,83,88,89]. Acetaldehyde causes mitochondrial dysfunction and in turn compromises acetaldehyde metabolism to result in the accumulation of acetaldehyde, leading to a vicious cycle. Acetaldehyde may also react with amino, hydroxyl, and sulfhydryl groups to interfere with or modify the structure and function of macromolecules in the body, such as proteins and enzymes [89,91].
Accumulating evidence suggested that acetaldehyde plays a key role in the pathogenesis of alcoholic cardiomyopathy [9297]. In particular, acetaldehyde has been shown to lead cardiac hypertrophy or dilated cardiomyopathy associated with significant increase in the hypertrophic marker skeletal actin and ANF [97]. Data from our laboratory have shown that acetaldehyde compromises myocardial excitation-contraction coupling, sarco (endo) plasmic reticulum [42] Ca2+ release and cardiac contractile function [34,75,98,99]. The mechanism underlying acetaldehyde-induced myocardial depression may be due, in part, to either reduced Ca2+ entry through voltage-dependent Ca2+ channels and/or depression of sarcoplasmic reticular Ca2+ release [75]. Our previous study showed that alcohol intake significantly reduced expression of the intracellular Ca2+ cycling proteins SERCA2a, Na+-Ca2+ exchanger and phospholamban in cardiomyocytes without overt change in the SERCA2a-to-phospholamban ratio [100]. Although the precise mechanism behind alcohol-induced change in the intracellular Ca2+ regulatory proteins is not fully clear, acetaldehyde is believed to play a role. Acetaldehyde was recently suggested to function as a ryanodine receptor activator to leading to disturbed cardiac contractile function [101] and elevated intracellular Ca2+ levels [102]. Acetaldehyde stimulates the release of signaling molecules (epinephrine, norepinephrine, histamine and bradykinin) and leads to the cardiovascular symptoms of the alcohol sensitivity reaction such as vasodilation and facial flushing. It also associated with abnormal heart beat and blood pressure [103]. As the major metabolite of ethanol, acetaldehyde production results directly in the formation of free radicals through aldehyde oxidase and xanthine oxidase-associated oxidation and indirectly in decreased antioxidant defenses (e.g., GSH levels) [34,104,105], resulting in oxidative stress. Acetaldehyde can also induce apoptosis via activation of stress signaling such as c-Jun phosphorylation [34,106,107]. This is supported by our experimental findings of elevated TUNEL-positive apoptotic cells in ADH murine hearts following ethanol challenge.
In addition to direct cytotoxicity, acetaldehyde-associated organ damage may also be mediated through inflammatory cytokines (e.g., tumor necrosis factor and the interferons), as well as the binding capability to certain proteins [108110]. In addition to direct organ damage, acetaldehyde may also be responsible for certain behavioral and physiological effects previously attributed to alcohol. For example, when acetaldehyde is administered to lab animals, it leads to uncoordination, memory impairment, and sleepiness, effects often associated with alcohol ingestion [103]. Moreover, the acetaldehyde-DNA binding has been considered to promote carcinogenesis in alcohol-dependent individuals [111]. Similarly, formation of crotonaldehyde [66] from acetaldehyde is also known as a potentially carcinogenic pollutant [112]. Paradoxically, acetaldehyde may also contribute to the beneficial effect following light to moderate alcohol intake. It was reported that attachment of acetaldehyde to a model Amadori product produces a chemically stabilized complex that cannot rearrange and progress to formation of advanced glycation endproducts, or AGEs [113]. Amadori products typically arise from the nonenzymatic addition of sugars to protein amino groups and are the precursors to the irreversibly bound, crosslinking moieties of AGEs, which are detrimental to health. Therefore, acetaldehyde-induced protein adduct may contribute to the beneficial effect of light to moderate alcohol intake, or the so-called “French paradox” by inhibiting advanced glycation.

3.3. Non-Acetaldehyde-Related Mechanism in Alcohol-Induced Damages

Recent evidence also indicates the contribution of acetaldehyde-independent mechanisms to the pathogenesis of alcoholic diseases. For example, ethanol may elicit direct toxic effects on the cardiovascular system or alter neurohumoral and/or hormonal regulation of cardiac function [78]. Certain metabolic product of ethanol such as fatty acid ethyl esters (FAEEs) may also interfere with the physiological function of the heart independently of acetaldehyde. The formation of FAEEs in the heart is an example of a non-oxidative metabolism of alcohol, and is distinguished from the oxidative metabolism of alcohol in the liver. FAEEs may prove to be the first link between the ingestion of alcohol and the development of alcohol-induced heart muscle disease. Although the amount of fatty acids in heart muscle is small, following consumption of alcohol, FAEEs concentration in the human myocardium can accumulate 115,000-fold higher than in the normal heart muscle [114,115]. Accumulation of fatty acid ethyl esters is capable of reducing the respiratory control ratio index of coupling of oxidative phosphorylation and maximal rate of oxygen consumption, and accounts for impaired mitochondrial function and inefficient energy production associated with toxic effects of ethanol on the heart [115]. Data from our group also suggested that acetaldehyde-induced cardiac mechanical dysfunction may be ablated by folate or thiamine supplementation [116,117], suggesting a possible interaction between acetaldehyde-induced cardiac toxicity and nutritional status. This is somewhat consistent with the favorable response of patients with alcoholic cardiomyopathy to thiamine and nutrition treatment [118].
Meanwhile, ethanol metabolism also produces stable and unstable protein adducts. For example, acetaldehyde binds to some proteins and becomes a Schiff base, thus forming protein-acetaldehyde adducts. Furthermore, the lipid peroxide-derived aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal may eventually form stable hybrid adducts by potential protein modifications. These multiple adducts were shown to have a cadre of inverse effects on the cells of the immune system and involved in the development of alcoholic organ disease, including liver, heart and brain [110,119].

3.4. Genetic Polymorphisms of Alcohol Metabolizing Enzymes

Alcoholism has been considered to be associated with different genetic factors in alcohol metabolism in different ethnic groups. Studies have identified numerous functional polymorphisms in genes encoding enzymes for ethanol metabolism. According to recent studies, the human ALDH gene superfamily comprises 19 genes encoding enzymes critical for NAD (P)+—dependent oxidation of endogenous and exogenous aldehydes [120]. Meanwhile, there are at least seven genes in the ADH family [121]. ADH2, ADH3, and ALDH2 are thought to be the pivotal genetic determinants in ethanol metabolism and alcoholism in humans.
Within the nine major members of ALDH families, mitochondrial ALDH2 has a rather unique role in aldehyde detoxification [122]. Deficiency in ALDH2 expression and/or activity is responsible for facial flushing and other vasomotor symptoms following alcohol ingestion. In addition, findings from Kawamoto’s group indicated that deficiency in ALDH2 enzymatic activity inhibits acetate formation via acetaldehyde [123]. Prevalence of the ALDH2*1 allele is associated with alcoholism. Deficiency in ALDH2 due to point mutation in the active ALDH2*1 gene, significantly alters blood acetaldehyde levels and vulnerability for alcoholism [124]. However, ALDH2*2, which is dominant over ALDH2*1, encodes a glutamate to lysine substitution at residue 487 in the mature enzyme, resulting in a loss of enzymatic activity [122]. In addition, individuals carrying the ADH2*2 allele display slightly facilitated alcohol metabolism due to higher enzyme activity compared with ADH2 *1 encoding populations [125].
Research reported that the allele frequencies of the genes ADH2*2 and ALDH2*2 were lower in Northwest Coast Amerindians, Africans, Europeans and Australian Aborigines than South America Indians and Asians including Chinese, Japanese and Koreans [125127]. The ALDH2*2 allele encodes an inactive subunit of ALDH2, which consists of four subunits, and ALDH2 shows lack of activity when even one inactive subunit protein is included [128]. Therefore, Asians always cannot drink a great amount of alcohol as compared with Caucasians.
Some studies also indicated that those who carry ALDH2*2 alleles were strikingly responsive to a small amount of alcohol. Large accumulation of acetaldehyde in the blood of these people produces a pattern of uncomfortable effects such as increasing skin temperature and facial flushing, dropping blood pressure, nausea, headache, palpitations and bronchoconstriction [103]. Of certain significance, some researchers suggested that acetaldehyde causing these symptoms may provide a protective role against heavy drinking intake, otherwise, alcoholism or worse outcome [36]. It has been suggested that the mutant ALDH2 gene of ALDH2*2/2 may protect against development of alcohol dependence and alcohol-related disease [129]. Nonetheless, this sort of epidemiological study fails to offer direct evidence regarding the role of acetaldehyde on cardiac function due to intolerance to alcohol among these individuals with genetic polymorphisms [124]. Our recent observation from animal study provided some convincing evidence regarding the role of ALDH2 in ethanol-induced cardiac toxicity. Overexpression of ALDH2 was found to be cardioprotective against acute ethanol-induced cardiac toxicity, possibly through inhibition of protein phosphatases. Our data further revealed that enhanced activation of Akt and AMPK, and subsequently, inhibition of Foxo3, apoptosis, and mitochondrial dysfunction may play a pivotal role in ALDH2 overexpression-induced cardioprotection against ethanol toxicity [130].
Alcoholism is a multifactorial disease including a complex mode of hereditary, psychological and social factors. More in depth genetic association studies is warranted to further identify and consolidate the genetic risk factors for alcoholism. Furthermore, according to the differing polymorphisms among racial populations, effective measures can be appropriately taken for the studies.

4. Alcohol-induced Social Problems and Effective Ways to Reduce Alcohol Abuse

Alcohol abuse and addiction are not only an individual problem but also a social problem. Alcohol abuse is closely associated with the society such as due to car accidents, social violence, broken homes, productivity losses, child abuse and any other crimes. Underage drinking is another serious public health concern in children and adolescents [131]. Researchers have suggested that people with a psychiatric condition called antisocial personality disorder may be particularly susceptible to alcohol-related aggression [27]. Alcohol may also affect female reproductive function at several stages of life. It has been shown to elicit a detrimental effect on puberty, to disrupt normal menstrual cycle and to alter hormonal levels in postmenopausal women. In addition, alcohol abuse also increases the economic burden on society [26,29]. Certain strategies were reported to reduce alcohol abuse, such as increased taxes and prices of alcoholic beverages, raising the Minimum Legal Drinking Age, setting maximum blood alcohol concentration (BAC) limits for drivers under 21, making warning labels on containers of alcoholic beverages, as well as community and educational interventions, e.g., alcohol misuse prevention study (AMPS) and drug abuse resistance education (DARE).

5. Conclusion

Given that alcohol drinking-induced effects may exhibit great individual variation, it is rather cumbersome to figure out where the line is between social drinking and problem drinking. Chronic alcohol ingestion or binge drinking may trigger detrimental bodily damage, which is heavily influenced by many interconnected factors such as races, genetics, environment and the emotional health. It is generally accepted that light to moderate alcohol consumption is beneficial to reduce the risk of some human diseases, although it may increase the risk prevalence for certain cancers especially in women. In addition, heavy drinking has been consistently found harmful and dangerous (with lethal damage such as cancer, heart and liver disease). Moreover, the social consequences of alcohol abuse can be just as devastating. In particular, the emerging trend of more harmful and risky drinking among young people and among women may have a severe health outcome [132]. It is essential to understand the drinking problems, the definition of moderate drinking, alcoholism and alcohol abuse. In order to minimize the harmful sequelae of alcohol use, it is also important to raise awareness in individual’s genetic trait in alcohol metabolizing enzymes ADH and ALDH, and then to apply corresponding and necessary measures (for example delay the drinking onset age) [133] to minimize the alcoholic injury.


The work in Jun Ren’s lab has been supported in part by NIH/NIAAA 1R01 AA013412, R151AA/HL13575 and University of Wyoming Northern Rockies Regional INBRE (5P20RR016474). We wish to express our sincere apology to those authors whose important work cannot be included here due to space limitation.

References and Notes

  1. Gaziano, JM; Gaziano, TA; Glynn, RJ; Sesso, HD; Ajani, UA; Stampfer, MJ; Manson, JE; Hennekens, CH; Buring, JE. Light-to-moderate alcohol consumption and mortality in the Physicians’ Health Study enrollment cohort. J. Am. Coll. Cardiol 2000, 35, 96–105. [Google Scholar]
  2. Klatsky, AL; Friedman, GD; Siegelaub, AB. Alcohol and mortality. A ten-year Kaiser-Permanente experience. Ann. Intern. Med 1981, 95, 139–145. [Google Scholar]
  3. Maraldi, C; Volpato, S; Kritchevsky, SB; Cesari, M; Andresen, E; Leeuwenburgh, C; Harris, TB; Newman, AB; Kanaya, A; Johnson, KC; Rodondi, N; Pahor, M. Impact of inflammation on the relationship among alcohol consumption, mortality, and cardiac events: the health, aging, and body composition study. Arch. Intern. Med 2006, 166, 1490–1497. [Google Scholar]
  4. Maskarinec, G; Meng, L; Kolonel, LN. Alcohol intake, body weight, and mortality in a multiethnic prospective cohort. Epidemiology 1998, 9, 654–661. [Google Scholar]
  5. Mukamal, KJ; Rimm, EB. Alcohol consumption: risks and benefits. Curr. Atheroscler. Rep 2008, 10, 536–543. [Google Scholar]
  6. Wold Cancer Research Fund; American Institute for Cancer Research Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR: Washington, DC, USA, 2007; pp. 1–14.
  7. Mocan, T; Agoston-Coldea, L; Rusu, LD; Pais, R; Gatfosse, M; Mocan, LC; Rusu, ML. The correlation between alcohol consumption, lipids, apolipoproteins and coronary heart disease. Rom. J. Intern. Med 2008, 46, 323–330. [Google Scholar]
  8. Mukamal, KJ. Alcohol and heart disease: where to next? Interview by Christine Forder. Future Cardiol 2009, 5, 219–225. [Google Scholar]
  9. George, A; Figueredo, VM. Alcohol and arrhythmias: a comprehensive review. J. Cardiovasc. Med. (Hagerstown) 2010, 11, 221–228. [Google Scholar]
  10. Marinho, V; Laks, J; Engelhardt, E; Conn, D. Alcohol abuse in an elderly woman taking donepezil for Alzheimer disease. J. Clin. Psychopharmacol 2006, 26, 683–685. [Google Scholar]
  11. Ikehara, S; Iso, H; Toyoshima, H; Date, C; Yamamoto, A; Kikuchi, S; Kondo, T; Watanabe, Y; Koizumi, A; Wada, Y; Inaba, Y; Tamakoshi, A. Alcohol consumption and mortality from stroke and coronary heart disease among Japanese men and women: the Japan collaborative cohort study. Stroke 2008, 39, 2936–2942. [Google Scholar]
  12. Ohkubo, T; Metoki, H; Imai, Y. Alcohol intake, circadian blood pressure variation, and stroke. Hypertension 2009, 53, 4–5. [Google Scholar]
  13. Cederbaum, AI; Lu, Y; Wu, D. Role of oxidative stress in alcohol-induced liver injury. Arch. Toxicol 2009, 83, 519–548. [Google Scholar]
  14. Mandrekar, P; Szabo, G. Signalling pathways in alcohol-induced liver inflammation. J. Hepatol 2009, 50, 1258–1266. [Google Scholar]
  15. Osna, N. Alcohol and liver disease. Semin. Liver Dis 2009, 29, 139. [Google Scholar]
  16. Seitz, HK; Becker, P. Alcohol metabolism and cancer risk. Alcohol Res Health 2007, 30, 38–41. [Google Scholar]
  17. Suzuki, T; Matsuo, K; Sawaki, A; Mizuno, N; Hiraki, A; Kawase, T; Watanabe, M; Nakamura, T; Yamao, K; Tajima, K; Tanaka, H. Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk. Cancer Epidemiol. Biomarkers Prev 2008, 17, 2742–2747. [Google Scholar]
  18. Zhang, FF; Hou, L; Terry, MB; Lissowska, J; Morabia, A; Chen, J; Yeager, M; Zatonski, W; Chanock, S; Chow, WH. Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland. Int. J. Cancer 2007, 121, 2060–2064. [Google Scholar]
  19. Lebowitz, MD. Respiratory symptoms and disease related to alcohol consumption. Am. Rev. Respir. Dis 1981, 123, 16–19. [Google Scholar]
  20. Morris, MJ. Alcohol breath testing in patients with respiratory disease. Thorax 1990, 45, 717–721. [Google Scholar]
  21. Baliunas, DO; Taylor, BJ; Irving, H; Roerecke, M; Patra, J; Mohapatra, S; Rehm, J. Alcohol as a risk factor for type 2 diabetes: A systematic review and meta-analysis. Diabetes Care 2009, 32, 2123–2132. [Google Scholar]
  22. Frericks, KG; Schurmann, A; Hempel, G. [Type 2 diabetes with alcohol abuse]. Med. Monatsschr. Pharm 2005, 28, 357–360. [Google Scholar]
  23. Mohs, ME; Leonard, TK; Watson, RR. Interrelationships among alcohol abuse, obesity, and type II diabetes mellitus: focus on Native Americans. World Rev. Nutr. Diet 1988, 56, 93–172. [Google Scholar]
  24. Callaci, JJ; Himes, R; Lauing, K; Wezeman, FH; Brownson, K. Binge alcohol-induced bone damage is accompanied by differential expression of bone remodeling-related genes in rat vertebral bone. Calcif. Tissue Int 2009, 84, 474–484. [Google Scholar]
  25. Chen, Y; Cui, L; Liao, J; Huang, L. Effects of alcohol on bone metabolism and biomechanical property of mice. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2009, 26, 780–782. [Google Scholar]
  26. Baumberg, B. The global economic burden of alcohol: a review and some suggestions. Drug Alcohol Rev 2006, 25, 537–551. [Google Scholar]
  27. Moeller, FG; Dougherty, DM. Antisocial personality disorder, alcohol, and aggression. Alcohol Res. Health 2001, 25, 5–11. [Google Scholar]
  28. Moeller, FG; Dougherty, DM; Lane, SD; Steinberg, JL; Cherek, DR. Antisocial personality disorder and alcohol-induced aggression. Alcohol Clin. Exp. Res 1998, 22, 1898–1902. [Google Scholar]
  29. Rehm, J; Mathers, C; Popova, S; Thavorncharoensap, M; Teerawattananon, Y; Patra, J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 2009, 373, 2223–2233. [Google Scholar]
  30. Lonczak, HS; Huang, B; Catalano, RF; Hawkins, JD; Hill, KG; Abbott, RD; Ryan, JA; Kosterman, R. The social predictors of adolescent alcohol misuse: a test of the social development model. J. Stud. Alcohol 2001, 62, 179–189. [Google Scholar]
  31. Preedy, VR; Patel, VB; Reilly, ME; Richardson, PJ; Falkous, G; Mantle, D. Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle. Front Biosci 1999, 4, e58–e66. [Google Scholar]
  32. Laposata, EA; Lange, LG. Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse. Science 1986, 231, 497–499. [Google Scholar]
  33. Hannuksela, ML; Liisanantti, MK; Savolainen, MJ. Effect of alcohol on lipids and lipoproteins in relation to atherosclerosis. Crit. Rev. Clin. Lab. Sci 2002, 39, 225–283. [Google Scholar]
  34. Zhang, X; Li, SY; Brown, RA; Ren, J. Ethanol and acetaldehyde in alcoholic cardiomyopathy: from bad to ugly en route to oxidative stress. Alcohol 2004, 32, 175–186. [Google Scholar]
  35. Thadhani, R; Camargo, CA, Jr; Stampfer, MJ; Curhan, GC; Willett, WC; Rimm, EB. Prospective study of moderate alcohol consumption and risk of hypertension in young women. Arch. Intern. Med 2002, 162, 569–574. [Google Scholar]
  36. Peng, GS; Wang, MF; Chen, CY; Luu, SU; Chou, HC; Li, TK; Yin, SJ. Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians. Pharmacogenetics 1999, 9, 463–476. [Google Scholar]
  37. Peng, GS; Yin, SJ. Effect of the allelic variants of aldehyde dehydrogenase ALDH2*2 and alcohol dehydrogenase ADH1B*2 on blood acetaldehyde concentrations. Hum. Genomics 2009, 3, 121–127. [Google Scholar]
  38. Dong, X. Genetic variation in alcohol dehydrogenase and myocardial infarction. N. Engl. J. Med 2001, 345, 221–222. [Google Scholar]
  39. Kloner, RA; Rezkalla, SH. To drink or not to drink? That is the question. Circulation 2007, 116, 1306–1317. [Google Scholar]
  40. Frid, A. Moderate alcohol drinking protects against heart disease. Lakartidningen 2000, 97, 946–947. [Google Scholar]
  41. Dey, AB; Choudhury, D. How frequent and how much alcohol prevents heart attack? Natl. Med. J. India 1997, 10, 284–285. [Google Scholar]
  42. Agarwal, DP; Srivastava, LM. Does moderate alcohol intake protect against coronary heart disease? Indian Heart J 2001, 53, 224–230. [Google Scholar]
  43. Camargo, CA, Jr; Stampfer, MJ; Glynn, RJ; Grodstein, F; Gaziano, JM; Manson, JE; Buring, JE; Hennekens, CH. Moderate alcohol consumption and risk for angina pectoris or myocardial infarction in U.S. male physicians. Ann. Intern. Med 1997, 126, 372–375. [Google Scholar]
  44. Samanek, M. Does moderate alcohol drinking decrease the incidence and mortality rate in ischemic heart disease? Cas. Lek. Cesk 2000, 139, 747–752. [Google Scholar]
  45. Elkind, MS; Sciacca, R; Boden-Albala, B; Rundek, T; Paik, MC; Sacco, RL. Moderate alcohol consumption reduces risk of ischemic stroke: the Northern Manhattan Study. Stroke 2006, 37, 13–19. [Google Scholar]
  46. Camargo, CA, Jr; Stampfer, MJ; Glynn, RJ; Gaziano, JM; Manson, JE; Goldhaber, SZ; Hennekens, CH. Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in US male physicians. Circulation 1997, 95, 577–580. [Google Scholar]
  47. Gillman, MW; Cook, NR; Evans, DA; Rosner, B; Hennekens, CH. Relationship of alcohol intake with blood pressure in young adults. Hypertension 1995, 25, 1106–1110. [Google Scholar]
  48. Desenclos, JA; Klontz, KC; Wilder, MH; Gunn, RA. The protective effect of alcohol on the occurrence of epidemic oyster-borne hepatitis A. Epidemiology 1992, 3, 371–374. [Google Scholar]
  49. Ajani, UA; Hennekens, CH; Spelsberg, A; Manson, JE. Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians. Arch. Intern. Med 2000, 160, 1025–1030. [Google Scholar]
  50. Cordain, L; Bryan, ED; Melby, CL; Smith, MJ. Influence of moderate daily wine consumption on body weight regulation and metabolism in healthy free-living males. J. Am. Coll. Nutr 1997, 16, 134–139. [Google Scholar]
  51. Hellenbrand, W; Seidler, A; Boeing, H; Robra, BP; Vieregge, P; Nischan, P; Joerg, J; Oertel, WH; Schneider, E; Ulm, G. Diet and Parkinson’s disease. I: A possible role for the past intake of specific foods and food groups. Results from a self-administered food-frequency questionnaire in a case-control study. Neurology 1996, 47, 636–643. [Google Scholar]
  52. Kallberg, H; Jacobsen, S; Bengtsson, C; Pedersen, M; Padyukov, L; Garred, P; Frisch, M; Karlson, EW; Klareskog, L; Alfredsson, L. Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case-control studies. Ann. Rheum. Dis 2009, 68, 222–227. [Google Scholar]
  53. Feskanich, D; Korrick, SA; Greenspan, SL; Rosen, HN; Colditz, GA. Moderate alcohol consumption and bone density among postmenopausal women. J. Womens Health 1999, 8, 65–73. [Google Scholar]
  54. Holbrook, TL; Barrett-Connor, E. A prospective study of alcohol consumption and bone mineral density. BMJ 1993, 306, 1506–1509. [Google Scholar]
  55. Weisse, ME; Eberly, B; Person, DA. Wine as a digestive aid: comparative antimicrobial effects of bismuth salicylate and red and white wine. BMJ 1995, 311, 1657–1660. [Google Scholar]
  56. Lipton, RI. The effect of moderate alcohol use on the relationship between stress and depression. Am. J. Public Health 1994, 84, 1913–1917. [Google Scholar]
  57. Rashidkhani, B; Akesson, A; Lindblad, P; Wolk, A. Alcohol consumption and risk of renal cell carcinoma: a prospective study of Swedish women. Int. J. Cancer 2005, 117, 848–853. [Google Scholar]
  58. Ahlgren, JD. Epidemiology and risk factors in pancreatic cancer. Semin. Oncol 1996, 23, 241–250. [Google Scholar]
  59. Aldoori, WH; Giovannucci, EL; Stampfer, MJ; Rimm, EB; Wing, AL; Willett, WC. A prospective study of alcohol, smoking, caffeine, and the risk of duodenal ulcer in men. Epidemiology 1997, 8, 420–424. [Google Scholar]
  60. Obisesan, TO; Hirsch, R; Kosoko, O; Carlson, L; Parrott, M. Moderate wine consumption is associated with decreased odds of developing age-related macular degeneration in NHANES-1. J. Am. Geriatr. Soc 1998, 46, 1–7. [Google Scholar]
  61. Popelka, MM; Cruickshanks, KJ; Wiley, TL; Tweed, TS; Klein, BE; Klein, R; Nondahl, DM. Moderate alcohol consumption and hearing loss: a protective effect. J. Am. Geriatr. Soc 2000, 48, 1273–1278. [Google Scholar]
  62. Leitzmann, MF; Giovannucci, EL; Stampfer, MJ; Spiegelman, D; Colditz, GA; Willett, WC; Rimm, EB. Prospective study of alcohol consumption patterns in relation to symptomatic gallstone disease in men. Alcohol Clin. Exp. Res 1999, 23, 835–841. [Google Scholar]
  63. Nelson, HD; Nevitt, MC; Scott, JC; Stone, KL; Cummings, SR. Smoking, alcohol, and neuromuscular and physical function of older women. Study of Osteoporotic Fractures Research Group. JAMA 1994, 272, 1825–1831. [Google Scholar]
  64. Cohen, S; Tyrrell, DA; Russell, MA; Jarvis, MJ; Smith, AP. Smoking, alcohol consumption, and susceptibility to the common cold. Am. J. Public Health 1993, 83, 1277–1283. [Google Scholar]
  65. Devos-Comby, L; Lange, JE. “My drink is larger than yours”? A literature review of self-defined drink sizes and standard drinks. Curr. Drug Abuse Rev 2008, 1, 162–176. [Google Scholar]
  66. Heng, K; Hargarten, S; Layde, P; Craven, A; Zhu, S. Moderate alcohol intake and motor vehicle crashes: the conflict between health advantage and at-risk use. Alcohol Alcohol 2006, 41, 451–454. [Google Scholar]
  67. Adolfsson, R; Karlsson, T. Alcohol abuse and memory disorders. Lakartidningen 1987, 84, 3923–3926. [Google Scholar]
  68. Bondi, MW; Drake, AI; Grant, I. Verbal learning and memory in alcohol abusers and polysubstance abusers with concurrent alcohol abuse. J. Int. Neuropsychol. Soc 1998, 4, 319–328. [Google Scholar]
  69. Larkin, JP; Seltzer, B. Alcohol abuse and Alzheimer’s disease. Hosp Community Psychiatry 1994, 45, 1040–1041. [Google Scholar]
  70. Guo, R; Zhong, L; Ren, J. Overexpression of aldehyde dehydrogenase-2 attenuates chronic alcohol exposure-induced apoptosis, change in Akt and Pim signalling in liver. Clin. Exp. Pharmacol. Physiol 2009, 36, 463–468. [Google Scholar]
  71. Vaiphei, K; Gupta, K; Lal, V. Chronic alcohol intake: indicator towards alcoholic liver disease. Indian J. Gastroenterol 2007, 26, 180–184. [Google Scholar]
  72. Bird, GL; Williams, R. Factors determining cirrhosis in alcoholic liver disease. Mol. Aspects Med 1988, 10, 97–105. [Google Scholar]
  73. Singh, GK; Hoyert, DL. Social epidemiology of chronic liver disease and cirrhosis mortality in the United States, 1935–1997: trends and differentials by ethnicity, socioeconomic status, and alcohol consumption. Hum. Biol 2000, 72, 801–820. [Google Scholar]
  74. Li, SY; Ren, J. Cardiac overexpression of alcohol dehydrogenase exacerbates chronic ethanol ingestion-induced myocardial dysfunction and hypertrophy: role of insulin signaling and ER stress. J. Mol. Cell Cardiol 2008, 44, 992–1001. [Google Scholar]
  75. Ren, J; Davidoff, AJ; Brown, RA. Acetaldehyde depresses shortening and intracellular Ca2+ transients in adult rat ventricular myocytes. Cell Mol. Biol. (Noisy-le-grand) 1997, 43, 825–834. [Google Scholar]
  76. Lang, CH; Frost, RA; Summer, AD; Vary, TC. Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart. Int. J. Biochem. Cell Biol 2005, 37, 2180–2195. [Google Scholar]
  77. Wang, L; Zhou, Z; Saari, JT; Kang, YJ. Alcohol-induced myocardial fibrosis in metallothionein-null mice: prevention by zinc supplementation. Am. J. Pathol 2005, 167, 337–344. [Google Scholar]
  78. Schoppet, M; Maisch, B. Alcohol and the heart. Herz 2001, 26, 345–352. [Google Scholar]
  79. Jones, WK. A murine model of alcoholic cardiomyopathy: a role for zinc and metallothionein in fibrosis. Am. J. Pathol 2005, 167, 301–304. [Google Scholar]
  80. Meister, KA; Whelan, EM; Kava, R. The health effects of moderate alcohol intake in humans: an epidemiologic review. Crit. Rev. Clin. Lab. Sci 2000, 37, 261–296. [Google Scholar]
  81. Sun, W; Schooling, CM; Chan, WM; Ho, KS; Lam, TH; Leung, GM. Moderate alcohol use, health status, and mortality in a prospective Chinese elderly cohort. Ann. Epidemiol 2009, 19, 396–403. [Google Scholar]
  82. Allen, NE; Beral, V; Casabonne, D; Kan, SW; Reeves, GK; Brown, A; Green, J. Moderate alcohol intake and cancer incidence in women. J. Natl. Cancer Inst 2009, 101, 296–305. [Google Scholar]
  83. Edenberg, HJ. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res. Health 2007, 30, 5–13. [Google Scholar]
  84. Mallikarjuna, K; Sahitya Chetan, P; Sathyavelu Reddy, K; Rajendra, W. Ethanol toxicity: rehabilitation of hepatic antioxidant defense system with dietary ginger. Fitoterapia 2008, 79, 174–178. [Google Scholar]
  85. Tanaka, E; Terada, M; Misawa, S. Cytochrome P450 2E1: its clinical and toxicological role. J Clin. Pharm. Ther 2000, 25, 165–175. [Google Scholar]
  86. Lieber, CS. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol 2004, 34, 9–19. [Google Scholar]
  87. Aberle, IN; Ren, J. Experimental assessment of the role of acetaldehyde in alcoholic cardiomyopathy. Biol. Proced. Online 2003, 5, 1–12. [Google Scholar][Green Version]
  88. Vonlaufen, A; Wilson, JS; Pirola, RC; Apte, MV. Role of alcohol metabolism in chronic pancreatitis. Alcohol Res. Health 2007, 30, 48–54. [Google Scholar]
  89. Ren, J; Wold, LE. Mechanisms of alcoholic heart disease. Ther. Adv. Cardiovasc. Dis 2008, 2, 497–506. [Google Scholar]
  90. Zakhari, S. Overview: how is alcohol metabolized by the body? Alcohol Res. Health 2006, 29, 245–254. [Google Scholar]
  91. Lieber, CS; DeCarli, LM; Feinman, L; Hasumura, Y; Korsten, M; Matsuzaki, S; Teschke, R. Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism. Adv. Exp. Med. Biol 1975, 59, 185–227. [Google Scholar]
  92. Aberle, NS, 2nd; Ren, J. Short-term acetaldehyde exposure depresses ventricular myocyte contraction: role of cytochrome P450 oxidase, xanthine oxidase, and lipid peroxidation. Alcohol Clin. Exp. Res 2003, 27, 577–583. [Google Scholar]
  93. Duan, J; McFadden, GE; Borgerding, AJ; Norby, FL; Ren, BH; Ye, G; Epstein, PN; Ren, J. Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol 2002, 282, H1216–H1222. [Google Scholar]
  94. Duan, J; Esberg, LB; Ye, G; Borgerding, AJ; Ren, BH; Aberle, NS; Epstein, PN; Ren, J. Influence of gender on ethanol-induced ventricular myocyte contractile depression in transgenic mice with cardiac overexpression of alcohol dehydrogenase. Comp. Biochem. Physiol. A Mol. Integr. Physiol 2003, 134, 607–614. [Google Scholar]
  95. Eriksson, CJ. The role of acetaldehyde in the actions of alcohol (update 2000). Alcohol Clin. Exp. Res 2001, 25, 15S–32S. [Google Scholar]
  96. Hintz, KK; Relling, DP; Saari, JT; Borgerding, AJ; Duan, J; Ren, BH; Kato, K; Epstein, PN; Ren, J. Cardiac overexpression of alcohol dehydrogenase exacerbates cardiac contractile dysfunction, lipid peroxidation, and protein damage after chronic ethanol ingestion. Alcohol Clin. Exp. Res 2003, 27, 1090–1098. [Google Scholar]
  97. Liang, Q; Carlson, EC; Borgerding, AJ; Epstein, PN. A transgenic model of acetaldehyde overproduction accelerates alcohol cardiomyopathy. J. Pharmacol. Exp. Ther 1999, 291, 766–772. [Google Scholar]
  98. Brown, RA; Jefferson, L; Sudan, N; Lloyd, TC; Ren, J. Acetaldehyde depresses myocardial contraction and cardiac myocyte shortening in spontaneously hypertensive rats: role of intracellular Ca2+. Cell Mol. Biol. (Noisy-le-grand) 1999, 45, 453–465. [Google Scholar]
  99. Ren, J; Brown, RA. Influence of chronic alcohol ingestion on acetaldehyde-induced depression of rat cardiac contractile function. Alcohol Alcohol 2000, 35, 554–560. [Google Scholar]
  100. Li, Q; Ren, J. Cardiac overexpression of metallothionein attenuates chronic alcohol intake-induced cardiomyocyte contractile dysfunction. Cardiovasc. Toxicol 2006, 6, 173–182. [Google Scholar]
  101. Oba, T; Maeno, Y; Nagao, M; Sakuma, N; Murayama, T. Cellular redox state protects acetaldehyde-induced alteration in cardiomyocyte function by modifying Ca2+ release from sarcoplasmic reticulum. Am. J. Physiol Heart Circ. Physiol 2008, 294, H121–H133. [Google Scholar]
  102. Carruthers, VB; Moreno, SN; Sibley, LD. Ethanol and acetaldehyde elevate intracellular [Ca2+] and stimulate microneme discharge in Toxoplasma gondii. Biochem. J 1999, 342, 379–386. [Google Scholar]
  103. Quertemont, E; Didone, V. Role of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol. Alcohol Res. Health 2006, 29, 258–265. [Google Scholar]
  104. Guerri, C; Montoliu, C; Renau-Piqueras, J. Involvement of free radical mechanism in the toxic effects of alcohol: implications for fetal alcohol syndrome. Adv. Exp. Med. Biol 1994, 366, 291–305. [Google Scholar]
  105. McDonough, KH. The role of alcohol in the oxidant antioxidant balance in heart. Front Biosci 1999, 4, D601–D606. [Google Scholar]
  106. Lee, YJ; Aroor, AR; Shukla, SD. Temporal activation of p42/44 mitogen-activated protein kinase and c-Jun N-terminal kinase by acetaldehyde in rat hepatocytes and its loss after chronic ethanol exposure. J. Pharmacol. Exp. Ther 2002, 301, 908–914. [Google Scholar]
  107. Svegliati-Baroni, G; Ridolfi, F; Di Sario, A; Saccomanno, S; Bendia, E; Benedetti, A; Greenwel, P. Intracellular signaling pathways involved in acetaldehyde-induced collagen and fibronectin gene expression in human hepatic stellate cells. Hepatology 2001, 33, 1130–1140. [Google Scholar]
  108. Diehl, AM. Cytokines and the molecular mechanisms of alcoholic liver disease. Alcohol Clin. Exp. Res 1999, 23, 1419–1424. [Google Scholar]
  109. Neuman, MG; Brenner, DA; Rehermann, B; Taieb, J; Chollet-Martin, S; Cohard, M; Garaud, JJ; Poynard, T; Katz, GG; Cameron, RG; Shear, NH; Gao, B; Takamatsu, M; Yamauchi, M; Ohata, M; Saito, S; Maeyama, S; Uchikoshi, T; Toda, G; Kumagi, T; Akbar, SM; Abe, M; Michitaka, K; Horiike, N; Onji, M. Mechanisms of alcoholic liver disease: cytokines. Alcohol Clin. Exp. Res 2001, 25, 251S–253S. [Google Scholar]
  110. Nakamura, K; Iwahashi, K; Furukawa, A; Ameno, K; Kinoshita, H; Ijiri, I; Sekine, Y; Suzuki, K; Iwata, Y; Minabe, Y; Mori, N. Acetaldehyde adducts in the brain of alcoholics. Arch. Toxicol 2003, 77, 591–593. [Google Scholar]
  111. Niemela, O. Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury. Free Radic. Biol. Med 2001, 31, 1533–1538. [Google Scholar]
  112. Burton, A. Acetaldehyde links alcohol consumption to cancer. Lancet Oncol 2005, 6, 643. [Google Scholar]
  113. Al-Abed, Y; Mitsuhashi, T; Li, H; Lawson, JA; FitzGerald, GA; Founds, H; Donnelly, T; Cerami, A; Ulrich, P; Bucala, R. Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol. Proc. Nat. Acad. Sci. USA 1999, 96, 2385–2390. [Google Scholar]
  114. Lange, LG; Sobel, BE. Myocardial metabolites of ethanol. Circ. Res 1983, 52, 479–482. [Google Scholar]
  115. Lange, LG; Sobel, BE. Mitochondrial dysfunction induced by fatty acid ethyl esters, myocardial metabolites of ethanol. J. Clin. Invest 1983, 72, 724–731. [Google Scholar]
  116. Aberle, NS, 2nd; Burd, L; Zhao, BH; Ren, J. Acetaldehyde-induced cardiac contractile dysfunction may be alleviated by vitamin B1 but not by vitamins B6 or B12. Alcohol Alcohol 2004, 39, 450–454. [Google Scholar]
  117. Aberle, NS, II; Privratsky, JR; Burd, L; Ren, J. Combined acetaldehyde and nicotine exposure depresses cardiac contraction in ventricular myocytes: prevention by folic acid. Neurotoxicol. Teratol 2003, 25, 731–736. [Google Scholar]
  118. Constant, J. The alcoholic cardiomyopathies--genuine and pseudo. Cardiology 1999, 91, 92–95. [Google Scholar]
  119. Freeman, TL; Tuma, DJ; Thiele, GM; Klassen, LW; Worrall, S; Niemela, O; Parkkila, S; Emery, PW; Preedy, VR. Recent advances in alcohol-induced adduct formation. Alcohol Clin. Exp. Res 2005, 29, 1310–1316. [Google Scholar]
  120. Black, WJ; Stagos, D; Marchitti, SA; Nebert, DW; Tipton, KF; Bairoch, A; Vasiliou, V. Human aldehyde dehydrogenase genes: alternatively spliced transcriptional variants and their suggested nomenclature. Pharmacogenet Genomics 2009. in print.. [Google Scholar]
  121. Holmes, RS. Opossum alcohol dehydrogenases: Sequences, structures, phylogeny and evolution: evidence for the tandem location of ADH genes on opossum chromosome 5. Chem. Biol. Interact 2009, 178, 8–15. [Google Scholar]
  122. Kitagawa, K; Kawamoto, T; Kunugita, N; Tsukiyama, T; Okamoto, K; Yoshida, A; Nakayama, K. Aldehyde dehydrogenase (ALDH) 2 associates with oxidation of methoxyacetaldehyde; in vitro analysis with liver subcellular fraction derived from human and Aldh2 gene targeting mouse. FEBS Lett 2000, 476, 306–311. [Google Scholar]
  123. Kiyoshi, A; Weihuan, W; Mostofa, J; Mitsuru, K; Toyoshi, I; Toshihiro, K; Kyoko, K; Keiichi, N; Iwao, I; Hiroshi, K. Ethanol metabolism in ALDH2 knockout mice—blood acetate levels. Leg Med. (Tokyo) 2009, 11, S413–S415. [Google Scholar]
  124. Ren, J. Acetaldehyde and alcoholic cardiomyopathy: lessons from the ADH and ALDH2 transgenic models. Novartis Found Symp 2007, 285. [Google Scholar]
  125. Kang, TS; Woo, SW; Park, HJ; Lee, Y; Roh, J. Comparison of genetic polymorphisms of CYP2E1, ADH2, and ALDH2 genes involved in alcohol metabolism in Koreans and four other ethnic groups. J. Clin. Pharm. Ther 2009, 34, 225–230. [Google Scholar]
  126. Chen, SH; Zhang, M; Scott, CR. Gene frequencies of alcohol dehydrogenase2 and aldehyde dehydrogenase2 in Northwest Coast Amerindians. Hum. Genet 1992, 89, 351–352. [Google Scholar]
  127. Goedde, HW; Agarwal, DP; Fritze, G; Meier-Tackmann, D; Singh, S; Beckmann, G; Bhatia, K; Chen, LZ; Fang, B; Lisker, R; et al. Distribution of ADH2 and ALDH2 genotypes in different populations. Hum. Genet 1992, 88, 344–346. [Google Scholar]
  128. Yamada, Y; Sun, F; Tsuritani, I; Honda, R. Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers. J. Hum. Hypertens 2002, 16, 479–486. [Google Scholar]
  129. Hashimoto, Y; Nakayama, T; Futamura, A; Omura, M; Nakarai, H; Nakahara, K. Relationship between genetic polymorphisms of alcohol-metabolizing enzymes and changes in risk factors for coronary heart disease associated with alcohol consumption. Clin. Chem 2002, 48, 1043–1048. [Google Scholar]
  130. Ma, H; Li, J; Gao, F; Ren, J. Aldehyde dehydrogenase 2 ameliorates acute cardiac toxicity of ethanol: role of protein phosphatase and forkhead transcription factor. J. Amer. Coll. Cardiol 2009, 54, 2187–2196. [Google Scholar]
  131. Spoth, R; Greenberg, M; Turrisi, R. Preventive interventions addressing underage drinking: state of the evidence and steps toward public health impact. Pediatrics 2008, 121(Suppl 4), S311–336. [Google Scholar]
  132. Hingson, RW; Zha, W; Weitzman, ER. Magnitude of and trends in alcohol-related mortality and morbidity among U.S. college students ages 18–24, 1998–2005. J. Stud. Alcohol Drugs 2009, 16, 12–20. [Google Scholar]
  133. Hingson, RW; Zha, W. Age of drinking onset, alcohol use disorders, frequent heavy drinking, and unintentionally injuring oneself and others after drinking. Pediatrics 2009, 123, 1477–1484. [Google Scholar]
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