Approximately 20% of primary care patients in the United States drink alcohol (ethanol) at levels harmful to health. A blood-alcohol concentration over 250 mg/dL is considered toxic and may result in loss of motor function, impaired consciousness, respiratory depression, and death. Other effects of alcohol exposure include cardiomyopathy, stroke, fatty liver disease, fibrosis, pancreatitis, increased risk of developing cancer, psychological disorders, and vitamin deficiency, as well as fetal alcohol syndrome for those exposed in utero. Ethanol ingestion by children may cause hypoglycemia.
Diagnostic criteria for alcohol use disorder (AUD) vary, but the most widely used criteria are found in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Laboratory tests for acute alcohol ingestion include ethanol, ethyl glucuronide (EtG), and ethyl sulfate (EtS) tests. Carbohydrate-deficient transferrin (CDT) and phosphatidylethanol (PEth) are useful markers for monitoring abstinence after long-term use.
Quick Answers for Clinicians
The most specific markers for detecting acute alcohol exposure are ethanol, ethyl glucuronide (EtG), and ethyl sulfate (EtS). Specific markers for chronic alcohol use are carbohydrate-deficient transferrin (CDT) and phosphatidylethanol (PEth). Nonspecific markers include gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), aspartate aminotransferase (AST), and alanine aminotransferase (ALT).
The window of detection depends on the sample type and quantity of alcohol consumed. See Attributes of Ethanol Biomarkers table for general ranges.
Oral fluid is easy to collect and shows a strong correlation with blood-alcohol levels.
Urine is the most widely used specimen type for drugs-of-abuse testing because of ease of collection and analysis; many tests can be performed on site. However, urine is susceptible to contamination and dilution and is not optimal for determining level of consumption.
Blood provides the best evidence of use and corresponding drug levels; it lends itself more to clinical and emergency toxicology settings than to routine screening.
Hair can provide a history of drug use because drugs can remain in the hair for a long period of time, but testing cannot distinguish drinking levels.
Sweat has been shown to be sensitive and accurate, but testing is less practical than for other specimen types.
In adults, some ethanol is absorbed by the stomach, although the majority is quickly absorbed into the intestines. Ingestion of food delays absorption. The distribution of ethanol into body tissues and fluids is proportionate to the body’s water content, which varies by age, weight, and sex. More than 90% of ethanol is metabolized by either alcohol dehydrogenase (ADH), cytochrome P4502E1 (CYP2E1), or catalase, and the rest is eliminated unchanged in breath, sweat, and urine. Of that metabolized, a small amount is not oxidized, which results in substrates that can be used as biomarkers of consumption.
In neonates and children, absorption may be reduced because of slower and more irregular stomach emptying, and the volume of distribution in children is greater because of greater body water content, less fat, and variable blood flow. Metabolism is affected by decreased ADH and CYP2E1 levels, and decreased renal function may slow elimination.
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) uses the following definitions :
- Moderate drinking is considered one drink per day for women and up to two drinks per day for men.
- Binge drinking refers to consumption that causes the blood alcohol concentration to reach 0.08 g/dL.
- Women are considered to be at low risk of developing alcohol use disorder (AUD) if they consume fewer than four drinks in 1 day and fewer than eight drinks per week; men are considered at low risk for AUD if they consume fewer than five drinks in 1 day and fewer than 15 drinks per week. For symptoms of AUD, see Criteria for Diagnosis.
Indications for Testing
Laboratory testing is appropriate in the context of suspicion of alcohol use or exposure, trauma-related injury, substance abuse treatment monitoring, or follow-up testing to investigate other biomarker abnormalities that suggest alcohol use or exposure, including abnormalities in mean corpuscular volume (MCV) or in gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) concentrations.
Acute Alcohol Use Biomarkers
Serum ethanol testing provides the most accurate determination of a patient’s alcohol level. Acute ethanol intoxication is not reliably detected by serum ethanol testing beyond the first 6-8 hours.
Ethyl Glucuronide and Ethyl Sulfate
EtG and EtS are direct minor metabolites of ethanol and are considered good markers of acute, short-term (up to 36 hours in the blood, up to 5 days in urine) alcohol ingestion. The sensitivity of these tests is highest in heavy drinkers but wanes after 24 hours and with lower doses. Results do not accurately correlate with the amount or frequency of ethanol use.
Refer to the ARUP Consult Emergency Toxicology topic for more information about acute alcohol use testing.
Chronic Alcohol Use Biomarkers
CDT, an indirect metabolite of ethanol, is a serum marker of long-term, heavy alcohol use (≥40 g/day for up to 2 weeks) or relapse. CDT concentrations generally correlate well with an individual’s drinking pattern, especially during the preceding 30 days, and is most useful for long-term abstinence monitoring. Factors that affect CDT levels include body mass index (BMI), female sex, and smoking. CDT testing cannot be used in individuals suspected of having congenital glycosylation disorders.
PEth is a direct ethanol metabolite and can be tested to detect longer term exposure (within 1-2 weeks or longer). Because blood PEth levels are closely correlated with alcohol consumption, PEth testing can be used to monitor alcohol consumption, identify early signs of harmful alcohol consumption, and track cases of AUD or dependence.
GGT is an inexpensive and sensitive indirect marker of alcohol consumption. Even moderate drinkers (<60 g/week), especially men, show higher levels of GGT than abstainers do.
The limitations of GGT include lack of specificity; levels may be elevated with nonalcoholic fatty liver disease, drug intoxication, obesity, diabetes, and hepatobiliary disorders. GGT is also age dependent; concentrations increase with age, even in abstinent individuals. Normalization of GGT requires 2-3 weeks of abstinence.
Mean Corpuscular Volume
MCV, the average size of a person’s red blood cells, increases with high quantities of alcohol ingestion. Compared with other biomarkers, MCV has low sensitivity but higher specificity for alcohol use. Because this test can detect previous alcohol exposure, even after a long period without alcohol consumption, it is not useful for monitoring abstinence in those recovering from AUD.
Aspartate Aminotransferase and Alanine Aminotransferase
AST and ALT enzymes have low sensitivity and specificity to screen for excessive alcohol consumption, but they are highly sensitive and specific for detecting alcohol-induced liver damage. The AST/ALT ratio increases with alcohol consumption; an AST/ALT ratio >1 is considered suggestive of alcohol as the cause of liver dysfunction. ALT is less sensitive than AST, but both can be effective tools in combination with other biomarkers to identify heavy drinking.
Attributes of Ethanol Biomarkers
|Biomarker||Window of Detection||Positive Cutoff Value||Associated ARUP Tests|
|Ethanol||1-12 hrs in blood or urine||Varies based on instrumentation||Ethanol, Serum or Plasma – Medical 0090120|
1-5 days in urine
36 hrs in blood
Months in hair, nails
Last trimester of full-term pregnancy in umbilical tissue
|≥100 ng/mL||Ethyl Glucuronide and Ethyl Sulfate, Urine, Quantitative 2007909|
|≥500 ng/mL||Ethyl Glucuronide Screen with Reflex to Confirmation, Urine 2007912|
|5 ng/g||Ethyl Glucuronide, Umbilical Cord Tissue, Qualitative 3000443|
|CDT||2-3 wks in serum/plasma||≥1.7%||Carbohydrate Deficient Transferrin for Alcohol Use 0070412|
|PEth||1-2 wks or longer (blood)||
≥20 (moderate alcohol consumption)
≥200 ng/mL (heavy alcohol consumption or chronic alcohol use)
|Phosphatidylethanol (PEth) 3002598|
|GGT||2-3 wks in serum/plasma||Varies based on instrumentation||Gamma Glutamyl Transferase, Serum or Plasma 0020009|
|AST||1-4 wks in serum/plasma||Varies based on instrumentation||Aspartate Aminotransferase, Serum or Plasma 0020007|
|ALT||Unknown||Varies based on instrumentation||Alanine Aminotransferase, Serum or Plasma 0020008|
|Blood cell counts (MCV)||2-4 mos (blood)||>100 fL||n/a|
Up to 24 hrs in serum
Months in hair
|>0.5 ng/mg of hair||n/a|
|AA-Ab||1-3 wks in blood||Not established||n/a|
1-2 wks in serum
2-4 wks in urine
|Varies based on instrumentation||n/a|
|Sialic acid||Variable in serum||>60 mg/dL||n/a|
AA-Ab, acetaldehyde adduct and associated antibodies; FAEE, fatty acid ethyl esters; n/a, not available
Criteria for Diagnosis
The DSM-5 includes a list of 11 criteria for defining AUD with mild, moderate, and severe subclassifications. Mild AUD is classified as the presence of two or three symptoms over the past year; moderate, four or five symptoms; and severe, six or more symptoms. A brief description of the 11 criteria follows :
- Alcohol is often used in larger amounts or over a longer period than intended.
- The individual has had a persistent desire or unsuccessful attempts to cut down or control alcohol use.
- A significant amount of time is spent in activities necessary to obtain, use, or recover from alcohol.
- The individual has a craving or urge to use alcohol.
- Recurrent alcohol use has resulted in failure to fulfill obligations at work, school, or home.
- Alcohol use has continued despite alcohol-related social or interpersonal problems.
- Alcohol use has continued despite persistent or recurrent alcohol-related physical or psychological problems.
- Important activities have been given up or reduced because of alcohol use.
- The individual has engaged in recurrent alcohol use in physically hazardous situations.
- The individual demonstrates evidence of tolerance.
- The individual has demonstrated withdrawal symptoms or syndrome.
ARUP Laboratory Tests
Use to identify acute alcohol ingestion
Use to identify ethanol, methanol, isopropanol, or acetone ingestion
Preferred method for general screening of ethanol exposure in urine
Qualitative Enzyme Immunoassay/Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Use to assess for ethanol exposure in the context of compliance and/or abuse
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Use to detect and document maternal use of ethanol
For additional test information, refer to the Ethyl Glucuronide, Umbilical Cord Tissue, Qualitative Test Fact Sheet
Qualitative Liquid Chromatography-Tandem Mass Spectrometry
Use to identify alcohol abuse or abuse relapse
Use to detect chronic ethanol use (≥40 g/day for 2 wks)
Biomarker associated with ethanol consumption; may be helpful in monitoring alcohol abstinence
Use to identify chronic heavy ethanol use for up to 28 days
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Indirect marker associated with ethanol consumption
Biomarker associated with alcohol-induced liver damage
Use to identify chronic heavy ethanol use
NIH - Alcohol Abuse and Alcoholism
National Institutes of Health. National Institute on Alcohol Abuse and Alcoholism. [Accessed: Jun 2020]
APA - Diagnostic And Statistical Manual Of Mental Disorders 5th ed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Publishing; 2013.
Drugs of Abuse: Body Fluid Testing - Specimens for Drugs-of-Abuse Testing, Ch. 2
Kadehjian L. Chapter 2: specimens for drugs-of-abuse testing. In: Wong RC, Tse HY, eds. Drugs of Abuse: Body Fluid Testing. Humana Press; 2005.
Marek E, Kraft WK. Ethanol pharmacokinetics in neonates and infants. Curr Ther Res Clin Exp. 2014;76:90-97.
Nanau RM, Neuman MG. Biomolecules and biomarkers used in diagnosis of alcohol drinking and in monitoring therapeutic interventions. Biomolecules. 2015;5(3):1339-1385.
NIAAA - Biomarkers of Heavy Drinking
Allen JP, Sillanaukee P, Strid N, et al. Biomarkers of heavy drinking. National Institute on Alcohol Abuse and Alcoholism. [Accessed: Jun 2020]
Jastrzebska I, Zwolak A, Szczyrek M, et al. Biomarkers of alcohol misuse: recent advances and future prospects. Prz Gastroenterol. 2016;11(2):78-89.
Niemelä O. Biomarker-based approaches for assessing alcohol use disorders. Int J Environ Res Public Health. 2016;13(2):166.
Clinical Chemistry, Immunology and Laboratory Quality Control
Dasgupta A, Wahed A. Clinical Chemistry, Immunology and Laboratory Quality Control. Elsevier; 2014.