Low-dose Alcohol Consumption Research Articles

Confounding and studies of ‘moderate’ alcohol consumption: the case of drinking frequency and implications for low‐risk drinking guidelines

Many observational studies suggest that increased drinking frequency is associated with reduced mortality among those with low-dose alcohol consumption. The purpose of this paper was to examine whether frequent drinkers consume lower-risk amounts during drinking days or have favorable risk factor profiles compared with those who drink less frequently, and discuss implications for the larger debate about the limitations of non-randomized studies about 'moderate' drinking and the development of low-risk drinking guidelines. Data from the 2008 Behavioral Risk Factor Surveillance System survey were used to characterize alcohol consumption characteristics and their relationship with risk factors among adult drinking men who consumed an average of fewer than two drinks per day and adult drinking adult women who consumed an average of less than one drink per day. Those who drank relatively infrequently (14 or fewer days per month) consumed more during drinking days, were more likely to exceed the US Dietary Guidelines drinking limits (41.0% versus 9.7%) and had a larger proportion of drinking days that included binge drinking (13.4% versus 4.3%). Infrequent drinkers also had a higher prevalence of 13 of 15 risk factors assessed. Findings from analyses of those aged ≥40 years were similar. Among those with low average alcohol consumption, infrequent drinkers drink more during drinking days and have unfavorable risk factors profiles compared with more frequent drinkers, suggesting that confounding may contribute to favorable associations with 'moderate' average alcohol consumption and increased drinking frequency observed in non-randomized studies.

Low-Dose Alcohol Consumption Protects against Transient Focal Cerebral Ischemia in Mice: Possible Role of PPARγ

BackgroundWe examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption.Methodology/Principal FindingsC57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8 weeks, orally treated with rosiglitazone (20 mg/kg/day), a peroxisome proliferator-activated receptor gamma (PPARγ)-selective agonist, or GW9662 (3 mg/kg/day), a selective PPARγantagonist, for 2 weeks. The mice were subjected to unilateral middle cerebral artery occlusion (MCAO) for 90 minutes. Brain injury, DNA fragmentation and nuclear PPARγ protein/activity were evaluated at 24 hours of reperfusion. We found that the brain injury and DNA fragmentation were reduced in 1% alcohol-fed mice compared to nonalcohol-fed mice. Rosiglitazone suppressed the brain injury in nonalcohol-fed mice, but didn't alter the brain injury in alcohol-fed mice. In contrast, GW9662 worsened the brain injury in alcohol-fed mice, but didn't alter the brain injury in nonalcohol-fed mice. Nuclear PPARγ protein/activity at peri-infarct and the contralateral corresponding areas of the parietal cortex was greater in alcohol-fed mice compared to nonalcohol-fed mice. Using differentiated catecholaminergic (CATH.a) neurons, we measured dose-related influences of chronic alcohol exposure on nuclear PPARγ protein/activity and the influence of low-dose alcohol exposure on 2-hour oxygen-glucose deprivation (OGD)/24-hour reoxygenation-induced apoptosis. We found that low-dose alcohol exposure increased nuclear PPARγ protein/activity and protected against the OGD/reoxygenation-induced apoptosis. The beneficial effect of low-dose alcohol exposure on OGD/reoxygenation-induced apoptosis was abolished by GW9662.Conclusions/SignificanceOur findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury. The neuroprotective effect of low-dose alcohol consumption may be related to an upregulated PPARγ.

Dose-Related Influence of Chronic Alcohol Consumption on Cerebral Ischemia/Reperfusion Injury

We examined the dose-related influence of alcohol consumption on cerebral ischemia/reperfusion (I/R) injury and the potential mechanism that accounts for the disparate effects of high-dose and low-dose alcohol consumption on cerebral I/R injury. Sprague-Dawley rats were fed a liquid diet with or without 1, 3, 5, or 6.4% (v/v) alcohol for 8 weeks and subjected to a 2-hour middle cerebral artery occlusion (MCAO). We evaluated the brain injury at 24 hours of reperfusion. In addition, we measured protein expression of NMDA receptor and excitatory amino acid transporters (EAATs) in parietal cortex and the effect of NMDA receptor antagonist, memantine, on 2-hour MCAO/24 h reperfusion-induced brain injury. Compared with non-alcohol-fed rats, the total infarct volume was not altered in 3 and 5% alcohol-fed rats but significantly reduced in 1% alcohol-fed rats and exacerbated in 6.4% alcohol-fed rats. Expression of the NMDA receptor subunit, NR1, was upregulated in 6.4% alcohol-fed rats, whereas expression of EAAT2 was downregulated in 6.4% alcohol-fed rats and upregulated in 1% alcohol-fed rats. Memantine reduced 2-hour MCAO/24 h reperfusion-induced brain injury in non-alcohol-fed and 6.4% alcohol-fed rats, but not in 1% alcohol-fed rats. The magnitude of reduction in the brain injury was greater in 6.4% alcohol-fed rats compared to non-alcohol-fed rats. Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury, whereas chronic consumption of high-dose alcohol has detrimental effect on cerebral I/R injury. The disparate effects of low-dose and high-dose alcohol consumption on cerebral I/R may be related to an alteration in NMDA excitotoxicity.

Effects of Low-Dose Alcohol Consumption on Postural Control with a Particular Focus on the Role of the Visual System

There is clear evidence that vision contributes to stabilizing posture and that large quantities of alcohol affect balance. It has, however, not yet been investigated whether and how the consumption of low doses of ethanol affects postural control and the visual system. The purpose of this study was therefore to assess the influence of low-dose alcohol intake on balance. After having performed stability tests in a sober condition, 26 healthy males were instructed to consume 0.32 g of ethanol/kg body weight. At predefined time points, blood samples were collected and stability index scores were calculated using computerized dynamic posturography. Thirty minutes after ethanol intake, blood alcohol levels reached a mean peak of 0.037%. Whereas the ability to maintain balance significantly deteriorated during eyes-open testing, it surprisingly did not decrease during eyes-closed testing. Apparently, the visual system is particularly affected by ethanol and plays a major role in maintaining postural stability.

Paradoxical Facilitatory Effect of Low-Dose Alcohol Consumption on Memory Mediated by NMDA Receptors

Epidemiological studies have suggested a negative correlation between alcohol intake and Alzheimer's disease. In vitro, ethanol negatively modulates NMDA receptor function. We hypothesized that chronic moderate alcohol intake leads to improved memory via adaptive responses in the expression of NMDA receptors and downstream signaling. We fed liquid diets containing no, moderate, or high amounts of ethanol to control and matched rats with hippocampal knock-down of the NR1 subunit. Rats with increased hippocampal NR1 expression were also generated to determine whether they had a phenotype similar to that of ethanol-fed animals. We found that moderate ethanol intake improved memory, increased NR1 expression, and changed some aspects of neurotrophin signaling. NR1 knock-down prevented ethanol's facilitatory effects, whereas hippocampal NR1 overexpression mimicked the effect of chronic low-dose ethanol intake on memory. In contrast, high-dose ethanol reduced neurogenesis, inhibited NR2B expression, and impaired visual memory. In conclusion, adaptive changes in hippocampal NMDA receptor expression may contribute to the positive effects of ethanol on cognition.

Risk factors for dyspepsia in a general population: Non-steroidal anti-inflammatory drugs, cigarette smoking and unemployment are more important than Helicobacter pylori infection

Objective. Dyspepsia, a common condition in the community, affects quality of life and imposes costs on both the individual and the community. Several factors including Helicobacter pylori, acetylic salicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs) use, low-dose ASA use, alcohol consumption, cigarette smoking and social status might be responsible. Material and methods. A cross-sectional study from the inclusion (intervention group) of a general population study evaluating rates of dyspepsia after H. pylori screening and eradication was carried out. A total of 10,007 individuals aged 40–64 years received questionnaires and an invitation to take part in H. pylori screening. Information on dyspepsia (the gastrointestinal symptom rating scale (GSRS) and “most bothersome symptom”), use of ASA/NSAIDs, use of low-dose ASA, lifestyle factors and level of education and employment status was obtained from the questionnaire. Dyspepsia was defined as a score of ≥2 in the GSRS dimension abdominal pain syndrome (aps), allowing for a maximum of one light problem score in any of the 3 items in the dimension to be overlooked. Results. In all, 5749/10,007 individuals participated in the study; 24.9% reported dyspepsia. In a multiple logistic regression analysis H. pylori infection was found to be a risk factor for dyspepsia, odds ratio (OR) 1.21 (CI; 1.03–1.42). However, the highest ORs for dyspepsia were: for daily use of ASA/NSAIDs 2.33 (CI; 1.72–3.15), unemployment 2.18 (CI; 2.86–2.56) and cigarette smoking ≥20 g/day 1.55 (CI; 1.29–1.86). Conclusions. H. pylori infection is a significant risk factor for dyspepsia although of less importance than ASA/NSAIDs use, unemployment and heavy smoking.

Enhanced Antithrombotic Effect of Warfarin Associated with Low-Dose Alcohol Consumption

A 58-year-old Caucasian man was receiving long-term anticoagulation with warfarin for the prevention of ischemic stroke; his international normalized ratio (INR) had been stable. His INR increased when he began consistent, low-dose beer consumption for its perceived cardiovascular protection. After he stopped drinking the alcohol, his anticoagulation control improved and returned to previous levels. Information on the effects of alcohol, particularly beer, is limited in nonalcoholic patients who receive warfarin therapy. This case reveals a potential for low-dose beer consumption to elevate INR. We propose that the increased antithrombotic effect of warfarin involved protein-binding interactions and decreased warfarin metabolism through the cytochrome P450 (CYP) enzyme system. Concurrent administration of aspirin and other drugs that are metabolized through or are inhibitors of the CYP system may have enhanced the interaction that occurred in this patient. Caution should be used whenever warfarin and alcohol in any amount are taken together, especially in patients receiving many drugs, and close monitoring of the INR is warranted.

Retrograde Enhancement of Kinesthetic Memory by Alcohol and by Glucose

Several studies have reported that administration of a low dose of alcohol is capable of retrograde enhancement of memory. It has been postulated that the neurobiological mechanisms underlying this effect may involve the liberation of glucose and/or activation of reward centers. Here the effects of a low dose of alcohol were compared to those of glucose on kinesthetic memory. Mood and blood glucose levels were also measured. Compared with a placebo, both glucose and alcohol significantly enhanced kinesthetic memory performance. Only glucose ingestion resulted in significantly elevated blood glucose levels. The three groups' mood scores were statistically indistinguishable. Low-dose alcohol consumption does not result in the release of glucose nor does it affect any aspect of mood, at least as measured here. These results confirm that kinesthetic memory can be improved by administration of alcohol and extend the range of tasks which are sensitive to enhancement by glucose.

Effects of a Single, Daily Alcoholic Beverage on Lipid and Hemostatic Markers of Cardiovascular Risk

There is substantial epidemiologic data, but limited experimental data, supporting the mortality benefit of low-dose alcohol consumption. A regimen of a single, daily alcoholic beverage was sufficient to increase both high-density lipoprotein (HDL) (4.4%, p = 0.03) and HDL2 (7.7%, p = 0.04) in men and women, but did not significantly affect hemostatic markers of cardiovascular risk.

Patient-directed, nonprescription approaches to cardiovascular disease

The control of coronary artery disease requires both physician-directed interventions and patient-directed lifestyle changes that may include nonprescription supplements. All patients should be encouraged to exercise regularly. They should be advised to avoid exposure to tobacco smoke and to strive to attain ideal body weight. Patients should also be encouraged to establish diets that are low in cholesterol and fat and high in dietary fiber. Supplements of water-soluble fiber may be useful for selected patients. Diets rich in antioxidant vitamins should also be stressed. Antioxidant supplements may be warranted in individuals with coronary artery disease or risk factors. Pending further study, patients should be encouraged to consume more fish but not fish oil supplements. Therapeutic doses of niacin should not be used without medical supervision. Chromium and other nutritional supplements, however, may merit consideration in selected cases. Physicians should stress the use of nonpharmacologic means to reduce blood pressure and discuss interventions that could reduce excessive stress. With appropriate screening and precautions, selected individuals should benefit from low-dose aspirin prophylaxis and possibly from low-dose alcohol consumption. Because these patient-directed interventions receive less attention in the scientific literature, they were selected for review herein. (Arch Intern Med. 1994;154:2283-2296)

Patient-Directed, Nonprescription Approaches to Cardiovascular Disease

The control of coronary artery disease requires both physician-directed interventions and patient-directed lifestyle changes that may include nonprescription supplements. All patients should be encouraged to exercise regularly. They should be advised to avoid exposure to tobacco smoke and to strive to attain ideal body weight. Patients should also be encouraged to establish diets that are low in cholesterol and fat and high in dietary fiber. Supplements of water-soluble fiber may be useful for selected patients. Diets rich in antioxidant vitamins should also be stressed. Antioxidant supplements may be warranted in individuals with coronary artery disease or risk factors. Pending further study, patients should be encouraged to consume more fish but not fish oil supplements. Therapeutic doses of niacin should not be used without medical supervision. Chromium and other nutritional supplements, however, may merit consideration in selected cases. Physicians should stress the use of nonpharmacologic means to reduce blood pressure and discuss interventions that could reduce excessive stress. With appropriate screening and precautions, selected individuals should benefit from low-dose aspirin prophylaxis and possibly from low-dose alcohol consumption. Because these patient-directed interventions receive less attention in the scientific literature, they were selected for review herein.

Safety concerns related to treatment of peptic ulcer

Peptic ulceration is a worldwide problem that often requires long-term treatment; hence, drugs used for this condition must be extremely safe. Five- to 10-year studies of patients dosed with H2-receptor antagonists are now becoming available, and no long-term adverse events have been detected. The occurrence of gastric carcinoids in some rats dosed with potent gastric antisecretory regimens has resulted in an explosion of work investigating the relationships between antisecretory drugs, plasma gastrin concentration, and proliferation of the gastric mucosa. However, there continues to be some concern that gastric antisecretory drugs may result in an increased risk of gastric cancer, with continuing research investigating possible drug-induced genotoxicity. Finally, there has been debate about a possible interaction between H2 antagonists and low-dose alcohol consumption.

Effect of low-dose alcohol use versus abstention on apolipoproteins A-I and B

An inverse association between low to moderate alcohol consumption and coronary heart disease has been demonstrated in epidemiologic studies of diverse design. An attempt was made to determine if this association might be due to an effect of alcohol on apolipoproteins A-I and B and to determine if low-dose alcohol intake might have a potentially protective effect by this mechanism in persons at increased risk for coronary heart disease. To address this, an eight-week prospective randomized clinical trial of abstention versus low-dose alcohol consumption, defined as one beverage per day, was conducted in white men, aged 21 to 60 years, most of whom were patients of a preventive cardiology program. Apolipoprotein A-I levels had a mean increase of 9 mg/dl in the 28 participants who drank alcohol compared with a mean decline of 5 mg/dl in the 28 participants who abstained (p <0.005). This association was independent of other cardiovascular risk factors. Low-density lipoprotein (LDL)-B levels had a mean increase of 7 mg/dl in both arms of the trial (NS). However, the ratio of apolipoprotein A-I to LDL-B increased by 4 percent in the drinkers and decreased 10 percent in the abstainers (p <0.03). No significant changes in mean levels of total high-density lipoprotein (HDL)-, HDL 2-, or HDL 3-cholesterol were observed with this low dose of alcohol. This effect on apolipoprotein A-I suggests a possible mechanism by which low-dose alcohol may lower the risk of coronary heart disease.