U.S. patent application number 12/824509 was filed with the patent office on 2011-01-06 for composition and method for reducing food intake.
Invention is credited to Jason Christian Grovenor Halford, Trevor Rodney Jarman.
Application Number | 20110003021 12/824509 |
Document ID | / |
Family ID | 42670576 |
Filed Date | 2011-01-06 |
United States Patent
Application |
20110003021 |
Kind Code |
A1 |
Halford; Jason Christian Grovenor ;
et al. |
January 6, 2011 |
Composition and method for reducing food intake
Abstract
The present invention features a composition and method for
reducing food intake. The composition of the invention is composed
of yerbe mate extract, guarana extract, and damiana extract in
combination with a dietary fiber.
Inventors: |
Halford; Jason Christian
Grovenor; (Manchester, GB) ; Jarman; Trevor
Rodney; (Haslingfield, GB) |
Correspondence
Address: |
Jane Massey Licata;Licata & Tyrrell P.C.
66 E. Main Street
Marlton
NJ
08053
US
|
Family ID: |
42670576 |
Appl. No.: |
12/824509 |
Filed: |
June 28, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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61222141 |
Jul 1, 2009 |
|
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Current U.S.
Class: |
424/728 ;
424/725 |
Current CPC
Class: |
A61K 36/77 20130101;
A61K 36/185 20130101; A61K 36/185 20130101; A61K 36/77 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61P 3/04 20180101;
A61P 3/00 20180101 |
Class at
Publication: |
424/728 ;
424/725 |
International
Class: |
A61K 36/254 20060101
A61K036/254; A61K 36/00 20060101 A61K036/00 |
Claims
1. A composition comprising yerbe mate extract, guarana extract,
damiana extract and a dietary fiber.
2. The composition of claim 1, wherein the dietary fiber is
fermentable.
3. The composition of claim 2, wherein the fermentable dietary
fiber is inulin, a beta-glucan, a pectin, a natural gum, an
oligosaccharide, psyllium seed husk, a resistant dextrin, or any
combination thereof.
4. The composition of claim 3, wherein the beta-glucan is isolated
from oat bran, whole oats, oatrim or rolled oats.
5. The composition of claim 3, wherein the natural gum is xanthan
gum, acacia gum or guar gum.
6. The composition of claim 3, wherein the oligosaccharide is a
fructooligosaccharide.
7. The composition of claim 1, further comprising an extract from
one or more of Buchu, Vervain, Kola nut, or Ginseng.
8. A method for reducing food intake comprising administering to a
subject in need thereof an effective amount of yerbe mate extract,
guarana extract, and damiana extract in combination with a dietary
fiber thereby suppressing the subject's food intake.
9. The method of claim 8, wherein the dietary fiber is
fermentable.
10. The method of claim 9, wherein the fermentable dietary fiber is
inulin, a beta-glucan, a pectin, a natural gum, an oligosaccharide,
psyllium seed husk, a resistant dextrin, or combination
thereof.
11. The method of claim 10, wherein the beta-glucan is isolated
from oat bran, whole oats, oatrim or rolled oats.
12. The method of claim 10, wherein the natural gum is xanthan gum,
acacia gum or guar gum.
13. The method of claim 10, wherein the oligosaccharide is a
fructooligosaccharide.
14. The method of claim 8, further comprising administering an
extract from one or more of Buchu, Vervain, Kola nut, or Ginseng.
Description
INTRODUCTION
[0001] This application claims benefit of priority to U.S.
Provisional Application Ser. No. 61/222,141, filed Jul. 1, 2009,
the content of which is incorporated herein by reference in its
entirety.
BACKGROUND OF THE INVENTION
[0002] The necessary condition for the reduction of body mass is a
negative energy balance. Energy intake must be consistently lower
than energy expenditure in order for weight loss to occur.
Therefore, any weight control strategy must address one or both
parts of the energy equation; intake or expenditure. With regard to
the control of energy intake, two broad strategies can be adopted:
the enhancement of the satiety response to food or the blockade of
absorption. The physical and chemical properties of various foods
can be used to achieve both effects.
[0003] With specific regard to the modulation of appetite, those
processes responsible for the termination of a meal and the
suppression of subsequent intake are of particular interest. The
within meal processes of satiation and the post-meal end state of
satiety are generated by the sensory, physical and chemical
characteristics of the food consumed. The strength of these signals
determines meal duration and meal size, and the length of the
post-meal interval before the next eating occasion. The activation
of such signals can be employed to enhance the appetite response to
food and limit caloric intake.
[0004] Various naturally occurring ingredients including herbal
extracts have been shown to produce beneficial effects on appetite
and weight control when used as supplements or food components
(Ruxton, et al. (2005) Br. Food J. 107:111-125; Ruxton, et al.
(2007) Br. Food J. 109: 416-428). ZOTRIM is a mixed herbal
preparation containing Yerbe Mate, Guarana and Damiana, common
ingredients of commercially available drinks, and the product is
available in the UK as a food supplement. This herb extract
formulation significantly delays gastric emptying, reduced the time
to perceived gastric fullness and induced significant weight loss
over 45 days in overweight patients (Anderson & Fogh (2001) J.
Hum. Nutr. Dietet. 14:243-250). A consumer study has also been
undertaken to test the efficacy of this preparation in the field. A
total of 48 free-living subjects completed a 28-day trial and
demonstrated a self-reported mean weight loss of 2.3 kg.
Questionnaire data suggested that subjects ate less at meals and
snacked less frequently (Ruxton (2004) Nutr. Food Sci. 34:25-28;
Ruxton, et al. (2005) Nut. Food Sci. 35:303-331; Ruxton, et al.
(2007) supra). However, the effects of ZOTRIM on human food intake,
feeding behaviour and subjective feelings of appetite and satiety
were not determined.
[0005] FIBRESURE is a 100% natural fiber supplement that can be
taken daily. The term fiber covers a wide variety of substances
belonging to the family of carbohydrates that resist hydrolysis by
human alimentary enzymes but are fermented by colonic micro flora
(Bianchi & Capurso (2002) Dig. Liver Dis. 34(Suppl 2):S129-33).
Fiber is normally connected with increases in satiety due to its
high viscosity and bulking effect (Burton-Freeman (2000) J. Nutr.
130:272 S-275S). However, FIBRESURE is a fiber product with little
effect on viscosity. Current recommendations for the management of
obesity and diabetes mellitus include an increase in dietary fiber
intake, as it may contribute to lower fasting and postprandial
plasma glucose concentrations and improvement of glycaemic control,
which can help control energy intake (Vinik & Jenkins (1988)
Diabetes Care 11:160-173). FIBRESURE contains the soluble fiber
inulin, which is a prebiotic carbohydrate derived from chicory
root. Inulin and inulin-type fructans are mostly oligosaccharides
or oligofructoses and stimulate colonic production of Short Chain
Fatty Acids (SCFAs), (Guarner (2005) Brit. J. Nutr. 93:S61-5).
Fiber fermentability which produces SCFA has been linked with
increasing satiety (Bosch (2008) Br. J. Nutr. 102:318-325).
[0006] The mechanism by which inulin and inulin-type fructans exert
a satiating effect has not been identified. There are many
gastrointestinal peptides that affect food intake such as ghrelin,
cholecystokinin (CCK), glucagon-like peptide-1 (7-36) amide
(GLP-1), oxyntomodulin, peptide YY (PYY) and pancreatic polypeptide
(PP). Fructans modulate gastrointestinal peptides involved in the
control of food intake, particularly GLP-1 and ghrelin (Orskov, et
al. (1989) J. Biol. Chem. 264(22):12826-12829). GLP-1 is an
anorectic peptide secreted by the L-cells which suppresses
meal-induced gastric acid and pancreatic juice secretion and slows
gastric emptying (Schjoldager, et al. (1989) Dig. Dis. Sci.
34:703-708). There are several studies showing that peripheral
injection of GLP-1 decreases food intake and consequently body
weight in rats and human subjects, (Meier, et al. (2002) Eur. J.
Pharmacol. 440:269-279; Zander, et al. (2002) Lancet 359:824-830).
Ghrelin is associated with the mesolimbic cholinergic dopaminergic
reward system. This reward link is composed of cholinergic input
from the laterodorsal tegmental area to the mesolimbic dopamine
system that originates in the ventral tegmental area and projects
to the nucleus accumbens (Jerlhag, et al. (2007) Addict. Biol.
12(1):6-16). In this respect, treatment of human volunteers with
approximately 20 g of oligofructose per day for 7 days increased
serum GLP-1 levels (Piche, et al. (2003) Gastroenterology
124(4):894-902). Furthermore, in a study of 14 healthy volunteers,
it was found that the gut peptide GLP-1 decreases motility in the
antro-duodeno-jejunal region thus inducing satiety (Hellstrom, et
al. (2008) Neurogastroenterol. Motil. 20(6):649-59).
SUMMARY OF THE INVENTION
[0007] The present invention features a composition for reducing
food intake, said composition being composed of yerbe mate extract,
guarana extract, damiana extract and a dietary fiber. In one
embodiment, the dietary fiber is a fermentable dietary fiber such
as inulin, a beta-glucan, a pectin, a natural gum, an
oligosaccharide, psyllium seed husk, a resistant dextrin, or
combination thereof. In certain embodiments, the beta-glucan is
isolated from oat bran, whole oats, oatrim or rolled oats; the
natural gum is xanthan gum, acacia gum or guar gum; and the
oligosaccharide is a fructooligosaccharide. In further embodiments,
the composition further includes an extract from one or more of
Buchu, Vervain, Kola nut, or Ginseng. A method for using the
composition of the invention for decreasing food intake is also
provided.
DETAILED DESCRIPTION OF THE INVENTION
[0008] It has now been found that a combination of selected herbal
extracts (i.e., yerbe mate extract, guarana extract, damiana
extract) and dietary fiber can significantly decrease food intake
compared to use of the herbal extracts alone or dietary fiber
alone. Specifically, the combination of herbal extract and dietary
fiber described herein provided a significant reduction in gram
(91.4 g, 24.3%) and kcal intake (202.kcal, 26.7%) as compared to
placebo-water. Further, the combined administration of herbal
extract and dietary fiber produced a significant reduction in gram
intake compared to placebo in all food groups except low fat sweet
items; intake of high fat savory items was reduced by 18.5 g
(27.6%), low fat savory intake reduced by 19.1 g (13.6%) and the
greatest reductions were seen for high fat sweet items where intake
was reduced by 31.1 g (48.8%). The study herein demonstrated a
significant and robust effect on food intake of a standard ad
libitum lunch. Accordingly, the present invention features a
composition composed of yerbe mate extract, guarana extract,
damiana extract and a dietary fiber for use in reducing food
consumption and/or calorie intake.
[0009] As is conventional in the art, appetite is a natural desire,
or longing for food. According to the present invention, increased
appetite generally leads to increased feeding behaviour. In this
respect, an appetite suppressant is a composition that decreases
the desire for food, as evidenced by a decrease in food consumption
and/or calorie intake.
[0010] The composition of the present invention is composed of
soluble extracts of yerbe mate (leaves of Ilex paraguayensis, I.
vomitora, or I. dahoon), guarana (seeds of Paullinia cupana or P.
sorbalis) and damiana (leaves of Turnera diffusa var. aphrodisiaca,
T. opifera, or T. ulmifoliei). Soluble extracts of the invention
can be prepared by conventional methods of drying and/or grinding
plant biomass and subjecting the same to one or more suitable
solvents, thereby providing an extract, which may be either used as
a crude extract or further fractionated.
[0011] Suitable methods for drying plant biomass include: sun
drying followed by a heated air-drying or freeze-drying;
lyophilization or chopping the biomass into small pieces, e.g.,
2-10 cm, followed by heated air-drying or freeze-drying. Once
sufficient moisture has been removed, e.g., more than 90%, the
material can be ground to a coarse particle size, e.g., 0.01-1 mm,
using a commercial grinder. For laboratory scale extraction, a
coffee grinder or equivalent can be used.
[0012] In general terms, a suitable method for preparing an extract
of plant biomass includes the steps of treating collected plant
biomass with a solvent to extract a fraction having appetite
suppressant or curbing activity, separating the extraction solution
from the rest of the plant biomass, removing the solvent from the
extraction solution and recovering the extract. The extract so
recovered may be further purified by way of suitable extraction or
purification procedures.
[0013] More specifically, plant biomass can be ground to a coarse
powder as described above. Subsequently, a suitable solvent, e.g.,
a food grade solvent, can be added to the powder. A good grade
solvent is any solvent which is suitable and approved for use in
conjunction with foods intended for human consumption. Examples of
suitable solvents are alcohol-based solvents, ethyl acetate, liquid
carbon dioxide, hexane, and one or more components of fusel oil,
e.g., ethyl acetate. Alcohol-based solvents, i.e., pure alcohol
solvents and mixtures thereof with water or other organic solvents,
are most desirable.
[0014] The extraction solution can then be separated from the
residual plant biomass by an appropriate separation procedure such
as filtration and/or centrifugation. The solvent can be removed,
e.g., by means of a rotary evaporator. The separated crude extract
can then be tested to confirm appetite suppressant or appetite
curbing activity in a suitable in vivo bioassay.
[0015] A suitable and accepted in vivo model for measuring appetite
suppression or appetite curbing activity in an animal model is
described in Example 2. A clinically effective and medically
approved anti-obesity drug, e.g., sibutramine, can be used as a
positive control for reduction in food intake in this model.
Positive results from this test model are an indicator of clinical
efficacy in the human context. Alternatively, suppression,
reduction or curbing of appetite can be assessed by any of the
methods referred to in WO 98/46243.
[0016] Plant extracts of the invention can be dried to remove
moisture, e.g., by spray-drying, freeze-drying or vacuum-drying, to
yield a free-flowing powder. Optionally, the extracts can be dried
on a pharmaceutically acceptable carrier, such as maltodextrin or
starch. As yet a further alternative, plant biomass can be
extracted and concentrated without drying to give a liquid extract,
which is effective in curbing or suppressing appetite.
[0017] In addition to yerbe mate, guarana and damiana extract, the
composition of the invention can further include one or more of:
extracts from the leaves of Buchu (Barosma Betulina, B. Crenulata,
B. Serratifolia) containing diosphenol (buchu camphor); extracts
from the leaves or flowers of Vervain (Verbena officinales, V.
jamaicensis, V. lappulacae, V. hesitate, V. urticifolia, V.
Sinuata) containing glycosides, adenosine, essential oils, tannin,
livertin and/or emulin; extracts of Kola nut (Cola nitida, C. vera)
containing caffeine; or extracts from the leaves or flowers of
Ginseng (Panax ginseng, P. quinquefolius L.) containing
triterpenoid saponins.
[0018] In addition to herbal extracts, the present composition also
features a dietary fiber. As used herein, dietary fiber is the
indigestible portion of plant foods that pushes food through the
digestive system and absorbs water. Dietary fiber can be soluble
(able to dissolve in water) or insoluble (not able to dissolve in
water). Soluble fiber, like all fiber, cannot be digested. But it
does change as it passes through the digestive tract, being
transformed or fermented by bacteria therein. In contrast,
insoluble fiber passes through the body largely unchanged.
Accordingly, in particular embodiments of the present invention,
the dietary fiber is fermentable or soluble.
[0019] Fermentable dietary fiber can be obtained from a variety of
plant foods, including, but not limited to legumes (e.g., peas,
soybeans, and other beans); grains such as oats, rye, chia, and
barley; some fruits and fruit juices including prune juice, plums,
berries, bananas, and the insides of apples and pears; certain
vegetables such as broccoli, carrots and Jerusalem artichokes; root
vegetables such as potatoes, sweet potatoes, and onions; and
psyllium seed husk. In particular embodiments, the dietary fiber is
isolated and/or substantially purified to homogeneity, e.g., at
least to 75%, 80%, 85%, or 90%, homogeneity or up to 99%
homogeneity.
[0020] For use in accordance with the present invention, the
isolated, fermentable dietary fiber is inulin, a beta-glucan, a
pectin, a natural gum, an oligosaccharide, psyllium seed husk, a
resistant dextrin, an alginate or a combination thereof. Inulin,
belonging to the class of fibers known as fructans, is typically
extracted from enriched plant sources such as chicory roots or
Jerusalem artichokes. Beta-glucans, polysaccharides of D-glucose
monomers linked by glycosidic bonds, are typically isolated from
oat bran, whole oats, oatrim or rolled oats. Pectins, a complex set
of polysaccharides that are present in most primary cell walls and
particularly abundant in the non-woody parts of terrestrial plants,
are composed of a linear chain of .alpha.-(1-4)-linked
D-galacturonic acid that forms the pectin-backbone. Natural gums,
which are polysaccharides of natural origin that are capable of
causing a large viscosity increase in solution, include, but are
not limited to xanthan gum, acacia gum or guar gum. Alginate is a
soluble fiber extracted from seaweed. According to the present
invention, oligosaccharides, saccharide polymers containing a small
number (typically three to ten) of component sugars (also known as
simple sugars), particularly include fructooligosaccharides. As is
conventional in the art, a resistant dextrin is a water-soluble
dietary fiber obtained by, e.g., subjecting starch to
high-temperature heating and enzymatic hydrolysis with
.alpha.-amylase and glucoamylase. The selection of the dietary
fiber to be used in the composition of the present invention can be
dependent upon the form of the composition and the manner in which
the formulation is administered, e.g., as multiple different
formulations or as one formulation containing yerbe mate extract,
guarana extract, damiana extract and dietary fiber. In particular
embodiments, the dietary fiber of the instant composition is
inulin.
[0021] According to this invention, the herbal extracts and dietary
fiber can be provided as a composition prepared as individual
formulations (e.g., the composition includes or comprises a
formulation containing yerbe mate extract, a formulation containing
guarana extract, a formulation containing damiana extract, and a
formulation containing a dietary fiber), or the composition can be
prepared as a combination of formulations (e.g., the composition
includes or comprises a formulation containing yerbe mate extract,
guarana extract, and damiana extract; and a formulation containing
a dietary fiber), or the composition can be prepared as a single
unitary formulation (e.g., the composition includes or comprises a
formulation containing yerbe mate extract, guarana extract, damiana
extract, and dietary fiber). Moreover, when the composition is
prepared as individual or a combination of formulations, said
formulations can be the same, e.g., all tablets; or different,
e.g., a capsule formulation and a liquid formulation. In addition,
when taken as individual formulations, said formulations can be
taken simultaneously or consecutively, e.g., within minutes of each
other.
[0022] Soluble plant extracts, dietary fiber or a combination
thereof can be admixed by conventional compounding procedures with
any conventional pharmaceutical or nutritionally acceptable
excipient, diluent or carrier in the preparation of
pharmaceuticals, nutraceuticals, nutritional compositions, such as
dietary supplements, slimming compositions, medical nutrition or
functional foods. Typically, this involves mixing the active
ingredients of the invention together with edible pharmaceutically
or nutritionally acceptable solid or liquid carriers and/or
excipients, e.g., fillers, such as cellulose, lactose, sucrose,
mannitol, sorbitol, and calcium phosphates; and binders, such as
starch, gelatin, tragacanth, methylcellulose and/or
polyvinylpyrrolidone (PVP). Optional additives include lubricants
and flow conditioners, e.g., silicic acid, silicon dioxide, talc,
stearic acid, magnesium/calcium stearates and polyethylene glycol
(PEG) diluents; disintegrating agents, e.g., starch, carboxymethyl
starch, cross-linked PVP, agar, alginic acid and alginates,
coloring agents, flavoring agents and melting agents. Dyes or
pigments may be added to tablets or dragee coatings, for example,
for identification purposes or to indicate different doses of
active ingredient.
[0023] The composition of the invention can optionally include
conventional food additives, such as any of emulsifiers,
stabilizers, sweeteners, flavorings, coloring agents,
preservatives, chelating agents, osmotic agents, buffers or agents
for pH adjustment, acidulants, thickeners, texturizers and the
like.
[0024] Suitable product formulations according to the present
invention include sachets, soft gel, powders, syrups, pills,
capsules, tablets, liquid drops, sublinguals, patches,
suppositories, and liquids. Also contemplated are food and beverage
products containing the composition of the present invention, such
as solid food products, like bars (e.g., nutritional bars or cereal
bars), powdered drinks, dairy products, breakfast cereals, muesli,
candies, confectioneries, cookies, biscuits, crackers, chocolate,
chewing-gum, desserts and the like; liquid comestibles, like soft
drinks, juice, sports drinks, milk drinks, milk-shakes, yogurt
drinks or soups, as well as pet treats, pet foods, etc.
[0025] The composition of the invention can be provided as a
component of a normal meal, e.g., a nutritional or slimming
composition, or dietary supplement, in the form of a health drink,
a snack or a nutritionally fortified beverage, as well as a pill, a
tablet or a softgel, for example. When used as a snack or dietary
supplement it will preferably be consumed between or before
meals.
[0026] Optionally, the composition according to the invention can
be nutritionally complete, i.e., may include vitamins, minerals,
trace elements as well as nitrogen, carbohydrate and fatty acid
sources so that it may be used as the sole source of nutrition
supplying essentially all the required daily amounts of vitamins,
minerals, carbohydrates, fatty acids, proteins and the like.
Accordingly, the composition of the invention may be provided in
the form of a nutritionally balanced complete meal, e.g., suited
for oral or tube feeding.
[0027] In addition to the herbal extracts and dietary fiber, the
composition of the invention may also include one or more further
active ingredients, e.g., capsaicin (red pepper); fatty acids,
especially linoleic acid (LA) and conjugated linoleic acid (CLA);
glycomacropeptide (GMP); Long Chain Triglyceride (LCT);
enterostatin; galactose; glucuronic acid; hydroxycitrate (HCA);
citrus; .beta.-hydroxy butyrate; medium chain tryglycerides (MCTs);
D-tagatose; caffeine; potato extract; green tea extract;
epigallocatechin gallate, or other catechins; peptide D4; vitamins
B, C and/or E; and chromium picolinate. Alternatively, the
composition of the invention may be combined with an anti-obesity
drug, such as sibutramine. For example, the composition of the
invention may be provided in the form of a kit for separate,
sequential or simultaneous administration in conjunction with an
anti-obesity drug such as orlistat (XENICAL.TM.), Hoodia extract,
and the like.
[0028] Daily dosage of a composition of the present invention would
usually be single or multiple servings per day, e.g., once or twice
daily, for acute or chronic use. However, benefit may be derived
from dosing regimens that can include consumption on a daily,
weekly or monthly basis or any combination thereof. Administration
of compositions of the invention, e.g., treatment, could continue
over a period of days, weeks, months or years, in order, for
example, to constantly control the weight, or until a healthy or
cosmetically beneficial loss of body weight has occurred.
Optimally, the composition of the invention is consumed at least
once a day on a regular basis, prior to (i.e., pre-prandial
administration), or during a meal. Preferably, the composition of
the invention is consumed prior to a meal.
[0029] The amount and dosage regimen of the composition of the
invention to be administered is determined in the light of various
relevant factors including the purpose of administration, the age,
sex and body weight of an individual subject, i.e., inter alia on
the severity of the subject's obesity or overweight. In this
respect, the compositions of the invention can be administered
under the supervision of a medical specialist, or may be
self-administered.
[0030] Preferred delivery formats for the appetite suppressing or
appetite curbing composition of the invention, would be as a
dietary supplement containing about 50 mg to about 150 mg, or
preferably about 100 mg to about 120 mg, dry weight of yerbe mate
extract; about 50 mg to about 120 mg, or preferably about 90 mg to
100 mg, of gaurana extract; about 20 mg to about 50 mg, or
preferably about 30 mg to about 40 mg, of damiana extract; and
about 2 grams to about 10 grams, or preferably about 5 grams to 7
grams, of dietary fiber.
[0031] An illustrative example of a formulation of herbal extracts
is 27.5% weight yerbe mate extract, 23.2% weight Guarana, 9% weight
Damiana extract, and 40.3% weight of dicalcium phosphate, talc,
sodium carboxymethylcellulose, magnesium stearate and
hydroxypropylmethylcellulose as additional ingredients.
[0032] The present invention also features a method for decrease
food intake and/or suppressing appetite by administering to a
subject in need thereof an effective amount of yerbe mate extract,
guarana extract, and damiana extract in combination with a dietary
fiber. Administration of the composition of the present invention
results in a 10% to 40% decrease in food consumption (gram weight)
or a 10% to 35% decrease in calorie intake (Kcal) as compared to a
subject not receiving the composition. In particular embodiments,
the composition of the present invention achieves a 20 to 30%
reduction in food consumption or calorie intake, levels which
unexpectedly surpass other nutritional weight loss compositions.
For example, while humans studies analyzing the effects of
Caralluma fimbriata have shown a 8.2% reduction in energy intake
(Kuriyan, et al. (2007) Appetite 48:338-344), human studies of
sodium alginate showed a 7% reduction in energy intake (Paxman, et
al. (2008) Appetite 51:713-719), human studies of oligofructose
(soluble fermentable non-viscous fiber) have shown a 5% reduction
in total intake (Cani, et al. (2006) Euro. J. Clin. Nutr.
60:567-572), and human studies of hydroxycitric acid (HCA-SX) and a
combination of HCA-SX and niacin-bound chromium (NBC) and Gymnema
sylvestre extract (GSE) have shown a 4% decrease in food intake
(Preuss, et al. (2004) Nutr. Res. 24:45-58), human studies with a
natural dietary compound of chromium picolinate, inulin, capsicum,
L-phenylalanine, and other lipotropic nutrients has not shown any
significant difference in energy intake (Hoeger, et al. (1998) Adv.
Ther. 15:305-14). Similarly, food intake and appetite ratings were
not significantly reduced when either beta-glucan and
fructooligosaccharides are used alone or in combination (Peters, et
al. (2009) Am. J. Clin. Nutr. 89:58-63; Kim, et al. (2006) Cer.
Foods World, pg. 29), or with a fiber system of alginate and guar
gum (Mattes (2007) Physiol. Behav. 90:705-711), or with supplements
of fermentable fibers (pectin, beta-glucan) and non-fermentable
methylcellulose (Howarth, et al. (2003) J. Nutr. 133:3141-3144).
Indeed, the levels of reduction in food/calorie intake of the
instant composition are more comparable to pharmacological options
including sibutramine (12-26% reduction; Rolls, et al. (1998) Obes.
Res. 6:1-11; Chapelot, et al. (2000) Physiol. Behav. 68:299-308),
diethylpropion (11-15% reduction; Porikos, et al. (1980) Clin.
Pharmacol. Ther. 27:815-822), fluoxetin (13-16% reduction; McGuirk
& Silverstone (1990) Int. J. Obes. 14:361-72) and
fenfluramine/d-fenfluramine (17-22% reduction; Goodall &
Silverstone (1988) Appetite 11:215-288. See, also, Halford, et al.
(2007) Drugs 67:27-55 and Halford, et al. (2004) Curr. Drug Targets
5:221-40.
[0033] Subjects benefiting from the method of the invention include
those in need of weight loss, e.g. overweight or obese subjects, as
well as subjects controlling food intake so as not to gain weight.
In some embodiments, subjects receiving the composition of this
invention are average or slightly overweight, i.e., having a BMI of
18.5-29.9 kg/m.sup.2. In other embodiments, subjects receiving the
composition of this invention are overweight, i.e., having a BMI of
greater than 29.9 kg/m.sup.2. In further embodiments, subjects
benefiting from the method of the invention are those that consume
high fat food, e.g., food containing greater than 8 g of fat per
100 g.
[0034] In addition to the uses described therein, the invention
further provides a composition according to the invention for use
in suppressing appetite.
[0035] The invention additionally provides the use of yerba mate
extract, guarana extract, daminiana extract and a dietary fiber in
the manufacture of a composition for suppressing appetite.
[0036] The invention is described in greater detail by the
following non-limiting examples.
Example 1
Materials and Methods
[0037] Study Design. This was a double-blind, placebo-controlled
study using a randomized within-subject design to evaluate the
effects of ZOTRIM and inulin fiber given together, separately and
against placebo control in terms of food intake in grams and
kilocalories and subsequent food ratings measured using visual
analogue scales (VAS) of hunger, fullness, prospective consumption,
desire to eat and satisfaction pre dosing, pre and post meals and
at hourly intervals across the day. The independent variables were
the four conditions--ZOTRIM (tablet form) and inulin fiber (powder
mixed with water), ZOTRIM and control, inulin fiber and placebo and
control and placebo. The dependant variables were food intake
measured in grams, kilocalories and macronutrients and the VAS
ratings. All food and water was recorded by weight scales
(Sartorius Model CPA 4202S, Sartorius Ltd, Epsom, UK; 0.1 gram
accuracy) before and after meals to ascertain intake in grams,
kilocalories and macronutrients, and food choice. There were two
VAS's: the first was given nine times throughout the study day and
measured hunger, fullness, prospective consumption, desire to eat,
satisfaction, nausea and thirst. The second VAS measured
pleasantness, palatability, tastiness, saltiness and sweetness and
was given after breakfast and lunch. The product/placebo was
administered 15 minutes before breakfast and lunch which were four
hours apart. Participants were randomized to the study by means of
a block plan created on an internet-based randomization
program.
[0038] Participants. Fifty-eight healthy, average and slightly
overweight (body mass index [BMI]: 18.5-29.9 kg/m.sup.2) women
completed the study. Volunteers were recruited by advertisement.
Upon response to the advertisements, individuals completed a
standardized telephone or email interview to assess their age,
height, weight, occupation, smoking status and ability to attend
the study center at the requisite times. Those who were aged over
65, with a BMI<18.5 kg/m.sup.2 or >29.9 kg/m.sup.2, who
disliked more than 25% of the ad-libitum lunch study foods, were
smokers, currently dieting, or who did not eat regular meals, were
not studied further.
[0039] Initial Screening. Following the initial telephone/email
interview, potential participants received detailed information on
the protocol, and were invited to the study center, (The Kissileff
Laboratory for the Study of Ingestive Behaviour in the School of
Psychology, The University of Liverpool), for a full screening no
more than 21 days before commencing the study. All volunteers
signed an informed consent before any study-specific procedures
were undertaken. Confidentiality and anonymity were assured.
[0040] At screening, the following measurements were taken: height
measured without shoes, using a stadiometer to the nearest cm and
weight using standard calibrated scales to the nearest 0.1 kg.
Participants also completed a medical history, diet history, and
eating behaviour questionnaire (The Dutch Eating Behaviour
Questionnaire [DEBQ-R]).
[0041] Exclusion Criteria. Following screening, participants were
excluded from the study if they reported any of the following:
significant health problems; not having dieted in the last 12
months to lose or control weight; currently adhering to a specific
food avoidance diet; gastrointestinal symptoms requiring treatment;
bariatric surgery; systemic or local treatment likely to interfere
with evaluation of the study parameters; taking medication known to
affect appetite or weight within the past month and/or during the
study; pregnant or planning to become pregnant or breastfeeding;
history of anaphylaxis to food; general or specific food allergies,
including caffeine and any of the study foods; dislike of more than
25% of the ad-libitum study foods; extreme dietary restraint; non
breakfast eaters; working in nutrition, dietetics, food research,
food manufacturing or supplements industry.
[0042] Those participants who fulfilled the study criteria were
recruited to the study and assigned a code number.
[0043] Study Supplement. The ZOTRIM formulation contained 112 mg
Yerbe Mate, 95 mg Guarana and 36 mg Damiana. Guarana, a dough made
from the seeds of Paullinia cupana, which grows in Brazil and
Venezuela, contains 3-6% caffeine, 5-8.5% tannins, 7.8% resins,
2-3% lipid, 0.06% saponin, 5-6% starch and 1.5% coloring agents
(Schery (1954) Plants for Man. London: George Allen and Unwin, pp.
518-519). Yerbe mate is an extract of Ilex paraguayensis from
Brazil, Argentina and Paraguay containing 1-1.5% caffeine, 4-10%
tannins and 3% resins and lipids (Hill (1952) Economic Botany. New
York: McGraw-Hill Book Company, pp. 479-481.). Damiana is obtained
from the leaves of the plant Turnera diffusa var. aphrodisiaca from
California, Mexico, Brazil and Bolivia and contains ethereal oils,
resins and tannins (Bradley (1992) British Medical Compendium, Vol.
1. London: British Herbal Medical Association, pp. 71-72.).
[0044] The placebo contained lactose and other ingredients minus
the active ingredients. ZOTRIM and placebo were supplied as
individual tablets and packaged in coded containers labeled A or B
to ensure the double-blind status of the study. All capsule
components (active and inert ingredients) were those approved and
commonly used for commercial supplements and health ingredients and
produced by a commercial capsule manufacturer. The inulin fiber
(FIBRESURE) was derived from chicory root and packaged in powder
form in 5.8 g individual stick packs, containing 5 g fiber per
pack. Each dose of 5 grams of fiber was mixed into 100 grams of
water.
[0045] Participants were instructed to take the dose of 3 tablets
with a glass of water (100 g) 15 minutes before their two main
meals of each day. The order of treatments was counter-balanced
across the four treatment conditions, with inulin being mixed in or
not mixed into the water according to condition.
[0046] Materials and Tools. VAS were used to rate degree of hunger,
fullness, satisfaction, desire to eat, perception of how much
participants could eat (prospective consumption), thirst and
nausea. VAS was composed of 100 mm horizontal lines anchored by
"not at all" and "extremely" at opposite ends, upon which
participants record with a vertical line their subjective ratings.
For example, hunger was rated along a 100 mm line that was preceded
by the question "how hungry do you feel at this moment?" and
anchored on the left by "not at all hungry" and on the right by
"extremely hungry", or "how pleasant was the breakfast?" being
anchored on the left by "not at all pleasant" and on the right by
"extremely pleasant".
[0047] Participants completed these ratings nine times (T1-T9)
during each test day. The exact times were: pre dose pre breakfast
(T1), pre breakfast (T2), post breakfast (T3), Interval 1(T4),
Interval 2 (T5), Interval 3 (T6), pre dose pre lunch (T), pre lunch
(T8), and post lunch (T9) Pleasantness VAS were completed at two
time points, viz; post breakfast and post lunch.
[0048] Procedure. At the screening visit, participants were asked
if they had read and understood the information sheet concerning
the study (which they were sent a minimum of two days before the
screening visit). Participants were then asked to sign two copies
of the consent form. Participants' height and weight were measured.
BMIs were calculated ensuring they were in a suitable range for the
study. Participant's medical history and weight control history
were taken. A DEBQ and list of study foods were shown to the
participants to ensure that they did not have any objections or
intolerances to the study foods. Following the screening,
participants were contacted to determine whether or not they were
able to continue in the study. Successful participants then
received an information pack which contained details of their
agreed times to visit the lab. Participants were asked to fill in
an evening food and activity diary prior to attending the
visits.
[0049] Visit two took place at a minimum of two days after
screening. Subsequent visits took place as soon as possible leaving
two days between visits (giving a total of four visits). Breakfast
was served between 8:30 AM and 9:45 AM (time depending on when
researcher and participant had arranged to meet at lab). If
participants failed to attend their visit within these time limits,
their session was rescheduled for another day.
[0050] The protocol for the laboratory visits (four in total) was
as follows: On the day preceding each study day participants were
asked to keep their food intake, fluid intake and activity levels
similar and not to consume any alcohol. On each pre-study evening
participants were requested to record in a diary the food and drink
they consumed and the activities they undertook from 5:00 PM until
they retired for the night. They were asked not to eat or drink
anything except water from 12:00 midnight until they attended at
the study center the following morning.
[0051] At 8:30 AM on each study day participants attended the study
center. The diary was collected and participants were given
instructions on completing the VAS, before filling in the first set
of VAS ratings (T1). The pre-breakfast dose of product/placebo and
a glass containing 100 ml water were presented to the participant
15 minutes before breakfast. They were instructed to consume all of
the tablets with all of the water. They were weighed and details of
compliance were recorded. Participants were then seated in the
testing area in individual cubicles. After completing the
pre-breakfast VAS ratings (T2), participants were given a
fixed-load breakfast as shown in Table 1, and were asked to consume
everything presented within 20 minutes. After breakfast,
participants completed a post-breakfast set of VAS appetite (T3)
and pleasantness ratings, and were then free to leave the study
center. They were instructed not to eat or drink anything except
water that was provided by the study. They were asked to complete
VAS ratings at hourly intervals (T4, T5 and T6) and to return to
the study center three three hours and forty minutes after their
first dose was given to ensure their second dose would be given on
time. On their return, the VAS measures and remaining water (if
any) were collected for assessment and a pre-dose VAS (T7) was
completed. Fifteen minutes before lunch was to be served (four
hours after breakfast had been served) the study product/placebo
was presented with a glass containing 100 ml water and participants
were instructed to swallow all of the tablets with all of the
water.
TABLE-US-00001 TABLE 1 Amount Food* (g) % Kellogg's Cornflakes 30
Semi-skimmed UHT Milk 125 Orange Juice 200 Sliced White Bread 60 %
Energy from (toasted) Protein 10 Flora Margarine 10 % Energy from
Fat 17 Strawberry Jam 20 % Energy from Carbohydrate 73 TOTAL WEIGHT
445 TOTAL KCALS 496 *Also included hot drink, 35 g milk and sugar
if required.
[0052] A 15-minute rest period followed, during which the
participants remained in the study center. They then completed
another VAS (T8) and were served an ad-libitum lunch as detailed in
Table 2. Participants were instructed to eat as much as they liked
from the choice of foods and water offered, taking as long as they
wished, and signaling when they had finished. Immediately following
ad-libitum consumption of the test meal, participants completed a
set of post-lunch VAS ratings (T9).
[0053] Participants were then free to leave the study center. All
food and water was weighed (Sartorius Ltd) to the nearest 0.1 g
before and after each meal to determine intake. The length of each
meal was timed by the study staff although participants were only
instructed there was a time limit (of 20 minutes) at breakfast.
After completion of the study participants were debriefed and were
reimbursed for their time and travel expenses (if any).
[0054] Test Meals. A standard fixed-load breakfast (496 kcal) was
dispensed to participants in all conditions (Table 1). In addition
to the fixed-load breakfast, at the first visit, participants were
offered a hot drink of tea or coffee with additional milk (35 g)
and sugar if desired. If requested, this drink had to be consumed
on each subsequent visit. The amount and energy composition of the
ad-libitum cold test lunch items is listed in Table 2. The protein,
carbohydrate and fat content of each test lung item are
respectively listed in Tables 3-5. This meal was designed to offer
a selection of high and low fat savory and sweet food items. Water
(500 ml) was offered at the test meal. Participants were instructed
to eat as much as they wished and to signal via a booth-based
buzzer when they had finished.
TABLE-US-00002 TABLE 2 Amount Kcal in Food (g) Kcal/100 g Serving
Tesco Medium Sliced White 144.00 240.00 345.60 Bread Flora 40.00
531.00 212.40 Tesco Sandwich Turkey 62.50 110.00 68.75 Tesco Danish
Salami 44.60 495.00 220.77 Tesco Medium Grated Cheddar 100.00
415.00 415.00 Cucumber 80.00 10.00 8.00 Walkers Ready Salted Crisps
25.00 530.00 132.50 Quaker Snack-a-jacks S&V 30.00 410.00
123.00 Tesco Value Cookies 100.00 515.00 515.00 Tesco Chocolate
Mousse 62.50 200.00 125.00 Tesco Value Fruit Cocktail 410.00 46.00
188.60 Tesco Jelly Babies 120.00 368.00 441.60 Total 2796.22
TABLE-US-00003 TABLE 3 Protein in Food Protein/100 g Serving Tesco
Medium Sliced White Bread 8.20 11.81 Flora 0.00 0.00 Tesco Sandwich
Turkey 21.20 13.25 Tesco Danish Salami 13.20 5.89 Tesco Medium
Grated Cheddar 24.40 24.40 Cucumber 0.70 0.56 Walkers Ready Salted
Crisps 6.50 1.63 Quaker Snack-a-jacks S&V 6.50 1.95 Tesco Value
Cookies 4.80 4.80 Tesco Chocolate Mousse 3.50 2.19 Tesco Value
Fruit Cocktail 0.40 1.64 Tesco Jelly Babies 2.30 2.76 Total
70.87
TABLE-US-00004 TABLE 4 Carbohydrate/ Carbohydrate Food 100 g in
Serving Tesco Medium Sliced White 47.80 68.83 Bread Flora 0.00 0.00
Tesco Sandwich Turkey 0.80 0.50 Tesco Danish Salami 7.00 3.12 Tesco
Medium Grated Cheddar 1.40 1.40 Cucumber 1.50 1.20 Walkers Ready
Salted Crisps 49.00 12.25 Quaker Snack-a-jacks S&V 77.00 23.10
Tesco Value Cookies 65.00 65.00 Tesco Chocolate Mousse 26.80 16.75
Tesco Value Fruit Cocktail 11.00 45.10 Tesco Jelly Babies 89.80
107.76 Total 345.01
TABLE-US-00005 TABLE 5 Fat in Food Fat/100 g Serving Tesco Medium
Sliced White Bread 1.50 2.16 Flora 59.00 23.60 Tesco Sandwich
Turkey 2.30 1.44 Tesco Danish Salami 46.00 20.52 Tesco Medium
Grated Cheddar 34.40 34.40 Cucumber 0.10 0.08 Walkers Ready Salted
Crisps 34.00 8.50 Quaker Snack-a-jacks S&V 8.00 2.40 Tesco
Value Cookies 26.10 26.10 Tesco Chocolate Mousse 8.40 5.25 Tesco
Value Fruit Cocktail 0.00 0.00 Tesco Jelly Babies 0.00 0.00 Total
124.44
[0055] Lunch time was fixed at precisely 4 hours after breakfast.
All meals were served in individual booths in the test study
center.
[0056] Adverse Events. If participants reported any adverse events
they had experienced while taking the study supplement the type,
severity, date of onset and resolution were recorded.
[0057] Statistical Analysis. Analysis was performed using SPSS for
WINDOWS, Version 16 (SPSS Inc., Chicago, US). Analysis of variance
(ANOVA) and post-hoc paired t-tests were used. The assumptions of
the ANOVA model were tested and if homogeneity of variance was not
found, multivariate tests were adopted for that variable. All tests
were two-tailed unless stated. Bonferroni corrections were applied
for multiple comparisons.
[0058] Intake at the test meal was initially analyzed for amount
consumed (in grams and kcal) using a two-way ANOVA with condition
(inulin fiber and ZOTRIM) as within-subject factors. Because
breakfast was fixed, this was not included in the statistical
analysis. Paired t-tests were used to investigate any significant
differences. This analysis was then re-run incorporating the kcal
content of breakfast and the kcal content in the inulin fiber
conditions. A two-way ANOVA with inulin and ZOTRIM as within
subject factors was performed to analyze food choice at the test
meal. Kcal intake of high and low fat savory and high and low fat
sweet items were compared between conditions.
[0059] Subjective parameters (e.g., hunger, gastric fullness) rated
on the VAS were analyzed using a within-subjects repeated measures
ANOVA with condition (ZOTRIM and placebo) and time (pre-dose
pre-breakfast, pre-breakfast, post-breakfast, 10 AM, 11 AM, 12 PM,
pre-dose pre-lunch, pre-lunch, post-lunch, 2 PM, 3 PM, 4 PM, and 5
PM; T1-T13) as within-subject factors. If a time-by-condition
interaction effect was found significant, paired t-tests were
conducted at each rating time between conditions.
Example 2
Herbal Extracts and Inulin Decrease Food Intake
[0060] Fifty-eight healthy average to slightly overweight women
were recruited to the study through advertising. A double blind,
placebo-controlled, cross-over design was employed. After
screening, eligible participants were invited to the laboratory on
four separate occasions for breakfast and lunch. The study days
were arranged according to the participants' availability and
always leaving a minimum of two days between each visit. On study
days, the participants were administered the first dose of ZOTRIM
and inulin fiber (5.8 g), ZOTRIM and water, inulin fiber and
placebo or water and placebo, 15 minutes before a fixed load
breakfast. Four hours after the initial dose, and 15 minutes before
lunch, the second dose of the same condition was given. The dose
was composed of three tablets, either ZOTRIM or a placebo, and a
hundred grams of water into which inulin fiber was or was not mixed
according to condition. Participants were then offered an
ad-libitum buffet lunch and the intake of each item of lunch was
measured. Appetite was assessed using VAS.
[0061] In total 71 participants were screened, 62 were recruited
and 58 completed the study. Nine participants were excluded, six as
their BMI was >29.9, two due to medication they were taking and
one as her BMI was <18.5. Of the four that were recruited to the
study but did not complete it, three could not fit the visits
around previous commitments and one could not be contacted after
her first visit. Their data has been excluded from analysis.
[0062] The demographic (age), and anthropometric (weight, height,
BMI) characteristics of the completing participants are shown in
Table 6.
TABLE-US-00006 TABLE 6 Mean (.+-.SD, n = 58) Age (years) 21.31 .+-.
3.79 Weight (kg) 60.16 .+-. 6.09 Height (m) 166.24 .+-. 5.23 Body
Mass Index (BMI) [kg/m.sup.2] 21.78 .+-. 1.99 DEBQ 2.56 .+-.
1.92
[0063] Intake at Test Meal. Total mean number of grams (g) and
kilocalories (kcal) consumed in each condition are displayed in
Table 7.
TABLE-US-00007 TABLE 7 Mean Intake in Mean Intake in Number Grams
(g) Kilocalories (N) (.+-.SD) (kcal) (.+-.SD) Condition A 58 375.60
(.+-.138.46) 752.14 (.+-.296.27) (placebo) Condition B 58 328.96
(.+-.177.20) 619.94 (.+-.263.51) (ZOTRIM) Condition C 58 356.50
(.+-.144.38) 662.30 (.+-.311.69) (FIBRESURE) Condition D 58 284.20
(.+-.105.47) 549.78 (.+-.182.16) (ZOTRIM and FIBRESURE)
[0064] Gram Intake. A 2.times.2 repeated measures ANOVA
demonstrated a significant main effect of ZOTRIM on gram intake
(F(1, 57)=26.110, p<0.001). The ANOVA also demonstrated a
significant main effect of inulin fiber on gram intake across
conditions, (F(1, 57)=12.661, p=0.001). There was no interaction
between ZOTRIM and fiber conditions (F(1, 57)=1.841, p=0.180) on
gram intake.
[0065] Paired samples t-tests showed that there was a significant
reduction in gram intake from control of 46.6 grams (12.4%) in the
ZOTRIM condition (t(57)=3.254, p=0.002) and of 91.4 grams (24.3%)
in the ZOTRIM and fiber condition combined (t(57)=5.757,
p<0.001). The reduction in intake of 19.1 gram (5.1%) from
control in the inulin only condition compared to the control
condition proved insignificant (p=0.188). Intake was significantly
lower in the ZOTRIM and fiber combined condition versus the ZOTRIM
alone (t(57)=3.852, p<0.001) or fiber alone conditions
(t(57)=4.624, p<0.001).
[0066] Energy Intake. A 2.times.2 repeated measures ANOVA
demonstrated a significant main effect of ZOTRIM on caloric intake
(F(1, 57)=16.681, p<0.001). The ANOVA also demonstrated a
significant main effect of inulin fiber on caloric intake across
conditions, (F(1, 57)=13.366, p=0.001). There was no interaction
between ZOTRIM and fiber conditions (F(1, 57)=0.193, p=0.662).
[0067] Paired samples t-tests showed there was a significant
reduction in caloric intake from control of 132.2 kcal (17.6%) in
the ZOTRIM condition (t(57)=3.365, p=0.001), of 89.9 kcal (11.9%)
in the fiber condition (t(57)=2.621, p=0.011) and of 202.4 kcal
(26.9%) in the ZOTRIM and inulin fiber condition combined
(t(57)=5.629, p<0.001). Caloric intake was significantly lower
in the ZOTRIM and fiber combined condition versus the ZOTRIM alone
(t(57)=2.504, p=0.015) or fiber alone conditions (t(57)=3.178,
p=0.002).
[0068] Analysis of the time taken to consume the ad-libitum lunch
revealed a significant main effect of ZOTRIM (F (1,57)=4.196,
p=0.045). There was no effect of inulin fiber (F (1,57)=0.010,
p=0.921) and no interaction between ZOTRIM and inulin fiber (F
(1,57)=3.316, p=0.074). Paired samples t-test showed there was a
shorter lunch duration with ZOTRIM alone compared to placebo (t
(57)=2.903, p=0.005).
[0069] Food Choice. The twelve food items offered at the ad-libitum
lunch were analyzed according to variation in fat content and
taste. Foods offered were grouped into high fat savory (HFSV), low
fat savory (LFSV), high fat sweet (HFSW), low fat sweet (LFSW)
sets, as shown in Table 8.
TABLE-US-00008 TABLE 8 HFSV LFSV HFSW LFSW flora bread Cookies
Jelly Babies salami turkey Chocolate Mousse Fruit Cocktail cheese
snack a jacks crisps cucumber
[0070] A four way within-subjects ANOVA was performed with taste
(savory/sweet), fat (high/low), inulin fiber (present/not) and
ZOTRIM (present/not) as within-subjects factors. Significant main
effects of taste (F (1,57)=10.457, p=0.002), fat (F (1,57)=90.637,
p<0.001), inulin fiber (F (1,57)=9.775, p=0.003) and ZOTRIM (F
(1,57)=23.944, p<0.001) were found on intake, but there were no
significant interactions (see FIG. 1). Subsequent t-tests revealed
that overall, gram intake of savory items was significantly greater
than intake of sweet items (t (57)=3.234, p=0.002) and gram intake
of low fat items was significantly greater than intake of high fat
items (t (57)=9.520, p<0.001).
[0071] There was a significant reduction in HFSV intake with inulin
fiber and ZOTRIM combined compared to placebo (t (57)=4.315,
p<0.001) and compared to inulin fiber alone (t (57)=3.127,
p=0.003). For LFSV intake, there was a significant reduction with
ZOTRIM alone (t (57) 2.593, p=0.012) and with the ZOTRIM and inulin
fiber combination (t (57)=2.470, p=0.017) compared to placebo.
Intake of LFSV items was also significantly reduced following
ZOTRIM alone (t (57)=2.004, p=0.050) and ZOTRIM+inulin fiber
combined (t (57)=2.036, p=0.046) compared to inulin fiber
alone.
[0072] It was also found that gram intake of HFSW items was
significantly reduced with ZOTRIM alone (t (57)=2.207, p=0.031) and
with ZOTRIM+inulin fiber combined (t (57) 5.099, p<0.001)
compared to placebo. HFSW intake was also significantly lower with
ZOTRIM+inulin fiber combined versus with ZOTRIM alone (t
(57)=2.440, p=0.018) or inulin fiber alone (t (57)=3.146, p=0.003).
No significant effects of ZOTRIM or inulin fiber were found on gram
intake of LFSW items.
[0073] Total Daily Intake. Total daily intake, including calories
from the product, breakfast and lunch was analyzed using a
2.times.2 repeated measures ANOVA. This demonstrated a main effect
of ZOTRIM on kcal intake (F (1,57)=16.681, p<0.001). There was
no effect of inulin fiber (F (1,57)=1.880, p=0.176) and no
interaction between inulin fiber and ZOTRIM (F (1,57), =0.193,
p=0.662). Paired t-tests revealed that there was a significant
reduction in kcal intake with ZOTRIM alone (t (57)=3.365, p=0.001)
and with the inulin fiber and ZOTRIM combination (t (57) 4.238,
p<0.001) compared to placebo. It was also found that the kcal
intake after ZOTRIM alone (t (57)=2.417, p=0.019) and after the
combination of inulin fiber and ZOTRIM (t (57)=3.178, p=0.002) was
less than with inulin fiber alone.
[0074] Appetite. Subjective parameters (hunger, gastric fullness,
satisfaction, desire to eat, prospective consumption, thirst and
nausea) rated on VAS were analyzed using within-subject ANOVA for
repeated measures with condition and time as within-subjects
factors. Main effects of time were observed, as expected,
reflecting changes in appetite ratings during the study days.
Trends for main effects of hunger and desire to eat were observed
as well as a main effect for nausea.
[0075] Trend for a main effect of ZOTRIM on hunger ratings (F(1,
56)=2.865, p=0.096). T-tests were used to investigate where the
significant differences lay and showed that compared to the control
condition a significant reduction in ratings of hunger was found in
the ZOTRIM and inulin fiber combined condition at the pre lunch
time point, (t(57)=2.071, p=0.043), mean values: 61.02 mm versus
54.41 mm respectively). Furthermore, compared to the inulin fiber
only condition a significant reduction in ratings of hunger was
found in the ZOTRIM and inulin fiber combined condition at the post
lunch time point, (t(57)=2.770, p=0.008, mean values: 7.73 mm and
4.71 mm respectively).
[0076] Trend for an interaction between fiber and time on desire to
eat (F(8, 456)=1.870, p=0.063). T-tests were used to investigate
where the significant differences lay and showed that, compared to
the control condition, a significant reduction in ratings of desire
to eat was found in the ZOTRIM and inulin fiber combined condition
at the pre dose lunch time point, (t(57)=2.302, p=0.025, mean
values=: 58.84 mm versus 51.29 mm respectively). Furthermore,
compared to the control condition a significant reduction in
ratings of desire to eat was found in the inulin fiber only
condition at the pre lunch time point, (t(57)=2.011, p=0.049, mean
values: 61.19 mm versus 55.26 mm respectively). Moreover, compared
to the control condition a significant reduction in ratings of
desire to eat was found in the ZOTRIM and inulin fiber combined
condition at the pre lunch time point, (t(57)=2.230, p=0.030, mean
values: 61.19 mm versus 53.86 mm respectively).
[0077] Significant main effect of fiber on nausea (F(1, 55)=6.203,
p=0.016). T-tests were used to investigate where the significant
differences lay and showed that compared to the control condition a
significant reduction in ratings of nausea was found in the inulin
fiber only condition 2 hours after breakfast time point,
(t(57)=2.390, p=0.020, mean values: 9.50 mm versus 5.69 mm
respectively). Furthermore, compared to the ZOTRIM only condition
there was a significant reduction in nausea in the inulin fiber
only condition at the 2 hours after breakfast time point,
(t(57)=2.584, p=0.012, mean values: 10.03 mm versus 5.69 mm
respectively). Furthermore, compared to the ZOTRIM and inulin
combined condition there was a significant reduction in the inulin
fiber only condition in ratings of nausea at the 2 hours after
breakfast time point, (t(57)=2.053, p=0.045, mean values: 7.60 mm
versus 5.69 mm respectively). Moreover, compared to the ZOTRIM only
condition there was a significant reduction in ratings of nausea in
the inulin fiber only condition at the pre dose lunch time point,
(t(57)=2.040, p=0.046, mean values: 8.88 mm versus 5.97 mm
respectively). In addition, compared to the ZOTRIM only condition
there was a significant reduction in ratings of nausea in ZOTRIM
and inulin fiber combined at the pre dose lunch time point,
(t(57)=2.407, p=0.019, mean values: 8.88 mm versus 6.00 mm
respectively).
Example 3
Animal Model for Food Intake
[0078] Studies are conducted with male Sprague-Dawley rats weighing
270-290 grams. Three days before the start of an experiment, the
animals are weighed and individually housed. Normal rat chow
pellets and tap water are present ad libitum and are provided by
food troughs and drinking spouts, which allow continuous recording
of the food consumed. Compositions containing plant extracts+inulin
are administered at predetermined times to the treatment group.
Food intake is recorded by continuously weighing the amount of food
remaining in a round stainless steel food basket. Food intake is
continuously or intermittently recorded over the entire time of an
experiment. The weight of each animal is determined on each day of
the experiment and recorded, together with any unusual
observations, e.g., stressed animals, difficulties with plant
extract application, etc. Statistical analysis to detect
differences in ingestive behaviour between the control group and
the treatment group is performed.
* * * * *