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False-positive breath-alcohol test after a ketogenic diet



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.
False-positive breath-alcohol test after a ketogenic diet
AW Jones
and S Ro
Department of Forensic Chemistry, National Board of Forensic Medicine and University Hospital, Linko
ping, Sweden and
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
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.
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.
Ketone bodies (acetone, acetoacetate and b-hydroxybuty-
rate) increase appreciably in the blood of people on VLCD.
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.
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.
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.
conversion of acetoacetate into b-hydroxybutyrate and the
reduction of acetone to isopropanol are both nicotinamide
adenine dinucleotide (NAD)-dependent redox reactions.
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).
An increased ADH activity after eating high
protein diets might help to promote reduction of acetone to
Among various strategies to reduce drunk driving and
improve road traffic safety, the use of alcohol ignition
interlock devices shows great promise.
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.
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
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.
However, the
secondary alcohol isopropanol (2-propanol) is oxidized at a
slightly faster rate than ethanol and these two alcohols
cannot be distinguished.
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
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
, 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.
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
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.
the half-life of isopropanol (t
¼ 3–5 h) is much shorter than
that of acetone (t
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.
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.
There was no external funding for preparing this article and
neither author considers there to be any conflicts of interest.
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International Journal of Obesity
... Belirli koşullar altında aseton hepatik alkol dehidrojenaz enzimiyle izopropanole indirgenir. İndirgenme ürünü olan izopropanol nefes alkol testinde yanlış pozitif sonuçlara yol açabilir [22]. Nefes alkol testleri, analizi etkileyen faktörlerin alımından hemen sonra veya ilk 15 dakika içinde yapılırsa yalancı pozitif sonuçlara neden olmaktadır. ...
... While the exspiration of isopropanol might mirror endogeneous uptake secondary to the use of disinfectant, this will hardly translate into the associations mentioned above. Instead, the reduction of acetone to isopropanol by means of a nicotinamide adenine dinucleotide dependent redox-reaction has to be considered 46 . The formation of isopropanol contributes to acetone metabolism and this pathway may be activated in T1DM patients and thus contributing to acetone elimination and indicating metabolic adaptation. ...
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Monitoring metabolic adaptation to type 1 diabetes mellitus in children is challenging. Analysis of volatile organic compounds (VOCs) in exhaled breath is non-invasive and appears as a promising tool. However, data on breath VOC profiles in pediatric patients are limited. We conducted a cross-sectional study and applied quantitative analysis of exhaled VOCs in children suffering from type 1 diabetes mellitus (T1DM) (n = 53) and healthy controls (n = 60). Both groups were matched for sex and age. For breath gas analysis, a very sensitive direct mass spectrometric technique (PTR-TOF) was applied. The duration of disease, the mode of insulin application (continuous subcutaneous insulin infusion vs. multiple daily insulin injection) and long-term metabolic control were considered as classifiers in patients. The concentration of exhaled VOCs differed between T1DM patients and healthy children. In particular, T1DM patients exhaled significantly higher amounts of ethanol, isopropanol, dimethylsulfid, isoprene and pentanal compared to healthy controls (171, 1223, 19.6, 112 and 13.5 ppbV vs. 82.4, 784, 11.3, 49.6, and 5.30 ppbV). The most remarkable differences in concentrations were found in patients with poor metabolic control, i.e. those with a mean HbA1c above 8%. In conclusion, non-invasive breath testing may support the discovery of basic metabolic mechanisms and adaptation early in the progress of T1DM.
... Thus, a correlation of acetone with blood glucose is difficult even under healthy conditions and the time-resolved calculation of the correlation coefficients in our study strengthen this observation. Furthermore, the impact of hepatic alcohol dehydrogenase, i.e., the reduction of acetone to isopropanol, has to be considered [49]. In fact, T1DM patients exhaled significantly more isopropanol than their healthy peers and both, the diurnal profile as well as the time resolved correlation coefficients, closely resembled that of acetone. ...
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An analysis of exhaled volatile organic compounds (VOC) may deliver systemic information quicker than available invasive techniques. Metabolic aberrations in pediatric type 1 diabetes (T1DM) are of high clinical importance and could be addressed via breathomics. Real-time breath analysis was combined with continuous glucose monitoring (CGM) and blood tests in children suffering from T1DM and age-matched healthy controls in a highly standardized setting. CGM and breath-resolved VOC analysis were performed every 5 minutes for 9 hours and blood was sampled at pre-defined time points. Per participant (n = 44) food intake and physical activity were identical and a total of 22 blood samples and 93 minutes of breath samples were investigated. The inter-individual variability of glucose, insulin, glucagon, leptin, and soluble leptin receptor relative to food intake differed distinctly between patients and controls. In T1DM patients, the exhaled amounts of acetone, 2-propanol, and pentanal correlated to glucose concentrations. Of note, the strength of these correlations strongly depended on the interval between food intake and breath sampling. Our data suggests that metabolic adaptation through postprandial hyperglycemia and related oxidative stress is immediately reflected in exhaled breath VOC concentrations. Clinical translations of our findings may enable point-of-care applicability of online breath analysis towards personalized medicine.
... Expired air could allow the real time monitoring of targeted food properties or the synergism of various food-stuffs or even diets enriched with specific groups of compounds (e.g. diet high in protein consumption) [103][104][105][106]. Research in this field is still limited; however, these characteristic breath markers could potentially be associated with short-and long-term health effects, beneficial actions or drawbacks of these products. ...
... Expired air could allow the real time monitoring of targeted food properties or the synergism of various food-stuffs or even diets enriched with specific groups of compounds (e.g. diet high in protein consumption) [103][104][105][106]. Re- search in this field is still limited; however, these characteristic breath markers could potentially be associated with short-and long-term health effects, beneficial actions or drawbacks of these products. ...
Chemical analysis (detection and monitoring) of compounds associated with the metabolic activities of an organism is at the cutting edge of science. Volatile metabolomics (volatolomics) are applied in a broad range of applications including: biomedical research (e.g. disease diagnostic tools, personalized healthcare and nutrition, etc.), toxicological analysis (e.g. exposure tool to environmental pollutants, toxic and hazardous chemical environments, industrial accidents, etc.), molecular communications, forensics, safety and security (e.g. search and rescue operations). In the present review paper, an overview of recent advances and applications of volatolomics will be given. The main focus will be on volatile organic compounds (VOCs) originating from biological secretions of various organisms (e.g. microorganisms, insects, plants, humans) and resulting fusion of chemical information. Bench-top and portable or field-deployable technologies-systems will also be presented and discussed.
... Under pathological conditions, isopropanol was detectable in plasma not only in the case of alcohol intoxication, but also in diseases such as diabetes mellitus as well as liver and gastrointestinal diseases, and the plasma acetone concentration was at the same time increased [49, 143-145, 150, 151]. Moreover, higher isopropanol level resulted in a false-positive ethanol test outcome for a man, who was under a ketogenic diet, during traffic control [152]. Transplacental isopropanol exposure in pregnancy was also reported [153]. ...
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In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels are important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings and the price of instruments. When considering the biological ranges of acetone personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information to disorders. In some diseases including diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident such as alcoholism or inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavours are needed for clarification of the exact distribution of acetone in different body compartments and evaluation its complex role in humans especially in those cases in which ketotic state also occurs.
... La variabilità biologica dell'esame ha varie componenti, tra le quali, oltre alla variazione "vera" del livello di alcol (che comunque oscilla nel tempo) e alla variabilità determinata dalla modalità di esecuzione (inspirazione di una maggiore o minore quantità di aria, presenza di muco nelle vie respiratorie ecc.), nonché delle possibilità di errore, dovute alla presenza di altri elementi che reagiscono come farebbe l'alcol etilico (ad esempio, in coloro che seguono una dieta ipocalorica (81), oppure nel corso di altre patologie accompagnate da acetonemia, come diabete mellito scompensato, stati febbrili con digiuno, digiuno in alcuni trattamenti dimagran-ti…). Infine, bisogna tenere conto della variabilità analitica dello strumento. ...
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We report the identification of acetone (0.45 mg/mL) and isopropanol (0.17 mg/mL) but without the presence of ethanol in a blood sample from a man suspected of driving under the influence of alcohol. A preliminary breath screening test with an electrochemical instrument (Alcolmeter S-L2) was positive and an evidential breath-test with a dual wavelength infrared analyzer (Intoxilyzer 5000), recognized the presence of an interferant in the subject's breath. The man admitted drinking moderate amounts of alcohol (vodka) the previous evening and was being treated by his doctor for hyperglycemia by special dietary control. This case scenario provides a good example of severe metabolic ketoacidosis in an ostensibly healthy man driving on the highway. Biotransformation of the abnormally high concentration of blood-acetone to isopropanol occurs through the alcohol dehydrogenase pathway.
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.
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.
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.