Direct alcohol metabolites: A new generation of biochemical markers detect covert alcohol use not found through standard testing

  • Covert alcohol use can be detected by biochemical markers that remain in the body.
  • Researchers examined the effectiveness of two relatively new markers, ethyl glucuronide (EtG) and phosphatidyl ethanol (PEth).
  • They found that EtG is a highly effective and sensitive marker of recent alcohol use.

The ability to detect covert alcohol use can be applied in various settings: identifying patients in treatment who may have lapsed or relapsed; ensuring that employees in safety-sensitive work environments are alcohol free; and helping to monitor recovering health professionals who must document their sobriety in order to continue their practice. A study in the March issue of Alcoholism: Clinical & Experimental Research has found that a relatively new biochemical marker called ethyl glucuronide (EtG) is a highly effective and sensitive marker of recent alcohol use.

"The data clearly suggest that EtG could be a useful tool in numerous settings, including alcohol and drug treatment, driving, the workplace, pregnancy, monitoring physicians or other professionals who are in recovery and working, and for forensic purposes," said Friedrich Martin Wurst, a psychiatrist at the University of Basel and first author of the study. "We found that] shortly after consumption of even small amounts of alcohol, EtG becomes positive. It also seems capable of detecting alcohol intake up to 80 hours after complete elimination of alcohol from the body. In short, it seems to meet the need for a sensitive and specific marker to elucidate alcohol use not detected by standard testing. The use of this marker alone, and along with other biological markers and self reports, could lead to significant improvements in treatment outcome, therapy effectiveness, and cost reductions."

"Both of the emerging markers examined in this study, EtG and phosphatidyl ethanol (PEth), are direct markers of alcohol intake," noted Martin Javors, professor of psychiatry at The University of Texas Health Science Center, San Antonio. "That is, the alcohol or ethanol molecule is chemically incorporated into a biochemical derivative that is directly measured. More traditional markers like GGT, MCV, and CDT are elevated with heavy drinking by the indirect effects of ethanol, that is, ethanol is not incorporated chemically into the molecules whose levels are measured."

Gamma glutamyl transferase (GGT), the most widely used biochemical marker of alcohol consumption, is an enzyme abundantly found in the kidney, liver, pancreas, and prostate gland. It is a general marker of liver damage (which is often associated with heavy drinking). Carbohydrate-deficient transferrin (CDT) is a carbohydrate-deficient variant of transferrin, a protein that transfers iron around the body, and is synthesized and secreted by the liver. Mean corpuscular volume (MCV) is a measure of red blood cell size.

"Direct markers such as alcohol, EtG or PEth are elevated or positive only if alcohol was consumed," added Wurst. "In contrast, GGT, CDT and MCV can be elevated due to nonalcohol-related diseases like viral hepatitis, obesity, nicotine use, or due to psychopharmacological drugs, contraceptives, or the antiepileptic drug and mood stabilizer, carbamazepine."

For this study, researchers examined 35 forensic psychiatric inpatients (32 males, 3 females), housed in a closed ward, for 12 consecutive months. All of the patients were substance-dependent and had committed a substance-related offense, but were allowed under German law to be committed for monitoring and treatment in lieu of jail. In the later stages of therapy, patients were allowed to begin social reintegration during weekdays and on the weekends. During the course of the study, complementary urine, breath and blood samples were collected both randomly and regularly from the patients at various intervals. Samples were tested for the presence of EtG, PEth, GGT, MCV, CDT and alcohol. Patients were also interviewed at least once per week regarding their alcohol consumption.

Of 146 urine samples collected, 14 tested positive for EtG. In all 14 cases, patients reported alcohol consumption of between 40 - 200 grams of alcohol (the equivalent of 3 - 15 standard drinks) in the 12 - 60 hours prior to testing. (All of the lapses in abstention from alcohol occurred during periods of social reintegration.) There were no self-reports of alcohol consumption in the remaining 132 cases. PEth and CDT did not test positive in any of the blood samples, thereby excluding regular intake of larger amounts of alcohol for longer periods of time (more than two weeks).

"The key finding of this study is that elevated EtG levels were found in a group of patients in treatment who had started to drink again," said Javors. "This finding is impressive in that each subject with an elevated EtG level also confirmed drinking within the previous 12 to 60 hours."

Javors called this line of research "important and significant." He said that being able to identify heavy drinkers at the early stage of their drinking is not simply an issue of ‘gotcha!,’ but is crucial to "helping the patient understand the potential seriousness of the problem. The same is true for the identification of a return to heavy drinking during recovery. Furthermore, these findings contribute to research in that this biochemical test could be used to assess levels of drinking in patients who are participating in clinical research treatment trials. This application would help investigators evaluate in an objective manner the effectiveness of pharmacological and other treatments."

"EtG gives the best information on recent alcohol intake, from just hours before, up to days previous," said Wurst. "The study design is unique, because of the very well-controlled and well-defined conditions of a closed ward for forensic psychiatric patients. This means we knew quite a bit about them and what they did. The cumulative findings emphasize that, altogether, EtG can be used for multiple purposes, ranging from evaluating treatment, to elucidating the role of hangovers in accidents, to screening and monitoring. For example, there are more than 9,000 American physicians in monitoring programs in which urine testing is used to document sobriety. Physicians recovering from substance-related disorders are usually able to return to practice contingent upon an agreement to remain abstinent and submit to frequent random urine testing. Alcohol, the most commonly abused substance by physicians, is difficult to monitor because of its short half-life. EtG can help resolve these difficulties."

Wurst added that an ELISA test, which utilizes EtG, can be easily used in hospitals. "The health, social and socioeconomic benefits arising from the use of EtG and PEth to detect alcohol use, along with other markers and self reports, is hard to overestimate."

Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.

Articles were written based on the following published research:

Wurst, F.M., Vogel, R.,Jachau, K., Varga, A.,Alling, C., Alt, A., Skipper, G.E. (March 2003). Ethyl glucuronide discloses recent covert alcohol use not detected by standard testing in forensic psychiatric inpatients. Alcoholism: Clinical & Experimental Research, 471-477, 27(3).