U.S. patent application number 10/911181 was filed with the patent office on 2005-01-13 for compositions incorporating (-)-hydroxycitric acid, chromium, and gymnemic acid, and related methods for promoting healthy body weight and improving related health factors.
This patent application is currently assigned to InterHealth Nutraceuticals Incorporated. Invention is credited to Bagchi, Debasis, Preuss, Harry G..
Application Number | 20050008726 10/911181 |
Document ID | / |
Family ID | 23346261 |
Filed Date | 2005-01-13 |
United States Patent
Application |
20050008726 |
Kind Code |
A1 |
Bagchi, Debasis ; et
al. |
January 13, 2005 |
Compositions incorporating (-)-hydroxycitric acid, chromium, and
gymnemic acid, and related methods for promoting healthy body
weight and improving related health factors
Abstract
Methods for promoting healthy body weight and improving a
variety of related physiological factors, including serum serotonin
levels, serum leptin levels, fat oxidation, cholesterol levels, and
body mass index, in persons or other mammals, include administering
to those persons or other mammals effective amounts of
hydroxycitric acid or a combination of hydroxycitric acid, chromium
and gymnemic acid, which work synergistically to further to promote
healthy body weight and improve these physiological factors.
Inventors: |
Bagchi, Debasis; (Concord,
CA) ; Preuss, Harry G.; (Fairfax Station,
VA) |
Correspondence
Address: |
SHEPPARD, MULLIN, RICHTER & HAMPTON LLP
333 SOUTH HOPE STREET
48TH FLOOR
LOS ANGELES
CA
90071-1448
US
|
Assignee: |
InterHealth Nutraceuticals
Incorporated
Benicia
CA
|
Family ID: |
23346261 |
Appl. No.: |
10/911181 |
Filed: |
August 3, 2004 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10911181 |
Aug 3, 2004 |
|
|
|
10325675 |
Dec 20, 2002 |
|
|
|
60343473 |
Dec 20, 2001 |
|
|
|
Current U.S.
Class: |
424/777 ;
514/184; 514/574 |
Current CPC
Class: |
A61K 31/555 20130101;
A61K 33/24 20130101; A23V 2002/00 20130101; A61K 36/27 20130101;
A61P 3/04 20180101; A23L 33/105 20160801; A61P 3/06 20180101; A61K
31/19 20130101; A23L 33/165 20160801; A61K 31/704 20130101; A61K
31/194 20130101; A61K 36/38 20130101; A61K 31/19 20130101; A61K
2300/00 20130101; A61K 31/194 20130101; A61K 2300/00 20130101; A61K
31/555 20130101; A61K 2300/00 20130101; A61K 31/704 20130101; A61K
2300/00 20130101; A61K 36/27 20130101; A61K 2300/00 20130101; A61K
36/38 20130101; A61K 2300/00 20130101; A23V 2002/00 20130101; A23V
2250/21 20130101; A23V 2250/1586 20130101; A61K 33/24 20130101;
A61K 2300/00 20130101 |
Class at
Publication: |
424/777 ;
514/184; 514/574 |
International
Class: |
A61K 031/555; A61K
031/19; A61K 035/78 |
Claims
1-54. (Canceled)
55. A method for reducing excess, or maintaining healthy, body
weight in a person or other mammal comprising: identifying a person
or other mammal suffering, or at risk for suffering, from excess
body weight; and administering to the person or other mammal a
composition comprising hydroxycitric acid, chromium and gymnemic
acid in an amount sufficient to reduce excess, or maintain healthy,
body weight in the person or other mammal.
56. A method as defined in claim 55, wherein the composition
comprises hydroxycitric acid bound to calcium and potassium.
57. A method as defined in claim 55, wherein the hydroxycitric acid
is derived from a plant of the genus Garcinia.
58. A method as defined in claim 57, wherein the plant is Garcinia
cambogia.
59. A method as defined in claim 55, wherein the composition
comprises niacin-bound chromium.
60. A method as defined in claim 59, wherein the composition
comprises oxygen-coordinated niacin-bound chromium.
61. A method as defined in claim 55, wherein the gymnemic acid is
derived from a plant of the genus Gymnema.
62. A method as defined in claim 61, wherein the plant is Gymnema
sylvestre.
63. A method as defined in claim 55, wherein the step of
administering comprises administering approximately 100 milligrams
to approximately 5,000 milligrams of hydroxycitric acid,
approximately 10 micrograms to approximately 1,000 micrograms of
chromium, and approximately 10 milligrams to approximately 1,000
milligrams of gymnemic acid daily.
64. A method as defined in claim 63, wherein the step of
administering comprises administering approximately 2,700
milligrams to approximately 2,800 milligrams of hydroxycitric acid,
approximately 400 micrograms of chromium, and approximately 100
milligrams of gymnemic acid daily.
65. A method as defined in claim 55, wherein the step of
administering comprises administering the composition daily in
three substantially equally divided doses, approximately 30 to 60
minutes before meals.
66. A method as defined is claim 55, wherein the step of
administering comprises administering the composition orally.
67. A method for reducing excess, or maintaining healthy, body mass
index in a person or other mammal comprising: identifying a person
or other mammal suffering, or at risk for suffering, from excess
body weight; and administering to the person or other mammal a
composition comprising hydroxycitric acid, chromium and gymnemic
acid in an amount sufficient to reduce excess or maintain healthy
body mass index in the person or other mammal.
68. A method as defined in claim 67, wherein the composition
comprises hydroxycitric acid bound to calcium and potassium.
69. A method as defined in claim 67, wherein the hydroxycitric acid
is derived from a plant of the genus Garcinia.
70. A method as defined in claim 69, wherein the plant is Garcinia
cambogia.
71. A method as defined in claim 67 wherein the composition
comprises niacin-bound chromium.
72. A method as defined in claim 71 wherein the composition
comprises oxygen-coordinated niacin-bound chromium.
73. A method as defined in claim 67 wherein the gymnemic acid is
derived from a plant of the genus Gymnema.
74. A method as defined in claim 73, wherein the plant is Gymnema
sylvestre.
75. A method as defined in claim 67, wherein the step of
administering comprises administering approximately 100 milligrams
to approximately 5,000 milligrams of hydroxycitric acid,
approximately 10 micrograms to approximately 1,000 micrograms of
chromium, and approximately 10 milligrams to approximately 1,000
milligrams of gymnemic acid daily.
76. A method as defined in claim 75, wherein the step of
administering comprises administering approximately 2,700
milligrams to approximately 2,800 milligrams of hydroxycitric acid,
approximately 400 micrograms of chromium, and approximately 100
milligrams of gymnemic acid daily.
77. A method as defined in claim 67, wherein the step of
administering comprises administering the composition daily in
three substantially equally divided doses, approximately 30 to 60
minutes before meals.
78. A method as defined is claim 67, wherein the step of
administering comprises administering the composition orally.
79-102. (Cancelled)
Description
[0001] This application claims the benefit of U.S. Provisional
Patent Application Ser. No. 60/343,473, filed Dec. 20, 2001.
[0002] The present invention relates generally to compositions and
related methods for promoting healthy body weight, including
reducing excess body weight or maintaining healthy body weight, and
improving related health factors, such as cholesterol levels and
body mass index, in persons and other mammals.
[0003] Excess body weight is becoming more prevalent worldwide at
an alarming rate, both in developing and developed countries.
Approximately 61 percent of adults in the U.S. are overweight
(i.e., having a body mass index (BMI) of greater than 25
kg/m.sup.2), while more than 26 percent of U.S. adults are obese
(i.e., having a BMI of greater than 30 kg/m.sup.2). Obesity is the
second leading cause of premature death in the U.S. Approximately
300,000 Americans die each year from complications caused by
obesity. According to the World Health Organization, there are over
300 million obese adults worldwide. Environmental and behavioral
changes brought about by economic development, modernization and
urbanization have been linked to the global rise in obesity in
adults and children, the true health consequences of which may not
be fully known for years to come. Consumption of western-style
diets, low levels of physical activity and sedentary lifestyles
generally have been implicated in the worldwide trend of weight
gain.
[0004] Increase in body weight results from an imbalance between
energy intake and expenditure in a person, manifested by excessive
expansion of adipose tissue mass in the person. Obesity leads to a
number of poor health factors. In particular, obesity increases the
risk of high blood pressure, hypertension, type II diabetes,
arthritis, elevated cholesterol, and cancer. Although 30-40% of
obese people claim they are trying to lose or maintain body weight,
their success rate is low. Dietary approaches for the management of
excess body weight have been unsuccessful due to improper caloric
restriction and/or lack of physical exercise. Low calorie diets can
provide for temporary weight loss, but they have not proven
themselves as long-term solutions for people trying to lose or
maintain weight. Drugs that suppress appetite, reduce food intake,
increase energy expenditure and/or affect nutrient partitioning or
metabolism have potential efficacy in reducing body weight.
Unfortunately, these also frequently are accompanied by adverse
side effects, some of which are life threatening.
[0005] High blood cholesterol, high blood triglyceride levels, and
obesity all are indicators of increased risk for heart disease and
other health maladies. In particular, high levels of total
cholesterol, LDL cholesterol or triglycerides, as well as low
levels of HDL cholesterol, all are risk factors for various
cardiovascular diseases. These conditions are exacerbated by many
factors, including poor diet, lack of exercise and obesity.
Prevalence for obesity can be reflected in excessive eating and
also by genetic factors. One method for reducing appetite, and
therefore excessive eating, is by raising serotonin levels in a
person. Increased brain levels of serotonin, an important
neurotransmitter involved in proper brain function, including
regulation of sleep and mood, have also been linked with appetite
suppression. Also, a known biomarker for genetic propensity of a
person toward obesity is serum leptin, a hormone encoded by the
gene that regulates body weight. Leptin binds to receptors in the
brain, where it activates signals that inhibit food intake and
increase energy expenditure. Studies have shown that plasma leptin
levels are higher in overweight than in non-overweight individuals,
and higher in women than in men.
[0006] The methods described above to treat obesity in humans may
be applicable to treating other mammals as well, including animals
commonly kept as pets, such as dogs and cats. Excess body weight
has reached epidemic proportions in, and is the most common
nutritional disorder among, pets. It is estimated that 50% of pets
(or roughly 60 million animals) in the United States are overweight
or obese (a weight ten percent over ideal body weight is considered
overweight, and a weight twenty percent over ideal body weight is
clinically defined as obese). An extra five pounds on a dog that
should weigh 17 pounds or an extra three pounds on a cat that
should weight 10 pounds is comparable to an extra 50 pounds on a
person who should weigh 170 pounds. Overweight pets are at higher
risk of developing health problems such as heart disease, skeletal
problems, breathing problems, diabetes and arthritis.
Traditionally, weight management in veterinary medicine relies on
one or more recommendations. A veterinarian may prescribe high
fiber/reduced calorie diets, or advocate other dietary changes
focusing on a decrease in overall caloric intake. Another method to
manage pet weight is to increase exercise. Untreated obesity can be
a devastating condition for a pet, and instituting an
obesity-management program will add quality years to a pet's
life.
[0007] Various methods exist for treating obesity and the other
related health factors discussed above, such as improved diet,
increased exercise, and various medications. These, however, have
not been entirely effective treatments. Diet modification and
increased exercise can be difficult for some individuals to
maintain for an extended period, and medications introduce the
possibility of negative side effects.
[0008] One dietary supplement known for promoting weight loss is
(-)-hydroxycitric acid (HCA). HCA is an organic acid similar to
citric acid that is found in citrus fruits, such as oranges and
lemons, but that has remarkably different properties from citric
acid. HCA has been shown to reduce appetite, inhibit fat synthesis,
and decrease body weight in persons consuming it, without
stimulating the central nervous system of those persons. Therefore,
ingestion of HCA will not cause nervousness, rapid heart rate, high
blood pressure, or insomnia associated with dietary stimulants such
as ephedra (Ma-Huang), caffeine or phenylpropanolamine.
Furthermore, in acute toxicity tests, HCA has been show to be even
safer than citric acid. HCA predominantly is present in the fruit
rind of plants in the genus Garcinia, such as Garcinia cambogia (of
the family Guttiferae), a tree native to South and Southeast Asia.
The dried fruit rind, also known as Malabar Tamarind, is
extensively used in Southern India for culinary purposes. The fruit
exhibits a distinctive sour taste and has been used for centuries
to make meals more "filling."
[0009] HCA has been sold as a dietary supplement since 1994, but
research on HCA and its effects stretches back over 30 years. In
1969, researchers demonstrated that HCA is a competitive inhibitor
of A TP-citrate lyase, the enzyme responsible for catalyzing the
extramitochondrial cleavage of citrate to oxaloacetate and
acetyl-CoA, a building block of fatty acid synthesis. A TP-citrate
lyase is important in maintaining the acetyl-CoA pool for fatty
acid and cholesterol biosynthesis, particularly during the
hyperlipogenic nutritional state produced by high carbohydrate
feeding. HCA has been shown to be a highly effective inhibitor of
fatty acid synthesis by rat liver in vivo. HCA is theorized to
reduce food consumption in humans by diverting carbohydrates away
from fat synthesis and towards the synthesis of stored energy in
the form of glycogen. Increased glycogen levels in the liver and
muscles are believed to send a satiety signal to the brain that the
body is "full," resulting in reduced appetite and food intake.
[0010] Another possible mechanism of action may be HCA's ability to
stimulate serotonin release and inhibit its reuptake in the body.
Serotonin (5-HT), a vital neurotransmitter, is involved in a wide
range of behavioral functions in the body, including mood, sleep
and appetite control. Studies have shown that serotonin affects
eating behavior and body weight. Increased plasma levels of
serotonin are associated with decreased food intake, reduced weight
gain and increased energy expenditure. Another benefit of
increasing serotonin levels in the body may be in addressing many
of the emotional issues overweight people face, including binge
eating and depression. It is well established that serotonin and
peptides such as neuropeptide Y are involved in the regulation of
eating behavior. It is not certain that HCA's ability to curb
appetite and reduce food intake derives from these mechanisms.
However, as stated above, HCA produces its effects without
stimulating the central nervous system, avoiding the related
disadvantages of this.
[0011] Another possible mechanism of action may be HCA's ability to
down-regulate the obesity regulatory gene as determined by serum
leptin levels. Leptin is a 167 amino acid protein hormone encoded
by the gene that regulates body weight. Synthesized and secreted by
adipocytes (fat cells), leptin binds to receptors in the brain,
where it activates signals that inhibit food intake and increase
energy expenditure. When receptor-binding activity is diminished, a
condition called "leptin resistance," plasma leptin levels increase
and the leptin loses its ability to inhibit food intake and
increase energy expenditure. As stated previously, studies show
that plasma leptin levels are higher in overweight than in
non-overweight individuals, and higher in women than in men. Leptin
is synthesized and secreted by adipocytes, is present in the
bloodstream in amounts related to the amount of fat in the body,
and acts primarily on the brain to regulate food intake. Leptin has
been shown to be able to modulate insulin secretion and action
through these receptors. These findings confirm earlier
observations of higher leptin levels in obese individuals than in
lean individuals.
[0012] Another possible mechanism of action may be HCA's ability to
increase fat oxidation. Fat metabolites are products of fat
degradation. Following exercise or other fat "burning" processes,
fat tissue breaks down into small molecular components, including
malondialdehyde, formaldehyde, acetaldehyde and acetone. Increased
urinary levels of fat metabolites indicates increased fat
degradation or "burning." While the majority of studies on HCA have
focused on its mechanism of action at the metabolic level, until
recently, no studies have investigated its effect on
neurotransmitters associated with the control of appetite, hormones
associated with the regulation of body weight, nor fat oxidation.
Recent studies on the effect of HCA on serum serotonin levels,
serum leptin levels, and fat oxidation, are discussed below.
[0013] The potential of HCA as an inhibitor of lipogenesis has been
examined, and it was demonstrated that HCA curbs appetite, reduces
food intake and inhibits fat synthesis. Oral administration of HCA
has been shown to significantly depress in vivo lipogenic rates in
a dose-dependent manner in the liver, adipose tissue and small
intestine. This hepatic inhibition has been shown to be significant
for the 8-hour period when control animals demonstrated elevated
rates of lipid synthesis. The kinetics of in vivo hepatic
lipogenesis reduction were identical after acute or chronic
administration of HCA. However, in relevant studies rates of
lipogenesis were depressed after chronic administration of HCA for
30 days, thus HCA may help prevent "fat rebound," a common
occurrence where most diets fail, resulting in fat regain once the
diet is discontinued. Rats receiving HCA consumed less food than
the untreated controls, but this decreased caloric intake was not
responsible for the drug-induced depression of hepatic lipogenesis,
as shown by studies using pair fed rats. In these studies, an acute
oral dose of HCA (2.63 mmoles/kg equivalent to roughly 594 mg/kg
body weight) given prior to a standardized synthetic meal caused a
significant decrease in liver lipogenesis (roughly 70%) for up to 8
hours after the meal. The production of lipids declined not only in
the liver, but in the other tissues in which fats are formed from
carbohydrates (i.e., small intestine and adipose tissues).
[0014] In one experiment, rats were given various amounts of HCA
over a thirty day period (in amounts of 2.63, 1.32, 0.66 or 0.17
mmoles/kg/day) once daily, or 0.33 moles/kg twice daily, to
demonstrate the effect on body weight gain in growing rats. A
dose-related reduction in weight gain was observed in the rats
treated with HCA. The decreases were significant at concentrations
of 2.63 mmoles/kg once daily or 0.33 mmoles/kg twice daily. Thus,
one-fourth the amount of HCA was required to reduce weight gain
when administered in two divided doses as compared to a single
dose. However, no significant reductions were observed with the
single daily administration of 0.17, 0.66 and 1.32 nmoles/kg. This
suggests that HCA is rapidly metabolized in the body and that
divided doses are more effective than a single dose at inhibiting
lipogenesis. Recent studies also have shown that HCA-induced
increases in energy expenditure may account, at least in part, for
the observed inhibitory effect of HCA on body weight gain in
rats.
[0015] A particularly preferred HCA composition, marketed under the
name Super CitriMax.RTM. (and also designated HCA-SX) by
InterHealth Nutraceuticals of Benicia, Calif., incorporates a
unique form of HCA bound to the minerals calcium and potassium.
HCA-SX is described and claimed in published Patent Cooperation
Treaty Application WO 99/03464, herein incorporated by reference.
This HCA-SX composition contains approximately 60% by weight of
HCA, 11% by weight of calcium and 16% by weight of potassium, with
the remaining 13% consisting of water and other naturally occurring
constituents of the natural Garcinia fruit rind. This is in
contrast to other, more common forms of HCA, which are not bound to
potassium, but instead are bound only to calcium. As a result of
being bound also to potassium, HCA-SX is virtually completely
water-soluble, and it is more bioavailable than regular HCA
compositions incorporating only calcium. HCA-SX is also
significantly less hygroscopic than HCA compositions bound only to
potassium, contains 60% HCA--twenty percent more HCA than that
typically found in HCA compositions geared toward weight loss--and
contains less than one percent sodium, which is of particular
benefit to people who have high blood pressure or are on a
sodium-restricted diet. HCA-SX also is virtually tasteless,
odorless and, in solution, colorless, and does not have the
aftertaste associated with other HCA compositions, making it ideal
for use in functional foods and beverages.
[0016] As stated above, HCA-SX is highly bioavailable and easily
retained by obese subjects. Using a new rapid and accurate gas
chromatography/mass spectrometric method for measuring blood levels
of HCA, scientists recently found that blood levels of HCA-SX
increased for at least 2 hours and remained in the blood for more
than 4 hours after ingestion. Absorption rates varied among
subjects. In a separate experiment, the same investigators found
that absorption of HCA-SX peaked two hours after administration,
and that the compound remained in the blood for more than nine
hours after ingestion. Eating a full meal shortly after taking
HCA-SX reduced its absorption by about 60%. HCA-SX was detectable
in urine, and therefore its concentration could be used to
determine relative HCA absorption.
[0017] As discussed above, serotonin affects eating behavior and
body weight. Increased plasma levels of serotonin are associated
with decreased food intake, reduced weight gain and increased
energy expenditure. Researchers have shown that HCA-SX increases
the release and availability of serotonin from rat brain cortical
slices ex vivo, with optimal concentrations at 300 micromolar, as
compared to concentrations of 10, 30, 100 and 1,000 micromolar,
indicating an optimal effective dose of HCA-SX. Subsequently, human
clinical studies have, for the first time, shown that effective
doses of HCA-SX significantly increase serum serotonin levels.
Because serotonin has been implicated in the regulation of eating
behavior and body weight regulation, appetite suppression induced
by administration of HCA could be mediated by this serotonin.
[0018] As discussed above, leptin is a biomarker for the gene that
regulates body weight. Leptin is present in the bloodstream in
amounts related to the amount of fat in the body, and acts primarly
on the brain to regulate food intake and energy expenditure. Leptin
levels are higher in overweight than in non-overweight individuals.
Recently, human clinical studies have, for the first time, shown
that effective doses of HCA-SX significantly reduce serum leptin
levels and, thus, may down-regulate the genetic propensity of a
person toward obesity.
[0019] As discussed above, a possible mechanism of action may be
HCA's ability to increase fat oxidation. Enhanced oxidation of fat,
including adipose tissue and triglycerides, is the primary source
of the fat metabolites malondialdehyde, formaldehyde, acetaldehyde
and acetone. Recently, human clinical studies have shown that
effective doses of HCA-SX significantly increase fat oxidation as
determined by increases in urinary metabolites malondialdehyde,
formaldehyde, acetaldehyde and acetone, and thus may increase fat
degradation or "burning."
[0020] Another dietary supplement known for use in regulating
appetite and modifying body composition is chromium. Chromium is an
essential trace element required for normal protein, fat and
carbohydrate metabolism. Chromium levels are known to decrease with
age, and marginal chromium deficiencies appear to be widespread.
Chromium is important for energy production and plays a role in
regulating appetite, reducing sugar cravings and increasing lean
body mass. Chromium helps insulin metabolize fat, turn protein into
muscle and convert sugar into energy. Chromium has been shown to
reduce levels of harmful LDL cholesterol, a form of cholesterol
linked to heart disease, and increase levels of beneficial HDL
cholesterol. Dietary trends that show increased consumption of more
highly processed foods may lead to deficiencies of chromium in
persons.
[0021] Chromium potentiates the action of insulin in vitro and in
vivo. Maximal in vitro activity of chromium requires a special
chemical form termed Glucose Tolerance Factor (GTF). GTF is a
chromium-nicotinic acid (i.e., niacin) complex and is described in,
for example, U.S. Pat. Nos. 4,923,855, 4,954,492 and 5,194,615, all
to Jensen and herein incorporated by reference. Chromium extracted
from Brewers yeast, which is in the GTF form, is absorbed better
than inorganic chromium. GTF is transported across the placental
barrier, has different tissue distribution from that of inorganic
chromium, and has access to the body pool of chromium that responds
to increases in blood insulin. The biologically active form of
chromium (GTF) is an essential dietary agent that potentiates the
action of insulin and thereby functions in regulating protein, fat
and carbohydrate metabolism.
[0022] A particular form of GTF chromium, marketed under the name
ChromeMate.RTM. by InterHealth Nutraceuticals, is a unique form of
niacin-bound chromium (called chromium nicotinate or
polynicotinate) that dramatically increases the effectiveness of
chromium in the effects discussed above. Normally, chromium is
poorly absorbed and utilized by the body. However, researchers have
found that the most potent form of chromium in nature (i.e., the
form that best activates insulin) is bound to the B vitamin niacin.
In particular researchers have found that a patented
oxygen-coordinated chromium-niacin complex is the most potent form
of all, being over 18-times more potent than the next closest form
of niacin-bound chromium tested. This oxygen-coordinated complex is
characterized by chromium bound to an oxygen atom of the carboxylic
acid group attached to niacin's pyridine ring structure.
[0023] As discussed above, chromium has been shown to reduce LDL
cholesterol levels. In particular, administration of this
oxygen-coordinated niacin-bound chromium complex (also designated
O-NBC) in sufficient amounts has been shown to reduce LDL
cholesterol in humans by an average of 14%. Researchers also have
shown that O-NBC is significantly more bioavailable than chromium
picolinate and chromium chloride. Supplementation with O-NBC
therefore has been shown to ameliorate type II diabetes, reduce
hypertension, decrease fat mass, and increase lean body mass, as
well as help reduce body weight in persons consuming O-NBC.
Additionally, high doses of O-NBC have been shown to be completely
safe and non-toxic. In contrast, chromium picolinate has been shown
to damage DNA and be mutagenic.
[0024] Previous studies also have shown the effectiveness of O-NBC
in promoting weight loss. In a prior study, young obese women
consuming 400 micrograms of chromium as O-NBC per day, in
combination with exercise, experienced significant weight loss over
an eight-week study period. In contrast, no change in weight was
observed in subjects who exercised and consumed chromium in the
form of chromium picolinate or a placebo. Also, subjects who
consumed chromium picolinate and did not exercise experienced
significant weight gain during the study period. In another study,
overweight African-American women consuming 600 mcg of chromium
daily as O-NBC for 8 weeks had a significant loss of body fat and
sparing of muscle compared with a prior placebo period of the same
duration. Increased fat loss also was observed among women who were
randomized to consume O-NBC first, followed by placebo, suggesting
a carry-over effect of the supplementation on fat loss. No adverse
effects were observed from ingestion of O-NBC on the women in these
studies.
[0025] Other known dietary supplements include plants in the genus
Gymnema, such as Gymnema sylvestre, a traditional Ayurvedic herb
known to balance elevated blood sugar levels. The active
ingredients in Gymnema sylvestre, gymnemic acid and gurmarin, have
molecular structures similar to that to glucose and possess a
number of health benefits. Gurmarin has the ability to fill taste
bud receptors and reduce the sweet taste of sugary foods, thus
greatly reducing the craving for sweets. Gymnemic acid helps
increase the production of insulin by stimulating the production of
new insulin-producing cells, called beta-cells, in the pancreas.
Gymnemic acid also facilitates insulin release from the beta-cells
into the blood stream by increasing beta-cell membrane
permeability. Gymnemic acid also inhibits the absorption of sugar
molecules in the intestines during digestion, thus reducing
increases in blood sugar levels. Finally, consumption of Gymnema
sylvestre also has been shown to significantly lower cholesterol in
animal models.
[0026] Each of the materials described above are known to exhibit
weight control and/or other health promoting properties in persons
or other mammals consuming them. However, individually, none
provide all of the weight control and health promoting properties
described above. It is apparent from the above that a need exists
for improved methods and compositions for controlling body weight
and improving the health condition of persons or other mammals
prone to excess body weight, including improvement of body mass
index (an indicator of healthy body weight), serum leptin levels,
serum serotonin levels, and the cardiovascular risk factors total
cholesterol, LDL cholesterol, HDL cholesterol and triglycerides.
The present invention fulfills this need and provides further
related advantages.
SUMMARY OF THE INVENTION
[0027] The present invention resides in a composition comprising
hydroxycitric acid, chromium, and gymnemic acid. In preferred
aspects of the invention, the hydroxycitric acid is bound to
calcium and potassium. The hydroxycitric acid in the composition
preferably is derived from a plant of the genus Garcinia, most
preferably Garcinia Cambogia. The chromium in the composition
preferably is niacin-bound chromium, and more preferably
oxygen-coordinated niacin-bound chromium. The gymnemic acid in the
composition preferably is derived from a plant of the genus
Gymnema, most preferably Gymnema sylvestre. The composition may be
in the form of a pill, tablet, capsule, lozenge, gum, liquid,
powder, food, beverage or other orally administered form.
[0028] The present invention also resides in related methods for
increasing serotonin level, decreasing leptin level, or increasing
fat oxidation in a person or other mammal, incorporating
identifying a person or other mammal that can benefit from
increased serotonin level, decreased leptin level and/or increased
fat oxidation, and administering to the person or other mammal a
composition comprising hydroxycitric acid in an amount sufficient
to provide the required effect. Preferred aspects of the method
incorporate administration of hydroxycitric acid in forms as
described above. The method preferably incorporates administering
approximately 100 milligrams to approximately 5,000 milligrams of
hydroxycitric acid daily, and more preferably approximately 2,700
milligrams to approximately 2,800 milligrams. In the method, the
composition preferably is administered daily in three substantially
equally divided doses, approximately 30 to 60 minutes before meals,
preferably orally. In preferred aspects of the method, the
composition also incorporates chromium and gymnemic acid in forms
as described above. Preferably, the method incorporates
administering approximately 10 micrograms to approximately 1,000
micrograms of chromium and approximately 10 milligrams to
approximately 1,000 milligrams of gymnemic acid daily, and more
preferably approximately 400 micrograms of chromium and
approximately 100 milligrams of gymnemic acid daily.
[0029] The present invention also resides in related methods for
providing the following effects in a person or other mammal:
reducing excess, or maintaining healthy, body weight or body mass
index; decreasing appetite and reducing food intake; and/or
decreasing total cholesterol, LDL cholesterol and/or triglyceride
levels, and/or increasing RDL cholesterol levels. The methods
incorporate identifying a person or other mammal suffering, or at
risk for suffering, from excess body weight, excess body mass
index, elevated total cholesterol level, elevated LDL cholesterol
level, elevated triglyceride level and/or reduced HDL cholesterol
level; and administering to the person or other mammal a
composition incorporating hydroxycitric acid, chromium and gymnemic
acid in an amount sufficient to provide the required effect. The
hydroxycitric acid, chromium and gymnemic acid preferably are in
the forms described above. Preferably, the composition administered
incorporates approximately 100 milligrams to approximately 5,000
milligrams of hydroxycitric acid, approximately 10 micrograms to
approximately 1,000 micrograms of chromium, and approximately 10
milligrams to approximately 1,000 milligrams of gymnemic acid
daily, and more preferably approximately 2,700 milligrams to
approximately 2,800 milligrams of hydroxycitric acid, approximately
400 micrograms of chromium, and approximately 100 milligrams of
gymnemic acid daily. Preferably, the method incorporates
administering the composition daily in three substantially equally
divided doses, approximately 30 to 60 minutes before meals,
preferably orally.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0030] The present invention resides compositions incorporating
(-)-hydroxycitric acid (HCA), chromium and gymnemic acid. The
present invention also resides in methods for controlling body
weight and improving the above-discussed health factors of persons
or other mammals, including increasing serum serotonin levels,
reducing serum leptin levels, increasing fat oxidation, reducing
food intake, lowering body mass index (BMI), and improving
cardiovascular risk factors by decreasing elevated total and LDL
cholesterol, increasing HDL cholesterol and reducing elevated
triglyceride levels. The methods include identifying a person or
other mammal who is, or is at risk for being, overweight, or who
would benefit from the above-described physiological changes, and
administering to the person or other mammal a composition
comprising sufficient amounts to effect the changes. The present
invention also resides in a composition which, when administered to
a person or other mammal, provides for the above-described
psychological changes, the composition comprising a salt of HCA and
other selected components.
[0031] The HCA used in the compositions preferably is in a form
incorporating both calcium and potassium, to provide for superior
solubility, bioavailability, and commercial utility. In preferred
methods of the present invention, the composition administered also
incorporates: chromium, preferably from oxygen-coordinated
niacin-bound chromium, and Gymnema sylvestre extract, providing
gymnemic acid and gurmarin. Preferably, the method involves
administering a composition incorporating approximately 100 to
5,000 milligrams, and more preferably 2,700 to 2,800 milligrams, of
HCA daily to a person or other mammal who would benefit from the
physiological changes discussed above. The preferred composition to
be administered also can incorporate approximately 10 to 1,000
micrograms, and most preferably 400 micrograms, of elemental
chromium daily, preferably from oxygen-coordinated niacin-bound
chromium, and approximately 10 to 1,000 milligrams, and most
preferably 400 milligrams, Gymnema sylvestre extract providing
approximately 5 to 500 milligrams, and most preferably 100
milligrams, of gymnemic acid daily.
[0032] The methods of the present invention provide for the safe,
effective and convenient reduction of excess body weight and
resulting reduction in body mass index (BMI), or maintenance of
healthy body weight and healthy BMI, in persons or other mammals.
Besides these effects, administration of the compositions also
provides for reducing serum leptin levels, increasing serum
serotonin levels, reducing food intake, increasing fat oxidation,
decreasing elevated total and LDL cholesterol, increasing HDL
cholesterol, and reducing elevated triglyceride levels in persons
or other mammals that would benefit from such effects.
[0033] It has been surprisingly found that compositions
incorporating the components discussed above increase serum
serotonin levels, reduce serum leptin levels and increase fat
oxidation. It has also been surprisingly found that optimal
concentrations of HCA exist for maximizing serum serotonin levels,
a possible mechanism for decreasing appetite and reducing food
intake. Another surprising finding is that compositions
incorporating the components described above provide for superior
improvement in reducing excess body weight and improving the
related health factors described herein than was expected based on
the previously know properties of the components. Specifically, the
combination of HCA, chromium and gymnemic acid was shown to reduce
body weight, lower body mass index, increase serum serotonin
levels, reduce food intake, reduce serum leptin levels, increase
fat oxidation, decrease harmful total and LDL cholesterol, increase
beneficial HDL cholesterol and lower triglycerides significantly
greater than HCA alone.
[0034] Preferred administration of the composition is orally, in
three equally-divided doses roughly 30 to 60 minutes before meals
administered daily. The composition also can include inert
ingredients or diluents, such as sugar, maltodextrin, cellulose, or
other inert ingredients commonly used in food and beverage
products. The composition may be in various forms commonly used for
dietary supplements, including pill, tablet, capsule, lozenge, gum,
food, liquid, or powder. The composition also can be incorporated
into food or beverage products, including bars, shakes, gums,
beverages, or other processed or prepared food or beverage
products, or any other orally administerable form.
[0035] Use of the methods and compositions of the present invention
is illustrated in the Example below.
EXAMPLE
[0036] The effects of administering compositions within the scope
of the methods of the present invention were tested. A
double-blind, placebo-controlled human clinical trial was conducted
using a composition incorporating: the HCA-SX extract described
above (Super CitriMaxm, supplied by InterHealth Nutraceuticals of
Benicia, Calif.); and HCA-SX extract in combination with chromium
(ChromeMate.RTM., supplied by InterHealth), and Gymnema sylvestre
extract (also supplied by InterHealth).
[0037] 82 moderately obese human subjects completed the study. All
subjects were placed on a daily diet of 2,000 kcal. All food was
prepared and delivered to the subjects, and all food intake was
strictly supervised by trained dieticians. All subjects also
underwent a 30 minute walking exercise program, five times a week,
which was supervised by a trained exercise specialist. The subjects
were randomly divided into three groups. The subjects in the first
group were given a placebo. The subjects in the second group was
given a daily dose of 4,667 mg of Garcinia cambogia extract
(providing 2,800 mg HCA per day). The subjects in the third group
were given a daily dose of 4,667 mg of a combination of Garcinia
cambogia (2,800 mg HCA), 4 mg of niacin-bound chromium (providing
400 mcg of elemental chromium), and 400 mg of Gymnema sylvestre
extract (providing 100 mg gymnemic acid). The subjects received
their respective compositions in three equally-divided doses 30 to
60 minutes before breakfast, lunch and dinner for eight weeks.
These dosage levels of HCA were determined by extrapolation of
successful earlier animal trials, as well as review of optimal
micromolar concentrations of HCA in ex vivo brain tissue resulting
in maximum serotonin release. Changes in body weight, lipid profile
(triglycerides, LDL, HDL and total cholesterol), obesity gene level
(determined by serum leptin level), serum serotonin levels, body
mass index, fat metabolites (urinary malondialdehyde, formaldehyde,
acetaldehyde and acetone levels) and appetite control were assessed
in the persons. These changes were averaged to produce figures for
analysis.
[0038] Results
[0039] Results of the testing are shown in Table I below.
1TABLE 1 Results of Administration of Compositions HCA-SX +
chromium + Tested Factor Placebo HCA-SX gymnemic acid Body Weight
Pounds 3.5 10.0 12.8 % change 1.9 5.0 6.5 LDL Cholesterol mg/dl 3.0
-14.5 -22.6 % change 2.8 -13.0 -19.0 HDL Cholesterol mg/dl -0.7 2.7
6.2 % change -2.7 9.0 21.4 Total Cholesterol mg/dl 1.1 -12.4 -16.6
% change 1.0 -7.4 -9.7 Triglycerides mg/dl 0.3 -12.9 -22.6 % change
0.3 -10.0 -19.0 Serum Leptin Level ng/ml 0.4 -12.2 -15.4 % change
1.0 -40.0 -42.6 Serum Serotonin Level mg/dl 20.1 119.1 149.3 %
change 10.9 48.5 70.4 Body Mass Index kg/m.sup.2 -0.7 -2.4 -3.2 %
change -2.0 -7.0 -9.2 Excreted Fat Metabolites % change Acetone 3.5
36.2 42.8 Formaldehyde 8.8 68.1 52.7 Malonaldehyde 12.6 60.6 65.3
Acetaldehyde 18.1 64.4 73.0 Food Intake Reduction grams per day
(average) 0 257 386.2 % change 0 11.4 17.2
[0040] Discussion
[0041] The data from the study show that administration of the
specified levels of HCA extract results in: significant weight
loss; decreases in body mass index (an index of obesity health
risk); reductions in triglycerides, LDL and total cholesterol
(cardiovascular risk factors); increases in beneficial HDL
cholesterol; increases in excretion of fat metabolites (indicating
increased fat oxidation or "burning"); decreases in serum leptin
levels (a biomarker of the obesity gene); increases in serum
serotonin levels (a mechanism of appetite control and eating
behavior); and, reductions in food intake. Further, the composition
incorporating all three components (HCA-SX, chromium and gymnemic
acid) resulted in even greater improvement in all of the tested
factors than use of the composition incorporating HCA-SX alone.
[0042] A number of interesting findings are observed from the
results presented above. The constituents of the compositions
demonstrated multifaceted activities, which collectively resulted
in a number of health benefits. Also, none of the constituents
activated the central nervous system, demonstrating the relative
safety of the compositions over, for example, ephedra-containing
weight management formulas. HCA-SX exhibited its predominant effect
on the biochemical regulation of leptin, which is an integral key
component of obesity regulatory genes. Serotonin level also was
modulated by HCA-SX alone, but it was more effectively modulated by
the combination of HCA-SX, chromium, and gymnemic acid. The effect
of serotonin level modulation was reflected in the reduced appetite
in the study subjects.
[0043] An examination of the lipid profile data clearly shows that
HCA-SX alone lowers LDL and triglyceride levels and increases HDL
levels, however, the combination of HCA, chromium and gymnemic acid
exhibited even greater changes in these key components. Also, a
high correlation exists between increased fat oxidation and
enhanced excretion of urinary lipid metabolites with a dramatic
reduction in the triglyceride level. Glycerol is a product of the
metabolism of triglycerides by adipose tissue and other brown
tissues that possess a high glycerol kinase level. Glycerol kinase
can activate the breakdown of triglycerides to glycerol, leading to
enhanced formation of formaldehyde via microsomal metabolism. This
indicates that the compositions of the present invention can
provide for enhanced biochemical induction of glycerol kinase,
which can serve to enhance two important biochemical functions:
biochemical reduction of triglyceride levels, and fat
oxidation.
[0044] Although the invention has been disclosed in detail with
reference only to the preferred embodiments, those skilled in the
art will appreciate that additional methods and compositions can be
made without departing from the scope of the invention.
* * * * *