Phosphatidylethanol

Alcohol use increases the risk of diseases, traumatic injury, and social harms. It is the third leading cause of preventable death in the United States. Biomarkers can detect alcohol use disorder and guide clinical interventions. 

Phosphatidylethanols (Peth) are a group of phospholipids consisting of two fatty acid chains and one phosphate ethyl ester that are formed from phosphatidylcholine and ethanol by the erythrocyte membrane enzyme, phospholipase D. PEth species are categorized by the number of carbon atoms (typically 14-22) and double bonds. PEth molecules with 16 or 18 carbon atoms and 1 or 2 double bonds (16:0/18:1 and 16:0/18:2) are the most common forms.

PEth is a whole blood marker of chronic alcohol consumption that is more sensitive than carbohydrate deficient transferrin (CDT), ethyl glucuronide, and ethyl sulfate. Since PEth can detect chronic and one-time alcohol consumption, it can be used to monitor alcohol consumption, abstinence, and relapse. 

PEth is formed only in the presence of ethanol. PEth formation and degradation are not affected by age, sex, chronic kidney disease, or hepatic dysfunction. The rate of PEth formation depends on the level and activity of phospholipase D, which varies among individuals. It can be detected in blood as soon as 1 to 2 hours after a single bout of alcohol consumption. The degradation rate of PEth also varies, with an estimated mean half-life of 4 to 10 days. However, PEth may be detectable up to 5 weeks after heavy alcohol consumption. Blood PEth level increases with higher quantity and frequency of alcohol consumption and decreases with time elapsed since last ingestion of alcohol.

A PEth concentration less than 20 ng/mL indicates minimal or no recent alcohol consumption. PEth concentrations of 20 ng/ml or higher is evidence of increased ethanol consumption. This cutoff has a sensitivity of 81% and specificity of 76% for the detection of heavy alcohol consumption. A PEth concentration greater than 200 ng/mL correlates with heavy alcohol consumption (4 or more standard drinks per day). A standard drink is defined as equivalent to 12 fl oz of beer, 5 fl oz of wine, or 1.5 fl oz of distilled spirits.

A false positive PEth test result may occur if an individual receives a blood transfusion from a person who recently consumed alochol, due to PEth in donated erythrocytes. Falsely low PEth concentrations may occur in patients with low haptoglobin levels, consistent with intravascular hemolysis.

Method of detection is quantitative liquid chromatography/Tandem Mass Spectrometry. Specimen requirement is a lavender or grey top tube of blood or a dried blood spot. Blood tubes should be refrigerated. 

References

Fleming MF et al. Phosphatidylethanol (PEth) detects moderate to heavy alcohol use in liver transplant recipients. Alcohol Clin Exp Res. 2017;41:857-862.

Jannetto PJ. Selecting and Interpreting Alcohol Biomarker Tests: Enough to Drive you to Drink. J Appl Lab Med. 2018;2:827-29. 

Andresen-Streichert H. et al. Alcohol Biomarkers in Clinical and Forensic Contexts. Dtsch Arztebl Int. 2018;115(18):309-15.

Hahn JA. Et al. Phosphatidylethanol vs Transdermal Alcohol Monitoring for Detecting Alcohol Consumption Among Adults. 2023;6(9):e2333182. doi:10.1001/jamanetworkopen.2023.33182.

Mazhar A and Cheung A. Blood Testing for Phosphatidylethanol. JAMA Network, published online May 15, 2024, doi:10.1001/jama.2024.3607