Specificity of Phosphatidylethanol as a Marker for Alcoholic Beverage Consumption

Utilizing blood phosphatidylethanol (PEth) testing as a means to detect beverage alcohol use vs abstinence among licensed professionals and others is a relatively new development. Phosphatidylethanol is a minor metabolite of ethanol formed when an enzyme, phospholipase D (PLD), binds ethanol to phosphatidylcholine lipids in cell membranes, including red blood cells. Over 48 homologues (similar molecules with varying length of fatty acid chains) of PEth have been discovered. Of the 48 homologues only one or two are typically tested, e.g. 16:0/18:1 and/or 18:0/18:0. Because it appears to require a significant amount of alcohol, >100g (about 7 standard drinks), to trigger a positive test (typical cutoff is 20ng/ml) it has been suggested that a positive test is proof of alcoholic beverage consumption. The rationale is that because such a significant amount of alcohol (to cause a positive test) is very unlikely to be due to extraneous or incidental sources of alcohol, e.g. mouthwash, hand gel, etc., and therefore must be from beverage alcohol use. This makes sense, however, we know historically that no test is 100% specific. So it is important to review the facts.

Fact #1:
Few studies have been conducted to determine the specificity of blood PEth to detect intentional alcoholic beverage use and none have been conclusive. It has been suggested that such a study would need to have a significantly large group of subjects carefully monitored, for example by wearing SCRAM devices or being under strict supervision, for the absence of any beverage alcohol use, while being tested for blood PEth to determine if there are any false positives. Such a study has not been performed. Only by performing PEth testing in subjects who have confirmed abstinence from alcoholic beverages can it be conclusively determined if there are false positive tests at various cutoff levels.

Fact #2:
The cutoff level for reporting a positive test is an important variable that affects specificity. Selected cutoff levels tend to be arbitrary without specific research to determine best cutoff levels to increase specificity without adversely affecting sensitivity. The blood PEth cutoff level used in most medical monitoring at this time is 20ng/ml. This is an arbitrary cutoff. In one study a cutoff value of 221ng/ml, greater than ten times higher, was selected to “avoid false positive readings.”

Fact #3:
When asked about false positive blood PEth tests some experts have opined that there has never been a confirmed false positive. However, there have been a number of studies where groups of individuals were tested and among them were those who claimed that they had not consumed alcoholic beverages but who did test positive. , Authors of these studies have assumed that the subjects were being dishonest, falsely claiming they had not been drinking, resulting in the positive tests. In fact, there is no way to know, from the available information, if the subjects were being dishonest or not. Some, or all, of these positive tests could have been false positives.

Fact #4:
A study attempted to correlate PEth levels (16:0/18.1 and 16:0/18.2) with cutoff of 10ng/ml in 300 light social drinkers to their reported alcohol use and AUDIT-C scores. Only 12 subjects (4%) reported total abstinence and all were negative for blood PEth. Further analysis plotting the Receiver Operating Characteristic (ROC) Curve estimated a specificity for PETH of 96.6%. If this is even close to accurate it suggests that a small portion of individuals may have false positive readings. The authors suggest that “relevant amounts of hidden alcohol in nutrition or medication as well as inter-individual variations of enzyme activities for the formation of PEth might cause unexpected elevated concentration levels of PEth.” Even if the PEth test is 99% specific for alcoholic beverage consumption that still means that 1 out of every 100 tests could be falsely positive. Additionally, the authors of this study determined that a blood PEth level of <112ng/ml corresponded statistically to what they called Moderate Drinking based on the Audit C scores (which correlated to less than an average of 10gm/d of alcohol or less than 1 standard drink per day). Clearly more research is needed in this area.

Conclusions
Until more extensive research is conducted, programs that monitor licensees with blood PEth tests should be careful in how the tests are used and interpreted. In particular when the specificity of a new test is not known with certainty a low positive test (see below for definition “low positive” by one author) should not be used as absolute proof of relapse. In administrative or criminal monitoring settings, this is frustrating to some because they want a test that is absolutely 100% specific.

Even if not 100% specific or if the specificity is not known with certainty new tests can still be helpful. For example, if a new test, such as the blood PEth test, is positive the monitor can question the monitoree and/or observe them more closely. When properly questioned the monitoree may admit relapse. Admission of use is the “gold standard” for diagnosing relapse. If the monitoree denies drinking and there is no other corroborating evidence of relapse continued observation and heightened monitoring may be the best course of action. If under enhanced scrutiny the monitoree starts showing other signs of relapse (e.g. missing meetings, dishonesty, poor work performance, irritability, etc.) then testing can be intensified further and relapse will likely be detected. One thing certain about addiction is its tendency to recur. In other words, if an alcoholic relapses it is almost certain they will continue drinking. Thus if monitoring is continued there will be an opportunity to validate the relapse.

In conclusion, new tests for monitoring alcohol or drug use, such as the blood PEth test, can be useful even though a low positive test (<112ng/ml) by itself may not be proof of relapse. It is unlikely that the specificity of the blood PEth test will be 100%. There are essentially no tests that are perfect. Until adequate studies are performed to document more accurately the specificity of the blood PEth test it seems reasonable that a low positive blood PEth level should not be used by itself as proof of intentional alcoholic beverage consumption.

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