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False-positive breath-alcohol test after a ketogenic diet

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Abstract

A 59-year-old man undergoing weight loss with very low calorie diets (VLCD) attempted to drive a car, which was fitted with an alcohol ignition interlock device, but the vehicle failed to start. Because the man was a teetotaller, he was surprised and upset by this result. VLCD treatment leads to ketonemia with high concentrations of acetone, acetoacetate and beta-hydroxybutyrate in the blood. The interlock device determines alcohol (ethanol) in breath by electrochemical oxidation, but acetone does not undergo oxidation with this detector. However, under certain circumstances acetone is reduced in the body to isopropanol by hepatic alcohol dehydrogenase (ADH). The ignition interlock device responds to other alcohols (e.g. methanol, n-propanol and isopropanol), which therefore explains the false-positive result. This 'side effect' of ketogenic diets needs further discussion by authorities when people engaged in safety-sensitive work (e.g. bus drivers and airline pilots) submit to random breath-alcohol tests.
SHORT COMMUNICATION
False-positive breath-alcohol test after a ketogenic diet
AW Jones
1
and S Ro
¨
ssner
2
1
Department of Forensic Chemistry, National Board of Forensic Medicine and University Hospital, Linko
¨
ping, Sweden and
2
Department of Obesity Research, Karolinska Hospital, Stockholm, Sweden
A 59-year-old man undergoing weight loss with very low calorie diets (VLCD) attempted to drive a car, which was fitted with an
alcohol ignition interlock device, but the vehicle failed to start. Because the man was a teetotaller, he was surprised and upset by
this result. VLCD treatment leads to ketonemia with high concentrations of acetone, acetoacetate and b-hydroxybutyrate in the
blood. The interlock device determines alcohol (ethanol) in breath by electrochemical oxidation, but acetone does not undergo
oxidation with this detector. However, under certain circumstances acetone is reduced in the body to isopropanol by hepatic
alcohol dehydrogenase (ADH). The ignition interlock device responds to other alcohols (e.g. methanol, n-propanol and
isopropanol), which therefore explains the false-positive result. This ‘side effect’ of ketogenic diets needs further discussion by
authorities when people engaged in safety-sensitive work (e.g. bus drivers and airline pilots) submit to random breath-alcohol
tests.
International Journal of Obesity (2007) 31, 559–561. doi:10.1038/sj.ijo.0803444; published online 8 August 2006
Keywords: acetone; alcohol; breath-test; driving; ignition interlocks; VLCD
Obesity constitutes a serious threat to health and longevity
and among various treatment options, very low calorie diets
(VLCD) are frequently used.
1,2
Such diets provide essential
proteins and fats but negligible amounts of carbohydrates
and they typically furnish 800 kcal/day. After a few days of
dieting, fat becomes the main source of energy, and VLCD
regimens are consequently ketogenic.
3
Ketone bodies (acetone, acetoacetate and b-hydroxybuty-
rate) increase appreciably in the blood of people on VLCD.
4,5
Acetone is a water-soluble volatile product of metabolism
and is therefore exhaled in the breath and excreted in the
urine. Indeed, monitoring breath-acetone has been advo-
cated as a way to ensure that patients comply with their
VLCD treatment.
5
The elimination half-life of acetone in man is fairly long
(15–25 h) and the biosynthesis and metabolic fate of this
endogenous metabolite are summarized in Figure 1.
6,7
Dur-
ing ketonemia, the reduction pathway toward isopropanol
becomes a strong possibility and, indeed, this secondary
alcohol has been identified in blood of patients with
hyperglycemia and poorly controlled diabetes.
8–10
The
conversion of acetoacetate into b-hydroxybutyrate and the
reduction of acetone to isopropanol are both nicotinamide
adenine dinucleotide (NAD)-dependent redox reactions.
7
Moreover, administration of amino acids, precursors of
proteins, can accelerate the elimination of ethanol from
blood by enhancing activity of hepatic alcohol dehydrogen-
ase (ADH).
11
An increased ADH activity after eating high
protein diets might help to promote reduction of acetone to
isopropanol.
Among various strategies to reduce drunk driving and
improve road traffic safety, the use of alcohol ignition
interlock devices shows great promise.
12
Such devices are
increasingly being fitted to buses and other public transpor-
tation vehicles as well as long-haul trucks and also in some
private cars, especially in Sweden.
13
Incentives to install
ignition interlock systems in private cars include lower
insurance costs and earlier return of the driving permit to
people convicted of drunk driving and especially to control
recidivism.
12,13
Most of the ignition interlock devices used today measure
alcohol (ethanol) in a person’s breath by electrochemical
oxidation. Endogenous breath volatiles like acetone are not
oxidized at the same electrode potential.
14
However, the
secondary alcohol isopropanol (2-propanol) is oxidized at a
slightly faster rate than ethanol and these two alcohols
cannot be distinguished.
14
Accordingly, if acetone is reduced
to isopropanol during ketonemia, there is a strong possibility
of false-positive results when ignition interlocks are used.
Indeed, the concentration threshold for a positive test and
Received 18 May 2006; revised 31 May 2006; accepted 2 June 2006;
published online 8 August 2006
Correspondence: Dr AW Jones, Department of Forensic Chemistry, National
Board of Forensic Medicine and University Hospital, Artillerigatan 12,
Linko¨ping 581 33, Sweden.
E-mail: wayne.jones@RMV.SE
International Journal of Obesity (2007) 31, 559561
&
2007 Nature Publishing Group All rights reserved 0307-0565/07
$
30.00
www.nature.com/ijo
failure to start the engine is often set fairly low, correspond-
ing to a blood alcohol concentration (BAC) of 0.01–0.02 g/
100 ml (10–20 mg/100 ml).
We report a case of a 59-year-old man, body mass index
26.6 kg/m
2
, who began a weight reduction program, partly
because of knee pains but also because he was a glider pilot
where weight is important. He used a Swedish textbook on
obesity treatment written by S Ro
¨
ssner together with the
commonly used Swedish VLCD Nutrilett (Cederroths,
Stockholm, Sweden), 5 packets/day for 3 weeks, which is an
approved standard regimen. This treatment resulted in a
weight loss of 7 kg.
During dieting, the man discovered that an alcohol
ignition interlock device, installed in an official company
car, indicated that he had consumed alcohol and the vehicle
failed to start. This was confusing because the man was a life-
long teetotaller and was therefore both surprised and upset
by the result. As he had been supervising private aviation
he had access to a second breath-alcohol analyzer, which
indicated a simultaneous BAC ranging from 0.01 to 0.02 g/
100 ml.
In an attempt to understand the reason for the positive
breath-test result, which obviously caused some discomfort
and practical problems, the man contacted the Obesity Unit
(Karolinska University Hospital, Stockholm, Sweden) for
advice, and the mechanism was elucidated. Although we
did not have the opportunity to measure acetone and
isopropanol directly in this subject, the most plausible
explanation for the positive breath-alcohol test is reduction
of acetone to isopropanol, which then undergoes electro-
chemical oxidation.
10
Most countries enforce statutory BAC limits above which
it is an offence to drive a motor vehicle. These limits differ
between countries owing to tradition, lifestyle and political
influences.
15
The punishable BAC limits for driving range
from as low as 0.02 g/100 ml in Norway and Sweden to
0.05 g/100 ml in most European countries and 0.08 g/100 ml
in UK, Ireland, USA and Canada. It seems important
therefore to consider the consequences of ketogenic diets
when blood- and breath-alcohol tests are interpreted in a
legal context.
Suspected drunk drivers first submit to a roadside breath-
alcohol screening test and if this is positive they provide
either an evidential breath-alcohol test or a blood specimen
is taken for laboratory analysis. Breath-alcohol screening
tests incorporate electrochemical detectors similar to those
used in the ignition interlock device and therefore respond
to isopropanol. By contrast, most evidential breath-testing is
performed by multifilter infrared analysis and these are
programmed to abort the test if acetone is detected on the
suspect’s breath above a certain threshold value.
10
Because
the half-life of isopropanol (t
1
2
¼ 3–5 h) is much shorter than
that of acetone (t
1
2
¼ 15–25 h), it is hard to envisage finding
elevated concentrations of isopropanol without concomi-
tant high concentrations of acetone. However, evidential
breath-alcohol analyzers based on electrochemical oxidation
cannot distinguish ethanol from isopropanol and this
resulted in a false-positive test after VLCD. An apparent
BAC of 0.02 g/100 ml seems likely according to the present
case report.
The reduction of acetone to isopropanol is not a problem
with blood-ethanol determination because gas chromato-
graphy is used and this highly specific method can resolve
ethanol from both acetone and isopropanol under normal
operating conditions.
15
In conclusion, we suggest that people on ketogenic diets
run the risk of false-positive breath alcohol tests owing to
reduction of acetone to isopropanol. People on VLCD need
to be warned about this artifact when alcohol ignition
interlock devices are used. This possibility also warrants
consideration in connection with workplace alcohol testing
and screening of drunk drivers with electrochemical sensors.
Both the manufacturers of ignition interlock devices and
government agencies that monitor performance and admin-
ister sanctions should consider these problem. Technological
improvements might be possible, for example, by measuring
not only the final reading but also the kinetics of the
detector response to different alcohols.
Acknowledgements
There was no external funding for preparing this article and
neither author considers there to be any conflicts of interest.
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NAD
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FFA
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FFA ¼ free fatty acids; ADH ¼ alcohol dehydrogenase; NAD
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Ketogenic diets are used therapeutically to treat intractable seizures. Clinically, it appears that the maintenance of ketosis is crucial to the efficacy of the diet in ameliorating seizures. To understand how ketosis and seizure protection are related, a reliable, noninvasive measure of ketosis that can be performed frequently with minimal discomfort is needed. The objective was to determine which index, breath acetone or urinary acetoacetate, is more strongly related to the plasma ketones acetoacetate and beta-hydroxybutyrate. After fasting overnight for 12 h, 12 healthy adults consumed 4 ketogenic meals over 12 h. Blood, breath, and urine samples were collected hourly. Blood was analyzed for plasma acetoacetate and beta-hydroxybutyrate, breath for acetone, and urine for acetoacetate. By the end of the 12-h dietary treatment, plasma acetoacetate, plasma beta-hydroxybutyrate, and breath acetone had increased 3.5-fold, whereas urinary acetoacetate increased 13-fold when measured enzymatically and 25-fold when measured with urinary ketone dipsticks. Plasma acetoacetate was best predicted by breath acetone (R(2) = 0.70, P < 0.0001). Plasma beta-hydroxybutyrate was equally predicted by breath acetone and urinary acetoacetate (R(2) = 0.54, P = 0.0040). Breath acetone is as good a predictor of ketosis as is urinary acetoacetate. Breath acetone analysis is noninvasive and can be performed frequently with minimal discomfort to patients. As an indicator of ketosis in epilepsy patients consuming a ketogenic diet, breath acetone may be useful for understanding the mechanism of the diet, elucidating the importance of ketosis in seizure protection, and ultimately, enhancing the efficacy of the diet by improving patient monitoring.
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Despite the description of the ways of acetone metabolism, its real role(s) is (are) still unknown in metabolic network. In this article, a trial is made to ascertain a comprehensive overview of acetone research extending discussion from chemistry to clinical implications. Mammals are quite similar regarding their acetone metabolism, even if species differences can also be observed. By reviewing experimental data, it seems that plasma concentration of acetone in different species is in the order of 10 microm range and the concentration-dependent acetone metabolism is common to all mammals. At low concentrations of plasma acetone, the C3 pathways are operative, while at higher concentrations, the metabolism through acetate becomes dominant. Glucose formation from acetone may also contribute to the maintenance of a constant blood glucose level, but it seems to be only a minor source for that. From energetical point of view, an interorgan cooperation is suggested because transportable C3 fragments produced in the liver can serve as alternative sources of energy for the peripheral tissues in the short of circulating glucose. The degradation of acetoacetate to acetone contributes to the maintenance of pH buffering capacity, as well. Special attention is paid to the discussion of acetone production in diseases amongst which endogenous and exogenous acetonemiae have been defined. Acetonemiae of endogenous origin are due to the increased rate of acetone production followed by an increase of degrading capacity as cytochrome p450IIE1 (CYPIIE1) isozymes become induced. Exogenous acetonemiae usually resulted from intoxications caused by either acetone itself or other exogenous compounds (ethanol, isopropyl alcohol). It is highlighted that, on the one hand, isopropanol is also a normal constituent of metabolism and, on the other hand, the flat opinion that the elevation of its plasma level is a sign of alcoholism cannot further be held. The possible future directions of research upon acetone are depicted by emphasizing the need for the clear-cut identification of mammalian acetoacetate decarboxylase, and the investigation of race differences and genetic background of acetone metabolism.
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The alcohol ignition interlock is an in-vehicle DWI control device that prevents a car from starting until the operator provides a breath alcohol concentration (BAC) test below a set level, usually .02% (20 mg/dl) to .04% (40 mg/dl). The first interlock program was begun as a pilot test in California 18 years ago; today all but a few US states, and Canadian provinces have interlock enabling legislation. Sweden has recently implemented a nationwide interlock program. Other nations of the European Union and as well as several Australian states are testing it on a small scale or through pilot research. This article describes the interlock device and reviews the development and current status of interlock programs including their public safety benefit and the public practice impediments to more widespread adoption of these DWI control devices. Included in this review are (1) a discussion of the technological breakthroughs and certification standards that gave rise to the design features of equipment that is in widespread use today; (2) a commentary on the growing level of adoption of interlocks by governments despite the judicial and legislative practices that prevent more widespread use of them; (3) a brief overview of the extant literature documenting a high degree of interlock efficacy while installed, and the rapid loss of their preventative effect on repeat DWI once they are removed from the vehicles; (4) a discussion of the representativeness of subjects in the current research studies; (5) a discussion of research innovations, including motivational intervention efforts that may extend the controlling effect of the interlock, and data mining research that has uncovered ways to use the stored interlock data record of BAC tests in order to predict high risk drivers; and (6) a discussion of communication barriers and conceptual rigidities that may be preventing the alcohol ignition interlock from taking a more prominent role in the arsenal of tools used to control DWI. Whether interlock programs can help public policymakers achieve their expressed goals of substantially reducing the level of impaired driving will remain uncertain until procedural barriers and intransigent judiciary practices can be overcome that provide for more systematic routine use of interlock programs. Despite strong effectiveness evidence in all studies to date, the real potential of this technology to reduce the road toll cannot be estimated until they are more widely adopted.