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Specificity of Phosphatidylethanol As A Marker For Alcoholic Beverage Consumptio

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Specificity of Phosphatidylethanol as a Marker


for Alcoholic Beverage Consumption
! JANUARY 14, 2020

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
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48 homologues (similar molecules with varying length of fatty acid chains) of PEth have been
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discovered. Of the 48 homologues only one or Privacy
two are typically tested, e.g. 16:0/18:1 and/or
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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

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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

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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.

2 Comments »
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Awesome post! Keep up the great work!

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Great content! Super high-quality! Keep it up!

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