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Nutrients Sep 2021Alcohol consumption has been shown to have complex, and sometimes paradoxical, associations with cardiovascular diseases (CVDs). Several hundred epidemiological studies... (Review)
Review
Alcohol consumption has been shown to have complex, and sometimes paradoxical, associations with cardiovascular diseases (CVDs). Several hundred epidemiological studies on this topic have been published in recent decades. In this narrative review, the epidemiological evidence will be examined for the associations between alcohol consumption, including average alcohol consumption, drinking patterns, and alcohol use disorders, and CVDs, including ischaemic heart disease, stroke, hypertension, atrial fibrillation, cardiomyopathy, and heart failure. Methodological shortcomings, such as exposure classification and measurement, reference groups, and confounding variables (measured or unmeasured) are discussed. Based on systematic reviews and meta-analyses, the evidence seems to indicate non-linear relationships with many CVDs. Large-scale longitudinal epidemiological studies with multiple detailed exposure and outcome measurements, and the extensive assessment of genetic and confounding variables, are necessary to elucidate these associations further. Conflicting associations depending on the exposure measurement and CVD outcome are hard to reconcile, and make clinical and public health recommendations difficult. Furthermore, the impact of alcohol on other health outcomes needs to be taken into account. For people who drink alcohol, the less alcohol consumed the better.
Topics: Alcohol Drinking; Animals; Biomarkers; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cardiovascular System; Diagnosis, Differential; Disease Susceptibility; Ethanol; Health Impact Assessment; Humans; Risk Factors
PubMed: 34684419
DOI: 10.3390/nu13103419 -
Trends in Neurosciences Dec 2021Alcohol use produces wide-ranging and diverse effects on the central nervous system. It influences intracellular signaling mechanisms, leading to changes in gene... (Review)
Review
Alcohol use produces wide-ranging and diverse effects on the central nervous system. It influences intracellular signaling mechanisms, leading to changes in gene expression, chromatin remodeling, and translation. As a result of these molecular alterations, alcohol affects the activity of neuronal circuits. Together, these mechanisms produce long-lasting cellular adaptations in the brain that in turn can drive the development and maintenance of alcohol use disorder (AUD). We provide an update on alcohol research, focusing on multiple levels of alcohol-induced adaptations, from intracellular changes to changes in neural circuits. A better understanding of how alcohol affects these diverse and interlinked mechanisms may lead to the identification of novel therapeutic targets and to the development of much-needed novel and efficacious treatment options.
Topics: Alcoholism; Brain; Chromatin Assembly and Disassembly; Ethanol; Humans; Neurons
PubMed: 34702580
DOI: 10.1016/j.tins.2021.09.006 -
Annual Review of Pathology Jan 2023Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related... (Review)
Review
Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis of ALD. We also summarize current understanding of innate immune responses, liver sinusoidal endothelial cell dysfunction and hepatic stellate cell activation, and gut-liver and adipose-liver cross talk in response to ethanol. In addition,we describe the current potential therapeutic targets and clinical trials aimed at alleviating hepatocyte injury, reducing inflammatory responses, and targeting gut microbiota, for the treatment of ALD.
Topics: Humans; Liver Diseases, Alcoholic; Liver; Ethanol; Hepatocytes; Fibrosis
PubMed: 36270295
DOI: 10.1146/annurev-pathmechdis-031521-030435 -
Drug Metabolism Reviews Nov 2019This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on... (Review)
Review
This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol's harmful effects or accentuate its beneficial effects.
Topics: Alcohol Drinking; Alcoholism; Animals; Ethanol; Humans; Immunologic Factors
PubMed: 31646907
DOI: 10.1080/03602532.2019.1679169 -
Alcohol and Alcoholism (Oxford,... May 2019To review current alcohol hangover research in animals and humans and evaluate key evidence for contributing biological factors. (Review)
Review
AIM
To review current alcohol hangover research in animals and humans and evaluate key evidence for contributing biological factors.
METHOD
Narrative review with alcohol hangover defined as the state the day after a single episode of heavy drinking, when the alcohol concentration in the blood approaches zero.
RESULTS
Many of the human studies of hangover are not well controlled, with subjects consuming different concentrations of alcohol over variable time periods and evaluation not blinded. Also, studies have measured different symptoms and use varying methods of measurement. Animal studies show variations with respect to the route of administration (intragastric or intraperitoneal), the behavioural tests utilised and discrepancy in the timepoint used for hangover onset. Human studies have the advantage over animal models of being able to assess subjective hangover severity and its correlation with specific behaviours and/or biochemical markers. However, animal models provide valuable insight into the neural mechanisms of hangover. Despite such limitations, several hangover models have identified pathological changes which correlate with the hangover state. We review studies examining the contribution of alcohol's metabolites, neurotransmitter changes with particular reference to glutamate, neuroinflammation and ingested congeners to hangover severity.
CONCLUSION
Alcohol metabolites, neurotransmitter alterations, inflammatory factors and mitochondrial dysfunction are the most likely factors in hangover pathology. Future research should aim to investigate the relationship between these factors and their causal role.
Topics: Alcoholic Intoxication; Animals; Brain; Ethanol; Humans; Inflammation; Neurotransmitter Agents
PubMed: 30916313
DOI: 10.1093/alcalc/agz016 -
Current Obesity Reports Mar 2015Recreational alcohol intake is a widespread activity globally and alcohol energy (7 kcal/g) can be a contributing factor to weight gain if not compensated for. Given... (Review)
Review
Recreational alcohol intake is a widespread activity globally and alcohol energy (7 kcal/g) can be a contributing factor to weight gain if not compensated for. Given that both excessive alcohol intake and obesity are of public health interest, the present paper provides an update on the association between alcohol consumption and body weight. In general, recent prospective studies show that light-to-moderate alcohol intake is not associated with adiposity gain while heavy drinking is more consistently related to weight gain. Experimental evidence is also mixed and suggests that moderate intake of alcohol does not lead to weight gain over short follow-up periods. However, many factors can explain the conflicting findings and a better characterization of individuals more likely to gain weight as a result of alcohol consumption is needed. In particular, individuals who frequently drink moderate amounts of alcohol may enjoy a healthier lifestyle in general that may protect them from weight gain. In conclusion, despite the important limitations of current studies, it is reasonable to say that alcohol intake may be a risk factor for obesity in some individuals, likely based on a multitude of factors, some of which are discussed herein.
Topics: Adipose Tissue; Alcohol Drinking; Alcoholic Beverages; Ethanol; Humans; Life Style; Obesity; Weight Gain
PubMed: 25741455
DOI: 10.1007/s13679-014-0129-4 -
Autophagy Nov 2022Ethanol increases hepatic mitophagy driven by unknown mechanisms. Type 1 mitophagy sequesters polarized mitochondria for nutrient recovery and cytoplasmic remodeling. In...
Ethanol increases hepatic mitophagy driven by unknown mechanisms. Type 1 mitophagy sequesters polarized mitochondria for nutrient recovery and cytoplasmic remodeling. In Type 2, mitochondrial depolarization (mtDepo) initiates mitophagy to remove the damaged organelles. Previously, we showed that acute ethanol administration produces reversible hepatic mtDepo. Here, we tested the hypothesis that ethanol-induced mtDepo initiates Type 2 mitophagy. GFP-LC3 transgenic mice were gavaged with ethanol (2-6 g/kg) with and without pre-treatment with agents that decrease or increase mtDepo-Alda-1, tacrolimus, or disulfiram. Without ethanol, virtually all hepatocytes contained polarized mitochondria with infrequent autophagic GFP-LC3 puncta visualized by intravital microscopy. At ~4 h after ethanol treatment, mtDepo occurred in an all-or-none fashion within individual hepatocytes, which increased dose dependently. GFP-LC3 puncta increased in parallel, predominantly in hepatocytes with mtDepo. Mitochondrial PINK1 and PRKN/parkin also increased. After covalent labeling of mitochondria with MitoTracker Red (MTR), GFP-LC3 puncta encircled MTR-labeled mitochondria after ethanol treatment, directly demonstrating mitophagy. GFP-LC3 puncta did not associate with fat droplets visualized with BODIPY558/568, indicating that increased autophagy was not due to lipophagy. Before ethanol administration, rhodamine-dextran (RhDex)-labeled lysosomes showed little association with GFP-LC3. After ethanol treatment, TFEB (transcription factor EB) translocated to nuclei, and lysosomal mass increased. Many GFP-LC3 puncta merged with RhDex-labeled lysosomes, showing autophagosomal processing into lysosomes. After ethanol treatment, disulfiram increased, whereas Alda-1 and tacrolimus decreased mtDepo, and mitophagy changed proportionately. In conclusion, mtDepo after acute ethanol treatment induces mitophagic sequestration and subsequent lysosomal processing. AcAld, acetaldehyde; ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; ALD, alcoholic liver disease; Alda-1, N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP, green fluorescent protein; LAMP1, lysosomal-associated membrane protein 1; LMNB1, lamin B1; MAA, malondialdehyde-acetaldehyde adducts; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MPT, mitochondrial permeability transition; mtDAMPS, mitochondrial damage-associated molecular patterns; mtDepo, mitochondrial depolarization; mtDNA, mitochondrial DNA; MTR, MitoTracker Red; PI, propidium iodide; PINK1, PTEN induced putative kinase 1; PRKN, parkin; RhDex, rhodamine dextran; TFEB, transcription factor EB; Tg, transgenic; TMRM, tetramethylrhodamine methylester; TOMM20, translocase of outer mitochondrial membrane 20; VDAC, voltage-dependent anion channel.
Topics: Mice; Animals; Mitophagy; Ethanol; Disulfiram; Tacrolimus; Autophagy; Ubiquitin-Protein Ligases; DNA, Mitochondrial; Protein Kinases; Acetaldehyde
PubMed: 35293288
DOI: 10.1080/15548627.2022.2046457 -
Behaviour Research and Therapy Jan 2017Understanding why people drink alcohol and in some cases develop drinking problems has long puzzled researchers, clinicians, and patients alike. In the mid-1940s and... (Review)
Review
Understanding why people drink alcohol and in some cases develop drinking problems has long puzzled researchers, clinicians, and patients alike. In the mid-1940s and early 1950s, experimental research began to systematically investigate alcohol's hedonic properties. Presumably, alcohol consumption would prove reinforcing as a consequence of its capacity either to relieve stress or to brighten positive emotional experiences. This article reviews experimental research through the years examining the impact of alcohol on both the relief of negative affect and the enhancement of positive affect. It covers initial accounts that emphasized direct pharmacological effects of ethanol on the central nervous system. These early studies offered surprisingly tepid support for the premise that alcohol improved emotional states. Next, studies conducted in the 1970s are considered. Informed by social learning theory and employing advances derived from experimental psychology, this research sought to better understand the complex effects of alcohol on emotion. Coverage of this work is followed by discussion of current formulations, which integrate biological and behavioral approaches with the study of cognitive, affective, and social processes. These current perspectives provide insight into the particular conditions under which alcohol can boost emotional experiences. Finally, future research directions and clinical implications are considered.
Topics: Alcohol Drinking; Emotions; Ethanol; Humans; Social Behavior
PubMed: 28110679
DOI: 10.1016/j.brat.2016.06.005 -
Revue Medicale de Liege May 2019Ethanol is rapidly and almost completely absorbed by the digestive tract, mainly in the small intestine. Alcohol is then metabolized mainly in the liver where it is...
Ethanol is rapidly and almost completely absorbed by the digestive tract, mainly in the small intestine. Alcohol is then metabolized mainly in the liver where it is converted into acetaldehyde. Two systems contribute to this metabolization, the predominant alcohol dehydrogenase pathway, and the pathway controlled by the microsomal ethanol oxidizing system (MEOS), which is inducible and is also involved in the metabolism of other drugs. Acetaldehyde is then metabolized to acetate, which largely leaves the liver to be converted into acetyl-CoA in other tissues. Alcohol is oxidized preferentially to other energetic substrates, leading, in turn, to a decrease in oxidation of lipids which are stored in adipose tissue.
Topics: Acetaldehyde; Alcohol Dehydrogenase; Ethanol; Humans; Liver; Oxidation-Reduction
PubMed: 31206264
DOI: No ID Found -
Gut Microbes 2021Alcohol is well known for promoting systemic inflammation and aggravating multiple chronic health conditions. Thus, alcohol may also be expected to serve as a risk... (Review)
Review
Alcohol is well known for promoting systemic inflammation and aggravating multiple chronic health conditions. Thus, alcohol may also be expected to serve as a risk factor in autoimmune diseases. However, emerging data from human and animal studies suggest that alcohol may in fact be protective in autoimmune diseases. These studies point toward alcohol's complex dose-dependent relationship in autoimmune diseases as well as potential modulation by duration and type of alcohol consumption, cultural background and sex. In this review, we will explore alcohol's pro- and anti-inflammatory properties in human and animal autoimmune diseases, including autoimmune diabetes, thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, experimental autoimmune encephalomyelitis and multiple sclerosis. We will also discuss potential mechanisms of alcohol's anti-inflammatory effects mediated by the gut microbiome.
Topics: Animals; Autoimmunity; Diabetes Mellitus, Type 1; Ethanol; Gastrointestinal Microbiome; Humans
PubMed: 34224314
DOI: 10.1080/19490976.2021.1916278