Although alcohol use is steadily declining in France, 10% of adults still have alcohol problems. Alcohol abuse gives rise to hepatic, cardiovascular, and neurological complications, together with cancer, and alcohol is still the second leading cause of death in France. Identifying high-risk users and reducing their alcohol use is currently a major challenge. Various vulnerability factors are being studied with a view to improving the identification and management of alcohol addiction.
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Understanding Alcohol & Health issues
Alcohol use has been steadily declining in France for approximately forty years: it halved between 1960 and 2009. Data from the 2014 Baromètre santé survey indicate that approximately 13.6% of adults do not drink, and 9.7% drink every day (14.6% of males and 4.9% of females). Wine is still the most widely consumed beverage by far.
Alcohol use most often begins in adolescence, a period in which beer and alcopops (sugary, flavored alcoholic drinks) are the most popular beverages. The average age at which teenagers first get drunk is 15.2 years. In 2014, 58.9% of 17 year-olds claimed to have already got drunk at some point in their lives, and more than a quarter (25.3%) had got drunk at least three times in the past 12 months (Source: ESCAPAD 2014).
Significant toxicity for the body
Alcohol use gives rise to multiple health risks, depending on the quantities ingested. It is responsible for over 200 diseases and various disorders. Some of these diseases can be exclusively attributed to alcohol, namely alcoholic cirrhosis and certain neurological disorders, such as Korsakoff's syndrome. Alcohol is also a risk factor for other disorders. This is the case for certain types of cancer (mouth, pharyngeal, laryngeal, esophageal, liver, breast, and colorectal cancer) and cardiovascular diseases (hypertension and ischemic heart disease). Furthermore, a number of cognitive disorders are observed in over 50% of alcoholics: memory impairment, abnormal movements, etc. These disorders are slowly reversible.
The liver, the main target for the effects of alcohol
Several liver disorders can be caused by excessive alcohol use: steatosis (lipid accumulation in the liver), alcoholic hepatitis, and cirrhosis. A French study, conducted on 2,000 excessive alcohol users having been admitted to hospital, showed that only 11% of these users had a normal liver: 34% presented alcoholic cirrhosis, 46% steatosis with or without fibrosis, and 9% acute alcoholic hepatitis. These are serious disorders: 5-year survival for cirrhosis and/or severe alcoholic hepatitis ranges from 20% to 60%.
Alcohol, the second leading cause of premature death in France
Excessive alcohol use directly or indirectly contributes to 13% of male deaths and 3% of female deaths. It is the second leading cause of premature death in France. Hence, 49,000 deaths were attributed to alcohol in France in 2009, with 22% of deaths among 15-34 year-olds, 18% among 35-64 year-olds, and 7% among over 65s. These deaths were mainly due to cancer (15,000 deaths), cardiovascular disease (12,000 deaths), gastrointestinal disease (8,000 deaths due to cirrhosis), and accidents or suicides (8,000 deaths). The other deaths were due to other disorders, including alcohol-related psychiatric disorders.
Excessive alcohol use also has a major social impact. In 2006, more than 271 sentences for involuntary manslaughter while under the influence of alcohol were issued by the courts. And, in 28% of domestic violence cases in the Paris region, the perpetrators regularly consumed large quantities of alcohol. In 2013, 111,550 sentences for driving under the influence (DUI) were filed at the National Criminal Records Office, i.e., accounting for one in five criminal sentences in France.
Guidance on alcohol use
The health authorities advise:
- against consuming more than three glasses of alcoholic beverages per day for males, or two glasses for females,
- keeping one day alcohol-free per week,
- never to drink more than four glasses on one occasion.
These guidelines apply to adults: no validated guidelines exist for young people, among whom any alcohol use can be harmful due as the developing brain is more vulnerable.
Below these limits, the risk of alcohol-related toxicity is largely reduced, but still nonetheless exists, particularly for the cancer risk. Even when consumed in small daily quantities, equivalent to 13 grams (i.e., 1.3 glasses), alcohol is said to cause 1,100 deaths per year. This is why these limits are being reviewed and could be further reduced in the future.
As a reminder, a glass of beer (250-300 ml), a glass of wine (150 ml), and a shot of spirits (30-50 ml) contain a similar quantity of alcohol (approximately 10 g of ethanol).
"Binge drinking": a growing trend among young people
Binge drinking, a trend among young people, involves getting drunk as quickly as possible. The limits are four glasses of alcohol or more in two hours for girls, and five for boys; however, alcohol use is generally much higher. In France, half of 17 year-olds have partaken in binge drinking in the past thirty days, and this is a growing phenomenon, particularly among girls.
However, when this practice is repeated, it has harmful consequences on health: reduced learning ability and impaired long-term memory function, increased impulsiveness, impact on reading emotions, anxiety and mood, hypertension, liver damage, and increased addiction risks later in life. A recent study demonstrated damage to white matter correlated with spatial working memory deficit in college student binge drinkers. The speed of consumption particularly appears to contribute to the harmful effects. Another study, conducted on the preclinical rat model, shows that memory remains impaired 48 hours after two binge drinking episodes.
"Binge drinking" : quand le cerveau trinque – interview - 3 min 42 – vidéo extraite de la série Questions de société (2011)
Alcohol and the brain
Alcohol acts directly on the brain, with variable consequences on behavior depending on the quantities ingested:
- For blood alcohol levels less than or equal to 0.50 g/l, ethanol has a stimulant effect, accompanied by loss of inhibitions: cognitive tasks are performed more rapidly and with a subjective sense of ease, but with a higher rate of mistakes.
- Above 0.50 g/l, it has a sedative effect and disrupts motor function (loss of balance, lack of coordination).
These effects also depend on individual susceptibility to the effects of alcohol, which is partly explained by genetic factors.
Fate of alcohol in the body
Ethanol (i.e., alcohol) concentration in the blood peaks after 45 minutes if alcohol is consumed on an empty stomach, or after 90 minutes if consumed during a meal. Elimination takes place at a rate of approximately 0.15 g/l/h for concentrations above 0.50 g/l, varying considerably from one person to another. Plasma ethanol concentrations are higher in women than men, based on the same quantity ingested. Furthermore, women metabolize alcohol more slowly. They are thus more vulnerable to the toxic effects of alcohol.
Multiple effects on neurons
Unlike other drugs, ethanol has no specific receptors in the brain: it acts on several targets and modifies their activity, disrupting the transmission of several excitatory and inhibitory nerve signals. Alcohol notably stimulates the release of dopamine, the pleasure neurotransmitter, involved in addiction.
At high doses, alcohol remodels the connections between neurons. This remodeling allows the brain to adapt to this consumption and to diminish the effects, which, paradoxically, incites consumption. This phenomenon explains the hazard alcohol represents during adolescence. The brain continues to develop up to the age of 25 (myelination and elimination of unnecessary neuronal connections). Alcohol consumption during this period disrupts normal brain development and increases the risk of addiction.
Alcohol and pregnancy: fetal alcohol syndrome
Prenatal exposure to alcohol has dramatic and permanent effects. Ethanol readily crosses the placental barrier and the concentrations detected in the fetus are higher than those measured in the mother due to the under-developed alcohol elimination system in the fetus. This has variable consequences, ranging from minor behavioral disorders, known as fetal alcohol spectrum disorders (FASD), to severe developmental abnormalities evidenced by fetal alcohol syndrome (FAS): malformation of the face and skull, growth retardation, behavioral and cognitive disabilities. Nearly one in two children with FAS display mental retardation, and the majority experience learning, memory, attention and behavioral problems.
In France, FAS affects at least 1% of births (1°/00 for serious forms of complete FAS), i.e., approximately 8,000 neonates per year. This suggests that nearly 500,000 French people suffer from the sequelae of fetal alcohol syndrome, to varying degrees (source: Académie de médecine, March 2016).
Alcohol intake is harmful throughout pregnancy and no zero risk level has ever been evidenced, hence the recommendation for "zero alcohol during pregnancy". Despite these risks, approximately 25% of pregnant women admit to drinking alcohol during pregnancy.
Abuse and addiction: alcohol use problems
Any intake of more than three glasses of an alcoholic beverage per day for men and two for women should be considered to present a risk, even without symptoms of addiction.
Addiction is characterized by compulsive use which persists despite the resulting negative consequences and the irrepressible and urgent need to drink (craving). The individual loses all control of their alcohol use. They start to tolerate the negative effects and display symptoms of withdrawal syndrome when alcohol intake ceases: confusion, tremor, or even seizures. There is a high and prolonged risk of recurrence after a period of abstinence or reduction.
A questionnaire (AUDIT) is able to screen for alcohol abuse and addiction. Approximately 10% of adults experience alcohol problems (15% of men and 5% of women), mainly aged between 25 and 64 years. This proportion has remained stable since the beginning of the 1990s. Unemployed males and the self-employed are the populations most at-risk.
All equal when it comes to addiction?
Individual vulnerability plays a role in addiction, influenced by several factors: genetic, behavioral (impulsiveness, seeking sensations and taking risks, early alcohol use) and environmental factors.
From a genetic perspective, studies conducted on families demonstrate the noteworthy contribution of genetic factors in the risk of developing an addiction. However, no predisposition genes for addiction have been identified to date, despite numerous studied conducted in this field. This vulnerability is thought to match the definition of a complex genetic disorder: numerous alterations of several genes constitute multiple decisive factors for the disorder, each modification being incapable of causing the disorder in itself.
Recent studies also indicate that exposure to alcohol in an early stage of development - during adolescence, or, indeed in utero - increases the risk of developing an addiction. Introduction to alcohol use from the age of 11-12 years gives rise to a ten-fold increase in the risk of developing an addiction compared with initiation around 18 years of age.
Lastly, the environment - social or family factors, or, indeed, the accessibility of this substance (price, availability, advertising, ease at inducing an addiction) - plays an important role. A recent study demonstrates that allowing a child to taste alcohol facilitates initiation into alcohol use during adolescence and the development of binge drinking behavior. A European study also showed that exposure to alcohol in the media and in films increases the prevalence of binge drinking.
Return to reasonable alcohol use
Despite the health and social "burden" arising from alcohol-related disorders, a small number of patients seek treatment, and less than 10% receive specialist care. This is partly explained by the fact that the goal of treatment has long been to achieve total, life-long abstinence, discouraging a number of individuals from embarking on the treatment process.
The goal of reducing alcohol use, proposed for the past few years, is more readily acceptable for some heavy drinkers and alcoholics not initially aiming for abstinence. The aim is then to return to "controlled" alcohol use. This option, chosen by approximately half of patients, already provides a substantial benefit to their health; however, it is only available for those with a moderate substance addiction.
To encourage heavy drinkers to follow this dynamic, early screening is essential and should be followed by a brief intervention informing and making them aware of the dangers of alcohol and the recommended intake limits, so as to bring about a change of behavior and reduce the risk of developing alcohol addiction.
Treatment for alcohol addiction is based on psychotherapy, changes in environmental and social relations, and medications, as recommended by the Société française d’alcoologie. Alcohol addiction is a chronic disorder with a high relapse rate, which requires long-term follow-up by an addiction specialist or psychologist. Moreover, alcoholism often goes hand in hand with neuropsychiatric disorders, such as anxiety, depression, mood disorders or personality disorders which complicate management and constitute a poor prognosis for a response to treatment.
All of the medicinal products currently recommended have been shown to be effective. These mainly aim to support abstinence and to prevent relapse. However, after treatment, only a third of patients are still abstinent after a year and 10 to 20% after 4 years. These medicinal products (acamprosate, naltrexone or even disulfiram) act on the central nervous system to dissuade against alcohol use. A new medicinal product, nalmefene, is currently the only treatment indicated for the reduction of alcohol use. It is an option for those who wish to return to controlled alcohol use (rather than abstinence).
Lastly, baclofen has been granted a temporary recommendation for use over a three-year period (since 2014), for maintaining abstinence and reducing alcohol use. It was the subject of two clinical studies in France (Bacloville and Alpadir), the results of which have not yet been published, together with a participatory pharmacovigilance study on its undesirable effects (Baclophone).
There is not yet any scientific evidence to suggest that a combination of several medicinal products would be more effective than administration of a single product. Current research aims to identify predictive factors for a better response to the different treatments available.
Challenges facing research
The main lines of research currently developed around the theme of "Alcohol and Health" cover several fields: epidemiology, social sciences, neurosciences, neurobiology, and oncology.
Several teams of researchers are studying the brain mechanisms associated with addiction, namely by focusing on the brain structures already known to play a role in addiction. The use of animal alcohol addiction models enables the neurobiological bases of this addiction to be studied and new treatments to be investigated. Different agents are currently being evaluated, such as sodium oxybate. These act on neurotransmission or on the "stress axis", the activity of which increases during withdrawal, representing a factor for relapse.
Deep brain stimulation targeting sites involved in addiction (nucleus accumbens or subthalamic nucleus of the brain) has been tested: positive results have been observed in rats and in humans (for multiple relapses). However, this is a burdensome method, which requires invasive surgery to insert electrodes deep into the brain. Partial inactivation of the nucleus accumbens also displays a good degree of safety and efficacy, with a relapse rate of only 25% at 12 months.
Understanding individual vulnerability
Another objective is to have clearer insight into the factors involved in individual vulnerability to addiction and the development of diseases such as cirrhosis or hepatitis.
Hence, genetic studies are being conducted, notably on the whole genome, to identify genetic variations associated with addiction. Researchers are also examining the mechanisms for developing organic disease associated with alcohol addiction. As an example, they have created an experimental model of the alcoholism-schizophrenia comorbidity in the rat. In this model, exposure to alcohol during adolescence, even when very low, makes the animals particularly vulnerable to alcoholism.
The intestinal flora could indeed play an important role in vulnerability to alcohol. Studies demonstrate a link between its composition and the risk of alcohol addiction, notably via anxiety/depression and craving which promote relapse. There is also a link between the composition of this microbiota and the development of complications among alcoholics, particularly those related to liver disease. Transplanting the microbiota from an alcoholic patient with severe alcoholic hepatitis to a healthy mouse, in fact, induces the onset of inflammation and hepatic lesions within a few days. However, flora taken from an alcoholic without hepatic complications does not give rise to hepatic disorders in transplanted mice. This represents a new avenue to be explored in the fight against addiction and alcohol-related risks.
As regards behavioral risk factors, studies show that early exposure to alcohol, whether in utero or in adolescence, could be a considerable risk factor for addiction later in life. Inserm is coordinating a European project along these lines (Alcobinge) relating to the impact of binge drinking on cognitive function and cerebral function. These studies are being conducted in young people and in animal models. Medical imaging examination of the brains of college students, with or without rapid ingestion of a large quantity of alcohol, showed that binge drinking induces brain damage associated with cognitive deficits. Ongoing studies are investigating this damage, which differs for boys and girls.
Will genetics soon predict treatment efficacy?
Certain genes involved in the development of alcohol addiction could also influence the patient's response to treatment. An Inserm study, conducted in collaboration with a Dutch team, showed that the response to naltrexone and acamprosate varies according to the patient's genetic polymorphism. These links have yet to be clarified in larger populations and the longer term effects, particularly on relapse, need to be studied. Secondly, the genetic variations to be taken into account when selecting the most suitable treatment for a patient with an alcohol addiction will then need to be defined. The most interesting candidate at present is a polymorphism of the OPRM1 gene, coding the mu receptor of endogenous opioids. This could be associated with superior efficacy of naltrexone; however, the available results are conflicting and inconclusive.
Burden on society
Studies involve evaluating the extent of the socioeconomic repercussions of excessive alcohol use. A recent study shows that this is the leading cause of hospital admissions in France (for the treatment of alcohol use itself and its consequences). Hence, in 2012, over 580,000 hospital stays in surgery, obstetric and dentistry departments were caused by problem alcohol use. Furthermore, more than 2.7 million days of hospitalization were recorded in psychiatric departments, accounting for 10.4% of the total.
Another study made it possible to specify the cost to society in terms of loss of quality of life, loss of productivity, expenditure on prevention, law enforcement, health care, etc., by incorporating revenue from tax generated by alcohol or savings from unpaid pensions. The scales are largely tipped against alcohol use, with alcohol representing a social cost of nearly EUR 120 thousand million per year, almost equivalent to tobacco.
Inserm Patient Associations Mission focuses on "Alcohol"
The Inserm Associations Mission is developing several projects with patient associations. Hence, since the end of 2006, a working group has brought together researchers and associations which support individuals with alcohol problems. This working group allows for reflection on interaction between researchers and associations, and also enables community research projects to be created and implemented. A debate is organized each year to promote exchanges between members of mutual support groups, researchers and healthcare professionals on common issues.