Fotis Kanteres

The more you drink, the harder you fall: a systematic review and meta-analysis of how acute alcohol consumption and injury or collision risk increase together.

Alcohol consumption causes injury in a dose-response manner. The most common mode of sustaining an alcohol-attributable injury is from a single occasion of acute alcohol consumption, but much of the injury literature employs usual consumption habits to assess risk instead. An analysis of the acute dose-response relationship between alcohol and injury is warranted to generate single occasion- and dose-specific relative risks. A systematic literature review and meta-analysis was conducted to fill this gap. Linear and best-fit first-order model were used to model the data. Usual tests of heterogeneity and publication bias were run. Separate meta-analyses were run for motor vehicle and non-motor vehicle injuries, as well as case-control and case-crossover studies. The risk of injury increases non-linearly with increasing alcohol consumption. For motor vehicle accidents, the odds ratio increases by 1.24 (95% CI: 1.18-1.31) per 10-g in pure alcohol increase to 52.0 (95% CI: 34.50-78.28) at 120 g. For non-motor vehicle injury, the OR increases by 1.30 (95% CI: 1.26-1.34) to an OR of 24.2 at 140 g (95% CI: 16.2-36.2). Case-crossover studies of non-MVA injury result in overall higher risks than case-control studies and the per-drink increase in odds of injury was highest for intentional injury, at 1.38 (95% CI: 1.22-1.55). Efforts to reduce drinking both on an individual level and a population level are important. No level of consumption is safe when driving and less than 2 drinks per occasion should be encouraged to reduce the risk of injury.

Causal considerations on alcohol and HIV/AIDS--a systematic review.

AIM The study aimed to explore the possible causal nature of the association between alcohol consumption and HIV/AIDS. METHODS A review based on meta-analyses and reviews was conducted according to standard epidemiological criteria to distinguish causality from association, examining (i) the potential impact of alcohol on the incidence of HIV and (ii) alcohols impact on worsening the disease course. RESULTS In terms of incidence of HIV, although we found a consistent and strong association with consumption, there was not enough evidence for a causal connection. In particular, it is not clear whether personality traits such as sensation seeking or sexual compulsivity and psychiatric disorders such as antisocial personality disorder impact both alcohol consumption and risky sex, subsequently creating an association between both behaviors. In terms of worsening the disease course of HIV/AIDS, we found enough evidence for a causal impact of alcohol. Alcohol affects the immune system, thus contributing to a worsened course of HIV/AIDS. In addition, alcohol negatively impacts on behaviors that include support seeking and medication adherence. CONCLUSIONS A randomized controlled clinical trial targeted toward at-risk HIV-negative individuals who live in areas with high HIV prevalence is suggested to test the effects of proven effective alcohol interventions on HIV incidence.

Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism

AIMS In addition to being produced in ethanol metabolism, acetaldehyde occurs naturally in alcoholic beverages. Limited epidemiological evidence points to acetaldehyde as an independent risk factor for cancer during alcohol consumption, in addition to the effects of ethanol. This study aims to estimate human exposure to acetaldehyde from alcoholic beverages and provide a quantitative risk assessment. METHODS The human dietary intake of acetaldehyde via alcoholic beverages was estimated based on World Health Organization (WHO) consumption data and literature on the acetaldehyde contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the European Food Safety Authoritys margin of exposure (MOE) approach with benchmark doses obtained from dose-response modelling of animal experiments. Life-time cancer risk was calculated using the T25 dose descriptor. RESULTS The average exposure to acetaldehyde from alcoholic beverages was estimated at 0.112 mg/kg body weight/day. The MOE was calculated to be 498, and the life-time cancer risk at 7.6 in 10,000. Higher risk may exist for people exposed to high acetaldehyde contaminations, as we have found in certain unrecorded alcohol beverages in Guatemala and Russia, for which we have demonstrated possible exposure scenarios, with risks in the range of 1 in 1000. CONCLUSIONS The life-time cancer risks for acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment set between 1 : 10,000 and 1 : 1,000,000. Alcohol consumption has thus been identified as a direct source of acetaldehyde exposure, which in conjunction with other sources (food flavourings, tobacco) results in a magnitude of risk requiring intervention. An initial public health measure could be to reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive.

Unrecorded consumption, quality of alcohol and health consequences.

ISSUES This contribution aims to examine systematically the evidence on the impact of the quality of unrecorded alcohol products on health consequences. APPROACH Systematic computer assisted review of the literature. KEY FINDINGS There are a number of pathways related to alcohol quality that may lead to acute or chronic health problems. The following constituents and contaminants of alcoholic beverages were identified as likely contributors to these problems: (i) toxic metals (e.g. lead) from contaminated water sources or unsuitable distillation equipment; (ii) volatile constituents, such as acetaldehyde or higher alcohols, which may be produced in significant amounts due to faults in production technology or microbiological spoilage; (iii) ethyl carbamate (urethane), a carcinogenic contaminant with major occurrence in certain fruit and sugarcane spirits; (iv) biologically active flavour compounds (e.g. coumarin in cosmetics used as non-beverage alcohol); (v) toxic compounds used to denature alcohol (e.g. methanol or diethyl phthalate). In addition, the often higher ethanol content may have detrimental health effects. These pathways should not be assumed as present for all subcategories of unrecorded alcohol, but are more relevant to certain types and geographic regions. IMPLICATIONS A health impact of unrecorded alcohol over and above the effect of ethanol cannot be excluded. More research is urgently needed, especially with respect to liver disease and alcohol poisoning as endpoints. CONCLUSION A feasible approach for new research on the effects of unrecorded alcohol could be based on a representative sample from low socioeconomic regions with high prevalence of unrecorded consumption.

Cancer risk assessment of ethyl carbamate in alcoholic beverages from Brazil with special consideration to the spirits cachaça and tiquira

BackgroundEthyl carbamate (EC) is a multi-site carcinogen in experimental animals and probably carcinogenic to humans (IARC group 2A). Traces of EC below health-relevant ranges naturally occur in several fermented foods and beverages, while higher concentrations above 1 mg/l are regularly detected in only certain spirits derived from cyanogenic plants. In Brazil this concerns the sugarcane spirit cachaça and the manioc (cassava) spirit tiquira, which both regularly exceed the national EC limit of 0.15 mg/l. This study aims to estimate human exposure in Brazil and provide a quantitative risk assessment.MethodsThe human dietary intake of EC via alcoholic beverages was estimated based on WHO alcohol consumption data in combination with own surveys and literature data. This data comprises the EC contents of the different beverage groups cachaça, tiquira, other spirits, beer, wine, and unrecorded alcohol (as defined by the WHO; including alcohol which is not captured in routine government statistics nor taxed). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses obtained from dose-response modelling of animal experiments. Lifetime cancer risk was calculated using the T25 dose descriptor.ResultsConsidering differences between pot-still and column-still cachaça, its average EC content would be 0.38 mg/l. Tiquira contained a considerably higher average EC content of 2.34 mg/l. The whole population exposure from all alcoholic beverages was calculated to be around 100 to 200 ng/kg bw/day, with cachaça and unrecorded alcohol as the major contributing factors. The MOE was calculated to range between 400 and 2,466, with the lifetime cancer risk at approximately 3 cases in 10,000. An even higher risk may exist for binge-drinkers of cachaça and tiquira with MOEs of up to 80 and 15, respectively.ConclusionsAccording to our risk assessment, EC poses a significant cancer risk for the alcohol-drinking population in Brazil, in addition to that of alcohol alone. Model calculations show that the implementation of the 0.15 mg/l limit for cachaça would be beneficial, including an increase of the MOE by a factor between 3 to 6. The implementation of policy measures for tiquira and unrecorded alcohol also appears to be advisable.

Is contaminated unrecorded alcohol a health problem in the European Union? A review of existing and methodological outline for future studies

AIMS Some European countries with high levels of unrecorded alcohol consumption have anomalously high rates of death attributable to liver cirrhosis. Hepatotoxic compounds in illegally produced spirits may be partly responsible. Based on a review of the evidence on the chemical composition and potential harm from unrecorded alcohol, the Alcohol Measures for Public Health Research Alliance (AMPHORA) projects methodology for identifying, analysing and toxicologically evaluating such alcohols is provided. METHODS A computer-assisted literature review concentrated on unrecorded alcohol. Additionally, we refer to our work in the capacity of governmental alcohol control authority and a number of pilot studies. RESULTS The risk-oriented identification of substances resulted in the following compounds probably posing a public health risk in unrecorded alcohol: ethanol, methanol, acetaldehyde, higher alcohols, heavy metals, ethyl carbamate, biologically active flavourings (e.g. coumarin) and diethyl phthalate. Suggestions on a sampling strategy for identifying unrecorded alcohol that may be most prone to contamination include using probable distribution points such as local farmers and flea markets for selling surrogate alcohol (including denatured alcohol) to focusing on lower socio-economic status or alcohol-dependent individuals, and selecting home-produced fruit spirits prone to ethyl carbamate contamination. CONCLUSIONS Standardized guidelines for the chemical and toxicological evaluation of unrecorded alcohol that will be used in a European-wide sampling and are applicable globally are provided. These toxicological guidelines may also be used by alcohol control laboratories for recorded alcohol products, and form a scientific foundation for establishing legislative limits.

Ethyl Carbamate in Alcoholic Beverages from Mexico (Tequila, Mezcal, Bacanora, Sotol) and Guatemala (Cuxa): Market Survey and Risk Assessment

Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and of the sugarcane spirit cuxa (n=16) were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (<0.15 mg/L). Risk assessment found the Margin of Exposure (MOE) in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico.

Epidemiology-based risk assessment using the benchmark dose/margin of exposure approach: the example of ethanol and liver cirrhosis

BACKGROUND A novel approach to derive a threshold dose with respect to alcohol-related harm, the benchmark dose (BMD) methodology, is introduced to provide a basis for evidence-based drinking guidelines. This study is the first to calculate a BMD for alcohol exposure using epidemiological cohort data. With this BMD we will be able to calculate the margin of exposure (MOE) for alcohol consumption, which can be used for comparative risk assessment and applied to setting public health policy. METHODS Benchmark dose-response modelling of epidemiological data gathered during a recent systematic review and meta-analysis of alcohol consumption as a risk factor for liver cirrhosis morbidity and mortality. RESULTS For a benchmark response (BMR) of 1.5%, the resulting BMD values were 30.9 g/day for males and 29.7 g/day for females; the corresponding lower one-sided confidence values were 25.7 and 27.2 g/day, respectively. The intake scenario for the Canadian population resulted in an MOE of 1.23. Intake scenarios for individuals as based on the Canadian drinking guidelines led to MOE values between 0.96 and 1.91. Using an uncertainty factor of 10, the acceptable daily intake for alcohol would be 2.6 g/day. CONCLUSIONS The BMD approach was feasible in developing evidence-based guidelines for low-risk drinking. As our calculated MOEs result around unity (i.e. 1) for moderate drinking, it is evident that the current guidelines correspond very well to low risk on the dose-response curve. The BMD methodology therefore validates current guidelines. The results again highlight the health risk associated with alcohol consumption.

The contribution of acetaldehyde from alcohol to cancer: a review and exposure estimate for Germany

Aims: The consumption of alcoholic beverages has been identified as carcinogenic by the International Agency for Research on Cancer. We aim to summarize the evidence on acetaldehyde as the main mechanism underlying this relation, because humans are exposed to acetaldehyde both through ingestion of acetaldehyde present in alcoholic beverages and acetaldehyde produced through ethanol metabolism. Methods: A literature review of alcohol, acetaldehyde and cancer was used as input for a risk assessment for acetaldehyde derived from alcohol consumption for Germany. Results: There is increasing evidence that acetaldehyde is carcinogenic. Risk assessment scenarios were below the 1:10,000 lifetime risk for cancer threshold (average scenario 8/10,000; extreme scenario 4/1,000), which is considered public health relevant. Conclusion: Acetaldehyde exposure from alcohol alone warrants interventions based on the precautionary principle of public health. It is recommended that high alcohol consumption should be reduced and acetaldehyde levels in alcoholic beverages should be reduced as low as technologically possible, along with the implementation of maximum limits.

Letter to the Editor in regard to Gil, Polikina, Koroleva, McKee, Tomkins, and Leon (2009): “Availability and Characteristics of Nonbeverage Alcohols in 17 Russian Cities in 2007” Unrecorded Alcohol in Russia: Is There More to it than Just Ethanol?

T HE RECENT ARTICLE of Gil and colleagues (2009) is the first systematic investigation into the availability of nonbeverage or surrogate alcohols in a range of Russian cities. According to WHO nomenclature, surrogate alcohols constitute a subgroup of ‘‘unrecorded alcohol,’’ defined as alcohol products not officially intended for human consumption (for details see the Global Information System on Alcohol and Health on http://www.who.int/globalatlas/default. asp; see also Lachenmeier et al., 2009). Examples for surrogate alcohol include cosmetics such as mouthwash or perfumes, denatured alcohol, automobile products such as alcohol-based antifreeze, or medicinal compounds such as rubbing alcohol (Lachenmeier et al., 2007). It is remarkable that even with the exclusion of homedistilled spirits (samogon), previously described as representing the majority of unrecorded alcohol in Russia (Popova et al., 2007), Gil and colleagues (2009) identified 271 surrogate alcohol products, available in 17 Russian cities. From those, medicinal tinctures, purchased almost exclusively from pharmacies, were the most common product identified (most common: Hawthorn tincture), followed by eau-de-colognes (most common: Troynoy brand). Many of the types of surrogate alcohols sold had been reported to be consumed by cases or controls in an earlier study of the same authors, the Izhevsk study (Leon et al., 2007). The authors concluded that plausible nonbeverage candidates for human consumption have a particular profile characterized by a high ethanol concentration combined with low unit cost ratio. In accordance with the authors’ previous findings, the high mortality associated with drinking nonbeverage alcohols in Russia was attributed to the toxic effects of high levels of ethanol per se (Gil et al., 2009; Leon et al., 2007). This is consistent with a number of previous studies on unrecorded alcohol, which generally contained higher alcoholic strengths than legal alcohol (Huckenbeck et al., 2003; Lachenmeier et al., 2009; Lang et al., 2006; McKee et al., 2005; Nuzhnyi, 2004; Savchuk et al., 2006). Overall, given recent results from a large autopsy study, it seems certainly possible, that most of the overmortality can be explained by ethanol alone (Zaridze et al., 2009; see also Rehm and Gmel, 2007). The authors seem to dismiss the possibility of other constituents of the unrecorded alcohol additionally contributing to the high mortality. For example, the citations of previous research on the chemical composition of surrogate alcohol show that these products had been measured with zero or very low levels of methanol and higher alcohols (Lang et al., 2006; McKee et al., 2005; Pärna et al., 2007). In general, we agree with this assessment, referring to our own research of surrogate alcohol from Lithuania, which confirms the absence of methanol and higher alcohols because such products are manufactured with so-called neutral alcohol (Lachenmeier et al., 2009). However, Gil and colleagues (2009) seem to ignore other compounds that may be contained in medicinal products or cosmetic products used as surrogate alcohol. The Hawthorn tincture is interesting in this regard, as hawthorn (Crataegus spp.) extract may have pharmacological properties [e.g., in some countries hawthorn is approved as a prescription medicine to treat chronic heart failure and clinical trials have shown a significant beneficial effect (Pittler et al., 2008)]. There is currently a lack of data on the safety of hawthorn preparations and adverse effects may include dizziness ⁄ vertigo or gastrointestinal complaints (Daniele et al., 2006). From Chemisches und Veterinäruntersuchungsamt (CVUA) (DWL), Karlsruhe, Germany; and Centre for Addiction and Mental Health (CAMH) (FK, JR), Toronto, Ontario, Canada. Copyright 2009 by the Research Society on Alcoholism.