Received: 12 February 2021
Revised: 29 March 2021
Accepted: 11 April 2021
Measuring ketone bodies for the monitoring of pathologic
and therapeutic ketosis
Joseph C. Anderson
|Samer G. Mattar
|Frank L. Greenway
|Richard J. Lindquist
Department of Bioengineering, University of
Washington, Seattle, Washington, USA
Department of Surgery, Baylor College of
Medicine, Houston, Texas, USA
Pennington Biomedical Research Center,
Baton Rouge, Louisiana, USA
Department of Family Medicine, Swedish
Medical Center, Seattle, Washington, USA
Joseph C. Anderson, Department of
Bioengineering, University of Washington,
Box 355061, Seattle, WA 98195‐5061, USA.
Medamonitor Corp, Seattle, WA; National
Institute of General Medical Sciences, Grant/
Award Number: 1 U54 GM104940
Background: The ketone bodies β‐hydroxybutyrate (BOHB) and acetone are
generated as a byproduct of the fat metabolism process. In healthy individuals,
ketone body levels are ∼0.1 mM for BOHB and ∼1 part per million for breath
acetone (BrAce). These levels can increase dramatically as a consequence of a
disease process or when used therapeutically for disease treatment. For example,
increased ketone body concentration during weight loss is an indication of elevated
fat metabolism. Ketone body measurement is relatively inexpensive and can provide
metabolic insights to help guide disease management and optimize weight loss.
Methods: This review of the literature provides metabolic mechanisms and typical
concentration ranges of ketone bodies, which can give new insights into these
conditions and rationale for measuring ketone bodies.
Results: Diseases such as heart failure and ketoacidosis can affect caloric intake and
macronutrient management, which can elevate BOHB 30‐fold and BrAce 1000‐fold.
Other diseases associated with obesity, such as brain dysfunction, cancer, and
diabetes, may cause dysfunction because of an inability to use glucose, excessive
reliance on glucose, or poor insulin signaling. Elevating ketone body concentrations
(e.g., nutritional ketosis) may improve these conditions by forcing utilization of
ketone bodies, in place of glucose, for fuel. During weight loss, monitoring ketone
body concentration can demonstrate program compliance and can be used to
optimize the weight‐loss plan.
Conclusions: The role of ketone bodies in states of pathologic and therapeutic
ketosis indicates that accurate measurement and monitoring of BOHB or BrAce will
likely improve disease management. Bariatric surgery is examined as a case study
for monitoring both types of ketosis.
β‐hydroxybutyrate, acetone, bariatric surgery, metabolism
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.
Obes Sci Pract. 2021;7:646–656. wileyonlinelibrary.com/journal/osp4
The recent popularity of the ketogenic diet (KD) has kindled a
renewed interest in the creation and metabolism of ketone bodies
and the state of ketosis. This diet, characterized by high‐fat and very
low‐carbohydrate (<50 g/day) intake, appears to result in improve-
ments in weight management, metabolic syndrome, and cognition.
Implicitly, the diet mandates a marked reduction in carbohydrate
intake, which results in the generation and utilization of ketone
bodies, instead of carbohydrates, to fuel the brain and other neuro-
logic tissues. Many authorities assumed that ketone bodies, in states
of carbohydrate restriction, are the primary drivers for the perceived
beneﬁts of the KD. Because of this success, an explosion in research
has taken place to identify additional interventions that may increase
ketosis (e.g., intermittent fasting and exogenous supplementation)
and to better understand the effects of ketosis in health and dis-
Ketosis is deﬁned as the elevated concentration of ketone bodies
in the blood. Ketone bodies are comprised of three chemicals: ace-
toacetate, β‐hydroxybutyrate (BOHB), and acetone. Acetoacetate is
created in the liver from free fatty acids (FFAs) when glucose avail-
ability is limited. Acetoacetate can be enzymatically interconverted
Additionally, acetoacetate can be decarboxylated,
spontaneously or by catalytic action, into acetone (Figure 1).
tone body concentrations increase with corresponding increases in
Recent studies have also demonstrated a number of non‐diet‐
related disease conditions that can cause elevated ketosis.
These diseases cause hyperketonemia for a variety of reasons,
including poor insulin signaling in diabetes, impaired fatty acid
metabolism in heart failure (HF), and slow ketone body elimination as
a result of genetic disorders. It is logical, therefore, that monitoring
ketosis levels may provide a complete picture of the behavior and
severity of the underlying disease. Additionally, periodic ketosis
monitoring may help in the management and treatment of the
Some diseases appear to respond favorably to an increase in
ketosis. It has been demonstrated that once ketones reach “thera-
peutic” levels, they help attenuate disease severity or result in dis-
Examples include neurologic diseases where the
ketone bodies provide fuel to metabolically compromised brain re-
gions and treatment of type 2 diabetes to improve diabetic sequelae
and reduce medications. Thus, monitoring ketosis levels can help
maintain therapeutic concentrations of ketone bodies to optimize
Additionally, weight loss creates an elevation in fat metabolism
that is reﬂected in elevated ketone body concentrations.
Elevated fat metabolism is correlated with increased ketone body
Thus, medical weight loss and weight loss prior to
bariatric surgery may be optimized and compliance assessed by
monitoring ketone bodies as surrogate markers of subject‐speciﬁc fat
Measurement of ketone bodies is becoming more common
because of an increase in the number of relatively inexpensive con-
sumer devices. These chemical sensors typically measure acetoace-
tate in urine, BOHB in blood, or acetone in breath (BrAce). While
urine samples are common, urine acetoacetate is not typically
assessed using a quantitative method causing signiﬁcant measure-
Currently, blood BOHB is the gold standard
for assessing ketosis. However, the measurement of BrAce is
becoming more widely accepted as a reliable indicator, particularly at
low ketone body levels where BrAce has greater sensitivity to change
than blood BOHB.
Ketone body concentrations for two reference
states are as follows (Table 1): (1) healthy individuals on a balanced
macronutrient diet typically have ketone body concentrations of
BOHB ∼0.1 mM or BrAce ∼1 part per million (ppm); and (2) subjects
in nutritional ketosis (i.e., keto‐adaptation) have ketone body con-
centrations of at least BOHB =0.5 mM
or BrAce ≥9 ppm.
The concentrations of ketone bodies observed for a range of
diseases haven't been summarized. This review describes diseases
that cause ketosis (ketogenic diseases), their underlying ketogenic
mechanisms, and the ranges of ketosis (as deﬁned by blood BOHB
and BrAce concentrations) that are associated with the disease. For
diseases that can be treated with an elevation in ketosis (therapeutic
ketosis), the underlying mechanism of therapeutic ketosis and the
thresholds of ketone body concentrations associated with a thera-
peutic beneﬁt are detailed. Measurement of ketone body concen-
trations is needed to demonstrate the achievement of a therapeutic
ketone body level. Additionally, ketone body elevation during weight
loss and how it can be used to optimize fat loss are reviewed. Finally,
a case study on bariatric surgery provides a vignette for how moni-
toring ketone bodies can be used for disease and therapeutic beneﬁt.
KETOSIS FROM DISEASE
In health, fatty acids provide 50%–70% of the heart's energy.
myocardial fatty acid metabolism is impaired which may be due to a
downregulation of myocardial proteins used to metabolize fatty
acids. However, lipolysis and FFAs are elevated in HF because of
increases in stress hormones (e.g., cortisol), cytokines, malnutrition,
FIGURE 1 Acetoacetate, formed primarily from β‐oxidation of
fatty acids, can be reduced to β‐hydroxybutyrate (BOHB) or
decarboxylated to acetone. Beta‐hydroxybutyrate dehydrogenase
(BDH) interconverts acetoacetate and BOHB depending on
intercellular conditions (e.g., NADH). Acetone is produced via
spontaneous or catalytic decarboxylation of acetoacetate. NADH,
nicotinamide adenine dinucleotide
ANDERSON ET AL.
or cardiac cachexia.
Unable to metabolize FFA, the failing
heart shifts to other fuels including ketone bodies which are elevated
Greater concentrations of ketone bodies are observed
because (1) the abundance of serum FFA causes a rise in liver
ketogenesis, the source of ketone bodies; and (2) skeletal muscles
have lower consumption of BOHB.
BOHB can be rapidly utilized
by the metabolically compromised myocardium because the enzymes
required for ketone body metabolism are more abundant in HF.
In scientiﬁc studies, subjects with HF have 2–20‐fold greater
levels of the ketone body acetone in breath (BrAce, Table 1) as
compared to healthy controls (BrAce ∼1 ppm) or to cardiac patients
Increases (decreases) in BrAce correspond to
increased (decreased) HF severity.
Thus, monitoring BrAC may
provide a marker of HF deterioration or improvement.
In healthy individuals, insulin in the blood interacts with the cell
membrane to facilitate the uptake of blood glucose by the cell.
Additionally, the interaction of insulin with adipose tissue suppresses
lipolysis. In individuals with diabetes, cells are unable to receive the
insulin signal because either insulin is not present (type 1 diabetes) or
the cell is insensitive to insulin and doesn't respond to its presence
(type 2 diabetes). Thus, glucose is not taken up by the cell, and the
concentration of glucose in the blood rises. Without the insulin signal,
lipolysis is no longer inhibited, plasma FFA rises, and hepatic ketone
body production increases.
In lieu of glucose as a primary fuel
source, cells can use fatty acids and ketone bodies to meet their
energy requirements. Without the insulin signal to reduce blood
sugar and suppress fat breakdown, glucose (hyperglycemia), ketone
bodies (hyperketonemia), and hydrogen ions (acidosis) can increase
dramatically in the blood and, without intervention, lead to diabetic
Because ketone bodies are a precursor and marker of DKA,
measurement of ketone bodies can help identify the development,
assess the severity, and assist in monitoring the resolution of DKA.
As ketoacidosis develops, BOHB and BrAce increase from healthy
levels (BOHB ∼0.1 mM or BrAce ∼1 ppm) to those associated with
the onset of ketoacidosis (BOHB >3 mM or BrAce >75 ppm) (Ta-
ble 1). Because of the large concentration range between healthy
ketone body levels and ketoacidosis, ketone body monitoring can
provide a critical tool to alert providers and patients that a healthy
ketosis state is developing into ketoacidosis, allowing expedient
treatment before it reaches a critical level.
When DKA is present,
measurement of BOHB and BrAce may help to assess the severity of
ketoacidosis. BOHB (3–20 mM) and BrAce (75–1250 ppm) range
considerably in people with DKA, and the magnitude of these ketone
bodies may be associated with increased severity of DKA.
the intervention, scientiﬁc studies have demonstrated that ketone
body measurement can improve the course of DKA resolution.
Four diabetes associations recommend ketone body monitoring,
TABLE 1Ketone body (BOHB in mM or BrAce in ppm) concentration ranges observed in health, for disease states and for therapeutic
beneﬁt (minimum concentration thresholds)
Range or threshold
ReferencesBOHB (mM) BrAce (ppm)
Health Balanced macronutrient diet 0.1 1
Nutritional ketosis 0.5 9
Disease Heart failure >0.2 2–20
Ketoacidosis >3.0 >75
Genetic disorders ― ― See text
Therapy Brain function: Alzheimer’s 0.5 9
Brain function: Parkinson’s 1.0 ―
Brain function: Dementia 0.5 9
Brain function: Migraine 4.0 ―See text
Cancer 0.5 9
Type 2 diabetes 0.5 9
Epilepsy 4.0 ―
Weight loss ―2
Bariatric surgery Ketoacidosis >3.0 >75 See text and references above
Weight loss ―2
Abbreviations: BOHB, β‐hydroxybutyrate; BrAce, breath acetone.
Nutritional ketosis. BrAce ≥9 ppm when BOHB =0.5 mM.
typically BOHB, during DKA resolution.
During DKA, the concen-
tration of BOHB is much greater than acetoacetate.
As DKA is
treated, BOHB decreases by conversion to acetoacetate, which
causes an elevation of acetoacetate. Because DKA is not resolved
until both BOHB and acetoacetate concentrations return to baseline,
monitoring BrAce, a product of acetoacetate decarboxylation, at 30‐
min intervals, can demonstrate the full resolution of DKA.
Additionally, monitoring ketone bodies during resolution should
reduce the duration and cost of medical treatment.
Prevention of DKA may be the best use of ketone body mea-
surement. DKA requires immediate medical attention (e.g., emer-
gency room visit), with an average cost for hospitalization of $26,566
To reduce DKA events and hospitalization, scientiﬁc
studies recommend self‐monitoring of ketone bodies in patients with
type 1 diabetes, insulin‐dependent type 2 diabetes, sustained blood
glucose concentration >300 mg/dl, acute illness, or stress.
Patients have indicated that measurements of elevated BOHB were
useful in determining subsequent insulin dose and food intake.
During sick days, particularly those involving nausea, vomiting, or
infections, scientiﬁc studies recommend monitoring BOHB
throughout the day, speciﬁcally for young children because of the
frequency of illness in this population.
Studies indicate that chil-
dren and adults who measure BOHB during “sick days” can prevent
the onset of DKA, reduce the time to DKA resolution, reduce mon-
etary costs, and decrease the rate of hospitalizations.
In addition to ketoacidosis associated with poorly controlled dia-
betes, ketoacidosis can occur in patients with diabetes who control
their blood sugar with a sodium–glucose cotransporter‐2 (SGLT2)
inhibitor. The SGLT2 inhibitor eliminates excess blood glucose
through excretion by the kidneys and may lead to ketoacidosis, in a
subset of individuals with diabetes, even though blood glucose is well
controlled (i.e., euglycemic ketoacidosis).
This condition appears to be driven by low insulin levels in in-
dividuals with impaired insulin secretion, poor ﬂuid intake, low car-
bohydrate intake, and/or fasting.
Because the SGLT2 inhibitor
maintains blood glucose within a “healthy range”, blood glucose
monitoring will not alert individuals or clinicians to the developing
ketoacidosis. Thus, measurement of ketone bodies is important for
these subjects, perhaps even more so on sick days. The monitoring
guidelines outlined for ketoacidosis (above) could be applied. The
large concentration differential between healthy ketone body levels
and ketoacidosis can be exploited to monitor elevations in ketosis.
Signiﬁcant elevations can be addressed before a crisis develops.
Interestingly, pregnant women with diabetes (<3% of all diabetic
gestations) can have euglycemic ketoacidosis which may progress
more rapidly as compared to nonpregnancy states.
body measurement may identify the early stages of hyperketonemia
before it escalates to DKA.
Genetic disorders can elevate ketosis through the overproduction
of ketone bodies or impairment of ketone body utilization. Hepatic
ketone body production elevates when low blood glucose causes a
reduction in insulin and an increase in circulating fatty acids.
Normal glucose levels, maintained via glycogen metabolism
or gluconeogenesis, are dependent on key enzymes such
as glycogen synthase, glycogen phosphorylase kinase, fructose‐
1,6‐diphosphatase, or glucose‐6‐phosphatase. Genetic disorders
can prevent the expression of these enzymes, which would cause
fasting hypoglycemia and accelerated ketogenesis leading to
A lack of peripheral tissue utilization will cause ketone body
elevation. The pathway for ketolysis is controlled by two enzymes
(Figure 2): succinyl‐CoA:3‐oxoacid‐CoA transferase (SCOT) and
acetyl‐CoA acetyltransferase1 (ACAT1), which early literature iden-
tiﬁed as 2‐methylacetoacetyl‐CoA thiolase (MAT). A lack of these
enzymes causes hyperketonemia and ketoacidosis, particularly in a
Monitoring ketonemia via BOHB or BrAce measurement can
provide a quantitative check on dietary compliance, particularly on
sick days, and a method to minimize the conversion of hyper-
ketonemia to ketoacidosis. Ketone body thresholds have not been
described but would likely be similar to those for ketoacidosis
(BOHB >3 mM or BrAce >75 ppm—see Section 2.2).
FIGURE 2 Pathway for utilization of ketone bodies (ketolysis) where deﬁciencies in SCOT or ACAT1 cause signiﬁcant ketonemia (adapted
from Aubert et al.
). β‐oxidation is output from β‐oxidation of fatty acids. ACAT1, acetyl‐CoA acetyltransferase1; BDH, β‐hydroxybutyrate
dehydrogenase; MCT, monocarboxylate transporter; SCOT, succinyl‐CoA:3‐oxoacid‐CoA transferase
ANDERSON ET AL.
KETOSIS FOR THERAPY
In addition to weight loss, multiple obesity‐associated diseases
respond favorably to elevated ketosis. These diseases appear to have
impaired glucose metabolism (e.g., brain dysfunction) or an inability
to manage elevated insulin and glucose (e.g., cancer, diabetes).
Elevated BOHB may provide relief by replacing glucose as a primary
source of energy and removing oxidant species.
obesity‐associated diseases, carbohydrate restriction may be the
optimal modality for elevating ketone bodies while decreasing insulin
and blood glucose concentration. Therapeutic BOHB concentrations
are primarily disease dependent and modulated by a multitude of
factors including age, gender, weight, diet, and disease severity. Thus,
sequential ketone body measurements over time can demonstrate
that the threshold for therapeutic ketosis has been achieved and
In health, glucose fuels the brain. During starvation, glucose is scarce
and FFAs are abundant. Because the brain cannot use fat for fuel, the
body converts fat into ketone bodies to fuel the brain.
studies have demonstrated that elevated ketone bodies (via KD,
supplementation with medium chain triglyceride, fasting, etc.) can
improve brain function in subjects with Alzheimer's, dementia, and
It appears that these diseases are characterized by the
inability of speciﬁc brain regions to use glucose for fuel, which
causes regional dysfunction in the brain. When available, ketone
bodies can fuel diseased brain regions resulting in improvement of
neurologic function. At BOHB concentrations >4 mM, ketone
bodies are estimated to supply more than 50% of the brain's en-
Many factors drive Alzheimer's disease including insulin resistance,
genetic defects, and a regional reduction in glucose metabolism
which is correlated to decrements in cognitive scores.
BOHB to ∼0.5 mM (BrAce ≥9 ppm) via consumption of ketogenic
foods appears to improve cognitive function.
improvement in cognitive function is associated with increased
The beneﬁts of elevated ketone bodies on mitochondrial activity
have been proposed for Parkinson's disease. While similar to the
mechanisms for other brain maladies, it is hypothesized that
BOHB increases energy production because BOHB may bypass a
defect in complex I of the electron transport chain.
study, subjects with Parkinson's on a 4‐week KD showed
improvement on the Uniﬁed Parkinson's Disease Rating Scale. A
pilot study showed some symptom resolution when BOHB =1.0
While additional studies are needed, it is expected that
BOHB must range between 2 and 7 mM to provide a therapeutic
Older subjects with mild cognitive impairment may experience
improved verbal memory performance using a very low carbohydrate
diet (<35 g/day on average). Improved memory performance corre-
lated with increases in ketone levels and reductions in insulin
Healthy geriatric individuals will also likely beneﬁt from the
best improvement found in subjects with strong dietary compli-
Based on the dietary criteria, subjects with cognitive
impairment may need BOHB concentrations >0.5 mM (BrAce ≥9
ppm) to achieve a beneﬁt.
Migraine can be characterized as a neurologic inﬂammation and a
reduction in brain metabolism.
To prevent or protect against
migraines, elevated ketone bodies may reduce neuroinﬂammation,
inhibit oxidative stress, and modulate mitochondrial function.
Ketotherapeutic beneﬁts for migraines have been known for
almost 100 years.
In recent studies, consumption of a very low
carbohydrate (<30 g/day) and low‐calorie KD was associated with
signiﬁcant reductions in the number of migraine attacks per
month (76% drop) and the number of days with headaches (82%
One subject had complete remission of migraine
Relief was observed within a few days of diet
Because the diets used are similar to those used for
epilepsy therapy, a BOHB greater than 4 mM may be required
Some subjects with epilepsy have intractable seizures, which are
unresponsive to antiepileptic drugs.
The frequency of these sei-
zures can, in many cases, be reduced with a KD. In children,
approximately 50% of subjects experienced an improvement in
seizure frequency when adhering to this diet for a few months.
children adhering to the diet for 1 year, almost 50% of subjects re-
ported a nearly complete (≥90%) reduction in seizures; similar out-
comes persisted for years after study termination.
epilepsy also experienced a reduction in seizure frequency when
placed on KDs. It is clear that elevations in ketone bodies correspond
to successful ketogenic therapy.
Scientiﬁc studies have shown a
relationship between elevated BOHB and improved seizure control
Ketone body measurement can demonstrate dietary compliance
required for therapeutic beneﬁt.
The therapeutic beneﬁt ap-
pears to be around 4 mM for BOHB
(Table 1). When adverse
effects of the diet occur (e.g., constipation, bloating, or irregular
menstrual cycles), ketone body measurement can provide positive
reinforcement, provide information to optimize dietary composition,
and hasten return to therapeutic ketosis after a “cheat” day.
Rapid and uncontrolled cell growth in cancer is fueled by glucose, an
observation named the Warberg effect.
Thus, restricting circulating
glucose (e.g., by consumption of a very low‐carbohydrate and high‐fat
diet) should cause tumor cells to starve and die.
In healthy cells,
energy is produced via aerobic respiration of glucose, fats, or ketone
bodies which requires healthy mitochondria, an intact tricarboxylic
acid cycle, and a functional electron transport chain. In cancer cells,
compromised aerobic respiration forces cancer cells to rely solely on
anaerobic glycolysis and aerobic fermentation of glucose for en-
High corresponding insulin levels signal the expression of
glucose transporters (e.g., GLUT3) and glycolytic enzymes.
Carbohydrate restriction will slow cancer growth in three ways.
Without fuel, these cells starve and become more susceptible to
A decrease in circulating insulin inhibits the
signal to upregulate the glucose transporters (e.g., GLUT3) and
glycolytic enzymes required for metabolism. Increased BOHB re-
duces oxidative stress and inﬂammation, induces apoptosis, and is
associated with regression of cancer growth.
healthy cells thrive via aerobic metabolization of fats and ketone
The few studies using ketotherapy have shown potential beneﬁts
(e.g., tumor stability or regression) to the brain (i.e., glioblastoma),
breast, lung, and colon cancer.
This regimen likely requires
carbohydrate restriction combined with one or more of the following:
high‐fat consumption, caloric restriction, fasting, or exogenous ke-
tone supplementation. Measurement of ketosis in cancer patients
may help monitor compliance, facilitate dietary modiﬁcations, and
achieve therapeutic levels of ketone bodies. The minimum threshold
for therapeutic beneﬁt appears to be 0.5 mM (BrAce ≥9 ppm) and
likely depends on the cancer type.
Type 2 diabetes
One hallmark of diabetes is elevated blood glucose. In people with
type 2 diabetes, tissues are insensitive to insulin, resulting in the rise
of blood glucose due to increased liver production and a lack of up-
take. To achieve normal levels of blood glucose, clinical investigators
have proposed “prescribing” a KD to restrict dietary carbohydrates
to <50 g/day.
After adaption to KD, subjects, on average,
experience an improvement in diabetic sequelae and medications,
including weight reduction, reduced exogenous insulin, improved
insulin sensitivity, and reduced HbA1c.
To achieve these results, clinical studies have measured BOHB
levels to verify carbohydrate restriction, to guide the reduction of
diabetes medication, and to adjust dietary therapy.
strive to maintain a state of nutritional ketosis, deﬁned as BOHB ≥
As an alternative to BOHB, a BrAce ≥9 ppm, which
corresponded to BOHB ≥0.5 mM for 95% of measurements, could
be used to demonstrate nutritional ketosis.
Daily ketone body
measurements demonstrate dietary and lifestyle compliance and may
provide a rationale for weaning patients from diabetic medica-
As lifestyle and dietary factors change with time, ketone
body measurements will reﬂect changes in carbohydrate restriction
and, thus, can be used to help compensate for these changes.
During calorie restriction, energy needs are met by mobilizing fat
from adipose cells. A portion of the circulating fatty acids is con-
verted into ketone bodies within the liver. The amount of ketone
bodies produced is proportional to the rate of fatty acid metabolism
within the liver. For subjects on a calorie‐restricted diet, the BrAce
concentration has been shown to be proportional to the rate of fat
While BrAce is ∼1 ppm for a typical subject, individuals who
lost one‐half pound of fat mass per week on a calorie‐restricted diet
had BrAce =2 ppm. Further elevations in BrAce correlated linearly
with increases in fat mass loss.
As a result of the relationship between BrAce and fat mass loss,
frequent monitoring of BrAce can be used as a tool by individuals and
clinicians to optimize fat loss. During calorie restriction, BrAce ≥2
ppm indicates an elevated state of fat metabolism and predicts fat
loss if these levels can be maintained. Frequent monitoring provides
individuals with immediate feedback to understand how their well-
ness choices (e.g., diet, exercise, sleep, stress, etc.) affect their state of
fat metabolism. Using this feedback, individuals can adjust their
choices, daily if needed, to optimize and maintain fat loss and in-
crease compliance (unpublished observations). Coaches and clinicians
can utilize longitudinal BrAce measurements to understand individual
fat metabolism, to customize the program for each individual, and to
counsel patients on how to overcome weight‐loss obstacles. Addi-
tionally, BrAce can be used in weight‐loss strategies when preparing
for bariatric surgery (discussed below).
One case for measuring BrAce could be tailoring the macronu-
trient composition to optimize weight loss. In general, customization
is difﬁcult because the optimal macronutrient composition for weight
loss is not clear. Scientiﬁc debates between proponents of a high
and supporters of a low carbohydrate diet
have not provided resolution. Optimal diet composition is likely
subject dependent. A recent study
suggests a high carbohydrate
diet (60% carbohydrate, 20% fat, and 20% protein) is preferred for
women with obesity who were insulin sensitive (fasting insulin <10
ANDERSON ET AL.
µU/ml) while a lower carbohydrate diet (40% carbohydrate, 40% fat
and 20% protein) is preferred for women with obesity who were
insulin resistant. For all subjects, the preferred macronutrient
composition gave a ∼twofold increase in body weight loss as
compared to the alternative. These ﬁndings would indicate that the
ability (inability) to efﬁciently metabolize carbohydrates, as predicted
by insulin sensitivity (resistance), may predict the best macronutrient
composition for weight loss.
As weight is lost, the body becomes more insulin sensitive. Thus,
at some point during weight loss, the best diet may change from a low
to a high carbohydrate diet. This change could be monitored with
measurements of fasting insulin. However, the cost and invasive
nature make this measurement impractical. A different inﬂection
point occurs for others during the ﬁrst 6 months of dieting. Often
when people reach a plateau in their weight loss, they give up dieting
and regain the weight.
Measuring BrAce over days and weeks can give feedback on
metabolic changes within the patient. A reduction in BrAce from
above 2 ppm to near 1 ppm indicates a loss of fat oxidation and, when
combined with a weight‐loss plateau, may suggest the need for a
dietary change. One cause of this plateau could be the increase in
insulin sensitivity which can be quantiﬁed via measurement of fasting
insulin. If insulin sensitivity has improved, an increase in the carbo-
hydrate content could restart weight loss. Thus, regular monitoring of
BrAce during a weight‐loss program could potentially enable
personalization of dietary carbohydrates and optimize weight loss
over the weight‐loss journey.
Bariatric surgery serves as a case study for monitoring ketone bodies
for both pathologic (i.e., ketoacidosis) and therapeutic (i.e., weight
loss) ketosis. Over the past half‐century, bariatric surgery has
emerged as a valid and effective treatment for signiﬁcant weight loss
and improvement, if not resolution, of associated comorbidities,
including diabetes, hypertension, and sleep apnea.
Most of these
operations, typically indicated for patients with a BMI >35, result in
the correction of the metabolic dysfunction at the center of the
metabolic syndrome and morbid obesity. The dramatic reduction in
hunger and the normalization of disturbed metabolic processes result
in signiﬁcant weight loss that is derived from a reduction in both fat
and fat‐free mass.
Prior to bariatric surgery, weight loss can reduce surgical com-
plications, surgery time, and length of hospital stay.
calorie diets (VLCD) are commonly used prior to bariatric surgery
as a means to both reduce initial weight and to reduce liver fat
Although VLCDs vary somewhat in calorie and nutrient
composition (typically <800 calories/day), they are as a group
effective in weight loss and metabolic improvement
maintaining fat‐free mass.
VLCD with carbohydrate levels of
<50 g/day result in nutritional ketosis. To demonstrate compliance
with the dietary plan and optimize weight loss, BrAce can be moni-
tored. In fact, measurement of BrAce has been shown to correlate
with weight loss and adherence to the prescribed VLCD
After bariatric surgery, patients are monitored by a multidisci-
plinary team of physicians, nurses, and dietitians, whose main
objective is to ensure that patients maintain optimal beneﬁts with
minimal harm, including that weight loss be predominantly from fat
mass components, and the sparing of fat‐free mass. While many
patients do achieve these healthy weight‐loss objectives, there is a
minority who, for a variety of reasons, may be unable to adhere to
nutritional recommendations and suffer the consequences of poor
oral intake if not rescued in a timely manner. It is imperative,
therefore, that patients at risk should have their ﬂuid status, elec-
trolyte levels, acid–base balance, and nutritional parameters closely
monitored. Comprehensive monitoring may beneﬁt from quantita-
tive measurement of ketone bodies (e.g., BrAce), which could be
used to enhance post‐bariatric diabetes management and distin-
guish between types and degrees of ketoacidosis such as SGLT2‐
associated euglycemic ketoacidosis and post‐surgery starvation
Starvation ketoacidosis can result secondary to poor oral intake
following bariatric surgery.
Poor oral intake rapidly depletes
hepatic and muscular glycogen stores. Aggravating this situation is
the vomiting and dehydration that are occasionally present and
stimulate the sympathetic system resulting in released cortisol,
adrenaline, glucagon, and growth hormone, which in turn suppress
insulin secretion. The cumulative effects of these changes are
lipolysis and FFA production from adipose tissue and hepatic ke-
tone formation, the basis for starvation ketoacidosis.
all patients who present with severe acid–base imbalance should
undergo ketone body measurement since their elevation is a key
determinant that ketoacidosis is the underlying mechanism for
In clinical settings, it is important to differentiate starvation
ketoacidosis from DKA, since the treatment for each condition can
have a critical impact on the outcome of these emergency conditions.
DKA is a potentially lethal condition that is more common in patients
with type 1 diabetes who exhibit poor compliance or inadequate
insulin replacement therapy. It is usually associated with hypergly-
cemia and dehydration, and is typically managed with dedicated
protocols that call for aggressive rehydration and insulin adminis-
tration in an attempt to correct the acid–base imbalance. It is
important to distinguish diabetic from starvation ketoacidosis since
glucose administration can be a life‐saving measure in the latter
situation. Although DKA after bariatric surgery is an uncommon
event, it has been documented in patients with type 1 diabetes who
have undergone gastric bypass.
Anesthesia and surgical stress,
abrupt discontinuation of insulin or inadequate treatment in the
perioperative period, postoperative infection, prolonged poor oral
intake, and severe dehydration can be the precipitating causes for
The measurement of ketone body concentration (BOHB or acetone)
can provide valuable information. Diseases such as congestive heart
failure, ketoacidosis, and genetic disorders create an elevated
ketosis which, in many cases, correlates to disease severity. Because
the magnitude of the increased ketosis is typically related to dis-
ease severity, early detection can aid in modifying behaviors before
disease symptoms clinically manifest. The intentional induction of
elevated BOHB concentrations can be used to treat obesity and
obesity‐associated diseases such as brain disorders and type 2
diabetes. Elevated BOHB levels provide a beneﬁt through modiﬁ-
cation of mitochondrial energy production and through reduction of
insulin and blood glucose when achieved via glucose restriction.
Measurement of ketosis is critical to verify that a therapeutic level
of ketosis has been achieved and maintained. Frequent measure-
ment of ketosis can allow users to adjust and personalize their diet
and behaviors to maintain therapeutic levels of ketosis. A case
study of bariatric surgery demonstrates that monitoring ketone
bodies before and after surgery may optimize surgical outcomes
and reduce complications.
To date, monitoring ketone concentrations has been shown to
address three conditions: ketoacidosis (prevention, acidosis severity,
and resolution monitoring), improvement of type 2 diabetes (achieve
nutritional ketosis and dietary adherence), and epilepsy (optimize
seizure control). These methods of ketone monitoring can be used as
starting points for the other conditions reviewed. Additional studies
are needed to demonstrate the value of ketone body monitoring for
the other diseases that generate elevated ketosis. For therapeutic
ketosis, ketone monitoring is necessary, at a minimum, to demon-
strate a therapeutic dose has been achieved. Additional research is
needed to better quantify the therapeutic dose as a function of
subject‐speciﬁc factors, which include disease severity, de-
mographics, and genetics.
All authors were involved in literature search, writing the manuscript
and ﬁnal approval of the submitted and published versions.
This work was supported, in part, by Medamonitor Corp, Seattle,
WA and by the National Institute of General Medical Sciences Grant
1 U54 GM104940 which funds the Louisiana Clinical and Trans-
lational Science Center. The content is solely the responsibility of the
authors and does not necessarily represent the ofﬁcial views of the
National Institutes of Health.
CONFLICTS OF INTEREST
Joseph C. Anderson consults for and holds stock in Medamonitor.
Samer G. Mattar has no conﬂicts to report. Frank L. Greenway re-
ports serving on science advisory boards for JC USA, Regeneron
Pharmaceuticals, and Pﬁzer; consulting for Jazz Pharmaceuticals,
Basic Research, Dr. Reddy's Laboratories, General Nutrition Corpo-
ration, Melior Discovery Inc., Novmeta Pharma, Novo Nordisk; grants
from Melior Discoveries, Novmeta Pharma; and stock/stock options
from Ketogenic Health Systems, Inc., Plensat Inc., UR Labs. Richard J.
Lindquist consults for Medamonitor.
Joseph C. Anderson
1. Hallbook T, Ji S, Maudsley S, Martin B. The effects of the ketogenic
diet on behavior and cognition. Epilepsy Res. 2012;100:304–309.
2. Hyde PN, Sapper TN, Crabtree CD, et al. Dietary carbohydrate
restriction improves metabolic syndrome independent of weight
loss. JCI Insight. 2019;4(12):e128308.
3. Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a
review of the therapeutic uses of very‐low‐carbohydrate (keto-
genic) diets. Eur J Clin Nutr. 2013;67:789‐796.
4. Westman EC, Feinman RD, Mavropoulos JC, et al. Low‐
carbohydrate nutrition and metabolism. Am J Clin Nutr.
5. Simone BA, Champ CE, Rosenberg AL, et al. Selectively starving
cancer cells through dietary manipulation: methods and clinical
implications. Future Oncol. 2013;9:959‐976.
6. Stubbs BJ, Cox PJ, Evans RD, et al. On the metabolism of exoge-
nous ketones in humans. Front Physiol. 2017;8:1‐13.
7. Veech RL. The therapeutic implications of ketone bodies: the ef-
fects of ketone bodies in pathological conditions: ketosis, ketogenic
diet, redox states, insulin resistance, and mitochondrial meta-
bolism. Prostagl Leukot Essent Fat Acids. 2004;70:309‐319.
8. Veech RL, Bradshaw PC, Clarke K, Curtis W, Pawlosky R, King MT.
Ketone bodies mimic the life span extending properties of caloric
restriction. IUBMB Life. 2017;69:305‐314.
9. Laffel L. Ketone bodies: a review of physiology, pathophysiology
and application of monitoring to diabetes. Diabetes Metab. Res. Rev.
10. Kalapos MP. On the mammalian acetone metabolism: from chem-
istry to clinical implications. Biochim Biophys Acta. 2003;1621:
11. Kundu SK., Bruzek JA, Nair R, Judilla AM. Breath acetone analyzer:
diagnostic tool to monitor dietary fat loss. Clin Chem. 1993;39:
12. Sasaki H, Ishikawa S, Ueda H, Kimura Y. Response of acetone in
expired air during graded and prolonged exercise. Adv Exerc Sports
13. Cartwright MM, Hajja W, Al‐Khatib S, et al. Toxigenic and meta-
bolic causes of ketosis and ketoacidotic syndromes. Crit Care Clin.
14. Mitchell GA, Mitchell GA, Kassovska‐Bratinova S, et al. Medical
aspects of ketone body metabolism. Clin Invest Med. 1995;18:
15. McPherson PAC, McEneny J. The biochemistry of ketogenesis and
its role in weight management, neurological disease and oxidative
stress. J Physiol Biochem. 2012;68:141‐151.
16. Stafstrom CE, Rho JM. The ketogenic diet as a treatment
paradigm for diverse neurological disorders. Front Pharmacol.
17. Wood TR, Stubbs BJ, Juul SE. Exogenous ketone bodies as prom-
ising neuroprotective agents for developmental brain injury. Dev
18. Rooth G, Carlstrom S. Therapeutic fasting. Acta Med Scand. 1970;
19. Anderson JC. Measuring breath acetone for monitoring fat loss:
Review. Obesity. 2015;23:2327‐2334.
20. Meas T, Taboulet P, Sobngwi E, Gautier J. Is capillary ketone
determination useful in clinical practice? In which circumstances?
Diabetes Metab. 2005;31:299‐303.
ANDERSON ET AL.
21. Musa‐Veloso K, Likhodii SS, Cunnane SC. Breath acetone is a
reliable indicator of ketosis in adults consuming ketogenic meals.
Am J Clin Nutr. 2002;76:65‐70.
22. Guntner AT, Kompalla JF, Landis H, et al. Guiding ketogenic diet
with breath acetone sensors. Sensors. 2018;18:3655
23. Kupari M, Lommi J, Ventilä M, Karjalainen U. Breath acetone in
congestive heart failure. Am J Cardiol. 1995;76:1076‐1078.
24. Lommi J, Kupari M. Koskinen P, et al. Blood ketone bodies in
congestive heart failure. J Am Coll Cardiol. 1996;28:665‐672.
25. Marcondes‐Braga FG, Gutz IGR, Batista GL, Saldiva PHN, Ayub‐
Ferreira SM, Issa VS, Mangini S, Bocchi EA, Bacal F. Exhaled
acetone as a new biomarker of heart failure severity. Chest.
26. Samara MA, Tang WHW, Cikach F, Jr, et al. Single exhaled breath
metabolomic analysis identiﬁes unique breathprint in patients with
acute decompensated heart failure. J Am Coll Cardiol.
27. Weber C, Kocher S, Neeser K, Joshi SR. Prevention of diabetic
ketoacidosis and self‐monitoring of ketone bodies: an overview.
Curr Med Res Opin. 2009;25:1197‐1207.
28. Levine JA, Karam SL, Aleppo G. SGLT2‐I in the hospital setting:
diabetic ketoacidosis and other beneﬁts and concerns. Curr Dia-
betes Rep. 2017;17:54.
29. Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC.
Study of the ketogenic agent AC‐1202 in mild to moderate Alz-
heimer's disease: a randomized, double‐blind, placebo‐controlled,
multicenter trial. Nutr Metab. 2009;6:31.
30. Reger MA, Henderson ST, Hale C, et al. Effects of β‐hydrox-
ybutyrate on cognition in memory‐impaired adults. Neurobiol Aging.
31. Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP.
Low‐fat versus ketogenic diet in Parkinson's disease: a pilot ran-
domized controlled trial. Mov Disord. 2018;33:1306‐1314.
32. Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, Clegg
DJ. Dietary ketosis enhances memory in mild cognitive impairment.
Neurobiol Aging. 2012;33:425.e19‐425.e27.
33. Fine EJ, Segal‐Isaacson CJ, Feinman RD, et al. Targeting insulin
inhibition as a metabolic therapy in advanced cancer: a pilot safety
and feasibility dietary trial in 10 patients. Nutrition. 2012;28:
34. Schmidt M, Pfetzer N, Schwab M, Strauss I, Kämmerer U. Effects of
a ketogenic diet on the quality of life in 16 patients with advanced
cancer: a pilot trial. Nutr Metab. 2011;8:54.
35. Saslow LR, Kim S, Daubenmier JJ, et al. A randomized pilot trial of a
moderate carbohydrate diet compared to a very low carbohydrate
diet in overweight or obese individuals with type 2 diabetes mel-
litus or prediabetes. PLoS One. 2014;9:e91027.
36. McKenzie AL, Hallberg SJ, Creighton BC, et al. A novel intervention
including individualized nutritional recommendations reduces he-
moglobin A1c level, medication use, and weight in type 2 diabetes.
JMIR Diabetes. 2017;2:e5.
37. Buchhalter JR, D'Alfonso S, Connolly M, et al. The relationship
between d‐beta‐hydroxybutyrate blood concentrations and
seizure control in children treated with the ketogenic diet for
medically intractable epilepsy. Epilepsia Open. 2017;2:317‐321.
38. Gilbert DL, Pyzik PL, Freeman JM. The ketogenic diet: seizure
control correlates better with serum β‐hydroxybutyrate than with
urine ketones. J Child Neurol. 2000;15:787‐790.
39. van Delft R, Lambrechts D, Verschuure P, Hulsman J, Majoie M.
Blood beta‐hydroxybutyrate correlates better with seizure reduc-
tion due to ketogenic diet than do ketones in the urine. Seizure.
40. Numis AL, Yellen MB, Chu‐Shore CJ, Pfeifer HH, Thiele EA. The
relationship of ketosis and growth to the efﬁcacy of the ketogenic
diet in infantile spasms. Epilepsy Res. 2011;96:172‐175.
41. Gershuni VM, Yan SL, Medici V. Nutritional ketosis for weight
management and reversal of metabolic syndrome. Curr Nutr Rep.
42. Volek J, Phinney SD. The Art and Science of Low Carbohydrate Per-
formance: A Revolutionary Program to Extend Your Physical and
Mental Performance Envelope. Miami, FL: Beyond Obesity; 2012.
43. Bedi KC, Jr., Snyder NW, Brandimarto J, et al. Evidence for intra-
myocardial disruption of lipid metabolism and increased myocar-
dial ketone utilization in advanced human heart failure. Circulation.
44. Kolwicz SC, Jr., Airhart S, Tian R. Ketones step to the plate. Cir-
45. McMurray J, Abdullah I, Dargie HJ, Shapiro D. Increased concen-
trations of tumour necrosis factor in “cachectic” patients with se-
vere chronic heart failure. Br Heart J. 1991;66:356‐358.
46. Janardhan A, Chen J, Crawford PA. Altered systemic ketone body
metabolism in advanced heart failure. Tex Heart Inst J. 2011;38:
47. Yokokawa T, Sato T, Suzuki S, et al. Change of exhaled acetone
concentration levels in patients with acute decompensated heart
failure. Int Heart J. 2018;59:808‐812.
48. Marcondes‐Braga FG, Batista GL, Gutz IG, et al. Impact of exhaled
breath acetone in the prognosis of patients with heart failure with
reduced ejection fraction (HFrEF). One year of clinical follow‐up.
PLoS One. 2016;11:e0168790.
49. Javeed N, Matveyenko AV. Circadian etiology of type 2 diabetes
mellitus. Physiology. 2018;33:138‐150.
50. Miles JM, Gerich JE. 3Glucose and ketone body kinetics in diabetic
ketoacidosis. Clin Endocrinol Metab. 1983;12:303‐319.
51. Qiu H, Novikov A, Vallon V. Ketosis and diabetic ketoacidosis in
response to SGLT2 inhibitors: Basic mechanisms and therapeutic
perspectives. Diabetes Metab Res Rev. 2017;33:e2886
52. Cahill GF, Jr., Veech RL. Ketoacids? Good medicine? Trans Am Clin
Climatol Assoc. 2003;114:149‐161.discussion 162‐143.
53. Briggs A. The management of diabetes as controlled by tests of
acetone in expired air. J Lab Clin Med. 1940;25:603‐609.
54. Rooth G. Insulin action measured by acetone disappearance. Pre-
liminary report. Acta Med Scand. 1967;182:271‐272.
55. Misra S, Oliver NS. Utility of ketone measurement in the preven-
tion, diagnosis and management of diabetic ketoacidosis. Diabet
56. Goldstein DE, Little RR, Lorenz RA, et al. Tests of glycemia in
diabetes. Diabetes Care. 2004;27:1761‐1773.
57. Klocker AA, Phelan H, Twigg SM, Craig ME. Blood β‐hydrox-
ybutyrate vs. urine acetoacetate testing for the prevention and
management of ketoacidosis in Type 1 diabetes: a systematic re-
view. Diabetes Med. 2013;30:818‐824.
58. Desai D, Mehta D, Mathias P, Menon G, Schubart UK. Health care
utilization and burden of diabetic ketoacidosis in the U.S. Over the
past decade: a nationwide analysis. Diabetes Care.
59. Samuelsson U, Ludvigsson J. When should determination of keto-
nemia be recommended? Diabetes Technol Ther. 2002;4:645‐650.
60. Laffel LMB, Wentzell K, Loughlin C, Tovar A, Moltz K, Brink S. Sick
day management using blood 3‐hydroxybutyrate (3‐OHB)
compared with urine ketone monitoring reduces hospital visits in
young people with T1DM: a randomized clinical trial. Diabetes Med.
61. Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis
and related events in the canagliﬂozin type 2 diabetes clinical
program. Diabetes Care. 2015;38:1680‐1686.
62. FDA Drug Safety Communication. FDA Warns that SGLT2 Inhibitors
for Diabetes May Result in a Serious Condition of Too Much Acid in
the Blood. (2015). https://www.fda.gov/Drugs/DrugSafety/ucm44
63. Fralick M, Schneeweiss S, Patorno E. Risk of diabetic ketoacidosis
after initiation of an SGLT2 inhibitor. N Engl J Med. 2017;376:
64. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB.
Euglycemic diabetic ketoacidosis: a potential complication of
treatment with sodium‐glucose cotransporter 2 inhibition. Diabetes
65. Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced
by SGLT2 inhibitors: possible mechanism and contributing factors.
J Diabetes Invest. 2016;7:135‐138.
66. Sibai BM, Viteri OA. Diabetic ketoacidosis in pregnancy. Obstet
67. Aubert G, Martin OJ, Horton JL, et al. The failing heart relies on
ketone bodies as a fuel. Circulation. 2016;133:698‐705.
68. Cotter DG, Schugar RC, Crawford PA. Ketone body metabolism
and cardiovascular disease. Am J Physiol. 2013;304:
69. Fukao T, Mitchell G, Sass JO, Hori T, Orii K, Aoyama Y. Ketone
body metabolism and its defects. J Inherit Metab Dis. 2014;37:
70. VanItallie TB, Nufert TH. Ketones: metabolism's ugly duckling. Nutr
71. Hashim SA, VanItallie TB. Ketone body therapy: from the ketogenic
diet to the oral administration of ketone ester. J Lipid Res. 2014;55:
72. Henderson ST. Ketone bodies as a therapeutic for Alzheimer's
disease. Neurotherapeutics. 2008;5:470‐480.
73. Ota M, Matsuo J, Ishida I, et al. Effects of a medium‐chain
triglyceride‐based ketogenic formula on cognitive function in pa-
tients with mild‐to‐moderate Alzheimer's disease. Neurosci Lett.
74. Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH.
Feasibility and efﬁcacy data from a ketogenic diet intervention in
Alzheimer's disease. Alzheimer's Dementia Transl Res Clin Interv.
75. Morrill SJ, Gibas KJ. Ketogenic diet rescues cognition in ApoE4+
patient with mild Alzheimer's disease: a case study. Diabetes Metab
Syndrome Clin Res Rev. 2019;13:1187‐1191.
76. Tieu K, Perier C, Caspersen C, et al. D‐β‐Hydroxybutyrate rescues
mitochondrial respiration and mitigates features of Parkinson
disease. J Clin Invest. 2003;112:892‐901.
77. Vanitallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsﬁeld
SB. Treatment of Parkinson disease with diet‐induced hyper-
ketonemia: a feasibility study. Neurology. 2005;64:728‐730.
78. Witte AV, Fobker M, Gellner R, Knecht S, Floel A. Caloric restric-
tion improves memory in elderly humans. Proc Natl Acad Sci. 2009;
79. Barbanti P, Foﬁ L, Aurilia C, Egeo G, Caprio M. Ketogenic diet in
migraine: rationale, ﬁndings and perspectives. Neurol Sci. 2017;38:
80. Di Lorenzo C, Coppola G, Sirianni G, et al. Migraine improvement
during short lasting ketogenesis: a proof‐of‐concept study. Eur J
81. Schnabel TG. An experience with a ketogenic dietary in migraine.
Ann Intern Med. 1928;2:341‐347.
82. Di Lorenzo C, Coppola G, Bracaglia M, et al. Cortical functional
correlates of responsiveness to short‐lasting preventive interven-
tion with ketogenic diet in migraine: a multimodal evoked poten-
tials study. J Headache Pain. 2016;17:58.
83. Strahlman RS. Can ketosis help migraine sufferers? A case report.
84. Kossoff EH, Zupec‐Kania BA, Amark PE, et al. Optimal clinical
management of children receiving the ketogenic diet: recommen-
dations of the International Ketogenic Diet Study Group. Epilepsia.
85. Kossoff EH, Zupec‐Kania BA, Auvin S, et al. Optimal clinical man-
agement of children receiving dietary therapies for epilepsy:
updated recommendations of the International Ketogenic Diet
Study Group. Epilepsia Open. 2018;3:175‐192.
86. Sirven J, Whedon B, Caplan D, et al. The ketogenic diet for
intractable epilepsy in adults: preliminary results. Epilepsia. 1999;
87. Gasior M, Rogawski MA, Hartman AL. Neuroprotective and
disease‐modifying effects of the ketogenic diet. Behav Pharmacol.
88. Neal EG, Chaffe H, Schwartz RH, et al. A randomized trial of
classical and medium‐chain triglyceride ketogenic diets in the
treatment of childhood epilepsy. Epilepsia. 2009;50:1109‐1117.
89. Schwartz RM, Boyes S, Aynsley‐Green A. Metabolic effects of
three ketogenic diets in the treatment of severe epilepsy. Dev Med
Child Neurol. 1989;31:152‐160.
90. Klement RJ, Kämmerer U. Is there a role for carbohydrate re-
striction in the treatment and prevention of cancer? Nutr Metab.
91. Seyfried TN, Yu G, Maroon JC, D'Agostino DP. Press‐pulse: a novel
therapeutic strategy for the metabolic management of cancer. Nutr
92. Hyde PN, Lustberg MB, Miller VJ, LaFountain RA., Volek JS.
Pleiotropic effects of nutritional ketosis: conceptual framework for
keto‐adaptation as a breast cancer therapy. Cancer Treat Res
93. Maroon JC, Seyfried TN, Donohue JP, Bost J. The role of metabolic
therapy in treating glioblastoma multiforme. Surg Neurol Int. 2015;
94. Shimazu T, Hirschey MD, Newman J, et al. Suppression of oxidative
stress by ‐hydroxybutyrate, an endogenous histone deacetylase
inhibitor. Science. 2013;339:211‐214.
95. Klement RJ, Brehm N, Sweeney RA. Ketogenic diets in medical
oncology: a systematic review with focus on clinical outcomes. Med
96. Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate
restriction as the ﬁrst approach in diabetes management: critical
review and evidence base. Nutrition. 2015;31:1‐13.
97. Saslow LR, Mason AE, Kim S, et al. An online intervention
comparing a very low‐carbohydrate ketogenic diet and lifestyle
recommendations versus a plate method diet in overweight in-
dividuals with type 2 diabetes: a randomized controlled trial. J Med
Internet Res. 2017;19:e36.
98. Hallberg SJ, McKenzie AL, Williams PT, et al. Effectiveness and
safety of a novel care model for the management of type 2 dia-
betes at 1 Year: an open‐label, non‐randomized, controlled study.
Diabetes Ther. 2018;9:583‐612.
99. Barnard RJ, Lattimore L, Holly RG, Cherny S, Pritikin N. Response
of non‐insulin‐dependent diabetic patients to an intensive program
of diet and exercise. Diabetes Care. 1982;5:370‐374.
100. Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low‐
carbohydrate diet for obesity. N Engl J Med. 2003;348:2082‐2090.
101. Cornier M‐A, Donahoo WT, Pereira R, et al. Insulin sensitivity
determines the effectiveness of dietary macronutrient composition
on weight loss in obese women. Obes Res. 2005;13:703‐709.
102. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a
systematic review and meta‐analysis. J Am Med Assoc.
103. le Roux CW, Aylwin SJB, Batterham RL, et al. Gut hormone proﬁles
following bariatric surgery favor an anorectic state, facilitate
weight loss, and improve metabolic parameters. Ann Surg. 2006;
104. Meek CL, Lewis HB, Reimann F, Gribble FM, Park AJ. The effect of
bariatric surgery on gastrointestinal and pancreatic peptide hor-
mones. Peptides. 2016;77:28‐37.
ANDERSON ET AL.
105. Triffoni‐Melo AT, Dick‐de‐Paula I, Portari GV, Jordao AA, Garcia
Chiarello P, Diez‐Garcia RW. Short‐term carbohydrate‐restricted
diet for weight loss in severely obese women. Obes Surg. 2011;
106. Holderbaum M, Casagrande DS, Sussenbach S, Buss C. Effects of
very low calorie diets on liver size and weight loss in the preop-
erative period of bariatric surgery: a systematic review. Surg Obes
Relat Dis. 2018;14:237‐244.
107. Rondanelli M, Faliva MA, Gasparri C, et al. Current opinion on
dietary advice in order to preserve fat‐free mass during a low‐
calorie diet. Nutrition. 2020;72:110667.
108. Sajoux I, Lorenzo PM, Gomez‐Arbelaez D, et al. Effect of a very‐
low‐calorie ketogenic diet on circulating myokine levels
compared with the effect of bariatric surgery or a low‐calorie diet
in patients with obesity. Nutrients. 2019;11.
109. Seraﬁm MP, Santo MA, Gadducci AV, Scabim VM, Cecconello I, de
Cleva R. Very low‐calorie diet in candidates for bariatric surgery:
change in body composition during rapid weight loss. Clinics. 2019;
110. Boshier PR, Fehervari M, Markar SR, et al. Variation in exhaled
acetone and other ketones in patients undergoing bariatric sur-
gery: a prospective cross‐sectional study. Obes Surg. 2018;28:
111. Beydoun H, Al Badri M, Azar S. The role of ketones in type two
diabetes remission post bariatric surgery. BAOJ Diabetes.
112. Song R, Cao S. Post‐bariatric surgery starvation ketoacidosis and
lipase elevation in the absence of DKA or pancreatitis. Am J Emerg
113. Tulipani S, Grifﬁn J, Palau‐Rodriguez M, et al. Metabolomics‐guided
insights on bariatric surgery versus behavioral interventions for
weight loss. Obesity. 2016;24:2451‐2466.
114. Aminian A, Kashyap SR, Burguera B, et al. Incidence and clinical
features of diabetic ketoacidosis after bariatric and metabolic
surgery. Diabetes Care. 2016;39:e50‐53.
115. Kirwan JP, Aminian A, Kashyap SR, Burguera B, Brethauer SA,
Schauer PR. Bariatric surgery in obese patients with type 1 dia-
betes. Diabetes Care. 2016;39:941‐948.
How to cite this article: Anderson JC, Mattar SG, Greenway
FL, Lindquist RJ. Measuring ketone bodies for the monitoring
of pathologic and therapeutic ketosis. Obes Sci Pract.