Note: Descriptions are shown in the official language in which they were submitted.
CA 02472371 2009-10-13
METHODS AND SYSTEMS FOR DETERMINING
AND CONTROLLRgG GLYCENIIC RESPONSES
BACKGROUND OF THE INVENTION
The present invention relates to methods for establishing the Equivalent
Glycemic Load of food products, and systems for selecting food products by
consumers for the management of their intake of foods that elicit glycemic
responses,
primarily from digestible carbohydrates.
Carbohydrates can be defined in three ways; structurally (based on molecular
structure), analytically (such as, for example, as defined by Federal labeling
regulations), and physiologically (based on glycemic impact).
Carbohydrates defined structurally include compounds composed of at least
one basic monosaccharide unit. Under this definition, carbohydrates may be
further
classified as simple carbohydrates and complex carbohydrates. Simple
carbohydrates
are monosaccharides and disaccharides. Complex carbohydrates are
polysaccharides,
or large molecules composed of straight or branched chains of monosaccharides.
For labeling purposes, the Food and Drug Administration (FDA) has declared
that the total carbohydrate content of a food "shall be calculated by
subtraction of the
sum of the crude protein, total fat, moisture and ash from the total weight of
the
product." Such a measurement of carbohydrate content is not precise. For
example,
errors in the measurement of the food components being subtracted carry over
into the
determination of carbohydrate content. When measuring carbohydrate content in
low-carbohydrate foods, such errors can typically be up to twenty to one
hundred
percent. (FAO/WHO Expert Panel on Carbohydrates. Carbohydrates in Human
Nutrition/Total Carbohydrate Section; Rome, Italy (1997),
http://hipocrates.univalle.edu.co/estudi/carbohyd.htm.) Additionally, since
only the
enumerated food components are subtracted, the FDA definition of carbohydrates
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CA 02472371 2009-10-13
includes components such as, lignin, gums, pectin and other fibers; as well as
waxes,
tannins, some Maillard products, flavonoids, organic acids, and polyols.
Accordingly,
the FDA definition of carbohydrates can include components which are not
structural
carbohydrates.
Carbohydrates defined physiologically are structural carbohydrates which
elicit an immediate and significant impact on blood glucose and plasma
insulin. Such
carbohydrates are termed "glycemic carbohydrates," "digestible carbohydrates"
or
"available carbohydrates." Structural carbohydrates which do not elicit a
significant
impact on blood glucose and insulin are termed "non-glycemic carbohydrates."
The Food and Drug Administration (FDA) nutritional labeling requirements
do not distinguish between glycemic carbohydrates and non-glycemic
carbohydrates.
For example, the FDA definition lumps together sugars and starches which have
an
immediate and significant impact on blood glucose, with fiber which does not
impact
blood glucose, as well as polyols, which have little, if any, impact on blood
glucose.
Glycemic carbohydrates include simple carbohydrates, and some complex
carbohydrates. After consumption, simple carbohydrates are rapidly absorbed,
while
some complex carbohydrates are typically broken down into simple carbohydrates
and then absorbed. After absorption, these simple carbohydrates can elicit a
rise in
blood glucose levels. Non-glycemic complex carbohydrates, and some of the
compounds labeled as carbohydrates on "nutritional facts" panels under the FDA
definition, are not broken down into simple carbohydrates or significantly
absorbed in
the small intestine, but pass into the colon where they may be fermented by
bacteria,
or pass through the gut intact. Molecules that are not absorbed in the small
intestine
do not produce a rise in blood glucose levels.
The rise in blood glucose levels immediately following absorption of glycemic
carbohydrates is termed the "glycemic response." Blood glucose is used
immediately
to provide energy, or is stored in the form of glycogen in the liver and
muscles to be
utilized when required by the body's energy demands. The transport of glucose
from
the blood into storage in liver and muscle cells is aided by the secretion of
pancreatic
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CA 02472371 2009-10-13
insulin into the bloodstream. Any excess glucose, i.e. glucose which is not
used as a
source of energy or stored as glycogen, is converted to fat.
The normal blood glucose concentration in a healthy person after a four to
eight hour fast is typically in a range of between 70 and 115 mg/100 ml of
blood
(Whitney and Rolfes 1993). During the first hour or so following a meal
containing
glycemic carbohydrates, blood glucose concentrations typically increase to 120
to 200
mg/100 ml. The secretion of insulin returns the glucose concentration to a
baseline or
controlled level usually within two hours after the last consumption of
carbohydrates.
In individuals with diabetes mellitus, the body's mechanism for the control of
blood glucose levels is defective. Either insulin production by the pancreas
is
diminished, or the ability of the body to use insulin is decreased. Without
sufficient
insulin, or without the ability of the insulin to move glucose into the cells,
the
consumption of glycemic carbohydrates, and subsequent absorption of glucose,
results in glucose remaining in the blood for longer than normal.
The blood glucose levels of diabetics are highly sensitive to even small
amounts of ingested carbohydrates or injected insulin. Such sensitivity can
result in
life threatening consequences. Blood glucose concentrations can rise to
hyperglycemic levels in response to a meal. Diabetic coma may result. The
blood
glucose levels in diabetics can be regulated with the injection of insulin.
However,
too much insulin causes hypoglycemia which can result in insulin shock. Thus,
a
precise control of blood glucose levels within a narrow range is critical for
diabetics.
(National Institute of Health (NIH) News Release: Benefits of Tight Blood
Sugar
Control Endure for Years; Feb 9 (2000)
(http://www.nih.gov/news/pr/feb2000/niddk-
09.htm.)
The long term effects of diabetes also may result in severe consequences.
These consequences may include heart disease, strokes, loss of vision due to
retinal
degeneration, loss of nerve and/or kidney function, and increased
susceptibility to
infection. Recent studies have shown that these long term effects of diabetes
can be
greatly reduced by keeping blood glucose levels under tight control.
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CA 02472371 2009-10-13
Other metabolic disorders may be related to, or caused by, persistently high
levels of blood glucose. Examples of such disorders include: insulin
resistance;
hyperinsulinism, which can lead to type II diabetes; hypoglycemia;
hyperlipidemia;
hypertriglyceridemia; and obesity.
The control of blood glucose levels in individuals without metabolic disorders
is also highly desirable. For example, recent studies have shown that even
transiently
high blood glucose levels can lead to disease. For example, glucose molecules
can
attach to amino groups in tissue proteins and cross-link them into stiff
yellow-brown
compounds known as advanced glycation endproducts (AGEs). AGEs can form on
the surfaces of long-lived proteins, such as collagen and elastin; in blood
vessels and
heart muscle; and in the crystallin of the lens. AGEs may destroy normal
protein
structure, inhibit protein physiological function and cause damage that leads
to
irreversible disease conditions in vital organs. (Vlassara H; Bucala R;
Striker L;
Pathogenic Effects of Advanced Glycosylation: Biochemical, Biologic and
Clinical
Implications for Diabetes and Aging. Lab. Invest. 70(2):138-51 (Feb 1994).)
The rate of AGEs accumulation and the degree of stiffness they produce are
proportional to blood glucose levels, and the length of time high levels
persist.
Additionally, controlling blood glucose levels can be critical in achieving
weight loss. (Ranjana Sinha et al. Prevalence of Impaired Glucose Tolerance
among
Children and Adolescents with Marked Obesity. New Eng J. Med 346(11):802-10
(Mar. 2002).) For example, effective weight reduction can be achieved with a
diet
which minimizes blood glucose levels to the point of inducing ketosis in the
body,
where fat instead of carbohydrates serves as a primary fuel source. (Robert C.
Atkins,
MD, Dr. Atkins' New Diet Revolution (2002)).
Also, it is beneficial for athletes to control their blood glucose levels in
order
to enhance athletic performance. Depending on whether an athletic activity
requires
prolonged endurance or a brief expenditure of energy, adjusting dietary intake
of
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CA 02472371 2009-10-13
glycemic carbohydrates to control blood glucose levels to suit the particular
activity
can benefit performance.
Accordingly, controlling blood glucose levels has many beneficial effects,
most significantly including the maintenance of good health.
A system by which to rank carbohydrate-containing foods by their ability to
raise blood glucose levels has been provided (Wolever et al., Journal of the
American
College of Nutrition 8(3):235-247 (1989)). The system provides the concept of
"glycemic index" (GI).
GI is defined as the glycemic response elicited by a food containing twenty-
five or fifty grams of glycemic carbohydrate expressed as a percentage of the
glycemic response elicited by twenty-five or fifty grams of a glycemic
carbohydrate
of a standard food, such as white bread or an oral glucose solution.
The blood glucose response produced by carbohydrate foods which are
digested and absorbed rapidly is fast and high. Such foods have high GIs.
Conversely, carbohydrates which are digested and/or absorbed slowly release
glucose
gradually into the blood stream, and have low GIs.
Factors which influence the rate of digestion include food form, particle
size,
chemical structure (e.g., stage of ripeness), processing (e.g., degree of
cooking) and
macronutrient content (i.e. fat, protein and soluble fiber content). Fat,and
protein
influence glycemic responses by delaying upper gastrointestinal transit and
increasing
insulin secretion, respectively.
The GI system is not easily applied by an average individual to his daily diet
for several reasons.
GI assesses the glycemic carbohydrate portion of food without taking into
account the food's glycemic carbohydrate density. Thus, average serving sizes
are
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CA 02472371 2009-10-13
not taken into account. For example, since carrots contain a large portion of
fiber and
water, in addition to glycemic carbohydrate, a fifty gram glycemic
carbohydrate
portion of carrots is about six or seven average servings of carrots. Whereas,
only a
quarter cup of sugar contains a fifty gram portion of glycemic carbohydrate.
That is,
measure for measure, sugar contains far more glycemic carbohydrate than
carrots
contain. Since the glycemic carbohydrate density of food products are not
taken into
account, the odd result is that carrots have a -GI of 71 and sugar has a GI of
65. Thus,
an individual may be misled to believe that art average serving size of
carrots
produces a greater rise in blood glucose levels than a quarter cup of sugar.
Additionally, GI is a number without units. Therefore, an individual is not
provided with a tangible measure by which to evaluate glycemic responses when
making dietary choices.
Moreover, the determination of GI presents researchers with several
difficulties. GI requires a determination of the glycemic carbohydrate content
of both
the standard food and the test food.
Most researchers obtain such content information from food composition
tables or from food manufacturers' data. However, as discussed above, due to
the
different ways in which carbohydrate content of food is measured, such
information is
not uniform. The variation in the GI values of similar foods reported by
researchers
reflects this lack of uniformity.
To avoid relying on composition tables and manufacturers' labels, an
individual researcher may measure the glycemic carbohydrate content of the
food
products. However, the addition of this step is cumbersome. Also, the methods
used
by different researchers to assess glycemic carbohydrate content vary.
Moreover, the measurement of glycemic response which relies on a measure
of the glycemic carbohydrate content in a food product is inherently an
approximation. That is, actual physiological conditions of the human body
which
may affect such responses may not fully be taken into account.
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Another system which attempts to assess the glycemic responses produced by
food uses the concept of glycenic load (GL) GL is calculated by multiplying
the
amount of glyeemic carbohydrate in a portion of a test food and the GI of the
food.
Accordingly, since the calculation of LiL values includes determining GI
values, the shortcomings and inaccuiacies originating from GI values catty
over to the
calculation of GL values. For example, Foster-Powell et al. determine
carbohydrate
content for the calculation ofGi values, and this necessarily for G ..'values,
from food.
composition tables. (Am J Cl1n Vutr 76:5-56 (2002).) Also, since the glyeemic
carbohydrate content in the test food is required to be measured to calculate
a GL
value, a further al proximation is included in the calculation of the GL
value.
Additionally, since Cl. includes the measurement of 01, the glyeemic
responses at either twenty-five or fifty grams of glyccrnic :carbohydrate are
used in the
calculation of GL. Accordingly, it has been assumed that the functional
relationship
between glycemic response and glyeemic carbohydrate load at either of these
loads
would apply to lower glycemic carbohydrate loads. That is, nutritional art and
technology have not determined the actual functional relationship between
glycemic
response and carbohydrate portions which are less than twenty-five grams.
However, the evaluation of the glycomie responses produced by foods
containing small glyeemic carbohydrate portions, such as less than fifty or
less than
twenty-five grams, is highly important for numerous applications.
For cxarnple, as described above, the ability for diabetics to precisely
control
their glycemic responses is critical. It may be necessary to know the glyeemic
response produced by a food containing it glyeemic carbohydrate portion of
less than
fifty grams in order to avoid insulin shock or diabetic coma.
Additionally, dieters, and those following a controlled carbohydrate
lifestyle,
typically consume small portions, and thus would benefit from an evaluation of
glyeemic responses produced, by small food portions. Without such information
about
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small pirtioris, a dieter may choose foods which produce high glycemic
responses
thereby stimulating appetite.
Also. athletes typically consume small portions before engaging in athletic
activities, or may consume tbod while pefforming an activity. Thus, it would
be
beneficial to have a method by which to assess glycemic responses of foods
containing small glycemic carbohydrate portions to enhance athletic
performance.
Accordingly, thcre 1, a need for the evaluation of the glycemic responses
produced by food products which is easily implemented and understood by an
average
individual. Additionally, there is a need for a method by which researcher=
would be
able to more easily and accurately evaluate food-produced giy'cemic responses.
There
is especially a need for a standard evaluation of glycemic responses produced
by
toods which contain less than twenty-five grams of glycemic carbohydrates.
SU:VLMkR'Y OE LVVENTIO1\
he present invention has several aspects all of which include a systematic
evaluation of glycemic responses elicited by the consumption of dietary
comeslibles.
The invention includes establishing a reliable ,glycemic response index for a
standard
comestible at several glycemic loads. The index correlates glyc mic response
with
glycemic load. The loads can be expressed iu prams of g]yceaiic carbohydrate
of the
standard comestible, grams of the total weight of the standard comestible, or
uniform
units of the standard comestible, such as a slice of white bread In terms of
glycemic
carbohydrate, preferably the loads are below fifty grams, more preferably
below forty
grams, and most preferably below thirty grams.
In one aspect of the invention, a method is provided by which a standard
comestible Equivalent Glycemic Load (EG. of 'L dietary comestible is
determined.
This method includes determining the glycemic response produced by the dietary
comestible. The st inciard c om stible glycemic load which is correlat d with
this
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glycem.ic-response is identified iforrl the index. Such load is the standard
comestible
EGL tit the dietary comestible.
The dietary comestible used in the method can be a single food product, or
more than one food product, i.e. a mixed meal. The standard comestible used in
this
method is preferably white bread or glucose.
An EGL, in tel7ns of glyccmie catbobydrate load of a standard comestible, ca
j,
be converted into terms of the total weight of the standard .comestible, or,
if
applicable, into terms of a uniform uriit of a standard comestible A preferred
uniform
unit is a slice ,f white bread.
The glycemic responses are preferably determined from plasma glucose levels
or from capillary glucose levels. Glycemic responses arc preferably calculated
in
terms of increrne'ntal area under a glyeemic response curve (LAUC). The JAUC
can
be calculated by several methods, such as by evaluating only the incremental
area
above a baseline, the baseline being i c glycemic response prior to
consumption of a
comestible; or by subtracting the incremental area below a baseline from the
incremental area above the baseline.
in another aspect of the invention, the standard comestible EGL is determined
for, and assigned to, several dietary comestibles The dietary comestibles are
classified according to their EGL values.
Moreover, the present invention includes a method of controlling blood
glucose levels in an individual. The method includes identifying, and
selecting, a
dietary comestible according to its TGL. A comestible which has a selected
EGl. is
included in the diet of the individual, thereby controlling the blood glucose
levels of
the individual. A dietary regimen can:be constructed for the individual
identifying
selected dietary comestibles.
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Preferably, the selected EGI. is low. An individual making such selection can
be a diabetic, or someone who is following a low ; lycernic diet. An example
of a
dietary comestible with a low white bread 1r GL is a comestible which produces
the
same glycemie response as less than a half slice of white bread rroduces.
The method can further include substituting a comestible with a low EGL for a
comestible, presently in the diet of the individual, which has a high EGL.
In yet a farther aspect of the invention, a method of delivering a comestible
which produces a low glycernic response in an individual, by identifying a
comestible
according to its ELL, is provided. A comestible with a low EGL is selected for
consumption, so that a comestible consumer delivers to hirniherself a
comestible
which produces a low glyeemic response.
1 In an additional aspect, the invention provides a method of controlling
glycemic comestible consumption o an individual aL a desired level. Dietary
comestibles are identified according to EGL. A dietary comestible is selected
which
contains an EGL which is within a desired level. A desired level i , evaluated
in terms
of amount of EGL to be consumed during a selected duration. The selected
comestible is consumed
Preferably, a desired level is a low level of glycemic comestible consumption.
An example of'a desired low level is approximately equal to a daily white
bread
equivalent of one to two slices of white bread.
2;i In another aspect, the invention provides a method of managing dietary
intake
of glvicemic comestibles of an individual to produce desired blood glucose
levels.
Dietary comestibles are identified according to EGL. A dietary comestible is
selected
which produces desired blood glucose levels. The selected comestible is
consumed.
Desired blood glucose levels are low to normal levels, for cxaniple, from
about 70 to
125 mg/' 100 ml of blood.
CA 02472371 2004-06-16
in yet a further aspect, the invention includes a system to reduce glycemie
responses in an individual. The system includes a distinct cumestibic, and
indicia
associated with the comestible which reports the F.GL contained in the
distinct
comestible.
J
The indicia can be associated with the distinct comestible in any way which
provides a comestible consumer with a report of the EGL contained in the
distinct
comcstiblc, e-g., the lildicia can appear on the packaging of the distinct
comestible.
An EGL can be in terms of the glycemic carbohydrate weight of the standard
comestible. Preferably, an EGL value; is in tears ot'the total weight of the
standard
comestible, and more preferably an EGL value is in terms of a portion size of
a
uniform, unit. The indicia can report EGL values in numerical form or in
graphical
form.
i)
The system can further include instructions for consumption of the distinct
comestible to reduce glycemic responses in an individual. The instructions
preferably
include guidance for substituting the indicia-associated comestible for
comestibles
presently in the diet of the individual which have a high EGL.
?0
the methods of evaluating food products according to the glycemic responses
they producc, and of controlling blood glucose levels in an individual, as
described
herein, provide several advantages over currently used methods.
25 For example, the invention provides methods of determining glycemic
response, and ciassil ying foods by glyeernic response, in a manner which is
more
easily conceptualized than current methods, i.e. 01. The CiI assigns a number
to a
food based on a comparison with a standard food which contains twenty-five or
fifty
grams of glyceric carbohydrate. Such an evaluation is difficult to envision
especially
30 since Cif is without units
A 1
CA 02472371 2004-06-16
T
In contrast, the invention assesses the glycemic response produced by a
dietary
food product in tends of standard food equivalent glycemic loads, such as
white bread
glycemic equivalents That is, the invention quantities glycemic response in
terms of
a standard food dose. Moreover, unlike Gl, the standard food equivalent
glycemic
loads provided by this invention evaluates the glycemic response produced by
actual
serving sizes. in this way, an individual is provided with an easily
implemented
method by which to guide his dietary choices.
Furthermore, unlike GI and GL, the invention does not require the
1, t7 determination of the glycemic carbohydrate content of foods. Thus, the
invention
avoids the inaccuracies and complications thal cc m e fr::,:: such
determinations.
As another benefit, the methods of the invention provide a systematic direct
evaluation of glycemic responses produced by food products containing glycemic
1 s loads of below twenty-five grams, iri particular food products containing
glycemic
carbohydrate loads of below twentyrfive grams. Thus, the invention allows
individuals to narrowly control their glycemic responses.
And, the present invention provides a functional relationship between
20 glycemic response and glycernic carbohydrate loads of below twenty-five
grams.
Before this invention, such a functional relationship was not adequately
defined.
As another advantage, the present invention provides a system to reduce blood
glucose levels in an individual This system includes a food product associated
with
25 indicia reporting glycemic response in 1crm5 of ;tandard food equivalent
glycemic
loads Such a system greatly benefits individuals with metabolic disorders and
dieters. Before this invention, food products associated with such'information
were
not available.
30 For a beLLCr understanding of the present invention, reference is made to
the
following description, taken in conjunction with the accompanying drawings,
and the
scope of the invention set forth in the claims.
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BRIEF DES `IE 1 TION OF TEE DR-iWi GS
Figurc 1 shows blood glucose response curves for.Atkins ' Indulge Chocolate
bar, and white bread at glycemic carbohydrate loads of -zero, five, ten and
twenty
clams.
Figure 2 shows blood glucose response curves for Atkins' Endulgre Chvicelute
Peanut bar, and white hrcad at glyceric carbohydrate: loads of zero, five, ten
and
twenty grams.
Figurc 3 shows blood glucose response curves for Atkins' Endulge Chocolate
Cr-uncr'r bar, and white bread at glycemic carbohydrate loads of zero, five,
ten and
twenty grams.
Figure 4 shows a glycemic response index for white bread loads of below
twenty grams of glycemic carbohydrate.
Figure 5 shows blood glucose response curves for Atkins' Vc nill,7 Shake, and
white hr;!ad at glycernic carbohydrate loads of zero. five, ten and twenty
grams.
Figure 6 shows blood glucose response curves for Atkins ' Pancake, and white
bread a: glycemic carbohydrate loads of zero, five, ten and twenty grams.
Figure. 7 shows blood glucose response curves for Atkins ' Blueberry Muffin,
?5 and white bread at glycemic carbohydrate loads of zero, five, ten and
twenty grams.
Figure 8 shows blood glucose response curves for Atkins' Blueber,y Muffin,
and white. bread at glycemic carbohydrate loads of zero, five, ten and twenty
grams,
with an outlier excluded-
Figure 9 shows blood glucose response curves for Atkins' White Bread, and
white bread at glycemic carbohydrate loads of zero, five, ten and twenty
grams.
1~
CA 02472371 2004-06-16
Figure 1U shows blood glucose response curves for Atkir_s' Rye Bread, and
white bread at glycemic carbohydrate loads of zero, five, ten and twenty
grants,
F'I ure 1 1 shows blood glucose response curves for Atkins ' nclui e Chocolate
Almond. and white bread at glycemic carbohydrate loads of zero, five, ten and
twenty
~+I'3II1S
Figure 12 shows a glycernic response index for white bread loads of below
twenty grams of glycemic carbohydrate.
Figure 13 shows blood glucose response curves for Atkins ' Advantage Mocha
bar, and white bread at glycemic carbohydrate loads of zero, five, tin and
twenty
gams. figure 14 shows blood glucose response curves for Atkn,y' Advantage
fisted
Cinnamon Swirl bar, and white bread at glycemic carbohydrate loads of zero,
five, ten
and twenty grants.
Figure 15 shows blood glucose response curves for Atkins ' A mond Brownie,
and white bread at glycemic carbohydrate loads of Leru, five, ten and twenty
grams.
Figure 16 shows blood glucose response curves for Atkins' Chocolate Delight
Shake, and white bread at glycemic carbohydrate loads of zero, five, ten and
twenty
grams.
Figure 17 shows a glycemic response index for white bread loads of below
twenty grams of glycemic carbohydrate.
14
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DETAILED DESCRIPTION OF THE LNTTY'ENT10N
The methods of the invention provide a systematic evaluation of glycemic
responses elicited by the consumption of dietary comestibles. The invention
also
includes methods and systems for controlling blood glucose levels lit a human
being,
and for managing the consumption of glycemic comestibles, par-ticularly those
comestibles containing glycemic carbohydrates. Coixyeptually simple methods to
assess the glycemic responses elicited by dietary comestibles are provided-
t0
A glycemic response elicited by the consumption of a dietary comestible is
evaluated in comparison with the glycemic response elicited by the consumption
of a
standard comestible. A glycemic response is the rise in blood glucose
concentration
in an individual following the consumption and absorption of a -lycemic
comestible,
I A glycemic comestible is a comestible which elicits a glycemic response.
Typically,
a glyceuiic response of a comestible is primarily elicited by the glycemic
carbohydrate content of the comestible.
A glycemic response is quantified by measuring the degree and duration that
blood glucose concentration is elevated in an individual in response to the
consumption of a particular comestible being tested at a particular load, This
elevation can he plotted with the time. of measurement on the horizontal axis
and the
blood glucose concentration on the vertical axis. Such a plot is termed a
blood
glucose response curve. Mood glucose concentrations are typically expressed as
milligrams per 100 milliliters of blood, or rriillirnoles per liter of blood.
The blood glucose concentration measured prior to consumption of the
comestible is typically shown at time zero on blood glucose response curves-
This
concentration is reigned to as the concentration at baseline. In response to
the
consumption of a comestible, the blood glucose concentration typically
increases to a
peak value and then returns to the baseline after a couple o hours
CA 02472371 2004-06-16
Examples of blood glucose response curves are shown in Figure 1 for five
different loads of the same comestible. As can be seen from the figure, each
of these
loads defines a different curve.
The glyceric response associated with a particular comstible at a particular
load can be expressed by a single numerical value. Foe example, the
incremental area
under a blood glucose response curve defined by the particular comestible can
be
calculated. This area can be referrad to as the 115.1 associated with the
particular
comestible at the particular load.
The invention includes establishing a eliable glycemic response index for a
standard ,oniestible. The index is a eon:clation of different glycemic loads
of 'a
standard comestible with the glycemic responses produced by such loads. A
glycemic
load is the amount, dose or portion of the standard comestible which
contributes to the
1 5 glycemic response elicited by the standard comestible. The glycemic load
can be
expressed in grans of glycemic carbohydrate of the standard comestible, in
grams of
the total weight of the standard comestible, or in uniform units of the
standard
comcsiiblc, such as a slice of white bread.
?t} The index is used to evaluate the glycemic response elicited by dietary
comestibles in comparison with the glycemic response elicited by a standard
comestible
A dietary comestible, for the purposes of this specification, is any substance
Zz which is ingest bie or edible. Dietary comestibles include food: from all
of the basic
food groups, and foods composed of any nutrient type, including, for example,
proteins, fats, and carbohydrates. Dietary comestiblc5 can be natural food
products,
e.g., fruits and vegetables; or manufactured and processed food products;
e.g., bakery
goods, confectionaries, breakfast cereals, processed meats, pasta, etc.
Further
30 examples of dietary comestibles include sports bars, snack foods,
convenience foods,
meal replacement products, nutritional supplements, functional foods, medical
foods,
enteral'parcnteral solutions and pharmaceutical products. Dietary comestibles
can be
16
CA 02472371 2004-06-16
in any form including, for example, solid, semi-solid and liquid, Examples of
dietary
comestible foams include gels, beverages, frozen foods. snack bars, food
components
and food ingredients, i.e. sweeteners. For the purposes of' his specification,
a dietary
comestible can be a mixed meal. A mixed meal is a composite of more than one
distinct food type and/or form. For example, a mixed meal can include a multi-
course
meal, such as a prepackaged frozen meal.
A standard comestible, such as a dietary comestible., is any substance which
is
ingestible or edible. Examples of a standard comestible include all the
dietary
iO comestibles enumerated above, for example, breads, fruits. table sugar.
potato, rice,
breakfast cereals, :etc. Since many factors c r. alter. the ch:enmic l
composition of a
comestible, and thus the glycemic response produced by a comestible (such as
stage
of ripeness, degree of cooking, type of processing, etc.), uniformly
manufactured
comestibles are preferred as standard comestibles. Examples of preferred
standard
5 ;omestibles are manufactured foods, such as a particular type of bread, for
example,
white bread and rye bread; an oral sugar solution, for example, a glucose,
sucrose
and/or fructose solution; a nutritional bar; and instant potatoes.
hi the embodiment in which glycemic load is expressed in grams of glycemic
20 carbohydrate contained in the standard comestible, a standard comestible
with a
readily quantifiable glycemic carbohydrate load is preferred. An example is a
standard comestible in which the total weight of the comestible is virtually
equal to
the glycemic carbohydrate weight of the standard comestible. Specific examples
of
such standard comestibles arc glucose, sucrose and fructose solutions
The index is established by measuring the glycemic responses in at least one
test subject after the consumption of a standard comestible at more than one
glycemic
load, preferably at more than two loads. Preferably, the glycemic response is
expressed as IAL'C; and the loads are expressed in grams, or in uniform units
of the
30 standard comestible, such as a portion of a slice of white bread.
17
CA 02472371 2004-06-16
Preferably, the number of test subjects evaluated is from about two to about
five hundred; more preferably, from about five to about one hundred; most
preferably
from about ten to about fifty; and optimally from about twenty to about
thirty.
_; T e index can evaluate the glycemic response produccd by a standard
comestible at any glycemic load. For example, glycemic loads can be evaluated
for
loads below two hundred grams, preferably below fifty grams; more preferably
below
forty grams, most preferably below thirty cams, and or timally below twenty-
five
grams. The loads can be evaluated at any incremental value. For example, the
index
can evaluate loads at one gram increments, more preferably at five and ten
gram
increments. As another example, glycemic loads can be evaluated for loads
below
eight slices of white bread, more preferably below four slices of white bread,
most
preferably below three slices of white bread, and optimally below two slices
of white
bread The loads can be evaluated at any incremental value. For example, the
index
l~ can evaluate loads in one third slice increments.
In one crrtbodiment, the index includes glycemic response data only of test
subjects who are healthy, i.e. the subjects do not have any known metabolic
disorder
In another embodiment, the index includes glycemic response data only of test
subjects who are known to have a particular metabolic disorder, such as
mellitus
diabetes type I or type 11.
The, index can be in any form which correlates the glycemic load of a standard
comestible with its corresponding Iycemic response. For example, the index can
be
in the form of a listing or a graph.
It has unexpectedly been discovered that below glycemic carbohydrate loads
of fifty grams, the functional relationship between glycemic carbohydrate load
and
lA- C is linear with a strong correlation coefficient (r). A strong
correlation
~0 coefficient, as defined herein, is greater than 0.97. That is, the
relationship is highly
amenable to a simple linear regression analysis. iZelatedly, the coefficient
of
determination (r2) was found to be unexpectedly :sigh. A high coefficient of
1s
CA 02472371 2004-06-16
determination, as defined herein, is greater than 0.95. Such a value shows
that over
95% of the variation of the glycemic response is explained by the variation in
the
glycemic carbohydrate load. Accordingly, it has been unexpectedly discovered
that
the glyceric response is sensitive to small loads of f lycernic carbohydrates.
Accordingly, for glyccrruc carbohydrate loads of below fifty grains, the index
can albu be expressed as a linear equation, and'or the plot of a lineal
equation. In
particular, the relationship bFutw(.-,en glycemic carbohydrate load below
fifty grams and
LkUC can be defined by the following linear equation:
1i:) La UC:= m(glyeemic carbohydrate load) -r b,
where in is a constant, h is the glycemic response at the baseline, and the
load
is below fifty grams.
The linear relationship implies that with each incremental increase in the
load,
t the value of IAUC increases by the constant value, m. Thus, the equation
allows the
calculation of the extent to which one grain of glycemic carbohydrate of a
standard
comestible would raise blood glucose levels.
The equation can be plotted. For example, the loads can be plotted on the
?t) horizontal axis; and the JAUC produced by each load can be plotted on the
vertical
axis. Preferably, the functions are plotted so that the load values increase
from left to
right.
Different standard comestibles typically provide different indices. Figure 7
25 shows an example of a glycemic response index for white bread at loads of
below ' .
twenty grains of glycemic carbohydrate. This index is defined by the following
cquation. IAUC = 4.70 (glycemic carbohydrate load) + 13.8.
Given observed LAUC values at a minimum of two loads, the linear
30 relationship allows for the deduction of IAUC values at unobserved loads
below fifty
19
CA 02472371 2004-06-16
grant;.. The values can be deduced atom the equation directly, or via
extrapolation or
interpolation.
In one embodiment of the invention, methods are provided for determining an
d Equivalent Glycemic Load (1sGL) of a dietary comestible. The method includes
establishing a reliable glycemi:; response index for a standard comestible.
in this embodiment, the glycemic response elicited by the consume io<< of a
certain dose of a particular dietary comestible is measured. This response is
located
0 on the index. The index correlates this response with a standard comestible
glycemic
load . This load is Identified from tllc index, and is the Equivalent Glycemic
Load
(EGL) of the particular dietary comestible for thy, particular standard
comestihle.
l'hus, the glycemic response elicited by a dietary comestible is provided in
terns of a
standard comestible glycemic load, i.e, a standard comestible EGL.
Identification of the EGL load from the index can include locating the load
from a list which correlates responses with the JiJ ceznie loads.
Alternatively, if the
response elicited by the dietary comestible is below the response elicited by
fifty
glycemic carbohydrate grams of the standard comestible, identification of the
EGL
?U can include the use of the linear equation shown above. If the standard
comestible is
white bread, the load can be located on a glycemic response index, such as
shown in
Figure 4.
A demonstration of one of the embodiments of the methods of the present
2-, invention is shown in the Examples, In these examples, the index expresses
glycemic
load in terms of glycemic carbohydrate contained in a standard comestible. The
glycemic. response of an Akins ' Endulge Chocolate bar was found to be 32 7
rnmolxznirvL in terms of LkUC. Uslang the index shown in f figure this
glycemic
response is located on the index. This glycemic response is correlated with a
load of
30 about 3.3 grams of white bread glycemic carbohydrate. Thus, the white bread
EGL of
the bar is 3.3 grams. That is, white bread which contains 3.3 grams of
glycemic
CA 02472371 2004-06-16
carbohydrate elicits the same glycern c response as the Atkins' Endulge
Chocolate
bar.
F,G1. can be in terms of a glycennic carbohydrate load of a standard
corncstihh., such as about 3.3 grams cf white bread glycemic carbohydrate for
the bar.
Preferably, the EGL is in terms of the total weight of a standard comestible.
The total weight of a comestible typically includes, in addition to its
glycernic
carbohydrate load, the weight of, for example, water, other nutrient types and
non-
glycemic carbohydrates. Accordingly, the glycemic carbohydrate load of a
standard
cornestib!e is not typically equal to the total weight of the standard
comestible. That
is, one gram of a standard comestible.,does not typically contain one gram of
glyce, rnic
carbohydrate.
As discussed above, the index can be constructed so that the standard
corncbtible is in terms of the total weight of, or a uniform unit of, the
standard
comestible. Alternatively, if the standard comestible is in terms of the
glycemic
carbohydrate portion of the standard comestible, it can be converted to the
total
weight of, or a uniform unit of, the standard comestible.
~a1
To convert an E, G L which is in terms of the glycemic carbohydrate load to be
tri terms of the total weight, the EGL in terms of glyceinic carbohydrate load
is
multiplied by the weight of the standard comestible which contains one gram of
glycemic carbohydrate. Tbus, the actual amount of a standard comestible which
2 contains the glyceinic carbohydrate load is provided. Accordingly, an
individual is
provided with a tangible serving. size of a familiar comestible by which to
evaluate the
glycemic response elicited by a dietary comestible of his choice.
For example, one gram of white bread typically contains approximately half a
3t gram of glycemic carbohydrate. Thus, if a particular dietary comestible
elicits the
glycemic response of four ¾lycemic carbohydrate grams of white bread, the four
grams is multiplied by two to get the glycemic response in terms of the total
weight of
21
CA 02472371 2004-06-16
white brad. Accordingly; eight total grams of white bread produces the same
glycemic response as the particular dietary comestible. Thus, it is important
to note
whether the standard comestible EGL is expressed in terms of glycemic
carbohydrate
weight of the standard comestible, or in tarns of the total weight of the
standard
a comestible.
If the standard comestible is available in a uniform unit, then the EGL is
preferably provided in a 1; .,.. = orti:n size ofth'e~ EYa. les of a uniform
unit are a
, ,.r.:.. ~:p
a particular candy or food bar, or a particular
dice of any type of bread, a piece of
:1- C-ookie.
"i o convert a standard comestible T--GL which is in terms of the glyccmic
carbohydrate dose to be in terms of a :niform unit, the total weight of a unit
of the
standard comestible, and glycemic carbohydrate dose contained in the unit, are
15 determined. For example, a slice of white bread may weigh approximately
twenty-
four grams and may contain approximately twelve grams of glycemic
carbohydrate.
Using this information, the glycemic response elicited by a dietary comestible
can be
expressed as being equivalent to the glycemic response elicited by a certain
unit
portion of a standard comestible, e.g., a certain slice amount of white bread.
For example, the glycemic response elicited by a particular pastry can be
expressed as being equivalent to the. glycemic response elicited by ten slices
of white
bread. Or, the glycemic response elicited by an Atkins ' Endulge Chocolate
Crunch
her (Atkins \t trltia.uais, inc.) can be expressed a:; being equivalent to the
glycemic
response elicited by approximately three tenths of a slice of white bread.
Thus, the
white bread EGL is three tenths of a slice of white bread. Accordingly, the
glycernic
response elicited by a dietary comestible is provided in an easily
conceptualized
manner.
htf EGL can be calculated for any dietary comestible at any glycemic load,.
e g. a two hundred gram load. In the embodiment in which FGI. is in terms of
glycemic: carbohydrate load; preferably'; the dietary comestible elicits a
glycemie
22
CA 02472371 2004-06-16
response which is below the glyc:Critic response elicited by the standard
comestible at
t r lycenruc carbohydrate load of app oximatcly fifty grams, more preferably
at a load
below forty grams, most preferably at a load below thirty grams, and optimally
at a
load below twenty-live grants.
S
In another aspect of the invention, a method of classifying dietary
comestibles
according to their EGL. value, with reference to a particular standard
comestible, is
provided. Preferably, the EGL is in terms of the total weight of a standard
eOlncstiuie,
4nd m,,re preferably the LGL is in tcrns of a portion size of a uniform unit
of n
standard comestible.
Classifying includes determining and assigning a standard comestible EGL
value to several dietary comestibles at various serving sizc;6. The dietary
comestibles
can contain any glycCmic load
A serving size of a dietary comestible can be in terms of the weight of the
dietary comestible, i.e grams; or in terms of a standard portion, a g, a
tablespoon, a
uniform unit of prepackaged brand name food, a standard size doughnut, a
standard
size slice of pizza, etc.
Preferably, EGL values are determined for at least ten, more preferably at
least
fifty, most preferably at least one hundred, and optimally at least five
hundred
commonly consurned dietary comestibles. EGL values were empirically derived
from
data obtained from nutritional studies conducted by Atkins Yurritlonals, Inc.
Since metabolic disorders may affect an individual's glycemic response to
dietary comestibles, preferably, more than one classification is provided. For
example, a classification can be provided for healthy individuals, i.e.
individuals who
do not have any known metabolic disorder Another classification can be
provided
30 for individuals who have known metabolic disorders. Alternatively, an
adjustment
factor can be applied to EGL values for healthy individuals to convert them to
values
23
CA 02472371 2004-06-16
that more accurately reflect glycemicl responses of individuals with known
metabolic
disorde..rs
Classif cations provided by the methods of this invention enable a comestible
consumer to evaluate a dietary comestible in terms of its ability to raise
blood glucose
levels. n classification can be used to evaluate which dietary comesnble of a
set of
dietary comestibles will elicit the greatest glycemic response. Thus, the
effect of a
dietary change on blood giucosc levels can be predicted. For example, an
individual
is enabled to exchange a dietary comestible with a relatively high EGL value
for more
than one dietary comestible with low ECGL values.
A EGL classification can be embodied in paper or computer readable form-
For example, a FGL value can be provided on lists, menus, food packaging or in
a
software package.
In a further aspect of the invention, a method of controlling the blood
glucose
levels of an individual is provided. A dietary comestible is sc;lc .ted
according to its
standard comestible EGL value. An individual can identify the dietary
comestible
with the selected value by, for example, referring to a classification, as
described
10 above Alternatively, the individual can rely on a medical practitioner's
guidance.
Such guidance can include determining the individual's own personal glycenric
responses to a series of comestibles, according to the invention.
A control can be an increase, a decrease, or maintenance of blood glucose
2 levels in an, individual. A dietary comestible with a high FGL value is
selected to
increase blood glucose levels; a dietary comestible with a low EGL value is
selected
to decrease and/or maintain blood glucose levels A dietary comestible which
has the
selected EGI, is included in the dietary regimen of the individual.
30 Preferably, dietary comestibles which have the selected EGL. are
substituted
for comestibles presently in, the diet of the individual. A dietary regimen
can be
24
CA 02472371 2004-06-16
constructed for an individual in which such substitutions are set forth. These
substitutions can be provided in it paper or corul:uter readable format.
A control of blood glucose levels of the individual can be for a short
duration
or for a long duration. If the blood glucose levels of the individual are to
be
controlled for a short duration, for example, for an hour to a week, the
selected
comestible is made part of the individual's diet for the duration. If the
blood Glucose
levels of the individual are to he con rolled for a long duration, for
exa*rp!e, frc.n six
months to an indefinite period of time, the selected comestible is included in
the daily
lit diet of the individual for such duration_
An example of an individual who would select a comestible that produces high
blood glucose levels for a short duration is an athlete performing a short
duration
exercise. High blood glucose levels may provide extra energy for the exercise.
An example of an individual who would select comestibles that produce low
blood glucose levels is an individual with a metabolic disorder Examples of
metabolic disorders include diabetes, insulin resistance, hyperirsulinism,
hypoglycemia, hyperlipidemia, hypettriglyceridemia and obesity. As described
above, an individual with a metabolic disorder, for example a diabetic, can
greatly
benefit from selecting dietary comestibles which keep blood glucose levels in
a
narrow normal rat:ge-
Another example of an individual who would select comestibles that produce
low blood glucose levels is an individual following a low glye e.nic diet,
i.e. low
glycemic carbohydrate diet. An example of a low glycemic carbohydrate diet is
set
forth in Dr. Atkins New Diet Revolution (Harper Collins Publishers, Inc.
2002).
Studies have shown that persistently high blood glucose levels can be
? ii associated with the following disca5os and/or disorders: metabolic
disorders;
cardiovascular disease; certain cancers, e.g., colon and breast cancer; high
blood
HD r -cholesterol concentration; and er AGES. (Foster-Powell et al. Am J Clin
Nutr
CA 02472371 2004-06-16
76:5-56 (2002).;) Accordingly, selecting comestibles that produce low blood
glucose
levels may --educe the risk of acquiring, or may prevent acquiring, the
aforementioned
diseases andior disorders.
Since a EGL value assigned to a particular comestible is evaluated in
reference
to a particular standard comestible, the standard comestible used in the
evaluation
should he considered when determining if a EUL value is low or high.
For example, a selected dietary comestible with a low white bread EGL, in
i 0 terms of slice of white bread, is about 0.5 slice. That is, in this case,
the selected
dietary comestible produces the same glyce.nic response as half a slice of
white bread-
Depending upon the degree to which Kan individual would like to maintain and-
'or
decrease his blood glucose levels, a low white bread EGL of a dietary
comestible can
be, for example, less than 0.85 of a slice, more preferably less than 0 65,
most
preferably less than 0.4, and optimally less than 0.1.
A selected dietary comestible with a high white bread EGL, in terms of slice
of white bread, is about 1.5 slice. That is, in this case, the selected
dietary comestible
produces the same glycemic response, as one and a half slices of white bread.
20 Depending upon the degree to which an individual would like to increase his
blood
glucose icvels, a high white bread EGL of a dietary comestible can be, for
example,
over one slice, more preferably over two slices, most preferably over three
slices, and
optimally over four slices.
25 In a further aspect of the invefition, a method of delivering a dietary
comestible which produces a low giycemic response in art individual is
provided. A
dietary comestible with a low EGL is selected for consumption. The individual
can
select the comestible by referring to a classification, as described above.
Alternatively, the individual can rely on guidance from a medical
practitioner, diet
30 plan organizer, or food packagers. The individual consumes the selected
dietary
comestible.
26
CA 02472371 2004-06-16
In another aspect of this invention, a method for controlling glycemic
comestible consunipticon, primarily glycemic carbohydrate consumption, of an
individual at a desired level is provided. Dietary comestibles are identified
according
to their FGL v alues_ An individual can identify comestibles according to
their EGL
values by, for example, referring to a classification, as described above.
Alternatively, the individual can rely on guidance from a medical practitioner
or diet
org anizer .
desired level of consurnptien is evaluated in terms of amount of EGL
consumed during a predetermined duration. Control of glycemic comestible
consumption of an individual at a d."-.sired level can include limiting the
consumption
of EGL to a maximum level over a predetermined period of tune.
For example, the consumption of glycemic comestibles can be limited to a
desired maximum daily level. In such case, the total amount of glycemic
comestibles,
in terms of EGL, to be consumed for the day is selected. This total daily
amount can
be chosen by the individual, or prescribed by a medical practitioner or diet
plan
organizer. A running total ofEGL values assigned to the comestibles consumed
by
an individual in the course of a day is recorded. Once the individual reaches
the
maximum daily level of EGI.. no more glycemic dietary comestibles are consumed
by
the indi-~ idual that same day.
An example of a desired daily level of glycemic comestible consumption in an
individual following a low glycemic comestible diet is approximately equal to
a daily
white bread EtiL, in terns of glycei iic carbohydrate weight, of five to forty
grams,
more preferably from approximately ten grams to thirty grams, most preferably
from
approximately ten to twenty-five grams, and optimally from approximately ten
to
twenty grams.
The daily total EGL value ispreferably in terms of the total weight of a
standard comestible. Since one gram of white bread typically contains
approximately
half a grain ol` glycemic carbohydrate, the aforementioned daily values can be
27
CA 02472371 2004-06-16
multiplied by two to obtain the daily total ECG in terms of total weight of
white
bread.
The daily total EGL value is more preferably in terms of a portion of a
uniform. unit of a standard comestible. For example, a slice; of white bread
may
contain approximately twelve grams! of glycemic carbohydrate Thus, in this
case,
approximately 1.7 slices of the whitr bread is equal to twenty grams of
glyccm.ic
carbohydrate. Accordingly, an individual tbllowing a low glycernic
carbohydrate diet
can, for example, limit his daily glyciemic carbohydrate intake to an EGL of
1.7 slices
of such white bread. Exampl::s of other total daily values for individuals
following a
low glyccmic carbohydrate diet are less than three slices of white bread, less
than two
slices, less than one slice and less than a half a slice.
Preferably, the control of carbohydrate consumption includes substituting
comestibles with low EGL values for comestibles presently in the diet of the
individual with high EGL values. A ,dietary regimen can be constructed for an
individual in which such substitution's are set forth. These substitutions can
be
provided in a paper or computer readable format.
20 In another aspect of the invention, a method of managing dietary intake of
glycemic comestibles of an individual to produce desired blood glucose levels
is
provided. Dietary comestibles are identified according to their EGL values, as
described above. Comestibles with high or low EG., values are selected for
consumption according to whether blood glucose levels are to be increased or
21 decreased, and the degree to which the levels are to increased or
decreased. A
selected comestible is consumed by the individual.
An 4xamplc of a desired low blood glucose level is in a range of between 70
and 125 ingi100 ml of blood. An example of a desired high blood glucose level
is in
1a ca?~ge of between 135 and 200 mgi 100 ml of blood. A high blood glucose
level is
typically desired by athletes performing short duration athletic activates.
2g
CA 02472371 2004-06-16
Methods by which to treat, o~ prevent, metabolic disorders ire provided. The
methods, discussed above, by which :to control blood glucose levels; control
glycemic
comestible consumption, in particular glycernic carbohydrate consumption, and
manage the dietary intake of glycemic comestibles can be used to treat, or
prevent,
metabolic disorders. Methods are provided by which to reduce the risk of
acquiring,
or prcvvnt acquiring, the following diseases and/or disorders: metabolic
disorders;
cardiovascular disease; certain cancers, e.g., colon and breast cancer; high
blood
HDL-chniesterol conceriuationn; aTLv- r AGES. :'he rniethods, discussed above,
by
which to control blood glucose levels; control glycernic comestible
consumption, in
particular glycemic carbohydrate consumption; and manage the dietary intake of
glyecatie comestibles can be used to'reduce the risk of acquiring, or prevent
acquiring, the above enumerated diseases and/or disorders
In one embodiment of the invention, the determination of EGL values for
Ii comestibles can be used to provide a 'system to reduce blood glucose levels
in an
individual. The system includes a distinct comestible which produces a low
glycemic
response; and indicia associated with the distinct comestible which reports
the Ec3L
contained in the distinct comestible. Preferably, the distinct comestible
produces a
glycernic response which is below the glycemic response produced by a standard
2U comestible containing approximately, unc hundred Warns of glycernic
carbohydrate,
more preferably approximately fifty grams, and most preferably approximately
twenty
grams.
The distinct comestible can be of any form or type, as described above for
,
dietary cuuiestibles. For example, the distinct comestible can be a packaged
food bar
a frozen mixed meal, or a food additive. Examples of distinct comestibles art-
Atkins'
Endulge Chocolate, Endulge Chocolate Peanut and Endulge Chocolate Crunch bars
(Atkins Nutritionals, bic ).
30 The indic;ia can be associated with the distinct comestible in any way
which
provides a comestible consumer witha report of the FGT, of the distinct
comestible.
For example: the indicia can appear or. the packaging of the distinct
comestible. If the
29,
CA 02472371 2004-06-16
comestible: is sold in loos: forni, the i4idieia can be provided in a listing
or iuenu.
Such listing or menu call be cmbodied in paper or computer readable format.
Preferably, a EC7L value is in terms of the total weight of the standard
comestible, and more preferably a EGL value is in terms of a portion size of a
uniform utut
Indicia can report EGL values in numerical form. Alternativoiy, EGL values
can be depicted in graphical form. For example, if a .EGL is reported in terms
of
white bread slices, then the EGL value can be depicted as a drawing of the
corresponding number of slices. Such a ;hawing can include fractional amounts,
e.g.,
a drawing of one and a half slices of white bread.
Indicia can also report an EGTL value in terms of a daily total amount of
glycemic comestible allowed on a particular low glycemic comestible diet. For
example, the EGL contained in the distinct comestible can be reported in terms
of a
fractional amount, or percent amount, of the daily total amount of allowed
glycemic
comestibles. Such fractional/percent amount can be reported in numerical form.
Alternatively; this fractional amount can be reported by a graphical
depiction, such as
a pie chart. For example, a whole pia chart can represent the total daily
amount of
allowed glycemic comestibles on a particular diet. A shaded portion of the pie
chart
can represent the contribution to the daily total that consumption of the
distinct
comestible would make.
For example, if a particular law glycemic comestible diet prescribes a.daily
total of twenty grants of glycemic carbohydrate, then a distinct comestible
which
contains two grams of EGL would contain one tenth of the daily amount.
4ccordingly, one tenth of a pie chart associated with the distinct comestible
would be
shaded.
The system can further include instructions for consumption of the distinct
comestible to reduce blood glucose levels in an individual. The instructions
CA 02472371 2004-06-16
preferably include guidance for substlutiug the icndicia-associated comestible
for
comestibles presently in the diet of the individual which have a relatively
high FGL _
J., is to be appreciated that the methods of the present invention described
> herein above may be performed using a general purpose computer or processing
system which is capable of running application software programs, such as an
MM
personal computer (PC) or suitable equivalent thereof_ preferably, the
application
program code is embedded in a computer readable medium, such as a floppy disk
or
computer compact disk (CD)- Furthermore, the computer readable medium maybe in
the term of a hard disk or memory random access memory or read only
memory) included in the general purpose computer.
As appreciated by one skilled in the art, the computer software code may be
written, using any suitable programming language, for example, C or Pascal, to
configure the computer to perform the methods of the present invention. WTtile
it is
preferred that a computer program be used to accomplish any of the methods of
the
present invention, it is similarly contemplated that the computer may be
utilized to
perform only a certain specific step or task in an overall method, as
determined by the
user.
Preferably, the methods of the, present invention are used with one or more
displays .te.g., conventional CRT or liquid crystal display) provided with the
processing syswm for presenting an indication of, for example, the final
result of the
method. The display may preferably be utilized to present such information
25 graphic=ally (e.g-, charts and graphs) for further clarity.
In addition to performing the necessary calculations and processing functions
in accordance with the present invention, the general purpose computer may
also be
used, for example, to store data pertaining to empirically donved EGL values.
Such
30 information may be stored on a hard disk or other memory, either volatile
or non-
volatile, included in the computer. Similarly, the information may be stored
on a
computer readable medium, such as floppy disk or CD, which can be transported
for
31
CA 02472371 2004-06-16
use on another c:oinputer system, as appreciated by those skilled in the art.
In this
manner, the methods of the present invention may he performed on any suitable
general purpose computer and are not limited to a dedicated system.
An example of perform inlg a method of the present invention by using a
general purpose computer or processing system which is capable of running
application software programs follows.
The method includes storing Ji to in a computer rnemor,y from which can be
obtained an EG L value for each of a variety of dietary comestibles in several
serving
sizes. E< <L values reference to at least one, preferably several, standard
comestibles are also stored. Preferably, ECG values in terms of glycemic
carbohydrate content of a standard comestible, in terns of the total weight of
a
standard comestible, and in terms of a uniform unit of a standard comestible
are also
1-5 stored An EGL value is obtained by the user (e.g., a comestible consumer,
or a diet
plan organizer) for a selected dietary comestible, at a selected serving size.
in
reference to a selected standard comestible. Preferably, a minimum and/or
maximum
daily total EGL value appropriate to produce glycemic comestible consumption
at a
selected ,iaily level is obtained from the computer memory or inputted by the
user. A
sutra of the comestible consumer's daily EGL value, including the EGL of the
selected
dietary comestible, is calculated. A determination is made as to whether the
calculated sum lies within the determined appropriate minimum and/or maximum
daily total EGL value. If the sum lies within the determined minimum and/or
maximum, the individual consume the selected dietary comestible.
General Experimental rotocols for Obtaining Glveemic Response Data
The procedures by which blood samples are obtained from test subjects, and
the methods used to quantify blood glucose levels, influence the value of a
glycemic
30 response. Accordingly, when comparing the glycemic responses elicited by
comestibles, it is preferable that similar procedures and methods are used to
obtain
and quantify the responses. In particular, when comparing the glycemic
response
32
CA 02472371 2004-06-16
elicited by a dietary comestible with * standard comestible, it is preferable
that similar
procedures and methods be used to obtain it:nd quantify the responses.
In order to assure that the glyqemic response is attributable to the
comestible
being tested, test subjects preferably fast for about :our to fifteen hours
before
consuming the test comestible. Preferably, the test subjects fast for
approximately
similar lengths of time.
The physical characteristics of a test subject can affect the glycemic
response
to a particular comestible.. For example, the responses of an individual test
subject to
a particular comestible can vary on a daily basis This variation can i c duc
to, for
example, the fasting blood glucose value of a test subject on the day of the
tesi. To
reduce such variability, the glycemic response of a particular subject to the
same
comestible is preferably evaluated onmore than one occasion, a-g. on three
separate
days. The mean of multiple responses is preferably calculated, and considered
as the
glycemic response of the test subject for the particular test comestible.
Additionally, different test subjects may differ in their glycemic responses
to a
particular comestible. Physical characteristics which may affect responses
include
age: sex, body fat index, and _glucose tolerance status. To reduce such
variability, the,
responses to a particular comestible are preferably determined for more than
one test
subject, and the mean of these responses is calculated. Such mean can be
considered
to be the glycemic response associated with a particular comestible. For
example, the
1-nean of the glycemic responses of three test subjects to a particular
comestible can be
calculated, and considered to be the glycemic response associated with the
particular
comestible.
The main physical characteristic that affects glycemic response is the glucose
tolerance status of the test subjects. accordingly, preferably, the glycemic
responses
ar test subjects who have kziown metabolic disorders are evaluated separately
from
healthy subjects, i.e. subjects who do not have a known metabolic disorder.
33
CA 02472371 2004-06-16
The period of time blood glucose levels are measured also affects the value of
the glyccmic response associated with a particular comestible. The fasting
blood
glucose level of a test subject is known as the baseline measurement. Return
to the
baseline after consumption of a comestible is typically within two to three
hours in
> healthy subjects, and typically within three to five hours in diabetics.
Accordingly,
the blood glucose level is measured within a three hour test period,
preferably within
a two hour test period, after consumption of a particular comestible in
healthy
subjects in diabetic subjects, the blood Glucose level is umeasuiiod within a
five hour
test period, preferably within a three hour test period, after consumption of
a
particular comestible.
As the r.umiber of blood glucose level measurcmun s obtained within a test
pcnod t=s increased, the more defined the glycemic response to a particular
comestible
becomes. The blood glucose levels are measured at least once during 'a test
period,
1 ~ more preferably at least twice during a test period, most preferably at
least four times
during a test period, and optimally at least eight times during a test period.
For
example, in a two hour test period, blood glucose levels are preferably
measured in
fifteen minute intervals
Cilycemic response determination is also affected by the method used to obtain
the blood samples. For example, blood glucose levels can be measured from
capillary
whole blood, or venous blood or plasma. Preferably, the blood glucose levels
are
based on measurement of capillary whole blood. The rise in blood glucose
levels in
esponse to glycemie carbohydrates is greater in capillary blood vis-a-vis
venous
plasma. Thus, differences between comestibles are easier to detect
statistically using
capillary blood glucose. Also, the results obtained from capillary blood are
less
variable than those obtained from venous plasma. (Jackson ct al. Metabolism
32:706-
10 (1)-83).) Blood glucose concentration can be analyzed by arty reliable
method
known in the art including, for example, by a glucose oxidase method with a
Beckman glucose analyzer and oxygen electrode (Fullerton, CA).
34
CA 02472371 2004-06-16
{
The incremental area under thr curve (IAtJC) can be calculated in several
ways. Preferably, only the JA C above the baseline is considered. The baseline
is
the glycemic response prior to consumption of the comestible being tested.
However.
the net f.pJJC can he calculated in5teao, i.e. the area below the baseline can
be
subtracted from the area above the baseline. A net IAUC calculation would
produce a
different value from the preferred IAUC calculation for a particular
comestible if the
glucose levels associated with the particular comestible fall below the
baseline during
the measurement period. Preferably, the same method for calculating I.~.UC is
used
for evaluating the glycemic responses ;ofthe standard and dietary-
comestibles.
in one embodiment, if more than ore 5uhject is tested, the mean of their
LAUCs can be used to provide an inde}t, as described above. For glycemic
carbohydrate loads of below fifty grams, another mean calculation can be used
instead. In this embodiment, the linear equation which relates load to IAUC is
15 calculated for each test subject. The rrtean of the glycemic responses at
baseline (b),
and the mean of the constants rn, are then calculated. These means are then
used in a
linear equation which defines an index. (See the Examples)
In any mean calculation according to the present invention, if an individual
20 test subiect's response data is an outlior, for example greater than two
standard
deviation units frolic the mean, it can be considered unrepresentative and be
discarded.
The EGL evaluation can be applied to dietary comestibles which are mixed
meals. In one embodiment, the mixcclirneal is considered to he a dietary
comestible
per se.. That is, the glycemic response 'to the mixed meal can be calculated
directly by
25 measuring the glycemic response after' the meal, and comparing this
response with the
index, Alternatively, the EGL of a mixed meal can be obtained by calculating
the
weighted average of the EGL of each dietary comestible component of the mixed
meal. The weighing can be based on the proportion of total meal glycemic
carbohydrate contributed by each of the dietary comestibles.
CA 02472371 2004-06-16
General Properties of_L'u4~ ear Regression Analysis
Linear regression analysis is a statistical procedure for fitting= the best
straight
line through a set of data points. The line generated by the linear regression
analysis
can be extrapolated beyond observed values (limited to a fifty gram load).
T'ne
extrapolation defines what the expected TALC is at a particular dose beyond
the
observed values of a particular blood sampling. For example, if the index does
not
include the observed value of the glycemic response at a zero gram load, i.e.
baseline,
the glycemic response at a zero gram load can be extrapolated from the other
observed values of the index. Similarly, givcn observed LAUC values at two
loads,
LALC values at loads in between the two observed values can be interpolated.
interpolation is an estimate of a function between two observed values
The quality of fit of the line to the measured values can be describud by R,
the
correlation coefficient. That is, r is a statistic which measures the strength
of the
straight-line relationship (the formula for r is: r = [(L xy) / ((?" x2) ( y2
)) "h}.) This
z'oefficirnt can vary between -1 and 1. A ' due of 0 indicates no correlation.
The
value of 1 indicates a perfect positive correlation That is, the value of the
LAUC is
predicted perfectly by knowing the value of a load. (The value of -1 indicates
a
perfect acl ative correlation. A negative correlation would apply if the doses
were
plotted in decreasing value from left to right.) As can be seen from the
Examples, the
correlation coefficient for load values of below fifty grams is greater than
0.95.
E MPLES
Example 1
`5 The glycemic responses of 1 serving (1 bar= 30g) of Eltkins ' Eudulge
Chocolate, Endulge Chocolate Peanut and Endulge Chocolate Crunch bars were
determined in 10 healthy subjects (4 male, 6 female; 39=5 years of age; body
mass
index 23.4 0.9kg/m), relative to the response from white bread. Each subject
was
studied on 7 occasions in the morning after 10-14h overnight fasts. On each
occasion,
30, each subject consumed a test meal. One of the test meals consisted of a
standard
drink alone. The standard drink did not contain glycemic carbohydrate. Three
of the
36
CA 02472371 2004-06-16
test meals consisted of one type of bar and the standard drink. Three of the
test meals
consisted of white bread containing 4 particular amount of glycemic
carbohydrate, i.e.
g, 10 g or 20 g; and the standard drink. The glycemic responses of each
subject
were determined after each test meal
The dose response curve for bread allowed calculation in each subject of the
extent to which 1 g glycemic carbohydrate from bread raised blood glucose.
This
allowed calculation of i) the amount of bread required to be consumed to
elicit the
same glycemic response of each test product, i.e. white bread equivalent ('Y
BB); and
2) the glycemic response of each bar relative to the same amount of
carbohydrate
from bread (relative glycemic response (RGR)). The incremental area under the
glycemic response curve (LA.UC) increased in a linear fashion as the amount of
carbohydrate consumed from bread increased from 0 to 20g, with the correlation
coefficient (r) being >0.95 in 7 of the 10 subjects. The regression equation
of mean
IAUC on dose of carbohydrate (d) was:
IAUC = 470d -t 13.8 (t-0.999).
The RGRs of the Endulge Chocolate, Endulge Chocolate Peanut and Endulge
Chocolate Crunch bars, respectively, were 39 5, 48x9 and 31 7. The amount of
glycemic carbohydrate from white bread which would raise blood glucose to the
saute
extent as the 3 bars, respectively, was 3.3 0.8g. 3.6 1.6g and 2.6 0.8g.
This is
equivalent to about 5-7g of white bread or about 1 /5 to 2/7 of a slice of
white bread.
37
CA 02472371 2004-06-16
METHODS
Subjects
Ten (10) healthy subjects (3-Smale and 3-5 female) aged 18-50 years of age
with a body mass index of 20-30kgr'rxt'_ Female subjects were excluded if they
reported being pregnant or interiding to become pregnant during the course of
the
study. Subjects were not following arestrictive diet, had no history of
diabetes or
heart disease, and were not he faking any prescription medication other than
birth
control pills.
1.0
TD Ethnicity Sex Age Height Height Weight Weight ;BMI
i
(y) (cm) (in) (kg) (1b) fkg/raz)
1 i African-Am M 35 173.0 68.1 87.0 191.4 29.07
27 ' Asian _ F 24 170.2 j 67.0 57.5 126.5 19.85
31. Caucasian r 53 162.0 63.8 ! 58.2 128.0 2218
33 Caucasian h 37 165.0 65.0 58.0 127.6 21.30
38 Caucasian M 20 187.5 73.8 90.6 199.3 25.77
39 Caucasian F 70 161.3 63.5 54.8 1 120.6 21.06
43 Caucasian F 53 167.6 66.0 64.8 142.6 23.07
44 1 Caribbean M 45 182.9 1 72.0 87.5 i 192.5 26.16
48 Caucasian F 1 22 162.6 64.0 ! 55.5 122.1 , 20.99
55 Caucasian M ' 27 179.5 ' 70.7 78.7 1 173.1 _ 24.43
Mean -J 38.6 171.2 67.4 69.3 152.4 ! 23.39 .
5BM 5.2 3.0 1.Z 4.7 10.4 0.92
Protocol
Subjects each underwent 7 treatments in randomized order on separate days,
15 with tests for each subject occurring at approximately weekly intervals. On
each test
day, subjects came to Glyeaernic Index Testing Laboratory (55 Queen St. East,
Suite
203) in the morning after a 10-14h overnight fast, and no ethanol consumption
within
24h. After being weighed and having a fasting blood sample obtained by finger-
38
CA 02472371 2004-06-16
prick, the subject then consumed a test meal within 10 minutes, and further
blood
samples were obtained at 15, 30, 45, 60, 90 and 120 minutes after the start of
the test
meal. Subjects were also given a drink- of their choice of 1 or 2 cups of
either water,
coffee or tea, with or without 60ml of 2% milk. The drink chosen by each
subject
remained the same on each test day.
The treatments consisted of one serving (I bar = 30g) of Endulge Chocolate,
Endul,~,e Chocolate Peanut and Endulge Chocolate Crunch bars, or the standard
drink
alone (Og white bread), or an amount of white bread containing 5, 10 or 20g
glycemic
carbohydrate. Bread was baked in a bread maker in loaves containing 50g
glycemic
carbohydrate. The ingredients for each loaf (250ml warm water, 334g all
purpose
flour, 7g sugar, 4g ,alt and 6.5g yeast) were placed into the bread maker
according to
instructions, and the machine turned on. After the loaf had been made, it was
allowed
to cool for an hour, and then weighcdand after discarding the crust ends, the
remainder was divided into portion sizes containing 5, 10 or 20g glycemic
carbohydrate. These portions were frozen prior to use.
Composition of test bars (data from t e label)
Weight Fat Protein Total Carb Fiber I Maltitol I
L__(g) (g) (g) (g) (g) it" (g)
Endulge Chocolate 30 13 1 3 1 11
Endulge ChocolatePeanut 30 1 2 15 3 11
.indulge. Chocolate 30 1 12 3 15 3 10
Crunch
Blood samples (2-3 drops each) were collected into 5ml tubes containing a
small amount of sodium fluoride/potassium oxalate, mixed by rotating the tube
vigorously, and placed into a refrigerator. After the last blood sample was
obtained,
subjects were offered a snack and then allowed to leave. Blood samples were
then
stored at -20 C prior to analysis of glucose using a YSI analyzer.
39
CA 02472371 2004-06-16
DataAnalysis
Incremental area under the .plasma glucose curves (LAUC) were calculated
using the trapezoid rule and Ignoring area beneath the baseline (the method
used for
the glycemic index). The blood glucose concentrations and increments at each
time
and the LA[C values were subjected to repeated-treasures analysis of variance
(.NOVA) examining for the effect of test meal. After demonstration' of
significant
heterogeneity, the significance ofthc,diff'erences between individual tr,eans
was
assessed using Tukry's test to adjust for multiple comparisons. The IAUC after
0, 5,
and 20g bread for each subject were regressed on the dose of carbohydrate
10 consumed to develop a dose-response curve. This was used to calculate the
LAUC
after consuming the same amount ofglyccrnic carbohydrate from bread as the
amount
of net carbohydrate (total carbohydrate minus dietary fiber) contained in the
test bars
(either 12 or 13g). These values were used to calculate the relative glyccn is
response
(RCR) of each test meal. The mean 1AUC for all subjects was regressed against
the
dose of carbohydrate consumed and this regression equation used to calculate
how
much white bread would have to be consumed to produce an U,,UC equal to the
mean
IAUC after each test bar, i.e the white bread equivalent.
RESULTS
Subiects studied
Details of the 4 male and 6 female subjects studied are shown in the table
below. One female subject dropped out after the 2"d test because she became
pregnant. She was replaced by a male subject.
Dose 2esponsee for White B eacd
I
Figure 4 shows the IALTC after the drink alone and the 3 doses of bread
plotted
against the amount of glycemic carbohydrate consumed. The plot uses the mean
values obtained from the tests. The regression equations and correlation
coefficients
(r values) are shown below. The r values ranged from 0.613 to 0.995, with 7 of
9
;0 subjects having r>0.95.
CA 02472371 2004-06-16
ID y-intercept Sjope Correlation Coefficient
12.3 3.30 0.979
27 1.7 6 87 0.995
~-- :1 - -4.7 11.02 0,991 33 18.6 2.60 0.8;8
38 21.7 2.63 0.959
39 28.7 3.68 _0.778
43 16.6_ 6.52 0.985
44 6.8 i 5.31 0.988
48 23 4 1.70 0.613
55 13.0 3.36 0.953
Mean. 13.8 4.70
Blood Glucose Responses
Figures 1 through 4 show the glycemic responses for each test bar, for the
drink alone and for the 3 doses of white bread. Blood glucose responses
increased
linearly. The regression equation of inean iAUC on dose of carbohydrate (d)
was:
IAUC = 4 70d ~ 13.8 (r=:-0.999).
The average areas under the curve after the Endulge Chocolate, Enduige
Chocolate Peanut and Endtdge Chocolate Crunch bars did not differ
significantly
from each other, and were similar or loss than the response after 5g
carbohydrate from
white bread. The ANOVA indicates that the IAUC values after the drink alone
and
each dose of white bread differed sign ficantly from each other, and there was
no
significant difference between the 3 teat bars.
i5
Analvsis of Variance,
An analysis of variance was performed to show the statistical comparisons for
palatability, and glucose response at each time point for the different
treatments. In
each case, Tukey's LSD (least square deviation) is the least significant
difference
41
CA 02472371 2004-06-16
based on Tukey's test, Means which differ by more than this amount are
statistically
significantly different.
Palatability: the bars were rated as significantly more palatable than bread,
but
the palatability ratings of the bars did not differ significantly from each
other.
Fasting glucose: there were small but significant differences in fasting
glucose
before the treatments. Evidence that this does not have an irn p rtant impact
on the
interpretation of the results is that thei dose-response carve for bread is
linear despite
the fact that the 0 and lOg doses had sig=nificantly lower fassting glucose
than the 5 and
20g doses
Postprandial time paints: Significant differences between treatments existed
at
15, 30, 45, 60, and 12Omin_ The areas under the glycemic response curve after
the
20g carbohydrate bread dose were significantly greater than that after the 1
Og dose,
which areas, in turn, were, significantly greater than the response to the 5g
dose,
which, in turn, were significantly greeter than the areas after Og bread. The
glycemic
response areas after the 3 bars were intermediate between the Ug and 5g bread
doses,
and did not differ significantly from each other, nor from the Og and 5g bread
responses.
Relative Glvicemic Response
The relative glycemic responses for the Endulge Chocolate, Endulge
Chocolate Peanut and Endulge Chocolate Crunch bars, respectively, were 39 5,
4St9
and 31 7,
Glycemic Ecttlivalent Amount of Bread
The regression of 1AUC after bread on dose of glycemic carbohydrate allows
calculation of the amount of bread which produces a given IAUC. This amount is
termed the glycernic equivalent. The bread glycernic equivalent for one
F.'ndulge
Chocolate bat is 3.3 0.8g glycemic carbohydrate, or approximately 6.6g of
the total
weight of the bread, or 0.28 slices (1 slice = 24g). Similarly, the bread
glycemic
42
CA 02472371 2004-06-16
equivalents of Endulge Chocolate Peexnut and Endulge Choeulale Crunch bars,
respectively, are amounts of bread containing 3.6 w 1:6g and 2.6 0.8g
glycemic
carbohydrate, or approximately 0,30 -nd 0.22 slices.
Example
The glycemic responses of 1 serving (1 bar = 30g) of Endulge Chocolate
Almand Bar, 1 serving (1 325rnl can)of Vanilla Shake, 1 slice (28g) of Atkins'
White
Bread, 1 slice (28g) Atkins' Rye Bread, 1 serving of Quick & Easy Pancakes and
1
serving of Quick & Easy Blueberry A(uffin3 were determined in 10 healthy
subjects (4
male, 6 female; 36;6 years of age; beady mass index 22.8t0.Skg/m2), relative
to the
response from white bread. Each subject was studied in the morning after 10-
14h
overnight fasts. In addition to a standard drink plus the 6 test products, the
glycemic
response of each subject was determined after the standard drink alone and the
drink
plus 5, 10 and 20g glycemic carbohydrate portions of white bread. The
incremental
area under the glycernic response curve (IAT.:C.) increased in a linear
fashion as the
amount of carbohydrate consumed from bread increased from 0 to 20g, with the
correlation coefficient (R) being '0.95 in 6 of the 10 subjects. "I he
regression
equation of mean 1AUC on dose of carbohydrate (d) was:
L - \ U C = 4.81d ... 12.7 (r=0.989)
The RGRs of the rye and white breads, vanilla shake, pancake, muffin and
chocolate
almond bar, respectively, were 88 12!, 102=.24, 22+8, 98-+20, 131 =31 and
5527. The
amount of glycernic carbohydrate fTo>n regular white bread which would raise
blood
glucose to the same extent as the 6 to t products, respectively, was 2.3 0.6g,
35 09g, 0.3=4.2g, 3.1-'-1.18, 5.5 2.18 and 4.5 1.1g. This is equivalent to
about 1-
2'> 9g of regular bread or about 1/20 to 3/8 of a slice.
METHODS
Subiects
Ten (10) healthy subjects (4 male and 6 female) aged 18-75 years of age were
studied.
43
CA 02472371 2004-06-16
ID Ethnicity Sex Age `Height Height t Weight Weight BMT
(y (cm) (in) (k) (Ib) (kgh112)
-r
African :-gym M 35 j 173.0 68.1 87.0 191.4 29.07
27 Asian F 24 170.2 67.0 57.5 126.5 19.85
---t
j 31 C i ucasian F 53 162.0 63.8 58.2 128.0 22 18_ i
33 Caucasian F 37 165.0 65.0 58.0 127.6 21.30
38 Caucasian M 20 187:5 73.8 90.6 199.3 25-77
39 Caucasian F 70 161.3 63.5 54.8 120.6 21.06
43 Caucasian F 53 167.6 66.0 64.8 142.6 23.07
48 . Caucasian F 22 1 162.6 64.0 55.5 1 122.1 20,.99
69 Caucasian M 22 185.4 73.0 71,0 156.2 20.66
'-"v fiddle East 21 185.4 73.0 76.0 67.2 22.11
Mean 35.7 172.0 67.7 67.8 148.2 22.61
SEM 5.5 4.0 1.3 4.0 9.2 0.89
Protocol
Subjects each underwent 8 tre4tinents in randomized order on separate days,
with tests for each subject occurring at approximately weekly intervals, as
set forth in
Example 1.
The treatments consisted of one serving (1 bar = 30g) of Endulge Chocolate
Almond Bar, 1 serving (1 325m1 can) of Vanilla Shake, 1 slice (28g) of Atkins'
White
Bread, 1 dice (28g) Atkins' Rye Bread, 1 serving of Quick & Easy Pancakes and
1
serving of Quick & Easy Blueberry Muffins, or the standard drink alone (Og
white
bread) or an amount of white bread containing 5, 10 or 20g glycemic
carbohydrate.
Quick & Easy Pancakes and B?,lueberry Muffins were made according to
package directions. For the pancakes,, 19 eggs, about 150m] oil and 3 1/6 cups
water
were added to the entire package of pancake mix (19 servings). Pancakes were
made
from the batter and the total weight of :pancakes made was determined. One
serving
44
CA 02472371 2004-06-16
consisted of the total weight divided by 19. Similarly, for the muffins, the
entire
package contents were mixed with 31': cup oil, 4 tbsp butter, 3 eggs and 1 1/4
cups
water and the hatter divided into 18 rriuffin cups and baked according to
package
directions. The total weight of muffs was determined and divided by 18 to
determine the single portion weight. Single portions of pancakes and muffins
were
weighed out, placed into individual zip-lock plastic bags and stored in the
freezer
prior to use. individual portions were warmed in a microwave oven on the
morning
of the test prior to consumption.
Regular bread was baked in a, bread maker in loaves containing 50g glycemic
carbohydrate. The ingredients for each loaf (250m1 warm water. 334g all purpos
flour, 7g sugar, 4g salt and 6.5g yeast) were placed into the bread maker
according to
instructions, and the machine turned on. After the loaf had been. made, it was
allowed
to cool for an hour, and then weighed and after discarding the crust ends, the
i 1 remainder was divided into portion sizes containing 5, 10 or ?.Ug
l;lycernic
carbohydrate. These portions were frozen prior to use
Composition of test bars (data from tire; label)
' _ - W'eight' Fat Protein Total Carb Fiber
(g) (g) W (g) (8)
Atkins Rve Bread 28 2 _ 7 I 7 4
Atkins White Bread 28 2 7 7 4
Vanilla Shake 325m1 9 20 4 _ 2
j Quick & Easy Pancake * 24 1.5 13 6 3
Quick & Easy Blueberry 18 0.5 6 9 6
muffin I Endulge Chocolate 30 13 2 14 3
1*Amounts of nutrients are amounts in mix only.
1C) Blood samples (2-3 drops each) were collected into Sm1 tubes containing a
small amount of sodium fluoride/potassium oxalate, mixed by rotating the tube
vigorously, and placed into a refrigerator. After the last blood sample was
obtained,
CA 02472371 2004-06-16
subjects were offered a snack and than allowed to leave. Blood samples were
then
stored at -20 C: prior to analysis of glucose using a YSI analyzer-
The data were analyzed as set forth in Example 1.
RESUL'fS
Dose Response for Whit r ad
Figure 12 shows .t e IAvC after the drink alone and the 3 doses of bread
plotted against the amount of glycemc carbohydrate consumed. The plot uses the
mean values obtained from the tests. The regression equations and correlation
coefficients (r values) are shown below. The r v lads ranged from 0,773 to
0.999,
with 6 of 10 subjects having r>0.95.
ID y-intercept Slope Correlation Coefficient
18.2 2.83 0.996
37 9.84 4.65 0.950
31 .,r.. -&83 10.53 I 0.97$
33 261 4 1 0.913
38 9.63 2.62 0.935
39 15.5 5.47 0.969
43 22.1 7.67 0.98"a
48 12.6 1.64 0.848
69 13.2 1.70 0.773
73 8.65 6.79 0.999
Mean 12.7 4.8 ~~ ^ J
i5
Blood Glucose Responses
Figures 5 through 11 show the glycemic responses for each test food plotted
with the response to the drink alone and the 3 doses of white bread. Blood
glucose
responses increased linearly with an increasing dose of bread ingested. The
regression equation of mean IALTC on dose of carbohydrate (d) was: LAl`iC =
4.8d +
46
CA 02472371 2004-06-16
12.7 (R-0 989). The blood glucose toncentratiou of subject I at 90min after
Blueberry Muffin was unexpectedly, high at 6.96rnmol.%L. This value results in
a
small peak of blood glucose at 90mirt which does not occur for any other food.
(Sce
Figure "7) The value was checked and verified, but appears to be an outlier
Figure 8
shows the results with this one outlier removed and replaced by the average
value of
the blood glucose concentrations at $0 and 120min. This results in a more
"normal"
looking glycemic response curve. Nevertheless, all the statistical analysis
are based
n inclwi no, the outlying data point
o
Analvsis of Variance
A n analysis of variaric;e was performed as, set forth in ,i.-, :ample 1.
Palatab ltty: there were significant differences in palatability between the 6
test products and the different doses of white bread. Pancake was
significantly less
palatable than all the other test meals. The chocolate almond bar was
significantly
more palatable than the reference White bread at 10- and the Atkins white
bread
Fasting glucose: there were no significant differences in fasting glucose
before
the treatments.
Postprand.al tune points: significant differences between treatments existed
at 15, 30, 45, and 60. The areas tmntder the glycemic response curve after the
20g
carbohydrate bread dose were sigzli.ficantly greater than that after the lOg
dose, which,
in turn, were significantly greater than the response to the 5g dose, which
areas, in
iurna, were significantly ¾ eater that the response after Og bread. The
glycemic
response areas after pancake, muffin, .Atkins breads and the chocolate almond
bar did
not differ significantly from each other or from the 5g dose of bread. The
vanilla
shake elicited a significantly lower glycemic response than all other test
meals except
the test containing Og bread.
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CA 02472371 2004-06-16
&eJalive.Glycernic Response
1 he relative glycemic responses (R&.sR) for Atkins white and rye breads,
pancake and muffin were similar to tliat for the reference bread. The RCR. for
shake,
22 8, and chocolate almond bar, 5517, were significantly less than reference
bread.
When the outlier value from the Blueberry muffin test was removed, there vas
no
significant impact on the RGR, filling from 13 1 30 to 10930.
(31veemic Equivalent Amount of Bread
The regression of IAUC after bread on dose of glycemic carbohydrate allows
catculaticn of the amount of broad which produces a given IAUC_ The bread
glycemic equivalent amounts ranged from 0.3 0.2g to 5.5 2.Ig, equivalent to
about
1-9g of regular bread or about 1/20 to 3/8 of a slice. Removal of the outlying
blood
glucose concentration from the blueberry muffin data reduced the bread
equivalent
from 5.a 2.18 to 3.8-r l.8g.
Example 3
The glycemic responses of I serving (1 bar = 60g) of Advantage Mocha Bar,
Advantage Frosted Cinnamon Swirl Bar, and Advantage Almond Brownie bar and 1
2t? serving (1 325m1 can) of Chocolate Delight Shake were determined in 10
healthy
subjects (4 male, 6 female; 36 6 years of age; body mass index 22.8=0.8kg/m
relative to the response from white bread. Each subject was studied on 8
occasions in
the morning after 10-14h overnight fasts. In addition to a standard drink plus
the 4
zest products, the glycemic response of each subject was determined after the
standard
drink alone and the drink plus 5, 10 and 20g glycemic carbohydrate portions of
white
bread. The incremental area under the glycemic response curve (I.AUC)
increased in
a linear fashion as the amount of carbohydrate consumed from bread increased
from 0
to 20g, with the correlation coefficient (R) being >0.95 in 6 of the 10
subjects. The
regression equation of mean IAUC on dose of carbohydrate (d) was:
IAUC 4.86d + 12.3 (r--0.992)
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CA 02472371 2004-06-16
The RGR of the mocha, cinnamon swirl and brownie bars and the chocolate shake,
respectively, were 40 6, 45 8, 32 4 and 57 23. The amount of glycemic
carbohydrate from regular white bread which would raise blood glucose to the
same
extent as the 4 test products, respectively, was 2.9 1.Og, 3.2: 1.2g, 2Ø
0.8g, and
0 6_ 0.4g. This is equivalent to about 1-6g of regular bread or about 1/20 to
1/4 of a
slice.
M lYiV1JS
Subjects
Ten (10) healthy subjects (44 male and 6 female) aged 18-75 years of age were
studied. The subjects are the same as in Example 2.
Protocoi
Subjects each underwent 8 treatments in randomized order on separate days.
1 5- with tests for each subject occurring P.1 approximately weekly intervals,
as set forth in
Example I.
The treatments consisted of one serving (1 bar = 60g) of Advantage Mocha
Bar, Advantage .h'rosted Cinnaxnork Swirl Bar, and Advantage Almond Brownie
Bar or
1 serving (1 325zxnl can) of Chvcolute Delight Shake, or the standard drink
alone (Og
white bread), or an amount of white bread containing 5, 10 or 20g glycemic
carbohydrate. The ingredients for each loaf, and methods of preparation, were
as set
forth in Example 2 for regular bread.
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CA 02472371 2004-06-16
Cotnncrsition of test bars (dat m the label)
g1it Fat I'rotcin ?oral Carb Fiber
(9) W (g) (g) (g)
4dvantage A1ocha Bar 60 10 20 22 10
Advantage Frosted 60 11 19 21 10
Cinnamon Swirl Bar
Advantage Almond 60 8 21 21. 7
Brownie Bar
L Chocolgre Deli rhi Shake 325rti1 9 20 5 3
Blood samples were collected, and analyzed as set forth in Example 2. ha
data were analyzed as set forth in -Example 2.
RESULTS
Dose Re! se for White Bread
Figure 17 shows the IAIJCfor each subject after the drink alone and the 3
doses of bread plotted against the amount of glyccmic carbohydrate consumed.
The
plot uses the mean values obtained from the tests. The regression equations
and
correlation coefficients (r values) are shown below. The r values ranged from
0.763
to 0.996, with 6 of 10 subjects having r>0.95.
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CA 02472371 2004-06-16
iD y-intercet Slope Correlation Coefficient
1 163 2.78 0.992 27 1.03 6.91 0.995
31^ 12.=~ 11.43 0.988 33 30.6 2.98 0.802
38 13.2 2.47 0.857
P 39 11.' I 5.65 0.982
43 24.0 7.55 i 0.985
48 16.2 1.75 0.33
69 9.2 I 1.59 ; 0.949
73 13.9 , 5.45 0.996
Mean 12.3 4,9 Blood Glucose _es pcuses
Figures 13 through 16 show Lhc glyce&nic responses for each test food plotted
with the response to the drink alone and the 3 doses of white bread. Blood
glucose
responses increased linearly with ap increasing dose of bread ingested. The
regression equation of mean 1AUC on dose of carbohydrate (d).was; IAUC = 4.9d
12.3 (R 0 992).
Analysis of Variance
An analysis of variance was performed as set forth in Example 1.
Palatabili.y: there were nd significant differences in palatability between
the 4
test products and the different doses of white bread.
is Fasting glucose: there were no significant differences in fasting glucose
before
the treatments.
Postprandial time points: Significant differences between treatments existed
at 15, 30, 45, and 60. The areas sunder the glycemic response curve after the
20g
:10 carbohydr :te bread dose was significantly greater than that after the l
Og dose, which
51
CA 02472371 2004-06-16
in turn v. as significantly greater than the response to the 5g dose, which,
in turn, was
significantly greater than the response after Og bread. The glycemic response
areas
after the 3 bars did not differ significantly from each other or from the 5g
dose of
bread. The mocha and cinnamon bars had glycemie response areas significantly
greater than that after Og bread, with the difference for brownie bar just
missing
.igriificance. The glycemie response after each of the 3 bars was
significantly less
than that after the l Og bread dose. The glycemie response after chocolate
shake was
no different Born Ipat after Og bread, and significantly less than those after
the 3 bars
and the 6g bread dose.
Relative Glyicemic Response
The relative glycemic responses (RGR) for the mocha, cinnamon and brownie
bars, respectively, were 40-+6, 468 and 32:4_ The RGR for chocolate shake was
57:23 The reason for the much greater variability in the RGR value for
chocolate
shake is that because the amount of carbohydrate in the product, 2g, is very
low, the
absolute responses are very low. Thus, the random variation in the glycernic
responses become very large when expressed as a ratio.
Glycemic Equivalent , punt of Bread
The regression of JAUC aster bread on dose of glyccmic carbohydrate allows
calculation of the amount of bread which produces a given LAUC for each
subject.
The bread glycemic equivalent amount-one Advantage Mocha bar was 2.9t l .Og of
carbohydrate, or approximately 6 of bread or 1.27 slices (1 slice = 22g).
Similarly,
the glycemie equivalents of theAglvantage Cinnamon and Almond Brownie,
respectively, arc amounts of bread containing 3.2=1 2g and 2.0=0.8g glycemic
carbohydrate, which equals about,`6 and 4g bread, or about 0.3 and 0.2 slices.
The
chocolate shake has a bread equivalent of only 0.6=0.4g, which equals about 1
g of
bread or about 1/20`h of a slice.
As can be seen from the above Examples, the glycemie responses elicited by
comestibles, such as the bars, are expressed in terms of white bread glycemie
52
CA 02472371 2004-06-16
carbohydrate equivalexits. Addition$Ily, as show:,, the glycemic responses are
expressed in terms of white bread sI~ce portions.
Thus, while there have been! described what are presently believed to be the
preferred embodiments of the presezit invention. other and further
embodiments,
modifications, and improvements will he known to those skilled in the art, and
it is
intended to include all such further imbodiments, modifications; and
improvements
and come wit in the true scope of the claims as set forth below.
i
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