Ketone bodies as markers for Type 1 (insulin-dependent) diabetes and their value in the monitoring of diabetic control

Summary Serum levels of acetoacetate, 3-hydroxybutyrate and the 3-hydroxybutyrate/acetoacetate ratio were determined in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients by a new sensitive method. Efforts were made to differentiate Type 1 and Type 2 diabetes by serum levels of ketone bodies and to determine whether their measurement is a useful way of monitoring diabetic control. In Type 2 diabetes, serum levels of total ketone bodies did not exceed 2.0 mmol/l even if the patients were untreated or poorly controlled. In Type 1 diabetic subjects, treated with once or twice daily injections of insulin, morning serum levels of acetoacetate, 3-hydroxybutyrate and total ketone bodies were significantly elevated by four-, ten- and sevenfold, respectively. In Type 2 diabetic subjects treated with diet or sulphonylureas, serum levels of 3-hydroxybutyrate were highest before breakfast, next highest before dinner and decreased after each meal. The changes were roughly inversely proportional to serum insulin levels. In addition, insulin treatment normalized fasting serum levels of ketone bodies better than diet or sulphonylurea treatment. Acetoacetate was also significantly increased in both types of diabetes to a lesser extent, but no apparent diurnal rhythm was observed. Determination of serum levels of ketone bodies is useful for the diagnosis of Type 1 diabetes (those with total ketone bodies > 2 mmol/l) and for detecting insufficient insulin therapy.     

The effect of glucose and insulin infusion on the fall of ketone bodies during treatment of diabetic ketoacidosis

During the treatment of diabetic ketoacidosis intravenous glucose is infused when blood glucose has fallen to around 14 mmol l-1. The use of hypertonic (10%) glucose has been recommended in order to hasten the clearance of blood ketone bodies. In a randomized controlled study 17 patients presenting with severe diabetic ketoacidosis were allocated to one of two regimens of intravenous glucose and insulin when blood glucose had fallen to less than 14 mmol l-1. Nine patients were given 5% glucose containing 10 U l-1 insulin and 8 patients received 10% glucose with 40 U l-1 insulin. Fluid was infused at a rate of 250 ml h-1 for 6 h. At the start of the infusions blood glucose had fallen from levels at presentation to 12.8 +/- 1.1 mmol l-1 (mean +/- SE) in the group which subsequently received the low infusion rate and to 13.7 +/- 0.9 mmol l-1 in the subsequent high infusion rate group. With glucose/insulin infusion blood glucose after 6 h was 11.5 +/- 0.9 mmol l-1 (low infusion rate group) and 15.7 +/- 1.3 mmol l-1 (high infusion rate group). This difference between groups at 6 h was significant (p less than 0.05). Over the 6 h of infusion the fall in blood total ketone bodies was significantly greater in the group receiving the higher rate of glucose/insulin infusion (7.34 +/- 0.57 vs 5.18 +/- 0.57 mmol l-1; p less than 0.05). Despite the greater fall in total ketone bodies in this group there was no difference in the improvement in capillary blood pH or bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ketone body kineticsin vivo using simultaneous administration of acetoacetate and 3-hydroxybutyrate labelled with stable isotopes

Summary Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single¹⁴C tracer and the so called ‘combined KB specific activity’. By definition, this approach does not allow to evaluate the individual kinetics of acetoacetate (AcAc) and 3-hydroxybutyrate (R-BHB) which is feasible only using the separate administration of¹⁴C tracer AcAc and R-BHB. In the present study we followed a different approach using the simultaneous administrationin vivo of [1,2,¹³C₂] AcAc and m [1,2,3,4¹³C₄] R-BHB which allows to evaluate the individual kinetics of the two KB in the some study, thus minimizing the magnitude of blood sampling and the potential changes in the metabolic conditions of each subject. The four isotopic¹³C/¹²C KB ratios of AcAc and R-BHB tracer and tracee blood concentrations along with the fluorimetric measurement of¹²C concentrations were determined in each blood sample. Using compartmental analysis following single dose bolus injection the production rate of KB was 206 ± 57 μmol/min/1.73 m² (mean ± SD). The turnover rate of KB using noncompartmental analysis, during continuous infusion in a separate study was 294 ± 41. The plasma clearance rates of AcAc and R-BHB were 1966 ± 502 and 1443 ± ml/min/1.73 m², respectively. The mean residence time was 17 ± 3 min and the total distribution volume 20 ± 9.7 1/m². We conclude that: (1) stable isotope tracer infusion allows the contemporaryin vivo administration of the two KB and the simultaneous assessment of individual AcAc and R-BHB kinetics; (2) the estimated compartmental and noncompartmental parameters of KB turnover were similar to those observed in normal overnight fasting subjects following separate radioactive tracer injections. This study was partially supported by CNR grant n^o 840084904 and by a grant from theMinistero della Pubblica Istruzione, Rome, Italy.     

Survey data need not underestimate alcohol consumption

BACKGROUND: There are two main ways to assess alcohol consumption in a population: per capita estimates, usually derived from data on taxable alcohol available for consumption, and population-based surveys. Population-based survey estimates of alcohol consumption are often compared with estimates based on taxable alcohol available for consumption as a measure of validity. Discrepancies between these two measures occur, with the majority of population-based surveys substantially underestimating taxable alcohol available for consumption. METHODS: This article argues, however, that high proportions of taxable alcohol available for consumption can be accounted for by population-based surveys and reports a method of data collection for a national alcohol survey that has accounted for 94% of the taxable alcohol in New Zealand. RESULTS: The ability of the survey methodology to account for this proportion of taxable alcohol is likely due to the within-location beverage-specific alcohol consumption measures used in the survey, the process of recording the quantity of alcohol consumed, the use of a computer-assisted telephone interview system, and the population coverage achieved. CONCLUSIONS: Population-based surveys using the methodology outlined in this article may account for, if not exceed, the high proportions of taxable alcohol available for consumption estimates for some populations.     

Ketone bodies increase glomerular filtration rate in normal man and in patients with Type 1 (insulin-dependent) diabetes mellitus

Summary The purpose of this study was to investigate whether the administration of acetoacetic and hydrochloric acids in a group of control and Type 1 (insulin-dependent) diabetic patients influenced renal haemodynamics. Renal plasma flow increased from 657±88 to 762±81 ml·min^–1. 1.73 m^–2 in diabetic patients (p<0.01) and from 590±71 to 691±135 in control subjects (p<0.01). Glomerular filtration rate increased from 135±9 to 180±8 ml·min^–1·1.73 m^–2 in diabetic patients (p< 0.001) and from 117±8 to 145±7 in control subjects (p<0.01). Similar effects on renal haemodynamics, even if less pronounced, were observed with low dose acetoacetic but not with hydrochloric acid infusion. Total protein, 2-microglobulin but not albumin excretion rates were increased by acetoacetic acid. We conclude that an acute increase in blood concentration of ketone bodies within the range found in diabetic patients with poor metabolic control (1) increases renal plasma flow and glomerular filtration rate both in control subjects and diabetic patients and (2) causes a tubular proteinuria.     

Influence of ketone bodies on oxidative stress parameters in brain of developing rats in vitro

Pro-oxidant and antioxidant properties have been found for acetoacetate (AcAc) and β-hydroxybutyrate (BHB) in peripheral tissues. In the present study we investigated the role of AcAc and BHB at concentrations found in diabetic patients during ketoacidotic crises and in individuals affected by succinyl CoA: 3-oxoacid CoA transferase and acetoacetyl-CoA thiolase deficiencies, disorders clinically characterized by neurological symptoms, on a large number of oxidative stress parameters in fresh cerebral cortex of developing rats. Lipid peroxidation (chemiluminescence and thiobarbituric acid–reactive substances levels), protein oxidative damage (carbonyl formation and sulfhydryl oxidation), 2′,7′-dichlorofluorescin diacetate oxidation and the non-enzymatic (total antioxidant reactivity and glutathione levels) and enzymatic (glutathione peroxidase, superoxide dismutase and catalase activities) antioxidant defenses were not changed by doses of BHB and AcAc as high as 25 mM in cortical supernatants under basal conditions. Furthermore, BHB did not affect the increased thiobarbituric acid–reactive substances levels provoked by 3-hydroxy-3-methylglutaric and 3-methylglutaconic acids and by a hydroxyl-induced generation system. Finally, BHB and AcAc were not able to oxidize sulfhydryl groups from a commercial GSH solution. Therefore, under basal conditions or under situations with high production of free radicals, AcAc and BHB were not able to reduce or increase the oxidative stress parameters in the brain. Taken together, our present results do not support the hypothesis that BHB and AcAc act as potent direct or indirect pro-oxidants or antioxidants in the CNS.     

Ethnic differences in positive alcohol expectancies during childhood: the Pittsburgh Girls Study

Background: Positive expectancies about alcohol’s effects are more likely to be endorsed with increasing age through adolescence, and the strength of positive alcohol expectancies in children appears to differ by ethnicity. Little is known about the extent to which differences in a measure’s psychometric properties as a function of development and ethnicity may account for changes that are observed over time and ethnic differences. This study used measurement invariance methods to examine ethnic differences in the development of alcohol expectancies, and examined risk factors associated with girls’ positive expectancies. Methods: African‐American (56%) and Caucasian (44%) girls (n = 570) in the age 7 cohort of the Pittsburgh Girls Study, and the girl’s primary caretaker, were followed annually for 4 years (ages 7–10). Girls reported on alcohol expectancies at each wave, and physical aggression at Year 1. In Year 1, caretakers reported on neighborhood drug use, their own substance‐related problems, and depression in the girl. Structural equation modeling was used to examine measurement invariance of positive alcohol expectancies, and to test associations of risk factors to initial level and change in expectancies. Results: Five of 8 positive alcohol expectancy items showed measurement equivalence for African‐American and Caucasian girls in cross‐sectional, but not longitudinal, analyses. Measurement equivalence over ages 7–10 was demonstrated for Caucasian girls, and over ages 7–8 and 9–10 (i.e., a two‐part model) for African‐American girls. Risk factor analyses indicated that, for Caucasian girls, greater physical aggression was associated with higher initial positive expectancies. Conclusions: Some developmental change and ethnic differences in the performance of positive expectancy items were identified, highlighting the utility of measurement invariance methods. Risk factor analyses suggest the potential benefit of targeted alcohol prevention interventions for certain girls.     

Socio-economic status and problem alcohol use: the positive relationship between income and the DSM-IV alcohol abuse diagnosis

AIMS: Epidemiological evidence indicates a positive relationship between income and the prevalence of alcohol abuse in the general population, but an inverse relationship between income and alcohol dependence. Among those with a diagnosis of alcohol abuse, the most prevalent criterion is hazardous use, which commonly requires sufficient resources to own or access a car. The present study investigated whether the association between income and the prevalence of current alcohol abuse is accounted for by the hazardous use criterion; specifically, the drinking and driving symptoms of the hazardous use criterion. DESIGN: Face-to-face survey conducted in the 2001-02 National Epidemiologic Survey on Alcohol and Related Conditions, interviewed with the Alcohol Use Disorders and Associated Disabilities Interview 4th edition (AUDADIS-IV). SETTING: The United States and District of Columbia, including Alaska and Hawaii. PARTICIPANTS: Household and group-quarters residents aged >18 years. Life-time dependence cases were excluded (n = 4781). MEASUREMENTS: Income was defined as past-year personal income. Outcomes were specific alcohol abuse criteria and symptom questions. Logistic regressions were performed controlling for demographics. The relationship between alcohol abuse severity indicators and income was modeled using polytomous regression. Findings Among the alcohol abuse criteria, hazardous use is the most prevalent and the only criterion to have a significant positive relationship with income (F = 20.3, df = 3, P < 0.0001). Among the hazardous use symptoms, driving after drinking (F = 13.0, df = 3, P < 0.0001) and driving while drinking (F = 9.2, df = 3, P < 0.0001) were related positively to income. CONCLUSIONS: Because hazardous use is the most commonly endorsed criterion of alcohol abuse, the link with income raises questions about whether the current alcohol abuse diagnosis can capture the full range of alcohol abusers in every socio-economic class. While many psychiatric disorders exhibit an inverse relationship with socio-economic status, a selection bias may cause the alcohol abuse diagnosis to have an artificially positive relationship with income due to the necessity for access to a vehicle to be diagnosed.     

Decreased incidence of venous thromboembolism found in trauma patients with positive blood alcohol concentration on admission

Background: The reported incidence of venous thromboembolism (VTE) disease in trauma is 1–58% and is considered a preventable cause of mortality. Positive blood alcohol concentration (BAC) is found in 8–45% of trauma admissions; however, its association with VTE is controversial.

Objectives: We hypothesized that a positive BAC on admission would be associated with a lower rate of VTE in a large national database of trauma patients.

Methods: We queried the largest United States trauma registry, National Trauma Data Bank (2007–2015), for any patient with positive BAC on admission. The primary outcome was VTE and the secondary outcome was mortality. A multivariable logistic regression model was used for analysis.

Results: From 2,725,032 patients (70.1% male, 29.9% female), 1,800,216 (66.1%) had a negative BAC while 924,816 (33.9%) had a positive BAC. A positive BAC was associated with lower rates of VTE (OR = 0.88, CI = 0.86–0.90, p < 0.001) and mortality (OR = 0.91, CI = 0.90–0.93, p < 0.001).

Conclusion: In a large national database, trauma patients with a positive BAC were associated with a lower rate of VTE compared to those with negative BAC. Additionally, trauma patients with positive BAC had a lower association with mortality. These findings remained after adjustment of well-known risk factors for VTE and mortality, respectively.     

Polyenylphosphatidylcholine protects against alcohol but not iron-induced oxidative stress in the liver

BACKGROUND: We reported before that, in baboons, the alcohol-induced oxidative stress in the liver is associated with depletion of dilinoleoylphosphatidylcholine [the major component of polyenylphosphatidylcholine (PPC)] and that both can be corrected by the administration of PPC, but we did not determine whether this protection extended to iron-induced oxidative stress. METHODS: To compare the effects of PPC on alcohol- and iron-induced hepatic oxidative stress, 56 Sprague Dawley male rats were pair-fed nutritionally adequate liquid diets containing ethanol (36% of energy) or isocaloric carbohydrate and PPC (3 mg/ml) or safflower oil (2.73 mg/ml), with or without 5 mg/ml carbonyl iron for 2 months. Markers of oxidative stress (4-hydroxynonenal and reduced glutathione), antioxidants (vitamin E, ubiquinol-9, and ubiquinol-10), and phosphatidylcholine (PC) species were assessed by HPLC and/or gas chromatography/mass spectrometry. RESULTS: Alcohol feeding increased hepatic 4-hydroxynonenal 3-fold and decreased glutathione by 19%, ubiquinol-10 by 53%, and PC species containing arachidonate (palmitoyl- and stearoylarachidonoylphosphatidylcholines by 24% and 21%, respectively) and total phospholipids by 14%. PPC feeding prevented the rise of 4-hydroxynonenal, restored glutathione, and increased the hepatic content of dilinoleoylphosphatidylcholine and of some other PC carrying polyunsaturated fatty acids. Administration of iron alone increased hepatic iron, doubled 4-hydroxynonenal and glutathione, whereas it decreased vitamin E, ubiquinol-9, total phospholipids, and several polyunsaturated PC. Alcohol given with iron further exacerbated the hepatic oxidative stress, as documented by the increase of 4-hydroxynonenal and the decrease in glutathione and ubiquinols-10. PPC did not prevent this oxidative stress, although it increased hepatic glutathione. Hepatic dilinoleoylphosphatidylcholine content was comparable with and without dietary iron. CONCLUSIONS: PPC prevents the alcohol-induced oxidative stress but only in the absence of iron overload.     

Estimating driver risk using alcohol biomarkers,interlock blood alcohol concentration tests and psychometric assessments: initial descriptives

Aim To identify alcohol biomarker and psychometric measures that relate to drivers' blood alcohol concentration (BAC) patterns from ignition interlock devices (IIDs). Design, setting, participants, measurements In Alberta, Canada, 534 drivers, convicted of driving under the influence of alcohol (DUI), installed IIDs and agreed to participate in a research study. IID BAC tests are an established proxy for predicting future DUI convictions. Three risk groups were defined by rates of failed BAC tests. Program entry and follow‐up blood samples (n = 302, 171) were used to measure phosphatidyl ethanol (PETH), carbohydrate deficient transferrin (%CDT), gamma glutamyltransferase (GGT) and other biomarkers. Program entry urine (n = 130) was analyzed for ethyl glucuronide (ETG) and ethyl sulphate (ETS). Entry hair samples were tested for fatty acid ethyl esters (FAEE) (n = 92) and ETG (n = 146). Psychometric measures included the DSM‐4 Diagnostic Interview Schedule Alcohol Module, Alcohol Use Disorders Identification Test (AUDIT), the time‐line follow‐back (TLFB), the Drinker Inventory of Consequences (DRINC) and the Temptation and Restraint Inventory (TRI). Findings Except for FAEE, all alcohol biomarkers were related significantly to the interlock BAC test profiles; higher marker levels predicted higher rates of interlock BAC test failures. PETH, the strongest with an overall analysis of variance F ratio of 35.5, had significant correlations with all nine of the other alcohol biomarkers and with 16 of 19 psychometric variables. Urine ETG and ETS were correlated strongly with the IID BAC tests. Conclusions The findings suggest that several alcohol biomarkers and assessments could play an important role in the prediction and control of driver alcohol risk when re‐licensing.     

An acute psychosocial stressor does not potentiate alcohol cue reactivity in non-treatment-seeking alcoholics

Background: Relapse risk factors, such as psychological stress and alcohol cues, are often encountered together. Understanding how they interact has the potential to improve alcoholism treatments. This study was conducted to examine whether an acute psychosocial stressor enhanced alcohol cue reactivity in non‐treatment‐seeking alcoholics. Methods: Seventy‐nine alcohol‐dependent individuals (39 women) randomly received either the Trier Social Stress Test or a no‐stress control condition. Stress reactivity was measured with serum adrenocorticotropic hormone and cortisol, mean arterial blood pressure, and subjective distress. Immediately following the stress manipulation, participants held and sniffed a neutral cue then their preferred alcoholic beverage. Cue reactivity was measured by 2 subjective measures of craving following each cue. Additionally, general craving was assessed with the Alcohol Urge Questionnaire at the beginning and end of the laboratory procedure. Results: The stress manipulation showed internal validity on all measures of stress reactivity. There was not a main effect of stress nor a stress × cue interaction on either cue reactivity measure. As expected, there was a main effect of cue (alcohol > neutral cue) on both measures of cue reactivity. General craving increased during the challenge, but not differently by stress group. Magnitude of stress reactivity was not associated with magnitude of cue reactivity, and all results were independent of gender. Conclusion: In this well‐controlled clinical laboratory study of non‐treatment‐seeking alcoholics, an acute psychological stressor did not make an alcohol cue a more potent urge‐inducing stimulus, and stress had no effect on general alcohol craving.     

How much alcohol do you buy? A comparison of self‐reported alcohol purchases with actual sales

Background Unrecorded alcohol has increased in the Nordic countries during recent years, above all in terms of cross‐border trade. This implies that trends and levels of per capita consumption would look different without estimates of this source of alcohol, estimates that in Sweden and other countries are made through surveys. Aim The overall aim is to analyse the validity of Swedish survey estimates of alcohol bought in the cross‐border trade and possibly to develop weights that can be applied to such estimates. Data and method The analysis consists of comparing self‐reported purchases of spirits, wine, cider/alcopops and beer at retail monopoly (Systembolaget) during 2008 (n = 18 000) with actual sales during the same period overall and monthly. Findings Of the recorded amount of purchases at Systembolaget, 87% was reported in the survey, compared with the 40–60% usually found for self‐reported consumption. Significant differences across beverages were revealed, showing a lower coverage rate for beer and spirits and a higher coverage rate for wine and cider. Changes in purchases of all beverages were captured fairly well, at least changes taking place from one month to another. Conclusions Self‐reported alcohol purchases achieve a higher coverage rate than found typically in studies based on self‐reported use of alcohol. If adjustments are to be made to correct for underreporting in self‐reported data on alcohol purchases, different weights should be applied to different beverages. Furthermore, at least major changes in how much alcohol is purchased in the population can be monitored using well‐designed population surveys.     

An international legal strategy for alcohol control: not a framework convention—at least not yet

Aims The perceived success of the Framework Convention on Tobacco Control (FCTC) in influencing national and global public health policies has led to growing interest in promulgating new international legal instruments to address global health issues—including calls for a Framework Convention on Alcohol Control (FCAC). Methods Despite broad support in the public health community, the authors caution that an analysis of the value of lawmaking for alcohol control cannot rest solely on the character of the underlying public health challenge and the similarities between alcohol control and tobacco control. Other factors must be considered, including the relative political feasibility for global health lawmaking. The potential contribution of non‐binding international legal instruments to advancing global alcohol control, in particular, deserves strong consideration. Results The authors propose a gradual international legal strategy for alcohol control, starting with a non‐binding code of practice focusing on areas of critical concern with wide political consensus, leading over time to a comprehensive binding treaty. Although often dismissed as ineffective relative to treaties, non‐binding international legal instruments have particular strengths and can create both norms and processes that impact the behavior of states and other actors, overcoming a number of limitations of more rigid legally binding strategies. Conclusions Ultimately, the authors contend that the negotiation and adoption of a non‐binding international legal instrument as a first step in a long‐run legal strategy offers a more politically realistic, and potentially superior, alternative to immediate efforts to achieve a Framework Convention on Alcohol Control.     

Protective effect of alcohol consumption for fatty liver but not metabolic syndrome

AIM:To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women.METHODS:A cross-sectional study was conducted in a medical health checkup program at a general hospital.This study involved 18 571 Japanese men and women,18-88 years of age,with a mean body mass index of 22.6 kg/m 2.A standardized questionnaire was administered.The total amount of alcohol consumed per week was calculated,and categorized into four grades.Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Educa-tion Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation.RESULTS:The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption,whereas the prevalence of MS was not so changed.The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption.In women with light to moderate alcohol consumption,prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption.By logistic regression analysis,the odds ratio (OR) for MS in women with light alcohol consumption was decreased to 1.0,but this change was not clear in men.The OR for fatty liver was clearly 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption.CONCLUSION:Light to moderate alcohol consumption has a favorable effect for fatty liver,but not for MS in Japanese men and women.     

Kudzu extract treatment does not increase the intoxicating effects of acute alcohol in human volunteers

Background: Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol‐abusing and alcohol‐dependent men. The precise mechanism of this action is unknown, but 1 possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol’s effects and thus delay the desire for subsequent drinks. This study was designed to test this hypothesis. Methods: Twelve (12) healthy adult men and women (27.5 ± 1.89 years old) who consumed moderate amounts of alcohol (7.8 ± 0.63 drinks/wk) participated in a double‐blinded, placebo‐controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/d) or matched placebo for 9 days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges, the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. Results: Alcohol resulted in a dose‐related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants’ subjective responses to the alcohol challenge or to alcohol’s effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10–15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. Conclusions: These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences, and furthermore the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol’s subjective or psychomotor effects.     

Laboratory tests for acute alcohol consumption: results of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence

BACKGROUND: The WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence aimed partly to evaluate the overall performance and cross-national validity of traditional and new biological markers of alcohol use and abuse. This article focused on the sensitivity and specificity of ethanol and methanol concentrations in plasma, and the 5-hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) ratio in urine, as laboratory tests to identify acute alcohol consumption. Comparison was made with self-reported drinking levels. METHODS: Subjects were recruited in Australia, Brazil, Canada, Finland, and Japan. They were interviewed thoroughly about their alcohol consumption habits, by using the standardized WHO/ISBRA Interview Schedule, and were classified into four categories: nondrinkers, light/moderate drinkers, heavy drinkers (> or =210 g ethanol/week for men, and > or =140 g/week for women), or patients who were receiving treatment for alcohol dependence. Ethanol and methanol determinations in plasma were carried out by headspace gas chromatography. Urinary concentrations of 5HTOL and 5HIAA were determined by using gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively. RESULTS: The baseline levels (in nondrinkers) for methanol and the 5HTOL/5HIAA ratio did not differ markedly between the five populations, except for a considerably higher, but probably artifactual, methanol level in the Finnish plasma samples. Moreover, there were no apparent age or sex differences. The urinary 5HTOL/5HIAA ratio was the most, and ethanol the least, sensitive indicator of recent alcohol consumption, and this was true for the different drinking categories as well as for the five study populations. The highest frequency of elevated test results was observed among those classified as heavy drinkers (e.g., 38% were positive for 5HTOL/5HIAA). However, elevated values also were obtained in nondrinkers and in drinking subjects who denied any intake of alcohol within 2 days before the interview and blood/urine sampling, which suggested a low accuracy of self-reports of alcohol consumption in certain individuals. CONCLUSIONS: The present investigation demonstrated that plasma ethanol and methanol and urinary 5HTOL/5HIAA provide useful exclusion markers for any study of biological parameters that are affected by previous acute ethanol intoxication. The major advantage of methanol and 5HTOL/5HIAA over ethanol is that they can detect recent alcohol consumption even several hours after the ethanol is no longer measurable. The results suggest that the cutoff limits to be used for these markers are not dependent on the country or population to be studied.