Solid-state fermented Chinese alcoholic beverage (baijiu) and ethanol resulted in distinct metabolic and microbiome responses.

Alcoholic beverages, which are consumed widely in most parts of the world, have long been identified as a major risk factor for all liver diseases, particularly alcoholic liver disease (ALD). Recent compositional analyses suggest that Chinese baijiu (CB), a clear alcoholic liquid distilled from fermented grains, contains large amounts of small molecule bioactive compounds in addition to a significant amount of ethanol (EtOH). Here, in an experimental mouse model, we show that CB caused lower degrees of liver injury than pure EtOH by protecting against the decrease of the relative abundance of Akkermansia and increase of the relative abundance of Prevotella in the gut, thereby preventing the destruction of the intestinal barrier. Furthermore, we demonstrated that EtOH-induced alteration of the gut microbiota profoundly affected the host metabolome. Compared with EtOH feeding, CB feeding resulted in higher concentrations of functional saturated long-chain fatty acids and short-chain fatty acids. The additional mouse models of low dosages of EtOH and of blending baijiu validated that volatile compounds in CB can attenuate EtOH-induced liver damages. Our results provide supporting evidence that ALD was profoundly influenced by host-gut microbiota metabolic interactions and that small molecule organic compounds in CB could attenuate ALD.-Fang, C., Du, H., Zheng, X., Zhao, A., Jia, W., Xu, Y. Solid-state fermented Chinese alcoholic beverage (baijiu) and ethanol resulted in distinct metabolic and microbiome responses.

Energy drink and alcohol combination leads to kidney and liver alterations in rats.

The aim of this study was to evaluate the acute toxicity of the association of energy drink and alcohol in male Wistar rats. Animals were treated by oral gavage with 10 ml/kg distilled water (control); 10 ml/kg energy drink (ED10); 3.2 mg/kg caffeine + 40 mg/kg taurine; 2 g/kg alcohol 20%; 2 g/kg alcohol 20% + ED10; and 2 g/kg alcohol 20% + 3.2 mg/kg caffeine + 40 mg/kg taurine. Behavioral alterations were observed for 6 h after treatment. Animals presented significant differences in the frequency of rearing, ambulation, grooming, wakefulness and tachypnea along time. Caffeine + taurine increased the levels of TBARS and total thiols in kidneys. ED10 increased lipoperoxidation in liver. The association of ED10 + alcohol induced nephrotoxicity observed by the increase of urinary N-acetyl-ß-d-glucosaminidase (NAG) activity. Histopathological analysis showed the presence of congestion and hydropic and hyaline degenerations in the livers of ED10 + alcohol treated rats, and hemorrhage in the liver of alcohol + caffeine + taurine group. In kidneys, hyaline degeneration was observed in ED10; ED10 + alcohol; caffeine + taurine; and alcohol + caffeine + taurine. Hemorrhage was present in the kidneys of all groups. The combination of energy drinks and alcohol is not safe for the consumers. Therefore, precautionary measures should be disseminated among risk populations, especially the teenagers.

Evaluating the Intoxicating Degree of Liquor Products with Combinations of Fusel Alcohols, Acids, and Esters.

To investigate the effects of fusel alcohols on the intoxicating degree of liquor products, formulated liquors (FLs) were prepared by blending 1-propanol, isobutanol, and isoamyl alcohol with ethanol, organic acids, and corresponding ethyl esters to simulate the formula of traditional Chinese liquors. The prepared FLs were submitted for evaluation of their intoxicating degree (ID). The results showed that the fusel alcohols had a biphasic effect on the IDs of the FLs, depending on the comprehensive coordination of the characteristic minor components. The importance of the suitable ratio of alcohols/acids/esters (RAAE) on the IDs was also revealed. Under an optimal ratio level, the fusel alcohols exhibited negligible effects on the IDs of the FLs. Moreover, the ratio of isoamyl alcohol to isobutanol (IA/IB) showed a strong positive correlation to the IDs of the FLs. This study lays a foundation for the potential application in producing low-ID liquor.

Effects of co-exposure to atrazine and ethanol on the oxidative damage of kidney and liver in Wistar rats.

Both ethanol (EtoH) and atrazine (ATZ) have hepatic and nephro-toxic effects in rats. In the present study, the toxicity of EtoH (5 g kg-1) on the kidney and liver in the absence or in the presence of different doses of ATZ (50, 100, 300 mg kg-1) was evaluated after 21 days in rats. Results showed that the mixture effects on catalase and superoxide dismutase activities were more severe in both tissues compared to EtoH alone, especially as the dose of ATZ was increased. Hepatic malondialdehyde level (an index of lipid peroxidation) was increased from 20.32% in the EtoH +50 mg kg-1 ATZ-treated rats to 34% in the EtoH +300 mg kg-1 ATZ-treated rats compared to the EtoH values. Renal malondialdehyde values remain as high as 81% in the EtoH-treated rats and the different combine exposure groups. Furthermore, as the dose of ATZ in the mixture was increased, serum uric acid level increased compared to the EtoH values. When the EtoH +300 mg kg-1 ATZ-animals were pretreated with curcumin (an antioxidant), the histopathological changes and peroxidative damages in both tissues were blocked. The exposure of EtoH-treated rats to ATZ enhanced renal and hepatic peroxidative damages in rats.

Carcinogenic compounds in alcoholic beverages: an update.

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes.

A large volume of alcoholic beverages containing aliphatic alcohols is consumed worldwide. Previous studies have confirmed the presence of ethanol-induced immunosuppression in heavy drinkers, thereby increasing susceptibility to infectious diseases. However, the aliphatic alcohols contained in alcoholic beverages might also impair immune cell function, thereby contributing to a further decrease in microbicidal activity. Previous research has shown that aliphatic alcohols inhibit phagocytosis by granulocytes but their effect on human monocytes has not been studied. This is important as they play a crucial role in engulfment and killing of pathogenic microorganisms and a decrease in their phagocytic activity could lead to impaired antimicrobial defence in heavy drinkers. The aim of this study was to measure monocyte phagocytosis following their treatment with those aliphatic alcohols detected in alcoholic beverages. Monocytes were separated from human peripheral blood and phagocytosis of opsonized zymosan particles by monocytes treated with ethanol and aliphatic alcohols individually and in combination was determined. It was shown that these alcohols could suppress the phagocytic activity of monocytes in a concentration-dependent manner and when combined with ethanol, they caused a further decrease in phagocytosis. Due to their additive effects, it is possible that they may inhibit phagocytosis in a clinically meaningful way in alcoholics and episodic heavy drinkers thereby contribute to their increased susceptibility to infectious diseases. However, further research is needed to address this question.

Effects of wine, alcohol and polyphenols on cardiovascular disease risk factors: evidences from human studies.

AIMS: The aim of this review was to focus on the knowledge of the cardiovascular benefits of moderate alcohol consumption, as well as to analyze the effects of the different types of alcoholic beverages. METHODS: Systematic revision of human clinical studies and meta-analyses related to moderate alcohol consumption and cardiovascular disease (CVD) from 2000 to 2012. RESULTS: Heavy or binge alcohol consumption unquestionably leads to increased morbidity and mortality. Nevertheless, moderate alcohol consumption, especially alcoholic beverages rich in polyphenols, such as wine and beer, seems to confer cardiovascular protective effects in patients with documented CVD and even in healthy subjects. CONCLUSIONS: In conclusion, wine and beer (but especially red wine) seem to confer greater cardiovascular protection than spirits because of their polyphenolic content. However, caution should be taken when making recommendations related to alcohol consumption.

Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach.

Alcoholic beverages have been classified as carcinogenic to humans. As alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, a quantitative approach is necessary to compare the risks. Fifteen known and suspected human carcinogens (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, lead, 4-methylimidazole, N-nitrosodimethylamine, ochratoxin A and safrole) occurring in alcoholic beverages were identified based on monograph reviews by the International Agency for Research on Cancer. The margin of exposure (MOE) approach was used for comparative risk assessment. MOE compares a toxicological threshold with the exposure. MOEs above 10,000 are judged as low priority for risk management action. MOEs were calculated for different drinking scenarios (low risk and heavy drinking) and different levels of contamination for four beverage groups (beer, wine, spirits and unrecorded alcohol). The lowest MOEs were found for ethanol (3.1 for low risk and 0.8 for heavy drinking). Inorganic lead and arsenic have average MOEs between 10 and 300, followed by acetaldehyde, cadmium and ethyl carbamate between 1,000 and 10,000. All other compounds had average MOEs above 10,000 independent of beverage type. Ethanol was identified as the most important carcinogen in alcoholic beverages, with clear dose response. Some other compounds (lead, arsenic, ethyl carbamate, acetaldehyde) may pose risks below thresholds normally tolerated for food contaminants, but from a cost-effectiveness point of view, the focus should be on reducing alcohol consumption in general rather than on mitigative measures for some contaminants that contribute only to a limited extent (if at all) to the total health risk.

Methanol in unrecorded fruit spirits. Does it pose a health risk to consumers in the European Union? A probabilistic toxicological approach.

Methanol is present at high concentrations in unrecorded fruit spirits, placing consumers of these beverages at risk of exposure at high levels. When assessing any health risk it is necessary to consider blood methanol levels (BMLs), reference dose (RfD), and maximum tolerable blood methanol level (MTBML). The aim of our study was to estimate daily methanol intake and related BMLs attributable to drinking unrecorded fruit spirits in the European population using a probabilistic Monte Carlo simulation. Data on the concentration of methanol in unrecorded fruit spirits in European Union member states were collected and the health risk posed by consumption of unrecorded fruit spirits was estimated. We found that drinking unrecorded fruit spirits containing methanol at a concentration higher than 8598.1 mg/litre of pure alcohol (p.a.) or 6382.1 mg/litre of p.a. and also at least 10 g ethanol can result in a methanol intake above the RfD by men and women, respectively. We confirmed that consumption of unrecorded fruit spirits containing methanol does not result in BMLs higher than the MTBML. Further studies are required to assess whether there is any health risk from chronic exposure to methanol above the RfD from unrecorded fruit spirits.

Prospective study of alcohol use and hearing loss in men.

OBJECTIVE: Hearing loss is a common and disabling sensory disorder, yet prospective data on potentially modifiable risk factors are limited. Previous studies suggest that alcohol consumption may influence the development of hearing loss, yet results have been inconsistent. The purpose of this study was to prospectively examine the relation between alcohol use and hearing loss in men. DESIGN: We examined prospectively the independent association between alcohol intake and self-reported professionally diagnosed hearing loss in 26,809 men aged 40 to 74 yrs at baseline in 1986. Study participants completed detailed questionnaires at baseline and every 2 yrs thereafter. Incident cases of hearing loss were defined as those professionally diagnosed after 1986. Cox proportional hazards multivariate regression was used to adjust for potential confounding factors. RESULTS: During 386,081 person-years of follow-up, 3447 incident cases of hearing loss were reported. Overall, there was no association between level of alcohol intake and risk of hearing loss. Compared with those who did not consume alcohol, the multivariate-adjusted hazard ratios (95% confidence interval) were 1.00 (0.89 to 1.12) for those who consumed 5.0 to 9.9 g/day, 1.08 (0.96 to 1.21) for 10.0 to 14.9 g/day, and 0.98 (0.85 to 1.13) for 30.0 to 49.9 g/day. The results did not differ by age group or folate intake. Among those with lower intake of vitamin B12, however, higher consumption of alcohol, specifically liquor, was associated with an increased risk of hearing loss. CONCLUSIONS: Our data suggest that low or moderate alcohol consumption does not influence the risk of hearing loss in older men. A possible relation between vitamin B12 intake, alcohol consumption, and hearing loss merits further investigation.

The effects of beverage type on suicide rate in Russia.

BACKGROUND: Research evidence has suggested that the consumption of different types of alcoholic beverage may have a differential effect on suicide rate. The aim of this study was to examine the relation between the consumption of different beverage types and suicide rates in Russia. SUBJECTS AND METHODS: Age-standardized sex- and age-specific suicide rate for the period 1980-2005 and data on beverage-specific alcohol sale were obtained from the Russian State Statistical Committee. Time-series analytical modeling techniques (ARIMA) were used to examine the relationship between the sale of different alcoholic beverages and suicide rates. RESULTS: Vodka consumption as measured by sale was significantly associated with both male and female suicide rate. The consumption of beer and wine were not associated with suicide rate. The estimates of the age specific models for men were positive (except for the 75+ age group) and ranging from 0.069 (60-74 age group) to 0.123 (30-44 age group). The estimates for women were positive for the 15-29 age group (0.08), 30-44 age group (0.096) and 45-59 age group (0.057). CONCLUSIONS: These findings suggest that public health efforts should focus on both reducing overall consumption and changing beverage preference away from distilled spirits in order to reduce suicide rate in Russia.

Margin of Exposure Analyses and Overall Toxic Effects of Alcohol with Special Consideration of Carcinogenicity.

Quantitative assessments of the health risk of the constituents of alcoholic beverages including ethanol are reported in the literature, generally with hepatotoxic effects considered as the endpoint. Risk assessment studies on minor compounds such as mycotoxins, metals, and other contaminants are also available on carcinogenicity as the endpoint. This review seeks to highlight population cancer risks due to alcohol consumption using the margin of exposure methodology. The individual and cumulative health risk contribution of each component in alcoholic beverages is highlighted. Overall, the results obtained consistently show that the ethanol contributes the bulk of harmful effects of alcoholic beverages, while all other compounds only contribute in a minor fashion (less than 1% compared to ethanol). Our data provide compelling evidence that policy should be focused on reducing total alcohol intake (recorded and unrecorded), while measures on other compounds should be only secondary to this goal.

New insights into the impacts of huangjiu compontents on intoxication.

Although huangjiu is a popular alcoholic beverage in China, the occurrence of quick-intoxication suppresses huangjiu consumption and impedes development of the huangjiu industry. In this study, the Cryprinus carpio intoxication model was used to compare the differences in intoxication effect of alcoholic beverages and to assess the impacts of huangjiu components on intoxication for the first time. Exposure to huangjiu led to the most rapid physical imbalance of C. carpio, followed by red wine and Western liquor. Higher alcohols, biogenic amines and aldehydes could cause physical imbalance of fish by themselves, and synergistic effects were observed when combined with ethanol. 2-Phenylethanoland and isopentanol had the greatest positive effect on huangjiu intoxication, followed by histamine and phenethylamine. No synergistic effect was observed between individual aldehydes and ethanol. Identification of these impactful huangjiu components provides a new perspective on the establishment of more rigorous control on the quality and flavor of huangjiu.

[Impact of HBV infection and alcohol surrogates on the lipid composition of lymphocytic membranes].

Our study was undertaken to reveal the specific features of changes in the content of different fractions of total and lymphocytic membrane phospholipids under the influence of HBV infection and alcohol substitutes. The lipid spectrum of lymphocytic membranes was determined in 50 healthy individuals, 50 patients with acute viral hepatitis, and 62 patients with toxic hepatitis. Once HBV infection occurs, there is a reduction in the content of total phospholipids, free cholesterol, phosphatidylcholine, and phosphatidylethanolamine and an increase in the level of triglycerides, free fatty acids, cholesterol esters, and lysophospholipids. There was also a decrease in the absolute content of total phospholipids and free cholesterol. The effect of alcohol substitutes was manifested by the higher concentrations of lysophospholipids, phosphatidylcholine, and phosphatidylethanolamine in the lymphocytic membranes.

Neocortical plasticity deficits in fetal alcohol spectrum disorders: lessons from barrel and visual cortex.

Fetal Alcohol Spectrum Disorder (FASD) is characterized by a constellation of behavioral and physiological abnormalities, including learning and sensory deficits. There is growing evidence that abnormalities of neuronal plasticity underlie these deficits. However, the cellular and molecular mechanisms by which prenatal alcohol exposure disrupts neuronal plasticity remain elusive. Recently, studies with the barrel and the visual cortex as models to study the effects of early alcohol exposure on neuronal plasticity shed light on this subject. In this Mini-Review, we discuss the effects of ethanol exposure during development on neuronal plasticity and suggest environmental and pharmacological approaches to ameliorate these problems.

The role of acetaldehyde outside ethanol metabolism in the carcinogenicity of alcoholic beverages: evidence from a large chemical survey.

Acetaldehyde is a volatile compound naturally found in alcoholic beverages, and it is regarded as possibly being carcinogenic to humans (IARC Group 2B). Acetaldehyde formed during ethanol metabolism is generally considered as a source of carcinogenicity in alcoholic beverages. However, no systematic data is available about its occurrence in alcoholic beverages and the carcinogenic potential of human exposure to this directly ingested form of acetaldehyde outside ethanol metabolism. In this study, we have analysed and evaluated a large sample collective of different alcoholic beverages (n=1,555). Beer (9+/-7 mg/l, range 0-63 mg/l) had significantly lower acetaldehyde contents than wine (34+/-34 mg/l, range 0-211 mg/l), or spirits (66+/-101 mg/l, range 0-1,159 mg/l). The highest acetaldehyde concentrations were generally found in fortified wines (118+/-120 mg/l, range 12-800 mg/l). Assuming an equal distribution between the beverage and saliva, the residual acetaldehyde concentrations in the saliva after swallowing could be on average 195 microM for beer, 734 microM for wine, 1,387 microM for spirits, or 2,417 microM for fortified wine, which are above levels previously regarded as potentially carcinogenic. Further research is needed to confirm the carcinogenic potential of directly ingested acetaldehyde. Until then, some possible preliminary interventions include the reduction of acetaldehyde in the beverages by improvement in production technology or the use of acetaldehyde binding additives. A re-evaluation of the 'generally recognized as safe' status of acetaldehyde is also required, which does not appear to be in agreement with its toxicity and carcinogenicity.

Avoiding the ingestion of cytotoxic concentrations of ethanol may reduce the risk of cancer associated with alcohol consumption.

Alcohol consumption is a known risk factor for cancer. Almost 6% of all cancers worldwide are attributable to alcohol use. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the mutagenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear why alcohol consumption preferentially exerts a local carcinogenic effect. Recent findings indicate that the risk of cancer in a tissue is strongly correlated with the number of stem cell divisions accumulated by the tissue; the accumulation of stem cell divisions leads to the accumulation of cancer-promoting errors such as mutations occurring during DNA replication. Since cell death activates the division of stem cells, we recently proposed that the possible cytotoxicity of ethanol on the cells lining the tissues in direct contact with alcoholic beverages could explain the local carcinogenic effect of alcohol. Here we report that short-term exposures (2-3 s) to ethanol concentrations between 10% and 15% start to cause a marked cytotoxic effect on human epithelial keratinocytes in a concentration-dependent manner. We propose that choosing alcoholic beverages containing non-cytotoxic concentrations of ethanol, or diluting ethanol to non-cytotoxic concentrations, may be a simple and effective way to reduce the risk of cancers of the oral cavity, pharynx, larynx and esophagus in alcohol users. This preventive strategy may also reduce the known synergistic effect of alcohol drinking and tobacco smoking on the risk of these cancers.