U.S. patent application number 14/152316 was filed with the patent office on 2015-07-16 for methods of determining energy balance using breath carbon isotope ratios.
The applicant listed for this patent is The United States of America, as represented by the Secretary of Agriculture, The United States of America, as represented by the Secretary of Agriculture, WISCONSIN ALUMNI RESEARCH FOUNDATION. Invention is credited to David H. Abbott, Daniel Elmer Butz, Mark E. Cook, Warren Paul Porter, Dale A. Schoeller, Leah D. Whigham.
Application Number | 20150196248 14/152316 |
Document ID | / |
Family ID | 53520296 |
Filed Date | 2015-07-16 |
United States Patent
Application |
20150196248 |
Kind Code |
A1 |
Cook; Mark E. ; et
al. |
July 16, 2015 |
METHODS OF DETERMINING ENERGY BALANCE USING BREATH CARBON ISOTOPE
RATIOS
Abstract
Described herein are methods of determining energy balance in
individuals such as exercising individuals, individuals consuming a
.sup.13C-enriched test composition and individuals consuming a
fixed diet with a known .delta..sup.13C. The .delta..sup.13C pre-
and post-exercise, or pre- and post-consumption of the test
beverage or fixed diet indicate whether the individual is in
neutral or positive energy balance, or in energy deficit. The
methods are particularly useful for individuals participating in
weight management programs, and individuals under the care of
health care professionals.
Inventors: |
Cook; Mark E.; (Madison,
WI) ; Whigham; Leah D.; (El Paso, TX) ; Butz;
Daniel Elmer; (Madison, WI) ; Porter; Warren
Paul; (Fitchburg, WI) ; Abbott; David H.;
(Madison, WI) ; Schoeller; Dale A.; (Belleville,
WI) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The United States of America, as represented by the Secretary of
Agriculture
WISCONSIN ALUMNI RESEARCH FOUNDATION |
Washington
Madison |
DC
WI |
US
US |
|
|
Family ID: |
53520296 |
Appl. No.: |
14/152316 |
Filed: |
January 10, 2014 |
Current U.S.
Class: |
600/531 |
Current CPC
Class: |
A61B 5/082 20130101;
A61B 5/4866 20130101; A61D 99/00 20130101; A61K 41/0028 20130101;
A61B 5/486 20130101; G01N 33/004 20130101; G01N 33/497 20130101;
A61K 49/0004 20130101 |
International
Class: |
A61B 5/00 20060101
A61B005/00; G01N 33/00 20060101 G01N033/00; A61D 99/00 20060101
A61D099/00; G01N 33/497 20060101 G01N033/497; A61B 5/083 20060101
A61B005/083; A61K 49/00 20060101 A61K049/00 |
Claims
1. A method of determining energy balance in an exercising
individual, comprising obtaining a pre-exercise breath sample from
the individual, exercising the individual for a period of time,
obtaining a post-exercise breath sample from the individual, and
determining a .delta..sup.13C of the pre-exercise breath sample and
a .delta..sup.13C of the post-exercise breath sample, wherein an
increased post-exercise .delta..sup.13C compared to the
pre-exercise .delta..sup.13C indicates that the individual is at
neutral or positive energy balance, and a substantially constant
post-exercise .delta..sup.13C compared to the pre-exercise
.delta..sup.13C indicates that the individual is in energy
deficit.
2. The method of claim 1, wherein the increased post-exercise
.delta..sup.13C is greater than or equal to 0.7.Salinity. during
neutral or positive energy balance, and the substantially constant
post-exercise .delta..sup.13C is increased less than 0.7.Salinity.
in energy deficit.
3. The method of claim 1, wherein the individual is a participant
in a weight-loss program consuming an energy-restricted diet.
4. The method of claim 3, wherein the individual is in weight
maintenance, and recommending a reduction in calorie intake or an
increase in exercise.
5. The method of claim 1, wherein the exercise intensity is aerobic
and less than one hour.
6. The method of claim 1, wherein the individual is in need of body
mass increase and is consuming an energy-excess diet.
7. The method of claim 6, wherein the individual is in energy
deficit, and recommending an increase in calorie intake or a
decrease in exercise.
8. A method of determining energy balance in an individual,
comprising obtaining a pre-test breath sample from the individual,
administering a .sup.13C-enriched test composition to the subject,
wherein a .delta..sup.13C of the .sup.13C-enriched test composition
is increased relative to a .delta..sup.13C of the pre-test breath
sample, obtaining a post-test breath sample from the individual
within 0.25 to 6 hours of administering the .sup.13C-enriched test
composition, and determining the .delta..sup.13C of the pre-test
breath sample and a .delta..sup.13C of the post-test breath sample,
wherein an increased post-test .delta..sup.13C compared to the
pre-test .delta..sup.13C indicates that the individual is in
neutral or positive energy balance, and a substantially constant
post-test .delta..sup.13C compared to the pre-test .delta..sup.13C
indicates that the individual is in energy deficit.
9. The method of claim 8, wherein the .delta..sup.13C of the
.sup.13C-enriched test composition is known.
10. The method of claim 8, wherein the increased post-test
.delta..sup.13C is greater than or equal to 0.7.Salinity. during
neutral or positive energy balance, and the substantially constant
post-test .delta..sup.13C is increased less than 0.7.Salinity. in
energy deficit.
11. The method of claim 8, wherein the individual is a patient
under the care of health personnel.
12. The method of claim 11, wherein the human individual is a human
individual in terminal care; an individual receiving intragastric
or intraparenteral nutrition; an individual undergoing cancer
treatment; an individual in elder care; an individual with AIDS; an
individual in convalescence following trauma, surgery or burn; or
an individual with an eating disorder.
13. The method of claim 11, wherein the individual is a patient in
an intensive care unit or a neonate in a neonatal care unit.
14. The method of claim 13, wherein the individual is subject to
intragastric feeding or total intraparenteral nutrition.
15. The method of claim 14, wherein the individual is in an energy
deficit, and the method further comprises increasing the rate of
gastric and/or parenteral feeding.
16. The method of claim 8, wherein the human individual is a
subject in a human study in which dietary compliance is determined
or monitored.
17. The method of claim 8, wherein the .sup.13C-enriched test
composition is a liquid sweetened with cane sugar, corn sugar, or
corn oil.
18. A method of determining energy balance in an individual
consuming a fixed diet with a known .delta..sup.13C, comprising the
individual consuming the fixed diet with known .delta..sup.13C on a
first day, wherein the .delta..sup.13C of the fixed diet is
increased relative to a .delta..sup.13C of the individual's breath,
and wherein the fixed diet includes at least a first meal and a
second meal, obtaining a first day breath sample from the
individual, obtaining a second day breath sample from the
individual, wherein the first day breath sample and the second day
breath sample are taken at approximately the same time of day and
about 24 hours apart, and determining a first day breath sample
.delta..sup.13C and a second day breath sample .delta..sup.13C,
wherein an increased second day .delta..sup.13C compared to the
first day .delta..sup.13C indicates that the individual is in
neutral or positive energy balance, and a substantially constant
second day .delta..sup.13C compared to the first day
.delta..sup.13C indicates that the individual is in energy
deficit.
19. The method of claim 18, wherein the individual is an
agricultural animal.
20. The method of claim 19, wherein the agricultural animal is
selected from cattle, swine, horses, sheep, chickens, ducks,
turkeys, pheasants, and fish.
21. The method of claim 18, wherein the individual is a
domesticated pet.
22. The method of claim 21, wherein the pet is selected from dogs
and cats.
23. The method of claim 18, wherein the individual is a human and
the increased second day .delta..sup.13C, when compared to the
first day .delta..sup.13C is at least 0.7.Salinity. during neutral
or positive energy balance, and the substantially constant
.delta..sup.13C from the first day to the second day is less than
0.7.Salinity. in energy deficit.
24. The method of claim 18, wherein the individual is a human
individual in terminal care; an individual receiving intragastric
or intraparenteral nutrition; an individual undergoing cancer
treatment; an individual in elder care, an individual with AIDS; an
individual in convalescence following trauma, surgery or burn; or
an individual with an eating disorder.
25. The method of claim 18, wherein the individual is a subject in
a human study in which dietary compliance is determined or
monitored.
26. The method of claim 18, where the individual is a human
individual adhering to a weight loss diet regimen.
Description
FIELD OF THE DISCLOSURE
[0001] The present disclosure is related to methods of use of
breath carbon isotope ratios to obtain non-invasive personalized
biofeedback and a medical health indication of the caloric needs of
a patient.
BACKGROUND
[0002] Innovative advances in breath analysis provide opportunities
for non-invasive personalized biofeedback for medical conditions.
Cavity ring-down spectroscopy (CRDS), in particular, provides a
highly accurate, precise, and rapid table-top methodology for
measuring stable isotopes in exhaled breath. Breath isotopes
provide information about metabolic processes within the body. One
such application is the decrease in .sup.13C natural abundance in
breath, a biomarker for the catabolic state.
[0003] A noninvasive, non-doping, rapid stable isotope method to
discern the onset of the catabolic state by detecting isotopic
changes in the exhaled CO.sub.2 in breath was described in U.S.
Pat. No. 5,912,178 (the '178 patent). The relative health of an
organism was determined by comparing the sampled ratio
(C.sup.13:C.sup.12) to a baseline ratio in the organism by testing
breath samples in a mass spectrometer, for example. The methods
disclosed in the '178 patent allow for a non-invasive determination
of net catabolic processes of organisms experiencing altered organ
function or a deficit in nutrient intake.
[0004] Similarly, in U.S. Pat. No. 7,465,276 (the '276 patent), the
relative amounts of first and second breath isotopes are measured
over time to determine if an organism is experiencing a viral or
bacterial infection. Advantages of the method of the '276 patent
are that breath samples from an isotopically unenriched organism
can be monitored for changes in isotope ratios over time to
determine if the organism is experiencing a bacterial or viral
infection. A baseline measurement from the healthy subject is
preferred so that changes from the baseline can be measured that
are indicative of infection. Measurements can be obtained over
several hours or even several days so that the change in isotope
ratio from the baseline ratio can be determined.
[0005] In addition, U.S. Pat. No. 8,512,676 describes the use of
oscillation modes in breath isotope ratio data to identify an
"unhealthy" state in an organism. Changes in the frequency and/or
amplitude of the oscillation modes can be correlated with the
health of an individual. Advantageously, advances in cavity
ringdown spectrometry allow for the continuous collection of breath
isotope data which permits the identification of oscillatory
patterns within the breath isotope data. The identified oscillation
modes are particularly useful in determining the transition from a
healthy to an infected state in an organism within the short-term
infection period, e.g., 30 minutes to 2 hours.
[0006] While previous methods using determination of breath isotope
ratios are well-suited for their intended purpose, it is desirable
to find additional uses for breath isotope ratios as a non-invasive
biofeedback tool.
BRIEF SUMMARY
[0007] In one aspect, a method of determining energy balance in an
exercising individual comprises obtaining a pre-exercise breath
sample from the individual, exercising the individual for a period
of time, obtaining a post-exercise breath sample from the
individual, and determining a .delta..sup.13C of the pre-exercise
breath sample and a .delta..sup.13C of the post-exercise breath
sample. An increased post-exercise .delta..sup.13C compared to the
pre-exercise .delta..sup.13C indicates that the individual is at
neutral or positive energy balance, and a substantially constant
post-exercise .delta..sup.13C compared to the pre-exercise
.delta..sup.13C indicates that the individual is in energy
deficit.
[0008] In another aspect, a method of determining energy balance in
an individual comprises obtaining a pre-test breath sample from the
individual, administering a .sup.13C-enriched test composition to
the subject, wherein a .delta..sup.13C of the .sup.13C-enriched
test composition is increased relative to a .delta..sup.13C of the
pre-test breath sample, obtaining a post-test breath sample from
the individual within 0.25 to 6 hours of administering the
.sup.13C-enriched test composition, and determining the
.delta..sup.13C of the pre-test breath sample and a .delta..sup.13C
of the post-test breath sample. An increased post-test
.delta..sup.13C compared to the pre-test .delta..sup.13C indicates
that the individual is in neutral or positive energy balance, and a
substantially constant post-test .delta..sup.13C compared to the
pre-test .delta..sup.13C indicates that the individual is in energy
deficit.
[0009] In yet another aspect, a method of determining energy
balance in an individual consuming a fixed diet with a known
.delta..sup.13C comprises the individual consuming the fixed diet
with known .delta..sup.13C on a first day, wherein the
.delta..sup.13C of the fixed diet is increased relative to a
.delta..sup.13C of the individual's breath, and wherein the fixed
diet includes at least a first meal and a second meal, obtaining a
first day breath sample from the individual, obtaining a second day
breath sample from the individual, wherein the first day breath
sample and the second day breath sample are taken at approximately
the same time of day and about 24 hours apart, and determining a
first day breath sample .delta..sup.13C and a second day breath
sample .delta..sup.13C. An increased second day .delta..sup.13C
compared to the first day .delta..sup.13C indicates that the
individual is in neutral or positive energy balance, and a
substantially constant second day .delta..sup.13C compared to the
first day .delta..sup.13C indicates that the individual is in
energy deficit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 shows breath .delta..sup.13C values of pre-breakfast
breath across 7 days on a hypocaloric diet. *Significantly
different from pre-breakfast day 1, p<0.05 by Dunnett's
comparisons.
[0011] FIG. 2 shows breath .delta..sup.13C values on day 7 during a
hypercaloric diet (breakfast, lunch, and dinner). Although excess
caloric intake started at breakfast (620 kcal vs. 420 kcal for
breakfast on days 1-6), subjects most likely did not reach positive
energy balance until lunch was consumed (1500 kcal). *Significantly
different from pre-breakfast day 7, p<0.05 by Dunnett's
comparisons.
[0012] FIG. 3 shows breath .delta..sup.13C values (squares) related
to meal .delta..sup.13C values (circles) and meal energy content
(open bars). Open squares represent pre-breakfast breath
.delta..sup.13C values shown in FIG. 1.
[0013] FIG. 4 shows the breath .delta..sup.13C values in response
to exercise underweight management conditions (WM) and
energy-deficit conditions (ED). *Significantly different from
pre-exercise, p<0.05. PreEx=before exercise, PostEx=immediately
after exercise, Post30/60/90=30/60/90 minutes after exercise.
[0014] The above-described and other features will be appreciated
and understood by those skilled in the art from the following
detailed description, drawings, and appended claims.
DETAILED DESCRIPTION
[0015] It has been discovered that breath carbon isotope ratio
(i.e., .sup.13CO.sub.2/.sup.12CO.sub.2; .delta..sup.13C value)
responds differently to exercise in people depending on if they are
in energy balance (i.e., consuming a weight-maintenance diet, WM)
compared to if they are in energy deficit (ED, consuming fewer
calories than their body needs). There is no current method for
monitoring energy deficit, per se. The state of the art method to
determine if a person is in WM or ED is simply body weight over
time. However, body weight is not an accurate indicator of energy
balance over short periods of time (it is best used 1-2 times per
week) because many factors influence body weight in the short-term.
Breath .delta..sup.13C analysis is useful for detecting changes in
energy balance in much shorter time (e.g., within a day). This
information would likely have a greater impact on changing a
person's behavior because the feedback will be more closely linked
in time with the behavior(s) impacting the energy balance.
[0016] In one aspect, a method of determining energy balance in an
exercising individual, comprises
[0017] obtaining a pre-exercise breath sample from the
individual,
[0018] exercising the individual for a period of time,
[0019] obtaining a post-exercise breath sample from the individual,
and
[0020] determining a .delta..sup.13C of the pre-exercise breath
sample and a .delta..sup.13C of the post-exercise breath
sample,
[0021] wherein an increased post-exercise .delta..sup.13C compared
to the pre-exercise .delta..sup.13C indicates that the individual
is at neutral or positive energy balance, and a substantially
constant post-exercise .delta..sup.13C compared to the pre-exercise
.delta..sup.13C indicates that the individual is in energy
deficit.
[0022] As used herein, the breath delta value (.delta..sup.13C) is
calculated using the following formula with Pee Dee Belemnite (PDB)
as the reference standard.
.delta. 13 C = ( 13 C / 12 C sample - 13 C / 12 C PDB ) 13 C / 12 C
PDB .times. 1000 ##EQU00001##
Data are expressed as delta values in parts per mil
(.Salinity.):
[0023] The standard isotope ratio of PDB is 0.0112372. A positive
.delta..sup.13C occurs when the measured isotope ratio is higher
relative to PDB, while a negative .delta..sup.13C occurs when the
measured isotope ratio is lower relative to PDB. Since PDB contains
the heaviest known naturally occurring .sup.13C/.sup.12C ratio, all
measurements of the natural abundance of carbon isotopes are
negative.
[0024] In one aspect, breath samples, such as the pre-exercise
breath sample and the post-exercise breath sample, are collected in
sample bags such as 1 L Tedlar or metal foil bags. Breath samples
can be directly collected into an instrument designed for such
collection. In one embodiment, the post-exercise sample is taken
within 1 minute to 5 hours after completion of exercise,
specifically 5 minutes to 4 hours after completion of exercise, and
more specifically 10 minutes to 2 hours after completion of
exercise.
[0025] In one embodiment, relative isotope measurements are made
using cavity ringdown spectroscopy (CRDS). CRDS uses infrared laser
absorption to measure the concentrations of .sup.13CO.sub.2 and
.sup.12CO.sub.2 carbon signals, and reports precise total CO.sub.2
levels as well as the .sup.13CO.sub.2/.sup.12CO.sub.2 ratio. An
exemplary instrument is a Picarro G2101-i Isotopic CO.sub.2
analyzer. Other methods to measure breath .delta..sup.13C include
isotope mass spectrometry.
[0026] In one aspect, the exercise intensity is aerobic exercise.
Aerobic exercise is sustained exercise that stimulates and
strengthens the heart and lungs, improving the body's oxygen
utilization. Examples of aerobic exercise include jogging, running,
brisk walking, rowing, swimming, cycling, and the like. Aerobic
exercise causes a temporary increase in respiration and heart rate.
The duration of the exercise is, for example, less than or equal to
one hour, although longer times are within the scope of the present
disclosure.
[0027] In one aspect, the individual is a participant in a
weight-loss program consuming an energy-restricted diet. The
methods of the present disclosure can be used to provide people who
are attempting to lose weight with an objective assessment of their
energy balance. Although the market for weight loss products and
services is very large, there exists a need for improved methods
for monitoring energy deficit. While the accepted method to
determine if a person is in weight maintenance (WM) or energy
deficit (ED, weight loss) is simply body weight over time, body
weight is not an accurate indicator of energy balance over short
periods of time. Shorter term, more reliable methods of monitoring
energy deficit would provide increased feedback to persons
attempting to lose weight, maintain their current weight, or gain
weight, thereby encouraging people to continue with a weight-loss
or weight-gain program.
[0028] For example, when an individual is trying to lose weight,
the individual typically attempts to maintain a negative energy
balance by consuming fewer calories than his/her body needs. To
test if this goal is being met, the individual would have a breath
sample analyzed before and after exercising. If the breath
.delta..sup.13C does not change after exercise, the individual has
confirmation of an energy deficit. If the breath .delta..sup.13C
increases after exercise, the individual knows fewer calories
should be consumed to achieve energy deficit and weight loss.
[0029] Diet is defined as the amount and type of food and drink
consumed by an individual on a daily basis. As used herein, an
energy-restricted diet is a diet that provides less energy intake
than expenditure. In general, the purpose of an energy-restricted
diet is weight loss and/or improvement in body composition.
Energy-restricted diets include calorie-restricted diets
(hypocaloric diets) as well as composition-restricted diets such as
diets restricted in sugars and carbohydrates. In one aspect, when
the individual is in weight maintenance according to the breath
.delta..sup.13C values, the method further comprises recommending a
reduction in calorie intake or an increase in exercise.
[0030] As used herein, an energy-excess diet is a diet that
provides more energy intake than expenditure. For example, if a
hypercaloric diet is consumed optionally in combination with
resistance training, both fat mass and muscle mass increases can
occur. In one embodiment the individual is an individual in need of
body mass increase, wherein the individual consumes an
energy-excess diet. Such individuals include athletes such as body
builders, contact sports athletes (e.g., football, wrestling,
boxing, hockey, basketball, and rugby) and endurance athletes. This
method is also useful for subjects with eating disorders such as
anorexia nervosa. In one aspect, when the individual is in energy
deficit according to the breath .delta..sup.13C values, the method
further comprises recommending an increase in calorie intake or a
decrease in exercise.
[0031] Patients with eating disorders such as anorexia nervosa, for
example, are often encouraged to eat enough calories to maintain or
gain weight. The simple exercise test disclosed herein can confirm
that the patient is successfully consuming enough calories. Such
information is critical because eating disorder patients are often
very resistant to eating and need to be coaxed into consuming
adequate calories. Eating disorder patients also typically like and
want to exercise, so performing a test based on exercise would
likely be accepted by the patient.
[0032] In one embodiment, the increased post-exercise
.delta..sup.13C is greater than or equal to 0.7.Salinity. during
neutral or positive energy balance, and the substantially constant
post-exercise .delta..sup.13C is increased less than 0.7.Salinity.
in energy deficit.
[0033] The method of determining energy balance in an exercising
individual can be used, for example, in health clubs or health
centers that promote weight loss to determine if clients are
successfully maintaining a negative or positive energy balance. The
health club can offer the test described herein to people who come
to the facility to exercise, providing a value-added service for
membership to the facility and increasing motivation to use the
facility and to regularly exercise.
[0034] In another embodiment, a method of determining energy
balance in an individual comprises
[0035] obtaining a pre-test breath sample from the individual,
[0036] administering a .sup.13C-enriched test composition to the
subject, wherein a .delta..sup.13C of the .sup.13C-enriched test
composition is increased relative to a .delta..sup.13C of the
pre-test breath sample,
[0037] obtaining a post-test breath sample from the individual
within 0.25 to 6 hours of administering the .sup.13C-enriched test
composition, and
[0038] determining a .delta..sup.13C of the pre-test breath sample
and a .delta..sup.13C of the post-test breath sample,
[0039] wherein an increased post-test .delta..sup.13C compared to
the pre-test .delta..sup.13C indicates that the individual is in
neutral or positive energy balance, and a substantially constant
post-test .delta..sup.13C compared to the pre-test .delta..sup.13C
indicates that the individual is in energy deficit.
[0040] In one embodiment, the increased post-test .delta..sup.13C
is greater than or equal to 0.7.Salinity. during neutral or
positive energy balance, and the substantially constant post-test
.delta..sup.13C is increased less than 0.7.Salinity. in energy
deficit.
[0041] In one embodiment, the .delta..sup.13C of the
.sup.13C-enriched test composition is known. For example, the
.delta..sup.13C of the .sup.13C-enriched test composition can be
calculated from known .delta..sup.13C values of the components of
the diet. In another aspect, diet can be analyzed by isotope ratio
mass spectroscopy as explained in the Examples herein. In one
aspect, the .sup.13C-enriched test composition is rich in
carbohydrates, such as a liquid sweetened with cane sugar, corn
sugar, or corn oil. For example, the .delta..sup.13C of cane sugar
is -12.9.Salinity. and .delta..sup.13C of corn syrup is
-11.8.Salinity.. In one embodiment, the .sup.13C-enriched test
composition is orally administered.
[0042] In one aspect, the .delta..sup.13C of a mixed meal is
calculated using the .delta..sup.13C of the individual food
components of the meal. The .delta..sup.13C of a food can be
calculated by freeze-drying the food, weighing the dried food, and
analyzing the dried food using, for example, an isotope ratio mass
spectrometer as described herein. In one aspect, the
.delta..sup.13C is weighted such that the contribution of
individual foods to the isotopic signature of a meal is relative to
the caloric contribution of the food item to the total caloric
contribution of the food item to the total caloric content of the
meal.
[0043] In one embodiment, the post-test breath sample from the
individual is obtained within 0.25 to 6 hours of administering the
.sup.13C-enriched test composition, specifically within 1 to 6
hours, and more specifically within 4 to 6 hours.
[0044] In one embodiment, the individual is a patient under the
care of health personnel such as an individual in terminal care, an
individual receiving intragastric or intraparenteral nutrition, an
individual undergoing cancer treatment, an individual in elder
care, an individual with AIDS, an individual in convalescence
following trauma, surgery or burn, or an individual with an eating
disorder. The methods disclosed herein are particularly useful to
heath care professionals to assess whether a patient is in energy
deficit or balance, that is, to determine if the patient is
consuming enough calories.
[0045] Cancer patients and the elderly often have appetite changes
and/or swallowing difficulties that make adequate caloric
consumption a challenge. If, for example, a cancer patient is not
feeling hungry due to effects of chemotherapy or the cachectic
response (muscle wasting and lack of appetite due to immune
response) typical of cancer and some other diseases, the test
disclosed herein could be used to monitor such patients and keep
encouraging them to eat until they achieve an energy balance on a
daily basis.
[0046] In another embodiment, the individual is a patient in an
intensive care unit or a neonate in a neonatal care unit. Such
patients are often subject to intragastric feeding or total
intraparenteral nutrition which present challenges for physicians
to determine if the patient is obtaining adequate nutrition. Not
only do intragastric and intraparenteral feeding present
difficulties in accurately calculating energy needs, but the
underlying cause of the illness can make calculating energy needs
difficult. For example, burn patients require additional calories
depending on the burn severity, but calculating the specific needs
of a specific patient is difficult. By subjecting the patient to a
challenge with a .sup.13C-enriched test composition and obtaining
breath samples, the physician can noninvasively determine the
energy balance in the patient. If it is determined that the patient
is in neutral or positive energy balance, the feeding rate can be
maintained. However, if the patient is in negative energy balance,
the physician can increase the rate of gastric and/or parenteral
feeding to provide a neutral or positive energy balance.
[0047] The methods described herein provide advantages over prior
art methods such as the metabolic cart. A metabolic cart is an
electronic medical tool to measure the body's metabolism through
oxygen consumption and carbon dioxide production when the body is
at rest using indirect calorimetry. In general, the components of
the device (a computer system, monitor, and breathing tubes) are
housed on mobile push cart. The consumption of oxygen for the body
and the production of carbon dioxide are measured to calculate the
REE, or resting energy expenditure. The metabolic cart measures the
calories burned by the individual. However, the metabolic cart
method has significant limitations including: (1) cart sampling
often requires at least 30 minutes of breath sampling per session;
(2) the data obtained from cart sampling can be unreliable if the
patient is disturbed during sampling; and (3) the equations used to
calculate the energy requirements using the metabolic cart are
often based on healthy individuals and do not account for the
altered metabolic needs during disease, injury and recovery from
illness. The methods of the present disclosure, in contrast, allow
for the measurement of energy balance rather than energy
expenditure (from which energy balance is calculated based on
assumptions about the individual's health status). The present
disclosure does not rely on the health status of the individual in
order to determine energy balance. In addition, in order to obtain
data with a metabolic cart, the patient must lie still with a mask
over their face or a hood over their head for at least 20 minutes,
generally 30-40 minutes, which may not be practical for ICU/NICU
patients (interfering with other tubing/equipment, getting infants
to lie still). Also, the metabolic cart method provides resting
energy expenditure, not total energy needs, so the physician still
has to guess as to the additional calories needed when the patient
is not at rest. This value could vary significantly from person to
person, particularly in athletes, eating disorder patients, and
people trying to lose weight, in addition to day to day variance in
individuals. Measuring energy balance factors in the individual's
needs and the day to day variance.
[0048] In another aspect, the individual is a subject in a human
study in which dietary compliance is determined or monitored. For
example, researchers are trying to find new ways to reduce obesity.
In some of these studies researchers are investigating the effects
of new diet or pharmaceutical agents to reduce energy consumption.
The use of the breath .delta..sup.13C would allow the researchers
to quickly assess the affects of the intervention in reducing
caloric need relative to intake. In addition, subjects in a weight
loss study might consume food other than that which has been
provided to them. The method disclosed herein would allow
monitoring of dietary compliance in weight loss studies in
free-living subjects which is desirable to researchers because
ultimately weight loss methods are for use by free-living
people.
[0049] A method of determining energy balance in an individual
consuming a fixed diet with a known .delta..sup.13C comprises
[0050] the individual consuming the fixed diet with known
.delta..sup.13C on a first day, wherein the .delta..sup.13C of the
fixed diet is enriched relative to a .delta..sup.13C of the
individual's breath, and wherein the fixed diet includes at least a
first meal and a second meal,
[0051] obtaining a first day breath sample from the individual,
[0052] obtaining a second day breath sample from the
individual,
[0053] wherein the first day breath sample and the second day
breath sample are taken at approximately the same time of day and
about 24 hours apart, and
[0054] determining a first day breath sample .delta..sup.13C and a
second day breath sample .delta..sup.13C,
[0055] wherein an increased second day .delta..sup.13C compared to
the first day .delta..sup.13C indicates that the individual is in
neutral or positive energy balance and a substantially constant
second day .delta..sup.13C compared to the first day
.delta..sup.13C indicates that the individual is in energy
deficit.
[0056] In one embodiment, the fixed diet is administered over a
period of 2 days to 7 days or longer, and a breath sample is taken
at approximately the same time each day over about 24 hour
intervals. This method allows energy balance to be determined over
an extended period of time. The breath sample can be taken pre-meal
(e.g., pre-breakfast) or post-meal (e.g., post-breakfast), as long
as the sample is taken under the same conditions each day.
[0057] In one embodiment, the increased second day .delta..sup.13C
is greater than or equal to 0.7.Salinity. during neutral or
positive energy balance, and the substantially constant second day
.delta..sup.13C is increased less than 0.7.Salinity. in energy
deficit.
[0058] In one embodiment, the individual is an agricultural animal
such as, for example, cattle, swine, horses, sheep, chickens,
ducks, turkeys, pheasants, and fish. In another embodiment, the
individual is a domesticated pet such as a dog or cat. The method
of determining energy balance in animals is particularly
advantageous because it is noninvasive and administering fixed
diets to animals is routinely practiced.
[0059] In one embodiment, the individual is a human and the
increased second day .delta..sup.13C, when compared to the first
day .delta..sup.13C is at least 0.7.Salinity. during neutral or
positive energy balance, and the substantially constant
.delta..sup.13C from the first day to the second day is less than
0.7.Salinity. in energy deficit.
[0060] In another embodiment, the individual is a human individual
in terminal care, an individual receiving intragastric or
intraparenteral nutrition, an individual undergoing cancer
treatment, an individual in elder care, an individual with AIDS, an
individual in convalescence following trauma, surgery or burn, or
an individual with an eating disorder. In another embodiment, the
individual is a subject in a human study in which dietary
compliance is determined or monitored. In yet another embodiment,
the individual is a human individual adhering to a weight loss diet
regimen. As used herein, a weight-loss diet regimen is a
calorie-restricted diet.
[0061] The invention is further illustrated by the following
non-limiting examples.
EXAMPLES
Example 1
Use of Breath Isotopes to Monitor Compliance to an Energy
Restricted Diet in Humans
Methods
[0062] This study was approved by the University of
Wisconsin-Madison Institutional Review Board. All volunteers
provided written informed consent. Healthy volunteers (n=5) 18
years and older with no metabolic or digestive problems or food
allergies were recruited for the study. Volunteers consumed three
study meals per day for 7 days. Volunteers decided what time to
consume meals but were instructed to follow similar meal times
throughout the 7 days. Meals on days 1-6 contained approximately
40% fewer kcal than required for weight maintenance and
approximately 50% excess kcal on day 7. On the morning of day 8,
volunteers consumed a breakfast comparable to days 1-6. Total
energy requirements were estimated using calculations for resting
energy expenditure (REE) based on age, height, weight, and sex
known in the prior art with a physical activity level of 1.65. The
following equations used were:
REE(males)=10.times.weight(kg)+6.25.times.height(cm)-5.times.age(y)+5
REE(females)=10.times.weight(kg)+6.25.times.height(cm)-5.times.age(y)-16-
1
[0063] Volunteers collected breath in 1-L air sampling bags (SKC
Inc., Eighty Four, Pa.) just prior to and 1 hour and 2 hour
following each meal. Breath was analyzed within 48 hours using a
CRDS (Picarro, Sunnyvale, Calif., USA). Diet was analyzed by
isotope ratio mass spectroscopy. Food items were homogenized,
freeze dried, and powdered. Approximately 1 mg of each food item
was added to tin capsules and inserted into the elemental analyzer
where it was oxidized and the .sup.13C abundance was analyzed using
a Delta V Isotope Ratio mass spectrometer coupled to the elemental
analyzer via a Finnigan Conflo III universal interface (Thermo
Electron, Bremen, Germany). The .sup.13C abundance for the meal was
calculated by weighing the .sup.13C abundance for each food item in
proportion to its fractional contribution to the total carbon of
the meal. The isotopic abundance of .sup.13C was expressed as a
relative change in the ratio of .sup.13C/.sup.12C in a sample
compared to a Pee Dee Belemnite as described herein.
[0064] This notation simply translated is ten times the percent
difference in the isotope ratio relative to the standard.
[0065] Statistical Analyses: Data are presented as mean.+-.standard
deviation (SD). Repeated measures analysis of variance (ANOVA) was
used to test for changes across time in pre-breakfast and in day 7
breath .delta..sup.13C. Dunnett's contrasts were used for post-hoc
comparisons; pre-breakfast breath .delta..sup.13C on days 2-7 were
compared to day 1; and postprandial day 7 time points were compared
to pre-breakfast day 7. SAS V9.2 (SAS Institute, Inc., Cary N.C.)
was used for all statistical analyses. P<0.05 was considered
significant.
Results
[0066] Non-obese volunteers (n=5; 2 female) were 48.0.+-.12.1 years
of age with a BMI of 25.2.+-.0.8 kg/m.sup.2. Estimated energy
requirements for these subjects were calculated to be 2550-2770
kcal (10,673-11,595 kJ). Consumption of the energy restricted diet
decreased the pre-breakfast breath .delta..sup.13C from
-22.4.+-.1.0.Salinity. on day 1 to -23.6.+-.0.6.Salinity. on day 3
(P<0.007, FIG. 1). The more negative, pre-breakfast breath
.delta..sup.13C were maintained for the remaining period of energy
restriction (range of -23.3 to -23.8.Salinity., P<0.05 compared
to day 1), including the day 7 pre-breakfast breath .delta..sup.13C
of -23.8.+-.0.6.Salinity.. By pre-dinner on day 7 (first day of
hypercaloric feeding), breath .delta..sup.13C increased (P=0.002)
to -21.9.+-.0.7 and remained elevated 2 hours after dinner (FIG.
2). FIG. 3 shows breath .delta..sup.13C across all time points
along with meal .delta..sup.13C and energy level of each meal.
Breakfast, lunch, and dinner .delta..sup.13C means on days 1-6 were
-22.1, -21.9, and -21.1.Salinity., respectively, compared to meal
.delta..sup.13C day 7 of -25.3, -21.3, and -20.9, respectively.
Discussion
[0067] This study was designed to demonstrate proof of concept for
a novel use of naturally occurring breath stable isotope ratios of
carbon to monitor compliance to an energy restricted diet in
humans. The technique provides a biofeedback tool for individuals
attempting to lose weight by consuming an energy restricted diet.
Consumption of an energy restricted diet resulted in a decrease in
pre-breakfast breath .delta..sup.13C after 3 days. Throughout the
remainder of the energy restricted phase of the diet, breath
.delta..sup.13C values remained relatively low despite transient
rises in meal .delta..sup.13C values (FIG. 3), potentially
indicating that breath was more representative of the substrate
being utilized (i.e., stored fat) than the diet consumed during
energy restriction.
[0068] On day 7, breath .delta..sup.13C became isotopically heavier
by dinner, despite meal .delta..sup.13C values differing little
from meals consumed during days 1-6. The breakfast meal on day 7,
while higher in energy than breakfast on days 1-6 (620 vs. 420 kcal
or 2594 vs. 1757 kJ, respectively), was likely not sufficiently
caloric to shift individuals from negative to positive energy
balance, especially following an overnight fast in a person
consuming an energy restricted diet for the previous 6 days.
Consumption of a subsequent 1500 kcal (6276 kJ) lunch, however,
appeared to shift subjects into positive energy balance, as
indicated by elevated breath .delta..sup.13C by pre-dinner. The
breath .delta..sup.13C remained elevated through pre-breakfast the
following day (day 8).
[0069] The ability to monitor compliance with an energy restricted
diet has value for investigators from a research standpoint and
subjects or patients from a motivational standpoint. Current
methods of monitoring compliance to prescribed dietary guidelines
for weight loss include monitoring changes in weight and body
composition and recording dietary intake. Tracking of weight and
body composition allows for feedback on a weekly basis at best, but
is not sensitive enough for daily feedback. Monitoring food intake
is a commonly used treatment technique for behavioral change, but
is inaccurate. Furthermore, maintaining this technique is
time-consuming so few people consistently use it long-term.
Personalized daily feedback, provided by breath .delta..sup.13C
values, could allow for immediate positive reinforcement for
compliance to a negative energy balance diet or timely counseling
when compliance is poor.
[0070] The design of this study was intended to emulate a real-life
scenario in which an individual follows a healthy, energy
restricted diet for several days, followed by a day in which
attempts to control energy intake are difficult to maintain in the
current food environment (e.g., donuts at a breakfast meeting,
drive-through fast food meal for lunch, and high-fat pizza for
dinner). Further validation under highly controlled conditions with
manipulation of diet .delta..sup.13C and caloric level
independently will help to fully test specificity, robustness, and
variability of responses across time of the breath .delta..sup.13C
method. In addition, optimization of this methodology as a weight
loss aid for individuals would be significantly enhanced by
development of a hand-held device capable of breath carbon isotope
ratio analysis. Current cavity ring-down technology, nevertheless,
offers options for center-based programs in locations such as
fitness centers or the work place.
Example 2
Changes in Breath .delta..sup.13C in Response to Exercise
[0071] Volunteers provided informed, written consent. The study was
overseen by the University of North Dakota Institutional Review
Board. Volunteers resided in the Metabolic Research Unit of the
USDA Grand Forks Human Nutrition Research Center. On days 1-10,
live-in human volunteers consumed a weight maintenance diet and
participated in a prescribed, supervised exercise episode each day.
On days 11-31, the volunteers were in 40% energy deficit and
continued with daily exercise. The study diet was based on a 3-day
menu that was individually adjusted to caloric needs (WM or ED) for
each study volunteer. Exercise episodes were conducted either
during the morning (following breakfast and prior to lunch) or in
the afternoon (following lunch and prior to dinner), but kept the
same time of day for each individual. Breath samples were collected
prior to, immediately after, and 30, 60 and 90 minutes post
exercise during weight maintenance and energy deficit. Study diet
menu day was the same (but different caloric levels) on comparison
days (WM and ED).
[0072] The results are shown in FIG. 4. The breath .delta..sup.13C
values increase in response to exercise under conditions of energy
balance (WM) (P.ltoreq.0.01), but do not change following exercise
under conditions of energy deficit (ED). These results differ from
the expected result which was an increase in breath .delta..sup.13C
in response to exercise regardless of energy balance.
[0073] The ability to determine or monitor negative energy balance
has value for investigators and health care providers. This
approach could be used in research environments in which compliance
to an energy restricted diet is required. Similarly, the approach
could be applied in health club or clinic environments as a tool to
confirm maintenance of an energy-restricted diet (e.g. individuals
attempting weight loss) or conversely to confirm maintenance of a
neutral or positive energy balance (e.g. patients recovering from
an eating disorder such as anorexia nervosa).
[0074] The use of the terms "a" and "an" and "the" and similar
referents (especially in the context of the following claims) are
to be construed to cover both the singular and the plural, unless
otherwise indicated herein or clearly contradicted by context. The
terms first, second etc. as used herein are not meant to denote any
particular ordering, but simply for convenience to denote a
plurality of, for example, layers. The terms "comprising",
"having", "including", and "containing" are to be construed as
open-ended terms (i.e., meaning "including, but not limited to")
unless otherwise noted. Recitation of ranges of values are merely
intended to serve as a shorthand method of referring individually
to each separate value falling within the range, unless otherwise
indicated herein, and each separate value is incorporated into the
specification as if it were individually recited herein. The
endpoints of all ranges are included within the range and
independently combinable. All methods described herein can be
performed in a suitable order unless otherwise indicated herein or
otherwise clearly contradicted by context. The use of any and all
examples, or exemplary language (e.g., "such as"), is intended
merely to better illustrate the invention and does not pose a
limitation on the scope of the invention unless otherwise claimed.
No language in the specification should be construed as indicating
any non-claimed element as essential to the practice of the
invention as used herein.
[0075] While the invention has been described with reference to an
exemplary embodiment, it will be understood by those skilled in the
art that various changes may be made and equivalents may be
substituted for elements thereof without departing from the scope
of the invention. In addition, many modifications may be made to
adapt a particular situation or material to the teachings of the
invention without departing from the essential scope thereof.
Therefore, it is intended that the invention not be limited to the
particular embodiment disclosed as the best mode contemplated for
carrying out this invention, but that the invention will include
all embodiments falling within the scope of the appended claims.
Any combination of the above-described elements in all possible
variations thereof is encompassed by the invention unless otherwise
indicated herein or otherwise clearly contradicted by context.
* * * * *