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Alcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic Studies
Open accessAbstract
In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer‐reviewed studies indicating the beneficial effects of light‐moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti‐inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol’s cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct “neuroprotective” actions—pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, β‐amyloid, a toxic protein intimately associated with Alzheimer’s, or gp120, the neuroinflammatory HIV‐1 envelope protein. The alcohol‐dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress‐associated, anti‐inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways.
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“a protective effect of light to moderate drinking has some biological plausibility 212, but evidence on this is inconsistent.”
From The relationship between different dimensions of alcohol use and the burden of disease—an update (2017) · cites this paper as [212]
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“Importantly, the effects observed in the current study, as well as previously reported protective effects of ethanol exposure, have been observed in protocols yielding average blood alcohol levels in a low-to-moderate range (Collins et al., 2009; Godfrey et al., 2015; Gunzerath, Faden, Zakhari, & Warren, 2004; Standri…”
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Is it merely a myth that alcoholic beverages such as red wine can be cardioprotective?
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Availability of Tobacco and Alcohol Products in Los Angeles Community Pharmacies
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“Although complete abstinence from alcohol may seem like the safest recommendation for any patient infected with HIV, this has to be tempered somewhat by the evidence that modest, social use of alcohol may infer mild cardio protective effects.(67) Thanks to effective antiretroviral therapies, HIV-infected individuals a…”
BackgroundDoes prevention for Alzheimer's disease exist?
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“function, that is the ability of the artery wall to expand and contract, thus providing a protective effect during the early phases of atherosclerosis [3–6].”
Pang, C., Cheng, H.-Y., Huang, L., Peng, H., Kuo, J., & Liew, H. (2018) · Tzu Chi Medical Journal · doi:10.4103/tcmj.tcmj_184_17 · Cited by 6
“Epidemiologic studies suggest that light to moderate ethanol consumption reduces the risk of adverse cerebrovascular events and overall mortality compared with those in abstainers while heavy drinkers (3–4 or more drinks per day) demonstrate increased risks [8,9].”
BackgroundModerate Ethanol Pre-treatment Mitigates ICH-Induced Injury via ER Stress Modulation in Rats
Lin, P. B., Wang, P., Pang, C., Hu, W.-F., Tsai, A. P., Oblak, A. L., & Liew, H. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.682775 · Cited by 6
“Moderate drinking is associated with a lower incidence of cardiovascular diseases such as stroke, while a higher level of alcohol use is associated with liver and kidney diseases (Mukamal et al., 2005; Collins et al., 2009).”
BackgroundInnovative trends and strategies for the integral valorization of products in the beer supply chain
Barbagallo, R. N., Rutigliano, C. A. C., Rizzo, V., & Muratore, G. (2024) · Italian Journal of Food Science · doi:10.15586/ijfs.v36i3.2542 · Cited by 5
Nutrient effects on working memory across the adult lifespan
Cansino, S., Torres-Trejo, F., Estrada-Manilla, C., Flores-Mendoza, A., Ramírez-Pérez, G., & Ruiz‐Velasco, S. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2022.2055378 · Cited by 5
“within the brain [35] and enhances the expression of N-methyl-D-aspartate receptor (NMDAR), which is very involved in the control of synaptic plasticity and”
BackgroundProteínas de choque térmico en la cardioprotección del consumo moderado regular de alcohol
Guisasola, M. C. (2016) · Medicina Clínica · doi:10.1016/j.medcli.2015.12.011 · Cited by 5
Strat, Y. L., & Gorwood, P. A. P. M. (2011) · American Journal on Addictions · doi:10.1111/j.1521-0391.2011.00125.x · Cited by 5
Lessons From the Besotted Heart
Karliner, J. S. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.06.052 · Cited by 5
Yao, J., Long, M., Zhang, T., Ding, M., Chen, X., Hong, T., Shi, H., Li, X., Mai, H., Zou, J., et al. (2025) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2025.104218 · Cited by 4
Associations of alcohol drinking with incident dementia: a prospective study from the UK Biobank
Chen, Y., Yin, X., Wang, X., Zheng, X., Yang, X., Zhou, J., Shi, M., & Zhang, Y. (2025) · European Journal of Epidemiology · doi:10.1007/s10654-025-01304-y · Cited by 4
“…can reduce cardiovascular risk through multiple mechanisms, including the elevation of high-density lipoprotein cholesterol levels [43], the reduction of metabolic syndrome risk [44], the decrease in fibrinogen and other thrombogenic factors [45], and the lowering of inflammatory markers [46].”
Love, S.-A. M., North, K. E., Zeng, D., Petruski‐Ivleva, N., Kucharska‐Newton, A., Palta, P., Graff, M., Loehr, L. R., Jones, S. B., & HEISS, G. M. (2020) · American Journal of Epidemiology · doi:10.1093/aje/kwaa006 · Cited by 4
Alcohol: the role in nutrition and health
Suter, P. M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818460-8.00025-3 · Cited by 5
Yang, Y.-S., Takahara, K., Kumrungsee, T., Kimoto, A., Shimamoto, F., & Kato, N. (2019) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.65.443 · Cited by 4
Treatment of vascular dementia
Brucki, S. M. D., Ferraz, A. C., de Freitas, G. R., Massaro, A. R., Radanovic, M., & Schultz, R. R. (2011) · Cited by 4
Kim, S. J., Bae, W. J., Han, J. H., Hong, S., Kim, S. W., Hwang, T., Kim, D., & Lee, J. Y. (2013) · International Urology and Nephrology · doi:10.1007/s11255-012-0342-6 · Cited by 3
Network Analysis of EtOH‐Related Candidate Genes
Guo, A., Sun, J., Jia, P., & Zhao, Z. (2010) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900318 · Cited by 3
Albakri, A. (2019) · Research and Review Insights · doi:10.15761/rri.1000150 · Cited by 4
“those with heart diseases [20,21] creating a debate of the amount”
BackgroundZhao, Y., Yang, H., Shan, W., Guo, A., & Wang, Q. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03661-6 · Cited by 3
“Previous studies suggested that ethanol intake at high levels (3–4 or more drinks) increases the risk for myocardial infarction, liver and brain injury [31, 32].”
BackgroundNatural molecules in neuroprotection and neurotoxicity in neurodegenerative diseases
Castillo, I. L. D., Vegas‐Gomez, L., Loureiro, J. A., & Moreno‐González, I. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23763-8.00001-4 · Cited by 3
Giltvedt, K., Voutour, L. S., Tursellino, B., Zella, A., Brasser, S. M., & Hong, M. Y. (2022) · International Journal of Cardiology Cardiovascular Risk and Prevention · doi:10.1016/j.ijcrp.2022.200132 · Cited by 3
“By contrast, several lines of evidence indicate that low-to-moderate ethanol exposure is associated with reduced incidence of cardiovascular disease [2,3] and may provide cardioprotective effects through modulation of inflammatory markers and gene expression and a reduction in oxidative damage [8,12].”
BackgroundThe French Paradox: 20 Years Later
Ellison, R. C. (2011) · Journal of Wine Research · doi:10.1080/09571264.2011.603214 · Cited by 3
“An excellent review of the mechanisms by which alcohol and wine polyphenols are cardioprotective and neuroprotective was published by Collins et al. (2009).”
BackgroundShrader-Frechette, K. (2011) · Biological Theory · doi:10.1007/s13752-012-0021-y · Cited by 3
“…Department of Philosophy, University of Notre Dame, Notre Dame, IN, USA DOI 10.1007/s13752-012-0021-y disease, and that drinking helps prevent dementia and diabetes (e.g., Klatsky 1996; Rimm et al. 1996; McConell et al. 1997; Ruitenberg et al. 2002; Ellison 2005; Collins et al. 2009).”
BackgroundInfluentialModerate alcohol consumption and atherosclerosis: Friend or foe?
Geroldi, D., & Emanuele, E. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.03.007 · Cited by 3
Nasehi, M., Zadeh‐Tehrani, S. N., Khakpai, F., & Zarrindast, M. (2020) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2020.106927 · Cited by 3
Influence of Dietary Nutrient Intake on Episodic Memory Across the Adult Life Span
Cansino, S., Torres-Trejo, F., Estrada-Manilla, C., Flores-Mendoza, A., Ramírez-Pérez, G., & Ruiz‐Velasco, S. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.724595 · Cited by 4
Alcohol and Neural Network Activity
de Gaetano, G., Costanzo, S., & Castelnuovo, A. F. D. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.04.018 · Cited by 3
Xiaobin, F., Chen, J., Yuming, G., Shuguo, Z., Jiang, P., Li, X., & Dong, J. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.02.015 · Cited by 2
“Other mechanisms of moderate alcohol exposure promoting anti-inflammatory processes involve adenosine receptors, protein kinase C (PKC), heat shock protein and nitric oxide synthase [10].”
BackgroundPetechial hemorrhages, ethanol, and opioids in victims from intoxication
Maehle, B. O., Eide, G. E., Morild, I., & Lilleng, P. K. (2022) · Forensic Science International · doi:10.1016/j.forsciint.2022.111406 · Cited by 2
The Effect of Alcohol Consumption on Progressive Supranuclear Palsy: A Cross‐Sectional Study
Tian, M., Zhang, B., Liu, H., Han, Y., Mu, Y., Duan, R., Guo, D., Song, C., Ma, J., & Liu, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70146 · Cited by 2
Piper, B. J., Henderson, C. S., & Meyer, J. S. (2013) · Developmental Psychobiology · doi:10.1002/dev.21169 · Cited by 3
McIntosh, J. (2013) · Communications in Statistics - Simulation and Computation · doi:10.1080/03610918.2012.762385 · Cited by 2
“This is confirmed by a recent survey by Collins et al. (2010). Consequently, the biases that are reported in the two simulations are probably somewhat larger than those which are present in the studies referred to in the introduction.”
ResultExploring the boundary between health protective and hazardous drinking in a community cohort
Murray, R. P., Tyas, S. L., Snow, W. M., Ekuma, O., Bond, R., & Barnes, G. E. (2009) · Addictive Behaviors · doi:10.1016/j.addbeh.2009.10.010 · Cited by 2
Parikh, M. C., Patel, S. N., Shen, Y., & Lau‐Cam, C. A. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-15126-7_25 · Cited by 2
Psychopharmacology and the Consequences of Alcohol and Drug Interactions
Ramchandani, V. A., Slattum, P. W., Patkar, A. A., Wu, L.-T. T., Lee, J. C., Mohanty, M., Coe, M. A., & Li, T. (2014) · Wiley eBooks · doi:10.1002/9781118430965.ch12 · Cited by 2
Alcohol: Its Role in Nutrition and Health
Suter, P. M. (2012) · doi:10.1002/9781119946045.ch55 · Cited by 2
Alcohol y envejecimiento: impacto sobre la longevidad y la salud cerebral
Redolat, R., Mesa‐Gresa, P., Monleón, S., Moragrega, I., & Vinader‐Caerols, C. (2025) · Revista Española de Drogodependencias · doi:10.54108/10116 · Cited by 1
Choi, S., & Je, Y. (2026) · Addiction · doi:10.1111/add.70558 · Cited by 1
Brust, J. C. M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-407824-6.00072-0 · Cited by 1
Hormetic Responses to Ethanol Ingestion
Korthuis, R. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814253-0.00009-7 · Cited by 1
Self-citationLambert, M. E. (2016) · Applied Neuropsychology Adult · doi:10.1080/23279095.2015.1092149 · Cited by 1
“Yet, mild alcohol consumption’s neuroprotection effects are more generalized with antioxidant and anti-inflammatory effects (Collins et al., 2009; Peters, 2009), likely impacting cellular signaling pathways to reduce cerebral tissue injury (Krenz & Korthuis, 2012).”
Background
Metadata
- Authors
- Collins, M. A., Neafsey, E. J., Mukamal, K. J., Gray, M. O., Parks, D. A., Das, D. K., & Korthuis, R. J.
- Affiliations
- San Francisco General Hospital (US)
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2009-01-22
- Volume
- 33
- Issue
- 2
- Pages
- 206-219
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC2908373
- OpenAlex
- W2111348890
- Cited by
- 235
- References
- 128
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 5 · 2022: 11 · 2021: 7 · 2020: 9 · 2019: 16 · 2018: 9 · 2017: 13 · 2016: 14 · 2015: 11 · 2014: 17 · 2013: 24 · 2012: 16
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01aa011723-03)
- National Institute on Alcohol Abuse and Alcoholism (R01AA013568, AA 11135, AA014945, R01AA011135, R01AA014945, AA013568, AA 13361, AA 011723, F31AA013361)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK043785)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Clinical Neurology › Alcoholism and Thiamine Deficiency
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- moderate drinking, cardioprotection, neuroprotection, coronary artery disease, ischemic stroke, dementia, cognitive decline, anti-inflammatory mechanism, adenosine receptors, protein kinase C, nitric oxide synthase, heat shock proteins, cerebral ischemia, amyloid-beta, gp120, reactive oxygen species, signal transduction
- MeSH terms
- Resveratrol, Alcohol Drinking, Ethanol, Animals, Antioxidants, Cardiotonic Agents, Cardiovascular Diseases, Central Nervous System Depressants, Dementia, Humans, Nitric Oxide, Protein Kinase C, Stilbenes, Neuroprotective Agents
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