Clinical Medicine Insights Received 25 June 2021 | Revised 22 July 2021 | Accepted 18 Aug 2021 | Published Online 31 Aug 2021 DOI: https://doi.org/10.52845/CMI/2021-2-3-5 CMI JOURNAL 2 (3), 169−184 (2021) ISSN (O) 2694-4626 REVIEW ARTICLE Alcohol and Noncommunicable Diseases: Part I Cardiovascular Diseases, Obesity, Respiratory Diseases, Depression, Liver Diseases Shashi K. Agarwal, MD ∗ 12227 US Highway 1, #309 North Brunswick, NJ 08902 USA Abstract Alcohol is a popular drink and is consumed globally. It has received considerable scrutiny in its effect on health. Although its relationship with most cardiovascular diseases is J/U shaped, in general, alcohol intake can increase the risk of several diseases. Heavy intake may induce weight gain. Although no definite relationship has been noted with COPD, asthma, and lung cancer, it does appear to increase the propensity for the development of pneumonia. Its use is strongly related to chronic liver disorders. Its relationship with depression is bidirectional, and deleterious for both conditions. In general, alcohol intake of 2 drinks per day for men and 1 drink per day for women appears to be relatively safe. Keywords: alcohol, non-communicable diseases, cardiovascular dis- eases, respiratory diseases, COPD, obesity, depression, liver diseases Copyright : © 2021 The Authors. Published by Medical Editor and Educational Research Publishers Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 INTRODUCTION Non-communicable diseases (NCD) are chronic andmay lead to prolonged disability and premature death1,2. It is estimated that NCDs are responsible for over 70% of total global deaths each year3. The majority of these occur in low- and middle-income countries4 and a severe financial burden5. The Sustainable Development Goals hope to reduce by 2030 (relative to 2015 levels) premature mortality from NCDs by one third6. The effects of alcohol on health can vary depending on the amount and pattern of intake7−9. In the United States, a standard drink contains 12–15 g of pure ethanol and this is present in 100–125 ml of wine, 240–300 mL of beer, and 30–37.5 mL of spirits10. Moderate alcohol intake is considered as two stan- dard drinks a day for men and one standard drink a day for women11,12. Heavy drinking is defined as, high-dose intake, of >60 g/day in men and >40 g/day in women, usually taken over long term13. Binge drinking is considered as 4 or more drinks for women and 5 or more drinks for men over a 2-hours or in CMI JOURNAL 2 (3), 169−184 MEERP LTD 169 Open Access Journal https://doi.org/10.52845/CMI/2021-2-3-8 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/ ALCOHOL AND NONCOMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, OBESITY, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES one sitting14,15. Compulsive excessive alcohol intake may lead to alcohol use disorder (AUD)16. The Na- tional Institute on Alcohol Abuse and Alcoholism defines AUD as “a chronic relapsing brain disease characterized by an impaired ability to stop or control EtOH use despite adverse social, occupational, or health consequences”17. Although low to moderate alcohol intake may have some beneficial effects, alcohol consumption, in general, is associated with several negative health consequences18. Besides its impact on diseases mentioned in this manuscript, alcohol intake can cause cancers of the breast, mouth, throat, esophagus, liver, and colon19, learning and memory difficulties (including dementia)20,21, and mental health disorders, such as depression and anxiety20,22. Alcoholics tend to be more prone to trauma20,23 and more likely to be involved in homicide, suicide, sexual assault, and violence24−27. Drinking alcohol during pregnancy can be extremely dangerous, and can increase the risk of miscarriage, stillbirth, or fetal alcohol disorder28−30. Alcohol poi- soning is a medical emergency and is associated with extremely high blood alcohol levels31. The World Health Organization estimated that, in 2018, around 5% of global deaths were attributable to alcohol consumption32. The health effects of alcohol on NCDs are discussed in this two-part manuscript. Part I discusses the re- lationship between alcohol intake and cardiovascu- lar diseases (CVD), chronic obstructive pulmonary disease (COPD), depression, and liver diseases. Part II discusses its impact on cancer, diabetes mellitus, kidney diseases, Alzheimer’s disease, and arthritis. Supplementary information The online version of this article (10.52845/CMI/2021-2-3-5) contains supplementary material, which is available to autho- rized users. Corresponding Author: Shashi K. Agarwal, MD Shashi K. Agarwal, MD 2227 US Highway 1, #309 North Brunswick, NJ 08902 USA Email: usacardiologist@gmail.com 2 DISCUSSION Cardiovascular diseases (CVDs) are an array of dis- eases that affect the cardiovascular system33. They include hypertension (HTN), coronary heart disease (CHD), stroke, heart failure (HF), cardiac arrhyth- mias, congenital heart disease, peripheral artery dis- ease (PAD), vasculogenic erectile dysfunction (ED), and venous thromboembolism (VTE)33. They cause considerable morbidity and are the number one cause of mortality worldwide34,35. Almost one-third of all worldwide deaths are attributable to CVDs36. In 2016, chronic respiratory diseases were responsi- ble for 7% of all global deaths37,38. Community- acquired bacterial pneumonia, although not an NCD, is strongly associated with alcoholism39. Pulmonary tuberculosis is also deleteriously affected by al- coholism40. Overweight refers to a BMI of 25– 29.9 kg/m2 while obesity exists when the BMI is ≥30 kg/m2.41. Obesity affected 42.4% of the US population in 2017–201842. Obesity is asso- ciated with several NCDs43,44, especially type 2 diabetes mellitus (DM) and CVDs45. Depression is a common cause of emotional suffering46. It is closely associated with anxiety47, dementia48, DM49, CHD50, Parkinson’s disease51, epilepsy52, pain53, several cancers54, osteoporosis55, and irrita- ble bowel syndrome56. Chronic liver pathologies are also common57. Themajor chronic diseases affecting the liver are hepatitis B virus (HBV)58 and hepatitis C virus (HCV) 59infections, steatohepatitis due to non-alcoholic fatty liver disease60, alcoholic liver disease61, hepatic cirrhosis62, and primary hepatocel- lular carcinoma63. The development and progression of NCDs are de- pendent on several modifiable and non-modifiable risk factors. Non-modifiable risk factors include heredity, age, race, and gender. Socioeconomic, cul- tural, political, and environmental factors may also play a role. The major modifiable factors include diet, obesity, physical activity, and non-smoking. Alcohol consumption is also a modifiable factor that impacts NCDs and is discussed in this manuscript. CMI JOURNAL 2 (3), 169−184 (2021) MEERP LTD 170 mailto:usacardiologist@gmail.com MEERP LTD SHASHI K. AGARWAL, MD 2.1 CARDIOVASCULAR DISEASES Light to moderate alcohol intake has been associ- ated with a lower risk of cardiovascular disease64. Heavy consumption has been associated with delete- rious CV outcomes including increased mortality65. Studies have established that alcohol consumption and CVD have a J- or U-shaped relationship66. Harmful CVD effects are also noted with binge drinking67 and alcohol use disorder68. About 5% to 24% of hypertension cases are associated with ethanol consumption69,70. It is estimated that intake of 3 to 4 drinks per day raises the prevalence of hypertension by 50%, when compared with non- drinkers, while an intake of 6 to 7 drinks per day, increases the prevalence by 100%71. Binge drinking, in the short term, raises the blood pressure from 4 to 7 mmHg systolic and 4 to 6 mmHg diastolic72−74. Reduction in alcohol intake to <2 alcoholic drinks per day helps reduce the blood pressure in a dose- response manner75. Most studies indicate that alco- hol consumption between 2.5 g/day and 30 to 60 g/day (mild to moderate drinking) is cardioprotec- tive for both CV mortality and CHD mortality76. In a meta-analysis done by Bagnardi and colleagues, the risk of CHD was higher in binge and heavy drinkers, when compared with non-drinkers77. A similar pattern has been noted between alcohol in- take and stroke78. Larsson et al in a systemic review and meta-analysis of 27 prospective studies con- cluded that light to moderate alcohol consumption (1-2 drinks/day) was associated with a lower risk of ischemic stroke, whereas heavy drinking (>2-4 drinks/day) was associatedwith an increased risk, es- pecially of hemorrhagic stroke78. HF also appears to be less in individuals consuming <7 drinks/week79. Wannamethee et al. found that heavier drinking (≥5 drinks/day or ≥35 drinks/week) significantly increased the risk for HF80. Heavy alcohol intake may also induce alcoholic cardiomyopathy81. The causal relationship between alcohol intake and atrial fibrillation has also been known for a long time82. In a recently published study of 107,485 subjects followed for nearly 14 years, Csengeri et al. found that alcohol increased the risk of developing atrial fibrillation by16%, irrespective of the type of bever- age consumed83. According to Koskinen and group, 5%-10% of all new episodes of atrial fibrillation are related to alcohol use84. Alcohol also plays a significant role in sudden cardiac death (SCD)85. In a study of the Finnish population, 4 of 10 victims of un- expected SCD exhibited evidence of alcohol intake before the fatal event86. Drinking during pregnancy is also harmful to the offspring, who may be born with congenital anomalies such as aberrant great vessels, atrial septal defects, and ventricular septal defects87,88. High levels of alcohol intake are also associated with an increased risk of PAD89. Wang et al, in ametanalysis, determined that light tomoderate alcohol intake (<21 drinks/week) correlated with a decreased risk of erectile dysfunction90. Alcohol is also associated with many other CVD risk factors, such as sleep disorders91, chronic kidney disease92, weight gain93, depression94, and smoking95. The beneficial effects of alcohol are related to several actions96−104. Alcohol intake has an inverse associa- tionwith T2DM (low tomoderate intake)96 and tends to increase HDL-C and apolipoprotein A-I97−99 – these effects are CVD protective. Alcohol helps alter the atherosclerotic plaque composition and provides stabilization100. Alcohol also exerts several effects on factors involved in hemostasis, such as inhibition of platelet aggregation101, lowering of fibrinogen levels102 and plasma viscosity103, as well as increas- ing levels of tissue plasminogen activator104. 2.2 OBESITY The relationship between alcohol intake and obesity has been well studied105,106. Several studies have however produced conflicting findings105,107. Since alcohol provides extra calories (1 gram of alcohol provides 7.1 kcal (29 kJ), its intakewith a regular diet may lead to a positive energy balance, and weight gain108. It is estimated that in the US, 16% of adult drinkers’ total energy intake comes from alcohol109. However, alcohol’s relationship with obesity is not that simple110−112. Several studies show that light- to-moderate alcohol intake is not associated with weight gain105,108. Moderate drinkers are more likely to follow healthier lifestyles, such as exercising regu- larly and eating fruits and vegetables, which tends to prevent weight gain107,113. Heavy drinking does tend to be associated with an increased risk of obesity107. MEERP LTD CMI JOURNAL 2 (3), 169−184 (2021) 171 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, OBESITY, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES A recent study confirmed that high alcohol con- sumption, especially binge drinking, was associated with higher risks of obesity in Korean men114. The increased tendency for men to gain weight with excessive alcohol drinking may be because they tend to drink about three times the amount of alcohol con- sumed by women and are more likely to drink beer and spirits115. Beer is rich in carbohydrates and may provide more calories108,116. Women tend to drink more wine, which is more likely to protect against weight gain105. Many other factors like socioeco- nomic status117, behavioral changes118, metabolic effects119, etc. may also play a role. The available data, however, does not conclusively confirm a pos- itive association between alcohol consumption and weight gain105,120. 2.3 RESPIRATORY DISEASES There is no definitive association between alco- hol intake and COPD, or lung cancer121−123. The association between alcohol abuse and pneumonia is, however, strong124−126. Although not an NCD, this association will be briefly discussed. AUD in- dividuals are often affected by bacterial pneumo- nia with Streptococcus pneumoniae and Klebsiella pneumoniae127,128. These patients are more prone to bacteremia, sepsis, septic shock126,129, and adult respiratory distress syndrome (ARDS)130. ARDS is almost four times more likely to occur in AUD pa- tients than nonalcoholic patients131,132. Its presence is associated with poorer outcomes, including persis- tent hospitalization and death133. Abusers of alcohol are not only less likely to receive preventive anti- pneumococcal vaccination134 but may also experi- ence a less protective response135. Individuals with AUD are also more likely to develop tuberculosis (TB)136 and respiratory syncytial virus infection137. Acute lung injury is also seen more commonly in alcoholics after major trauma, such as a motor ve- hicle accident, gunshot wound, or burns138,139. Ex- cessive alcohol consumption increases susceptibility to pneumonia through multiple mechanisms140−143. These include a reduced immunity140, altered micro- bial composition in the lung passages and alveoli141, and an increased risk of aspiration142. Several other factors are also known to play a deleterious role143. 2.4 DEPRESSION Alcohol misuse and depression commonly co- occur144,145. AUD individuals are many times more likely to have suffered from major depres- sive disorder146,147. Depression may also lead to alcohol abuse in some individuals148. The alcohol–depression relationship appears to be curvilinear, with alcohol abstinence and heavy drinking both being associated with a higher risk of depression149,150. Both conditions are interlinked and co-existence results in greater severity and a worse prognosis for both disorders than either condition independently151−154. Data indicates that men usually develop AUD before depression, while women develop depression and then progress on to AUD155,156. Patients who abuse alcohol may also exhibit more depression and tend to be not adherent to treatment157. Alcohol abstinence appears to significantly improve depressive symptoms in depressed individuals158. Antidepressants may be useful for the treatment of depression, alcohol dependence, or both, concurrently. Behavioral treatments are also effective in both159−161. 2.5 LIVER DISEASES Alcohol-related hepatoxicity appears to be the “old- est form of liver injury known to humankind”162,163. Alcohol-related damage to the liver is broadly called alcoholic liver disease (ALD) and includes alco- holic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis164. About 90% of alcoholics develop al- coholic fatty liver (steatosis), about 25% develop alcoholic hepatitis, about 15% develop alcoholic cirrhosis, and about 10% develop hepatocellular carcinoma (HCC)165−168. Continued alcohol con- sumption usually leads to progression from alco- holic fatty liver to hepatitis and then on to cirrho- sis. Alcoholic steatosis is usually asymptomatic (al- though some nausea, anorexia, and vomiting may be present)169 and these patients exhibit mild elevations of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), and alanine aminotrans- ferase (ALT) levels170. There is no abnormality of the serum bilirubin, International Normalized Ra- tio (INR), or albumin level. On liver biopsy, there CMI JOURNAL 2 (3), 169−184 (2021) MEERP LTD 172 MEERP LTD SHASHI K. AGARWAL, MD is microvesicular and macrovesicular fat accumula- tion within hepatocytes, minimal inflammatory re- action, and no hepatic fibrosis171. Abstinence will often revert these changes172. Patients with alco- holic hepatitis may have jaundice, pyrexia, uninten- tional weight loss, malnutrition, and an enlarged, tender liver173. There are moderate elevations in GGT, AST, and serum bilirubin174. Typically, the AST:ALT ratio is ≥ 2:1 in these patients175. The liver biopsy usually shows neutrophilic infiltration, hepatocyte necrosis, steatosis, and the presence of Mallory bodies176. Patients with alcoholic cirrho- sis may also exhibit gynecomastia, palmar ery- thema, spider angiomata, testicular atrophy, parotid gland enlargement; signs of portal hypertension, and Dupuytren’s contracture177. Laboratory findings of- ten include hypoalbuminemia, hyperbilirubinemia, thrombocytopenia, and prolonged prothrombin time, and increased INR173. The liver biopsy usually re- veals bridging fibrosis and regenerating nodules, and these are uniformly sized and micronodular178. In Western countries, alcohol is responsible for up to 50% of end-stage liver disease179. It is estimated that almost 50% of all deaths from cirrhosis in the world are related to ALD180. Potentiating factors for ALD include metabolic syndrome181, diabetes182, smoking183, obesity184, iron overload185, and chronic viral hepatitis B or C186,187. Genetic factors may also play a role188. Although abstinence markedly reducesmortality189, the only definitive treatment for ALD remains liver transplantation190−193. Alcohol abuse in patients with hepatitis B or HCV infection will often hasten the development of cirrhosis and its complications including HCC194. Alcohol abuse is reported to be responsible for approximately 15%– 30% of HCC195,196. 3 CONCLUSION Alcohol drinking is popular all over the world. This manuscript focuses on the relationship between al- cohol intake and cardiovascular diseases, obesity, respiratory diseases, depression, and liver disorders. Alcohol consumption is generally safe, provided the consumption is in low to moderate amounts. It ap- pears to be beneficial in these amounts for CVDs. However higher levels of alcohol consumption are harmful. Alcohol intake of more than 3 drinks per day in men and more than 2 drinks in women, should be avoided. 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