A pharmacological dose of estradiol can enhance appetites for alcoholic beverages

Each of 30 female Sprague-Dawley rats were given 2 mg of estradiol valerate (EV), 30 others were given placebos. EV is a preparation that delivers estradiol for more than 12 days, but probably less than 20. Fifteen days later, the females had the opportunity to take sweetened alcoholic beverage 24 h a day across 25 days. Subsequently, they could self-administer other alcoholic beverages, including one of only alcohol and water. After a period of abstinence, rats had another opportunity to take sweetened alcoholic beverage (94 to 96 days after the single injection of EV). With every measurement, rats given EV consumed significantly more ethanol than controls. For example, mean of measurements representing daily intake for the fourth week of availability of palatable alcoholic beverage for placebo-treated=5.29 grams of ethanol per kilogram of bodyweight (g'E/kg); for EV-treated=8.13 g'E/kg; P=.003. The data support the conclusion that pharmacological doses of estradiol can induce marked, enduring changes in appetite for alcoholic beverages.     

Estradiol valerate and intake of sweetened water

Recently, it has been shown that female rats receiving very large doses (e.g., 2 mg) of estradiol valerate (EV) take considerably more alcoholic beverage than placebo controls. The question asked, with these procedures, is whether the enhanced appetite for alcoholic beverages was specific to those beverages or was a reflection of a general increase in appetite. Female rats were provided with various sweetened beverages. In one experiment, they were provided a palatable saccharin solution (0.25% solution) and a less palatable one (2% saccharin solution). EV treatment led to more intake of the palatable saccharin solution and reduced intake of the less palatable solution. EV induces changes leading to enhanced appetite for some ingesta (including palatable saccharin solutions and alcoholic beverages), but surely not all ingesta.     

Estradiol valerate and alcohol intake: dose-response assessments

Background

An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from.001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies.

Results

With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake.

Conclusion

The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries.     

Exposure-dependent effects of ethanol on serum estradiol and uterus mass in sexually mature oophorectomized rats: a model for bilaterally ovariectomized-postmenopausal women

Factors that may affect the estrogenization of postmenopausal women are important because estrogen levels may modulate the risk of osteoporosis and cardiovascular disease in postmenopausal women. Ethanol, a potential estrogenization factor, has received scant attention, particularly in postmenopausal women who are moderate users of alcoholic beverages. Because as many as 22.6% of postmenopausal women are reported to have had a bilateral oophorectomy, mature oophorectomized rats were used as a model. Low to moderate ethanol consumption was approximated by administering graded doses of ethanol in drinking water (0, 1.8, 3.7 or 5.5% ethanol, v/v) to 90 oophorectomized rats for 4 or 10 weeks. In rats exposed for 4 weeks, neither estradiol levels nor uterus weight differed among the four groups. In contrast, among rats exposed for 10 weeks, there was a significant positive correlation between ethanol dose and both uterus weight and estradiol; analysis of variance demonstrated that inclusion of the data obtained from rats receiving the 5.5% ethanol dose accounted for the significance of these associations. Based on these findings, it is suggested that, at least in oophorectomized rats, prolonged exposure to moderate ethanol doses is required to induce sufficient aromatization of androgens to produce detectable changes in plasma estradiol or in uterus weight. Further studies will be required to determine whether low or moderate alcoholic beverage use by postmenopausal women may result in biologically relevant increases in serum estradiol.     

Absence of a differential induction of cytochrome P450 2E1 by different alcoholic beverages in rats: implications for the aetiology of human oesophageal cancer

Alcohol is an important risk factor for human oesophageal cancer. There is evidence from epidemiological studies that some specific alcoholic drinks, e.g. Calvados apple brandy, are associated with a greater risk than others. Alcohol induces cytochrome P450 2E1 (CYP2E1) and the hypothesis was tested that different alcoholic beverages, containing a variety of alcoholic compounds, could differentially induce expression of cytochrome P450 enzymes. Twelve groups of five rats each were treated for 3 days with different alcoholic beverages (ethanol alone, whisky, farm-produced or commercial Calvados brandy, beer, cider, wine) adjusted to 4, 10 or 20% of ethanol in drinking water. Immunoblotting using a monoclonal antibody specific for rat CYP2E1 revealed a single protein band in liver microsomes. Densitometric quantitation of microsomal proteins demonstrated a significant two-, three- and sixfold increase in band intensity after treatment with ethanol concentrations of 4, 10 and 20% respectively, compared to control rats drinking water alone. There was a dose-dependent increase in liver microsomal metabolism of CYP2E1 substrates (para-nitrophenol and dimethylnitrosamine) in ethanol-treated rats. However, there were no significant differences in the level of CYP2E1 protein or enzymatic activity between the different alcoholic beverages at the same ethanol concentration. There was a slight increase in hepatic CYP1A-related enzymatic activities in the alcohol-treated rats compared to the controls, but no difference between the treated groups either with dose of ethanol or type of beverage. These data show that induction of CYP2E1 with acute alcohol treatment is predominantly determined by the ethanol content of the beverage. Received: 10 February 1997 / Accepted: 26 May 1997     

Agreement between two dietary methods in reported intake of beer, wine and liquor

This study compares reported beer, wine and liquor intake from a dietary quantity-frequency questionnaire and a 16-day diet diary kept by the same respondents in the 1984-85 University of Michigan Food Frequency Study. The study subjects were 228 black and white men and women, aged 24-51 years. On the two methods, the reported mean ethanol intake derived from each beverage, mean frequency of intake of each beverage and mean quantity for each beverage were similar. The relative rankings of individuals by the amount of ethanol for each beverage were also similar. The methods agreed less well on whether a particular beverage was ever consumed. The absolute amount of ethanol from each beverage agreed more closely between methods than did the percent of ethanol from each beverage. Results were similar for each race-sex subgroup. These findings suggest that analyses should use the reported amount of ethanol from each beverage, rather than converting to percentages or classifying according to the most used beverage. The good general agreement in the types and amounts of alcoholic beverages reported promotes some confidence in the relative validity of data from these two dietary methods for describing moderate alcohol intake in the general population.     

Beverage preference, beverage type and subject gender as determinants of alcohol consumption in the laboratory

Effects of beverage preference, beverage type and subject gender on ad libitum consumption of alcoholic beverages in the laboratory were evaluated. Undergraduate social drinkers (18 male, 18 female), with equal numbers of each gender stating a preference for beer, wine or mixed drinks, were selected. Subjects participated in three separate 30-minute ad lib drinking sessions and were presented with one of the three types of alcoholic beverage at each session. Data on total volume of beverage and of absolute ethanol consumed as well as blood alcohol concentration (BAC) attained were collected in each session. Subjects preferring wine or mixed drinks drank more alcohol and reached higher BACs when imbibing their beverage of choice than when drinking non-preferred beverages. Subjects preferring beer, however, showed no differences on these drinking measures as a function of beverage type. Men's reports of routine alcohol use had a high positive correlation with actual alcohol consumption observed in the laboratory, whereas for female subjects the correlation was near zero. Implications for interpretation of past ad lib drinking studies and the planning of future ones are discussed.     

Amlodipine, a calcium channel inhibitor, and cocaine and ethanol's reinforcing effects.

The effects of amlodipine (from 0.1 to 3.0 mg/kg) on rats' pressing for rewarding brain stimulation, with and without cocaine administration, were assessed. None of the doses reliably modified the effects of cocaine. Also, amlodipine was given to two groups of rats taking alcohol: one group that was regularly taking a sweetened alcoholic beverage and the other taking an unsweetened alcoholic beverage. The only discernible effects of amlodipine on alcohol intake were associated with the highest dose and only with rats taking the sweetened beverage. The effects of this high dose could easily be attributable to behavioral toxicity elicited by the dose. In contrast, and confirming previous work, isradipine, another calcium channel inhibitor, produced reliable reductions on both cocaine's and alcohol's reinforcing effects. Despite the similarity of isradipine and amlodipine, isradipine apparently has some unique features with respect to cocaine and alcohol.     

Effects of estradiol valerate on voluntary alcohol consumption, beta-endorphin content and neuronal population in hypothalamic arcuate nucleus

The main goal of the present experiment was to study the voluntary consumption of alcohol before and after a single injection of estradiol valerate (EV); another goal was to assess beta-endorphin (beta-EP) neurons and beta-EP peptide in hypothalamic arcuate nucleus 10 weeks after the injection of EV. Wistar female rats were injected either with a single 2.0 mg/rat injection of EV or with 0.2 ml of corn oil/rat (vehicle group). Two weeks before the injection and 10 weeks after it, every other day both groups were exposed to a free-choice alcohol drinking procedure. In weeks 4 and 5, the post-injection-consumption of alcohol was higher in the EV group than the vehicle group. In the EV group, food intake decreased and coincided with body weight lost in week 1 of post-EV injection. EV treated females showed significantly lower number of beta-EP neurons than control group (reduction of 51.22%); however, beta-EP content was similar in both groups, and they did not differ in the number of TSH and LHRH neurons. The present results suggest a positive relationship between high alcohol consumption and possible initial deficiency of beta-endorphin content. The transient increase in alcohol consumption suggests a possible compensatory secretory effect of the surviving beta-endorphinergic neurons, particularly when they are chronically stimulated with alcohol.     

Alcohol intake and nutrition]

This article contains summaries of our studies carried out at the society of the research "alcohol and health" with discussions on some related studies. Items included: (1) Discussions on "could alcoholic beverage regard as a nutrient?". (2) Nutrients in alcoholic bevarages. Distilled alcoholic beverages contain little nutrients except energy, while brewered alcoholic beverages contains nutritionally significant amounts of magnesium, niacin, and vitamin B2. (3) Dietary habits and alcoholics. Survey studies on researchers working at a brewing industry revieled that positive correlations were observed between intakes amounts of alcoholic beverages and intakes amounts of pulses, fishes, eggs, and seasonings and spices. While, negative correlations were observed between intake amount of confectioneries, fruits and daily products, and intake amount of alcohol. As nutrients, intakes of energy and sodium increased and intakes of dietary fibers, niacin, vitamin C, carotene, and zinc decreased in proportion to increase in alcoholic intakes. (4) Effect of alcohol intake on metabolism of nutrients. To clarify the influence of alcohol intake on nutrients metabolism, our research group carried out several animal experiments. Thiamin status evaluated by blood thiamin level and erythrocyte transketolase activity a thiamin dependent enzyme, decreased significantly by excess administration of alcohol. Effect of alcohol on metabolism of zinc, a cofactor of alcohol dehydrogenase, was not significant in our experiments, although other researchers reported that zinc metabolism was influenced by alcohol intake. In addition, we found that copper concentration in liver decreased significantly in alcohol administered rats as compared to control rats. The mechanisms concerning alcohol intakes on copper metabolism remains to be clarified.     

Acute and chronic effects of dinner with alcoholic beverages on nitric oxide metabolites in healthy men

1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NOx), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with four glasses of red wine, beer, spirits (Dutch gin) or sparkling mineral water (control) for 3 weeks. At the end of each 3 week period, serum NOx concentrations were measured just before and 1, 5 and 13 h after dinner. 3. Serum NOx concentrations were approximately 50% higher 1 and 5 h after dinner with any beverage compared with just before dinner (P = 0.0001). At 1 h after dinner, the serum NOx concentration was approximately 11% lower after dinner with alcoholic beverages compared with concentrations observed after dinner with water (P = 0.01). The fasted serum NOx concentration (13 h after dinner) was similar to the preprandial concentration and there were no differences in serum NOx concentrations between the alcoholic beverages. 4. Food intake acutely and transiently increased serum NOx concentrations, an effect that was slightly attenuated if combined with alcoholic beverages. Chronic moderate alcohol consumption had no effect on serum NOx concentration.     

Alcohol mixed with energy drink: Use may be a consequence of heavy drinking

AimsIn recent years, studies have indicated that consumers of alcohol mixed with energy drink (AmED) are more likely to drink heavily and experience more negative consequences than consumers who avoid these beverages. Although researchers have identified a number of plausible hypotheses that explain how alcohol-energy drink co-ingestion could cause greater alcohol consumption, there has been no postulation about reverse causal relations. This paper identifies several plausible hypotheses for the observed associations between AmED consumption and greater alcohol consumption, and provides initial evidence for one such hypothesis suggesting that heavy drinking may be a determinant of AmED use.MethodData collected from 511 bar patrons were used to examine the plausibility of one of the proposed hypotheses, i.e., AmED is an artifact of heavy drinking. Associations between the consumption of an assortment of alcoholic beverage types and total alcohol consumption were examined at the event-level, to assess whether AmED is uniquely related with greater alcohol consumption.ResultsIncreased alcohol consumption was associated with greater odds of consuming most alcoholic beverage types; this association was not unique to AmED.ConclusionsResults support the overlooked hypothesis that AmED use is an artifact of heavy drinking. Thus, AmED consumption may be a consequence or marker of heavier drinking. Much of the existing research on alcoholic beverage types is limited in its ability to implicate any specific type of drink, including AmED, as a cause of increased alcohol consumption and related harm. More rigorous study designs are needed to examine causal relationships.     

Europe. An Analysis of Changes in the Consumption of Alcoholic Beverages: The Interaction Among Consumption,Related Harms,Contextual Factors and Alcoholic Beverage Control Policies

This AMPHORA study's aim was to investigate selected factors potentially affecting changes in consumption of alcoholic beverages in 12 European countries during the 1960s–2008 (an average increase in beer, decreases in wine and spirits, total alcohol drinking decrease). Both time series and artificial neural networks-based analyses were used. Results indicated that selected socio-demographic and economic factors showed an overall major impact on consumption changes; particularly urbanization, increased income, and older mothers’ age at their childbirths were significantly associated with consumption increase or decrease, depending on the country. Alcoholic beverage control policies showed an overall minor impact on consumption changes: among them, permissive availability measures were significantly associated with consumption increases, while drinking and driving limits and availability restrictions were correlated with consumption decreases, and alcohol taxation and prices of the alcoholic beverages were not significantly correlated with consumption. Population ageing, older mother's age at childbirths, increased income and increases in female employment, as well as drink driving limitations were associated with the decrease of transport mortality. Study's limitations are noted.     

An inter-gender effect on ethanol drinking in rats: proximal females increase ethanol drinking in males

Three groups of male Long-Evans hooded rats were assessed for effects of social opportunity on drinking of ethanol or water. The ethanol/female group received intermittent presentations of a sipper containing ethanol that was followed by 15 s of social interaction opportunity with a female rat. The ethanol/male group received similar training except the social interaction opportunity was with a male rat. The water/female group received training similar to the ethanol/female group except that the sipper contained water. For the ethanol groups, the concentration of ethanol [3%, 4%, 6%, 8% and 10% (vol/vol)] in the sipper was increased across sessions. With 10% ethanol in the sipper, social opportunity with females induced more drinking and ethanol intake than did social opportunity with males. Social opportunity with females induced more intake of ethanol than water. Post-session plasma samples revealed social opportunity with females induced higher corticosterone and testosterone levels than did social opportunity with males, irrespective of the sipper fluid. This study documents, for the first time, an inter-gender effect on ethanol drinking in rats.     

Defining maximum levels of higher alcohols in alcoholic beverages and surrogate alcohol products

Higher alcohols occur naturally in alcoholic beverages as by-products of alcoholic fermentation. Recently, concerns have been raised about the levels of higher alcohols in surrogate alcohol (i.e., illicit or home-produced alcoholic beverages) that might lead to an increased incidence of liver diseases in regions where there is a high consumption of such beverages. In contrast, higher alcohols are generally regarded as important flavour compounds, so that European legislation even demands minimum contents in certain spirits. In the current study we review the scientific literature on the toxicity of higher alcohols and estimate tolerable concentrations in alcoholic beverages. On the assumption that an adult consumes 4 x 25 ml of a drink containing 40% vol alcohol, the maximum tolerable concentrations of 1-propanol, 1-butanol, 2-butanol, isobutanol, isoamyl alcohol and 1-hexanol in such a drink would range between 228 and 3325 g/hl of pure alcohol. A reasonable preliminary guideline level would be 1000 g/hl of pure alcohol for the sum of all higher alcohols. This level is higher than the concentrations usually found in both legal alcoholic beverages and surrogate alcohols, so that we conclude that scientific data are lacking so far to consider higher alcohols as a likely cause for the adverse effects of surrogate alcohol. The limitations of our study include the inadequate toxicological data base leading to uncertainties during the extrapolation of toxicological data between the different alcohols, as well as unknown interactions between the different higher alcohols and ethanol.     

Effects of self-administered alcohol or sucrose preloads on subsequent consumption in the rat

OBJECTIVE: The initial drink of alcohol is often conceptualized as "priming" the individual for the following drinking bout. For the alcoholic, this priming effect has been considered a key for the loss of control that then occurs. Although there have been a few animal studies examining the effects of an investigator-administered ethanol preload on subsequent ethanol self-administration, the effects of a small self-administered oral preload on subsequent consumption have not been examined. METHOD: Adult, male rats, initiated to self-administer ethanol using the sucrose-substitution procedure, were given brief access periods to drink ethanol or water, 5 minutes prior to a second opportunity to press a lever for an additional 20-minute access to a 10% ethanol solution. A second group of rats were trained to press a lever to gain access to a 3% sucrose solution, and the effects of sucrose or water preloads were examined and compared with results in the ethanol group. Results: In the ethanol group, both the ethanol and water preload intakes increased as preload access time increased and were not different from each other. However, ethanol preloads at the longer access times (60 seconds and 120 seconds) decreased subsequent ethanol consumption and at the highest time also affected ethanol-seeking behavior. Equal volumes of water intake at these longer access times had no effects on subsequent ethanol consumption. In the sucrose group, sucrose preload intakes increased as access time increased, but water preload intakes did not. Neither sucrose nor water preloads had any effect on subsequent sucrose consumption. CONCLUSIONS: The data failed to find any priming effect of ethanol preloads in terms of increased subsequent ethanol consumption. It appears that a major factor in the regulation of ethanol intake for the rat in this training procedure is the postingestional effects of ethanol, because taste stimuli did not appear to be important. However, it appears that these ethanol postingestive stimuli are not identical to those involved in the regulation of sucrose consumption.     

The detection of flunitrazepam in beverages using portable Raman spectroscopy

Portable Raman spectroscopy has been used for the detection of the date‐rape drug flunitrazepam in spiked beverages that may be involved in cases of drug‐facilitated sexual assault. Solutions of flunitrazepam with different concentrations were prepared in water and for each beverage type. Although some bands attributable to the beverage matrix are present, they did not interfere with the identification of the drug. Definitive evidence for contamination of the spiked drink concerned can be acquired within 10 s. The data can be acquired in situ and sample extraction and/or preparation steps are unnecessary. The ability of portable Raman spectrometers to interrogate spiked alcoholic beverages with flunitrazepam has been demonstrated. Copyright © 2016 John Wiley & Sons, Ltd.     

Alcoholic beverages in acute porphyria.

Alcohol consumption habits and the clinical consequences of intake of alcoholic beverages were examined in 254 individuals with a diagnosis of acute intermittent porphyria or variegate porphyria, using a questionnaire. The study failed to demonstrate a connection between the amount of ethanol consumed, or the frequency of ingestion, and the development of symptoms of acute porphyria, other than in extreme consumption patterns. It was concluded that agents in alcoholic beverages other than ethanol play important roles in precipitating the porphyric symptoms. A majority of the individuals were able to identify alcoholic beverages that were less well tolerated and those that were better tolerated. The results suggest that polyphenolic compounds and 3 to 5 carbon chain hydrophobic alcohols may be responsible for the induction of clinical symptoms in acute porphyria by some alcoholic beverages. On the basis of these findings advice is proposed on alcohol counseling in inducible porphyria.     

Alcoholic beverages as a source of estrogens

Alcoholic beverages contain not only alcohol but also numerous other substances (i.e., congeners) that may contribute to the beverages' physiological effects. Plants used to produce alcoholic beverages contain estrogenlike substances (i.e., phytoestrogens). Observations that men with alcoholic cirrhosis often show testicular failure and symptoms of feminization have suggested that alcoholic beverages may contain biologically active phytoestrogens as congeners. Biochemical analyses have identified several phytoestrogens in the congeners of bourbon, beer, and wine. Studies using subjects who produced no estrogen themselves (i.e., rats whose ovaries had been removed and postmenopausal women) demonstrated that phytoestrogens in alcoholic beverage congeners exerted estrogenlike effects in both animals and humans. Those effects were observed even at moderate drinking levels.     

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.