The measurement of ethanol in blood is widely used for determination of intoxication in both clinical and forensic settings. These results are often used to extrapolate the blood alcohol content (BAC) at the time of a specific incident using the Widmark equation. The ethanol metabolites ethylglucuronide (EtG) and ethylsulfate (EtS) are typically measured in urine and extend the window of detection to several days after consumption. Several limitations exist with EtG and EtS, including the inability to determine the degree of alcohol use, formation after incidental exposure to ethanol, and in vitro formation and hydrolysis after sample collection for EtG. Two less commonly encountered markers of alcohol use include fatty acid ethyl esters (FAEE) and phosphatidylethanol (PEth). For measurements in blood, FAEEs have a shorter window of detection compared to PEth and there are close to 50 species of PEth previously identified. The good news is that greater than 50% of measurable PEth is attributed to two species, 16:0/18:1 and 16:0/18:2. PEth is by no means the newest marker but one could argue it remains one of the most underappreciated.
Phosphatidylethanol is an ethanol-derived phospholipid (a molecule with a hydrophilic head and two hydrophobic tails). Normally, water is the molecule of choice for the enzyme phospholipase D and removal of choline from the head produces phosphatidic acid. Phospholipase D’s preference for ethanol is more than 1000 times that of water, and when ethanol is present phospholipase D will place ethanol onto the phospholipid head producing phosphatidylethanol. PEth species are named based on fatty acid composition using [number of carbons]:[number of double bounds] nomenclature to arrive for example at 16:0/18:1 for an individual species.
PEth concentration is dependent on blood alcohol concentration with a strong correlation between alcohol consumption and blood PEth concentration. This relationship has been shown to encompass drinking behavior for the prior 2 weeks with a potential window of detection extending up to 4 weeks after heavy drinking has stopped. As of the writing of this Scientific Short there are nearly 800 peer-reviewed articles on PEth spanning over four decades of research. But the number of publications about this ethanol-derived phospholipid contrasts with its absence on many laboratory test menus. Its utility seems obvious, however, establishing a reliable method and providing the needed guidance for accurate interpretation may be roadblocks.
PEth interpretation is less established, though numerous publications continue to propose that concentrations below 20 ng/mL are consistent with abstinence or light drinking, 20 to 200 ng/mL is indicative of moderate drinking, and greater than 200 ng/mL is associated with heavy drinking. In addition, the few number of PEth assays available are not harmonized on which species are reported despite the majority of interpretive evidence being based on the measurement of the predominant 16:0/18:1 species.
For now, there is no one-size-fits-all marker of choice with the utility of each alcohol marker being based on the context in which it is being used. The bar for implementing a new diagnostic analyte into laboratory medicine is understandably high and it may be that trying to make sense of nearly 800 articles on PEth is like trying to eat this alphabet soup with a fork when all we really need is one good vowel movement.
REFERENCES
- Mastrovito R, Strathmann FG. Distributions of alcohol use biomarkers including ethanol, phosphatidylethanol, ethyl glucuronide and ethyl sulfate in clinical and forensic testing. Clin Biochem 2020.
- Viel G, Boscolo-Berto R, Cecchetto G, Fais P, Nalesso A, Ferrara SD. Phosphatidylethanol in blood as a marker of chronic alcohol use: A systematic review and meta-analysis. Int J Mol Sci 2012;13:14788-812.
- Helander A, Zheng Y. Molecular species of the alcohol biomarker phosphatidylethanol in human blood measured by lc-ms. Clin Chem 2009;55:1395-405.