Original Article
Detection of alcohol use: Guidance of direct biomarker phosphatidylethanol
Dilek Salkim IslekReceiving Date: 17 January 2023
Accept Date: 03 March 2023
Available Online: 18 March 2023
Acknowledging the fact that alcohol is an important source of fatalities in traffic, the amount of alcohol consumed and the exact time of the consumption could enlighten forensic cases and guide the justice system correctly. However, determining the alcohol use is a difficult problem due to alcohol metabolism in individuals and parameters such as sex, age, amount of alcohol in the drink, satiety, should be taken into account which can be challenging for amount of alcohol interpretation. Considering that blood alcohol concentration (BAC) may not be reliable, alternative metabolic products of alcohol has arisen after alcohol consumption. One of the most interesting alcohol biomarker phosphatidylethanol (PEth) has caught attention due to its long half-life and not being affected from sex, liver diseases or age in addition to that it is only synthesized under the presence of ethanol. PEth is synthesized in cell-membranes and not being a single molecule, its homologues should be considered when determining the amount of alcohol intake. Although the homologues of PEth could be isolated from whole blood, less invasive dried blood spots (DBS) also provides reliable information. The analysis of PEth is performed in LC-MS/MS which is highly sensitive and specific. For forensic applications, direct alcohol biomarker PEth may be useful for distinguishing the alcohol use and helpful for justice system. This review focuses on studies about PEth biomarker, its applications and limitations conducted from 2010 to 2019.
Keywords: Direct biomarker PEth, LC-MS/MS, alcohol
INTRODUCTION
According to the report published from OECD, alcohol-related traffic accidents in Europe is approximately 12.9% [1]. Alcohol is an easily accessible legal drug and used in social environments. According to World Health Organization, in 2016, 3 million people died worldwide due to alcohol-based reasons [2]. Giving the importance of alcohol in terms of forensic sciences, determining the amount of alcohol consumed become essential. Although it is hard to detect the ethanol in biological matrices after 10-12 hours after consumption [3], other biomarkers produced in the body might be more convenient for detection of alcohol. There are indirect and direct alcohol biomarkers to identify alcohol consuming for helping the justice. Among indirect biomarkers aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), mean corpuscular volume (MCV) and carbohydrate deficient transferrin (CDT%) provide information with indirect response of body after the ethanol consumption [4]. Indirect biomarkers generally used for supportive evidence of alcohol use due to their low sensitivity and specificity [4]. To obtain reliable information for alcohol use, direct biomarkers which are ethyl glucuronide (EtG), ethly sulfate (EtS), fatty acid ethyl esters (FAEE) and phosphatidylethanol (PEth), are relied upon due to their power of being ethanol metabolites [5]. However, there are some limitations in every biomarker. For instance, EtG and EtS are the most common used biomarkers for clinical studies and forensic laboratories, although their detection time in both urine and serum is short [3]. FAEEs are generally used for chronic alcohol determination from hair [4] and alcohol misuse of the mother from meconium [6].
PEth as a Biomarker
PEth is the name of different phospholipids found in the outer layer of the cell membranes. Not representing a single molecule, PEth is synthesized from one of the basic homologues forming the outer cell membrane phosphatidylcholine (PC). PC is an interesting substance that is affected by the nutrients intake and when water is present in the cell, with the help of phospholipase D (PLD) enzyme, it is converted to phosphatidic acid (PA) and choline. However, if there is an alcohol intake, PLD enzyme has more affinity to ethanol than water, PC forms PEth and choline which makes the reaction highly specific [3,4,7,8].
PEth homologues can be detected in various parts of the body including brain, liver, and kidney. Although it is found in some parts of the body, antemortem forensic cases require different matrices for detection of PEth. The fact that PEth is successfully isolated from erythrocytes in whole blood, it is routinely analyzed in some countries for determining alcohol misuse. In whole blood, the most abundant homologue of PEth is 16:0/18:1. This homologue made up 37% of all PEth and it is formed by PC 16:0/18:1, which the left side represents the number of carbon atoms and the right side shows the number of double bonds in the homologues. Among forty homologues, other PEthsbe considered while deciding the amount of alcohol intake are 16:0/18:2, 16:0/20:4, 18:1/18:1from high percentage to low, respectively [7-9].
As being discovered at 1983 in rats and seen as a potential alcohol biomarker at 1997 [7], scientists have studied PEth homologues and their applicability for approximately 40 years. PEth is a powerful source for deciding chronic alcohol use and abstinence. In addition, it can guide to differentiate between moderate and low alcohol consumption. There has been studies for PEth and promising results have been found (Table 1).
CONCLUSION
In conclusion, phosphatidylethanol (PEth) has emerged as a promising alcohol biomarker due to its high specificity and sensitivity for detecting recent heavy alcohol consumption. PEth is formed in the body when alcohol is metabolized, and its levels in blood and other bodily fluids can be used to determine the extent and duration of alcohol consumption. Its reliability is based on the fact that PEth is produced only in the presence of ethanol and is not influenced by other factors such as food intake or non-alcoholic beverages.
In the light of the results obtained from the previously mentioned articles, studies on PEth in 2020 and beyond show us that PEth shows promise as a biomarker [17-22].
PEth is advantageous over traditional alcohol biomarkers such as blood alcohol concentration (BAC) and liver function tests (LFTs) because it is less susceptible to short-term fluctuations and can detect alcohol use up to several weeks after consumption. Additionally, PEth testing is non-invasive and can be performed using a simple blood test, making it a more convenient option for both patients and healthcare providers. PEth has been shown to be useful in a variety of settings, including clinical practice, forensic toxicology, and alcohol research. Although PEth has limitations such as inter-individual variability and the need for specialized analytical equipment, its advantages make it a valuable tool for assessing alcohol consumption in both clinical and research settings.
Further research is needed to establish standardized cutoff levels for PEth and to determine its usefulness in detecting different patterns of alcohol consumption, such as binge drinking or chronic heavy drinking. Nevertheless, PEth is a promising alcohol biomarker that has the potential to improve the accuracy of alcohol assessment and to inform treatment decisions for individuals with alcohol use disorders.
- Vissers L, Houwing S, Wegman, F. Chapter-1. In: alcohol-related road casualties in official crash statistics. ITF: International Transport Forum, Paris, 2018;9-14.
- World Health Organization. Health Consequences. In: global status report on alcohol and health. Geneva, 2018;62-85.
- Andresen-Streichert H, Müller A, Glahn A, et al. Alcohol biomarkers in clinical and forensic contexts. Dtsch Arztebl Int. 2018;115:309-15.
- De Vos A, De Troyer R, Stove C. Biomarkers of alcohol misuse. In: Preedy Victor R, eds. Neuroscience of alcohol: mechanisms and treatment. London, Academic Press, 2019;557-65.
- Ghosh S, Jain R, Jhanjee S, et al. Alcohol biomarkers and their relevance in detection of alcohol consumption in clinical settings. Int Arch Subst Abuse Rehabil. 2019;1:002.
- Bakhireva LN, Savich RD, Raisch DW, et al. The feasibility and cost of neonatal screening for prenatal alcohol exposure by measuring phosphatidylethanol in dried blood spots. Alcohol Clin Exp Res. 2013;37:1008-15.
- Hill-Kapturczak N, Dougherty DM, Roache JD, et al. Phosphatidylethanol homologs in blood as biomarkers for the time frame and amount of recent alcohol consumption. In: Preedy Victor R, eds, Neuroscience of alcohol: mechanisms and treatment. London, Academic Press, 2019;567-76.
- Stenton J, Walther L, Hansson T, et al. Inter individual variation and factors regulating the formation of phosphatidylethanol. Alcohol Clin Exp Res. 2019;43:2322-31.
- Luginbühl M, Willem S, Schürch S, Weinmann W. Formation of phosphatidylethanol from endogenous phosphatidylcholines in animal tissues from pig, calf, and goat. Forensic Sci Int. 2018;283:211-8.
- Marques P, Tippetts S, Allen J, et al. Estimating driver risk using alcohol biomarkers, interlock blood alcohol concentration tests and psychometric assessments: initial descriptives. Addiction. 2010;105:226-39.
- Gnann H, Weinmann W, Thierauf A. Formation of phosphatidylethanol and its subsequent elimination during an extensive drinking experiment over 5 days. Alcohol Clin Exp Res. 2012;36:1507-11.
- Schröck A, Hernández Redondo A, Martin Fabritius M, et al. Phosphatidylethanol (PEth) in blood samples from “driving under the influence” cases as indicator for prolonged excessive alcohol consumption. Int J Legal Med. 2016;130:393-400.
- Walther L, de Bejczy A, Löf E, et al. Phosphatidylethanol is superior to carbohydrate-deficient transferrin and γ-glutamyltransferase as an alcohol marker and is a reliable estimate of alcohol consumption level. Alcohol Clin Exp Res. 2015;39:2200-8.
- Javors MA, Hill-Kapturczak N, Roache JD, et al. Characterization of the pharmacokinetics of phosphatidylethanol 16:0/18:1 and 16:0/18:2 in human whole blood after alcohol consumption in a clinical laboratory study. Alcohol Clin Exp Res. 2016;40:1228-34.
- Hill-Kapturczak N, Dougherty DM, Roache JD, et al. Differences in the synthesis and elimination of phosphatidylethanol 16:0/18:1 and 16:0/18:2 after acute doses of alcohol. Alcohol Clin Exp Res. 2018;42:851-60.
- Schröck A, Thierauf-Emberger A, Schürch S, Weinmann W. Phosphatidylethanol (PEth) detected in blood for 3 to 12 days after single consumption of alcohol-a drinking study with 16 volunteers. Int J Legal Med. 2017;131:153-60.
- Beck O, Mellring M, Löwbeer C, et al. Measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spots and venous blood-importance of inhibition of post-sampling formation from ethanol. Anal Bioanal Chem. 2021;413:5601-6.
- Jørgenrud B, Kabashi S, Nadezhdin A, et al. The association between the alcohol biomarker phosphatidylethanol (PEth) and self-reported alcohol consumption among russian and norwegian medical patients. Alcohol Alcohol. 2021;56:726-36.
- Jørgenrud B, Skadberg E, de Carvalho Ponce J, et al. Determination of the alcohol biomarker phosphatidylethanol 16:0/18:1 and 33 compounds from eight different drug classes in whole blood by LC-MS/MS. J Pharmacol Toxicol Methods. 2021;107:106939.
- Finanger T, Spigset O, Gråwe RW, et al. Phosphatidylethanol as blood biomarker of alcohol consumption in early pregnancy: an observational study in 4,067 pregnant women. Alcohol Clin Exp Res. 2021;45:886-92.
- McGinnis KA, Tate JP, Bryant KJ, et al. Change in alcohol use based on self-report and a quantitative biomarker, phosphatidylethanol, in people with HIV. AIDS Behav. 2022;26:786-94.
- Novak L, Soravia LM, Bünter A, et al. Alcohol biomarker phosphatidylethanol as a predictor of the severity of alcohol withdrawal syndrome. Alcohol Alcohol. 2023;58:198-202.
Conflict of interests
The authors declare that there is no conflict of interest in the study.
Financial Disclosure
The authors declare that they have received no financial support for the study.
Ethical approval
Ethics committee approval is not required.
8,603 total views, 3 views today
CITATION
Islek DS, Kula FB, Kiris E, et al. Detection of alcohol use: guidance of direct biomarker phosphatidylethanol. NOFOR. 2023;2(1):18-20.
DOI: 10.5455/NOFOR.2023.03.03
Corresponding Author: Dilek Salkim Islek, Istanbul University-Cerrahpasa Institute of Forensic Medicine and Forensic Sciences, Istanbul, Türkiye
Email: salkimdilek@gmail.com
