Phosphatidylethanol (PEth) testing is a clinical tool used to monitor alcohol consumption over the preceding two to four weeks. Unlike traditional markers that are easily affected by other health conditions, PEth is highly regarded as a direct biomarker for ethanol, boasting a specificity often cited above 99%. This reliability makes a truly false positive—a result caused by a substance other than ethanol—extremely rare. However, the term “false positive” often refers to a positive result that does not accurately reflect chronic heavy drinking, which can occur due to incidental exposure, biological variability, or procedural errors. Understanding these limitations is necessary for the accurate interpretation of the test results.
The Mechanism of PEth Formation
The reliability of the PEth test stems from its unique formation process, which requires the direct involvement of ethanol. PEth is an abnormal phospholipid created when the enzyme Phospholipase D (PLD) acts on the phospholipids in the red blood cell membrane. Normally, PLD uses water to convert phosphatidylcholine into phosphatidic acid, a process involved in normal cell signaling.
When ethanol is present in the bloodstream, the PLD enzyme mistakenly uses the ethanol molecule instead of water in this reaction. This enzymatic substitution results in the formation of PEth, covalently attaching the alcohol to the cell membrane structure. Because this reaction only happens when ethanol is circulating in the blood, the presence of PEth confirms recent exposure to ethanol. The PEth molecules become trapped in the red blood cell membranes, providing the extended detection window.
Non-Beverage Sources of Ethanol Exposure
While PEth formation requires ethanol, the ethanol source does not need to be an alcoholic beverage. Certain household and over-the-counter products contain enough ethanol to be absorbed into the bloodstream. These incidental exposures, while unlikely to cause high PEth levels, can potentially push a result above the lowest detection threshold.
Alcohol-based hand sanitizers and mouthwashes are the most frequently cited non-beverage sources of concern. Studies suggest that even with regular, intensive use of an alcohol-based mouthwash, the resulting PEth level is generally below the 20 nanograms per milliliter (ng/mL) cutoff used to indicate meaningful consumption. However, concentrated or frequent topical exposure, such as habitual use of high-concentration alcohol sprays, has been shown in some case studies to cause PEth levels above the lowest thresholds.
Certain fermented foods and herbal remedies also contain trace amounts of ethanol. Examples include specific nutritional supplements, some cold medications, and products like kombucha or Bach Flower Remedies, which can contain ethanol in the range of 1% to 27%. For a positive result, the exposure must be sustained and significant, meaning small, isolated exposures are generally insufficient to generate a PEth concentration above the lowest clinical cutoff.
Biological Factors and Interpretation Thresholds
PEth is a quantitative biomarker, meaning the numerical result is interpreted against established cutoff levels that distinguish between consumption patterns. A common cutoff of 20 ng/mL is often used to delineate between abstinence or incidental exposure and recent intentional alcohol consumption. Levels above 210 ng/mL are widely accepted as indicating chronic, heavy alcohol use.
Individual biological differences significantly influence how any given amount of alcohol translates into a PEth value. The rate at which PEth is metabolized and cleared from the body varies widely, with a reported half-life ranging from 4 to 12 days between individuals. Someone with a slower PEth elimination rate may retain the marker for longer, meaning a low positive result could reflect moderate drinking from several weeks prior, rather than recent use.
Variability in the activity of the Phospholipase D enzyme, which creates PEth, also differs among people. This means that for the exact same amount of consumed alcohol, one person may form more PEth than another, complicating the direct correlation between the numerical result and consumption volume. Factors such as Body Mass Index (BMI) and certain liver conditions may also affect PEth sensitivity, highlighting the need for cautious interpretation of results that fall near the lower cutoff.
Sample Collection and Laboratory Integrity
Procedural errors during the collection and handling of the blood sample represent an external cause of inaccurate positive results. Contamination of the sample with external ethanol is a primary concern, particularly when using the dried blood spot (DBS) method. If the collection site is not properly disinfected or if an alcohol-based wipe is used immediately prior to the finger prick, ethanol can contaminate the blood before it dries.
Issues with sample stability can also lead to an elevated PEth concentration after the blood is drawn. Since the enzyme PLD remains active in wet blood, PEth can continue to form post-collection if the sample is not stored correctly or if there is a delay in the drying process. Laboratories mitigate this risk by using specific collection cards containing PLD inhibitors or by adhering to strict drying and storage protocols.
While rare in accredited facilities, analytical and clerical errors within the testing laboratory can compromise the integrity of the result. These issues can include instrument malfunction or miscalibration, reagent contamination, or a mix-up in the chain-of-custody where a sample is mistakenly attributed to an abstainer. Rigorous adherence to quality control and chain-of-custody procedures is mandatory to prevent these procedural mistakes.