U.S. patent application number 12/576113 was filed with the patent office on 2010-04-22 for irvingia gabonensis to treat and prevent metabolic syndrome and reduce total cholesterol, ldl cholesterol, blood glucose, c-reactive protein, and leptin levels and increasing adiponectin levels.
This patent application is currently assigned to GATEWAY HEALTH ALLIANCES, INC.. Invention is credited to Julius E. Oben.
Application Number | 20100098793 12/576113 |
Document ID | / |
Family ID | 42107303 |
Filed Date | 2010-04-22 |
United States Patent
Application |
20100098793 |
Kind Code |
A1 |
Oben; Julius E. |
April 22, 2010 |
IRVINGIA GABONENSIS TO TREAT AND PREVENT METABOLIC SYNDROME AND
REDUCE TOTAL CHOLESTEROL, LDL CHOLESTEROL, BLOOD GLUCOSE,
C-REACTIVE PROTEIN, AND LEPTIN LEVELS AND INCREASING ADIPONECTIN
LEVELS
Abstract
In one embodiment, a method is provided for lowering C-reactive
protein levels in a mammal. The method comprises administering a
composition containing an effective amount of Irvingia gabonensis
seed to a mammal to reduce C-reactive protein levels in the mammal.
Other embodiments include, among other things, lowering leptin
levels, increasing adiponectin levels, reducing body weight,
decreasing LDL and total cholesterol levels, increasing fat loss,
and reducing waist size in a mammal using administering a
composition containing an effective amount of Irvingia
gabonensis.
Inventors: |
Oben; Julius E.; (Yaounde,
CM) |
Correspondence
Address: |
GREENBERG TRAURIG LLP (LA)
2450 COLORADO AVENUE, SUITE 400E, INTELLECTUAL PROPERTY DEPARTMENT
SANTA MONICA
CA
90404
US
|
Assignee: |
GATEWAY HEALTH ALLIANCES,
INC.
Fairfield
CA
|
Family ID: |
42107303 |
Appl. No.: |
12/576113 |
Filed: |
October 8, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61106508 |
Oct 17, 2008 |
|
|
|
Current U.S.
Class: |
424/776 |
Current CPC
Class: |
A61P 3/04 20180101; A61P
3/00 20180101; A61K 36/185 20130101 |
Class at
Publication: |
424/776 |
International
Class: |
A61K 36/00 20060101
A61K036/00; A61P 3/04 20060101 A61P003/04; A61P 3/00 20060101
A61P003/00 |
Claims
1. A method for lowering C-reactive protein levels in a mammal, the
method comprising: administering a composition containing an
effective amount of Irvingia gabonensis seed to a mammal to reduce
C-reactive protein levels in the mammal.
2. A method of claim 1, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 0.5 mg to 50 mg
daily.
3. A method of claim 1, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 1 mg to 10 mg
daily.
4. A method of claim 1, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 50 mg to 1000 mg
daily.
5. A method for lowering leptin levels in a mammal, the method
comprising: administering a composition containing an effective
amount of Irvingia gabonensis seed to a mammal to reduce leptin
levels in the mammal.
6. A method of claim 5, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 0.5 mg to 50 mg
daily.
7. A method of claim 5, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 1 mg to 10 mg
daily.
8. A method of claim 5, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 50 mg to 1000 mg
daily.
9. A method for increasing adiponectin levels in a mammal, the
method comprising: administering a composition containing an
effective amount of Irvingia gabonensis seed to a mammal to
increase adiponectin levels in the mammal.
10. A method of claim 9, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 0.5 mg to 50 mg
daily.
11. A method of claim 9, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 1 mg to 10 mg
daily.
12. A method of claim 9, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 50 mg to 1000 mg
daily.
13. A method for reducing body weight in a mammal, the method
comprising: administering a composition containing an effective
amount of a purified and isolated Irvingia gabonensis seed extract
to a mammal to reduce weight in the mammal.
14. A method of claim 13, wherein the effective amount of isolated
and purified Irvingia gabonensis seed extract administered is
approximately 0.5 mg to 50 mg daily.
15. A method of claim 13, wherein the effective amount of isolated
and purified Irvingia gabonensis seed extract administered is
approximately 1 mg to 10 mg daily.
16. A method of claim 13, wherein the effective amount of isolated
and purified Irvingia gabonensis seed extract administered is
approximately 50 mg to 1000 mg daily.
17. A method for decreasing LDL and total cholesterol levels in a
mammal, the method comprising: administering a composition
containing an effective amount of Irvingia gabonensis seed to a
mammal to decrease LDL and total levels in the mammal.
18. A method of claim 9, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 0.5 mg to 50 mg
daily.
19. A method of claim 9, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 1 mg to 10 mg
daily.
20. A method of claim 9, wherein the effective amount of Irvingia
gabonensis seed administered is approximately 50 mg to 1000 mg
daily.
21. A method for increasing fat loss in a mammal, the method
comprising: administering a composition containing an effective
amount of Irvingia gabonensis seed to a mammal to increase fat loss
in the mammal.
22. A method for reducing waist size in a mammal, the method
comprising: administering a composition containing an effective
amount of Irvingia gabonensis seed to a mammal reduce weight size
in the mammal.
Description
RELATED APPLICATION
[0001] This application claims the benefit of and priority to U.S.
Provisional Application Ser. No. 61/106,508, filed Oct. 17, 2008,
the contents of which are incorporated by reference herein in its
entirety.
BACKGROUND
[0002] Metabolic syndrome, like many other obesity-related
conditions, is on the rise in Cameroon and other parts of the
world. Experiments were performed to determine, among other things,
whether Irvingia gabonensis, an extract of the West African plant,
could be used as a treatment for metabolic syndrome, to reduce
total cholesterol, LDL cholesterol, blood glucose, C-reactive
protein, and leptin levels and increase adiponectin levels in a
mammal.
[0003] Methods: A ten-week, randomized, double-blind,
placebo-controlled study was performed involving 102 healthy,
overweight and obese participants (53% male, 47% female, ages
19-50; mean age=34). The subjects were randomly divided into two
equal groups--placebo and IGOB131 treatment, and all received one
150 mg capsule containing placebo or extract twice a day before
meals. A total of nine anthropomorphic and serological measurements
were taken at baseline and at four, eight, and ten weeks.
[0004] Results: Compared to the placebo group, the IGOB131 group
showed a statistically significant different on all nine variables
by week ten. These included the three anthropomorphic variables
(body weight, body fat, waist size) and the six measures of
serological levels (plasma total cholesterol, LDL cholesterol,
blood glucose, C-reactive protein, adiponectin, and leptin).
[0005] Conclusion: Serum leptin levels were lower in the IGOB131
group while their serum adiponectin level was higher. These
results, combined with those on the other seven variables, suggest
that the Irvingia gabonensis extract, IGOB131, may be used to
manage metabolic syndrome through control of obesity and lipid
profile.
SUMMARY
[0006] Obesity, once considered a major health problem in developed
countries, is now on the increase worldwide; e.g., in Cameroon, the
reported incidence of obesity in urban areas ranges from 17-21%
(Sobngwi et al., 2002; Pasquet et al., 2003). This high incidence
reflects the social, nutritional, and lifestyle changes involved in
rural-urban migration and the urbanisation of rural areas. As in
other countries, urbanisation in Cameroon has also led to an
increased incidence of other non-communicable diseases related to
obesity (Sobngwi et al., 2002). Obvious causes include the change
from a high-fiber to a high-fat diet and a reduction in physical
activity (Lee et Sobal, 2003; Cabellero, 2001; Galal, 2002).
Obesity, coupled with an unbalanced diet and still largely unknown
genetic factors, interact to produce a cluster of metabolic
cardiovascular risk factors, including type-2 diabetes mellitus,
essential hypertension, dyslipidemia, and ischemic heart
disease--known as the metabolic syndrome (Reaven, 1989).
[0007] Metabolic syndrome, like many other obesity-related
conditions, is on the rise in Cameroon (Mandob et al., 2008) and
other parts of the world (Ford and Butt, 2002; Movakovic and
Popovic, 2001). The National Cholesterol Education Program Adult
Treatment Panel III defined metabolic syndrome traits as the
conjoint presence of the following factors: blood pressure
elevation, low HDL cholesterol, high triglycerides, and
hyperglycemia (NCEP-ATP III, 2002). Adipose tissues are known to
store triglycerides and release free fatty acid/glycerol in
response to changing energy demands (Spiegelman and Flier, 1996).
The adipose tissue also regulates energy homeostasis by secreting
biologically active adipocytokines, such as adiponectin, adipsin,
leptin, plasminogen activator inhibitor-1, resistin, and tumor
necrosis factor (Mohamed-Ali et al., 1998).
[0008] Obesity and metabolic syndrome are also associated with
inflammation, as seen by an increase in C-reactive protein (CRP)
(Marjolein et al., 1999). People with a greater number of metabolic
syndrome components generally show higher CRP levels, thus
permitting CRP's use as an indicator of metabolic syndrome
severity.
[0009] Although caloric restriction and weight reduction are
beneficial in enhancing insulin action on peripheral tissues
(Goodpaster et al., 1999), Kelley et al., 1999) and preventing the
development of type 2 diabetes (Knowler et al., 2002), popular
weight loss tactics have not taken into consideration the complex
nature of this condition. In general (other than recommending
healthy lifestyle activities and calorie reduction), popular weight
loss products target a single mechanistic path (e.g., fat blocking,
appetite suppression, cortisol inhibition, central nervous system
stimulation, etc.). In contrast to this type of single-focus
approach, preliminary research has already illustrated the healthy
effects of Irvingia gabonensis extract (IGOB131) in overweight and
obese humans on a variety of physiological dimensions, including
weight, body composition factors, various blood lipid fractions,
antioxidant activity, inflammation, blood glucose, cardiovascular
health factors, and gene expression.
[0010] IGOB131 extract is obtained from a sweet fleshy fruit
(resembling a mango) borne by the West African culinary plant,
Irvingia gabonensis (Irvingiaceae). The plant's leaves and seeds
have traditionally been valued for the treatment of dysentery and
soup-thickening, respectively. The seeds, moreover, contain
naturally high levels of oils, albumin proteins, soluble fibers,
and antioxidants. Thus, the purpose of this randomized,
double-blind, placebo-controlled clinical study was to assess the
possibility of the multi-faceted IGOB131 extract as a tool in the
management of metabolic syndrome, among other things.
DETAILED DESCRIPTION
[0011] Methods
[0012] Participants: Participants (age 19-50) were recruited from
the global population of the city of Yaounde, Cameroon through
radio advertisements and posters. Inclusion criteria included: (1)
being a basically healthy person; (2) not having a current/recent
cold or flu; (3) having a BMI between 26 kg/m.sup.2 and 40
kg/m.sup.2; (4) not following any particular dietary regimen; (5)
not currently following a weight loss program (6) being a
non-smoker; (7) able to cope with multiple blood sampling; and (8)
willingness to sign the consent form.
[0013] Based on the above criteria, 102 persons were selected to
participate in an information session in which the nature, purpose,
and potential risks of the study were clearly explained. All
participants gave their written informed consent before the study
began. The protocol was approved by the Cameroon National Ethics
Committee; the study was conducted in accord with the Helsinki
Declaration (1983 version).
[0014] Study design/intervention: The study was a randomized,
double-blind, placebo-controlled design. The 102 West African
participants were randomly divided into two groups: placebo (n=50);
IGOB131 (n=52). The demographics for the two groups were very
similar.
[0015] Placebo group: males=27, females=23; mean age=34
[0016] IGOB group: males=27, females=25; mean age=34
[0017] Five subjects in the placebo group versus six subjects in
the treatment group had a family history of diabetes. One subject
in the placebo group versus three in the treatment group had a
history of gestational diabetes. Body weight, body fat percentage,
and waist size were also monitored at the same time. No major
dietary changes or physical exercises were suggested during the
course of the study.
[0018] Test materials: All test materials were supplied by Gateway
Health Alliances, Inc. (Fairfield, Calif., USA) in individual
packets of capsules. The identical-looking placebo and active
formulation capsules contained, respectively, a maize-based powder
consisting of 150 mg starch, or a maize-based powder containing 150
mg IGOB131.
[0019] Sample collection: The participants consumed either one
capsule of placebo or IGOB131 twice daily before meals. Fasting
blood samples (5 ml of blood) were collected at baseline, and at
four, eight, and ten weeks after product administration. Blood
collection was performed by means of venipuncture coupled to
vacutainer tubes. The serum was prepared after blood
centrifugation, split into 500 .mu.l aliquots and stored at -20
degrees C. until needed to assess changes in the biochemical
parameters; i.e., blood cholesterol, fasting blood glucose,
C-reactive protein, adiponectin, and serum leptin.
[0020] Anthropometric Measurements
[0021] Anthropometric measurements (body weight, percent body fat,
and waist circumference were assessed using a Tanita.TM. BC-418
Segmental Body Composition Analyzer/Scale that uses bio-electrical
impedance analysis for body composition analysis. Height was
measured with a standard tape measure affixed to a wall while the
subject stood on a level, hard surface. Hip and waist measures were
obtained with a flexible tape measure, without restrictive
garments, to the nearest 0.1 cm. Waist circumference was measured
mid-point between the bottom rib and hip bone, taking care to keep
the tape in contact with the curve of the back. Hip circumference
was obtained at the widest point of the hip. Participants were
measured at approximately the same time of day each visit to ensure
consistent results.
[0022] Analytical methods: Serum total cholesterol was assayed
using the cholesterol oxidase method, (Richmond, 1973) while
triglycerides were determined using the method described by Buccolo
and David (1973), serum glucose was measured enzymatically
(Trinder, 1969). Quantitative determinations of C-reactive protein
(CRP) were determined in duplicate using a high sensitivity
immunoassay (Oxis International, Foster City, Calif. USA). Serum
leptin was determined in duplicate using an enzyme-linked
immunosorbent assay (ELISA) (Diagnostic Systems Laboratory,
Webster, Tex. USA). All samples were run in the same assay with an
intra-assay variance of 3.2%. Serum adiponectin was determined in
duplicate using an enzyme immunoassay (APLCO Diagnostics, Salem,
N.H. USA). All samples for each hormone were determined in the same
assay to avoid inter-assay variance. Assay intra-assay variance was
.ltoreq.5%.
[0023] Statistical analysis: The data for each parameter was
summarized (n, mean, and standard deviation) for Week Zero
(Initial) and Weeks Four, Eight, and Ten, and for the intra-group
percent differences (Initial versus Weeks Four, Eight, and Ten).
Several measurements were made for each parameter. The percent
change from baseline was tested for differences using the Mixed
Effects Mode--a flexible tool for analyzing longitudinal and
repeated treatments. Statistical Package for the Social Sciences
(SPSS) software was used for all statistical analysis.
[0024] Results
[0025] Anthropomorphic Characteristics (Body Weight, Body Fat
Percentage, Waist Size)
[0026] The IGOB131 (versus placebo) group showed a significant
decrease in all three variables by week four, with the magnitude of
the differences continuing to increase throughout the trial period.
By week ten, the differences in measures of body weight, body fat
percentage, and waist size between the treatment and placebo groups
were all statistically significant at the p<0.01 level (Tables
1, 2, 3).
[0027] Body weight (Table 1): After four weeks of treatment, the
placebo group lost 0.6 kg compared to the IGOB131 group, which lost
3.6 kg (3.7%). To translate the difference in amounts lost to final
outcomes, the ten-week mean body weight of the placebo group was
95.7 kg versus 85.1 kg for the treatment group (p<0.01). In
terms of intra-group mean percent change in body weight from
baseline to ten weeks, the placebo and treatment groups lost 0.7%
and 13.1% (p<0.01), respectively.
[0028] Body fat percentage (Table 2): As was true of body weight,
the placebo group showed no significant change (1.4%) in %-body fat
after 4 weeks compared to the IGOB131 group, which lost 2.6%-body
fat (a 7.49% reduction). To translate the difference in amount lost
to final outcomes, the ten-week mean body fat percentage of the
placebo group was 32.7% versus 27.9% for the treatment group
(p<0.05). In terms of intra-group mean percent change from
baseline to ten weeks, the placebo and treatment groups lost 5.7%
and 18.4% (p<0.05), respectively.
[0029] Waist size (Table 3): Waist circumference appears to be one
of the most important determinants in the diagnosis of metabolic
syndrome and obesity. Although the placebo group showed a 3.7 cm
decrease after four weeks, the IGOB131 group lost 7.1 cm. By week
ten, the 5.3 cm reduction in waist size for the placebo group was
less than one-third the 17.0 cm reduction shown by the treatment
group (p<0.01). In terms of intra-group mean percent change in
waist size from baseline to ten weeks, the placebo and treatment
groups lost 5.0% and 16.2% (p<0.01).
[0030] Serological Characteristics--I (Total Cholesterol, LDL
Cholesterol, Fasting Blood Glucose)
[0031] As shown in Tables 4, 5, and 6, the IGOB131 treatment
(versus placebo) group showed a large decrease in these three
variables by week four. As with the three anthropomorphic variables
(see above), the magnitude of the losses continued to increase
throughout the entire ten-week trial period.
[0032] Plasma total cholesterol level (Table 4): In contrast to the
small (1.34 mg/dL) decrease shown by the placebo group, by week
four the reduction for the IGOB131 group was 18.0 mg/dL (11.9%). To
translate the difference in the amounts of decrease to final
outcomes, the ten-week mean total cholesterol level of the placebo
group was 142.5 mg/dL versus 111.9 mg/dL for the treatment group
(p<0.05). In terms of intra-group mean percent change from
baseline to ten weeks, the decreases made by the placebo and
treatment groups were 1.9% versus 26.2% (p<0.05).
[0033] Plasma LDL cholesterol level (Table 5): Again, in contrast
to the small (0.96 mg/dL) decrease in LDL shown by the placebo
group, by week four the reduction for the IGOB131 group was 10.4
mg/dL (12.6.0%). To translate the difference in the amounts
decreased to final outcomes, the ten-week mean LDL cholesterol
level of the placebo group was 4.8 mg/dL versus 27.30 mg/dL for the
treatment group (p<0.05). In terms of intra-group mean percent
change from baseline to ten weeks, the decreases made by the
placebo and treatment groups were 4.8% versus 27.30%
(p<0.01).
[0034] Fasting blood glucose levels (Table 6): As with the measures
of cholesterol levels (above), the small (1.9 mg/dL) decrease in
blood glucose level shown by the placebo group by week four can be
contrasted with the large 8.91 mg/dL decrease (10.4%) shown by the
IGOB131 group. To translate the difference in amounts decreased to
final outcomes, the ten-week mean blood glucose level of the
placebo group was 77.1 mg/dL versus 66.3 mg/dL for the treatment
group (p<0.05). In terms of intra-group mean percent change from
baseline to ten weeks, the decreases made by the placebo and
treatment groups were 5.3% versus 22.5% (p<0.05).
[0035] Serological Characteristics--II (C-Reactive Protein,
Adoponectin, Leptin)
[0036] As shown in Tables 7, 8, and 9, the IGOB131 treatment
(versus placebo) group showed large changes in these three
variables by week four. The magnitude of the changes increased
through week eight and remained constant through week ten.
[0037] C-reactive protein levels (Table 7): In contrast to the
minimal (0.017 mg/dL) decrease shown by the placebo group through
the entire trial period, by week four the reduction for the IGOB131
group was 0.58 mg/dL (38.9%). To translate the difference in the
amounts of decrease to final outcomes, the ten-week mean C-reactive
protein level of the placebo group was 1.445 mg/dL versus 0.715
mg/dL for the treatment group (p<0.01). In terms of intra-group
mean percent change from baseline to ten weeks, the decreases made
by the placebo and treatment groups were 1.2% versus 52.0%
(p<0.01).
[0038] Adiponectin levels (Table 8): In contrast to the small (1.83
mg/l) increase in adiponectin levels shown by the placebo group, by
week four the increase for the IGOB131 group was 12.7 mg/dL
(104.3%). To translate the difference in the amounts increased to
final outcomes, the ten-week mean adiponectin level of the placebo
group was 14.9 mg/dL versus 31.6 mg/dL for the treatment group
(p<0.05). In terms of intra-group mean percent change from
baseline to ten weeks, the increases made by the placebo and
treatment groups were 23.4% versus 159.8% (p<0.05).
[0039] Leptin levels (Table 9): The small (2.0 ng/ml) decrease in
blood leptin levels shown by the placebo group by week four can be
contrasted with the large 14.8 ng/mL decrease (45.0%) shown by the
IGOB131 group. To translate the difference in amounts decreased to
final outcomes, the ten-week mean leptin level of the placebo group
was 28.4 ng/mL versus 16.9 mg/dL for the treatment group
(p<0.01). In terms of intra-group mean percent change from
baseline to ten weeks, the decreases made by the placebo and
treatment groups were 9.4% versus 48.7% (p<0.01).
[0040] Adverse Events
[0041] Adverse events with an incidence >3 included headache
(5), lack of sleep (6), and gas (6). Since the incidence of all
reported side effects was observed in the placebo group as well as
in the treatment group, it is probably safe to conclude that the
IGOB131 formulation had few, if any, negative side effects.
[0042] Discussion
[0043] A variety of naturally occurring plant extracts appear to
have beneficial effects on animal and human health. Some compounds
have attracted considerable attention due to the cumulative
evidence of their physiological qualities serving as anti-obesity
and anti-diabetic agents, as well as their relative safety
(Bhathena et Velasquez, 2002). In accordance with this trend, the
present study showed that one of these compounds, the IGOB131
extract, safely and significantly (versus placebo) reduced body
weight and visceral fat mass, as well as plasma total and
LDL-cholesterol concentrations. The IGOB131 treatment group also
showed an increase in plasma adinopectin level and decreases in
leptin and CRP levels compared to the placebo group.
[0044] Insulin resistance is the hallmark of the metabolic syndrome
and is strongly associated with excess adiposity (Kahn et Flier,
2000 ; Maison et al., 2001). A variety of adipocyte-derived
biologically active molecules termed "adipocytokines" have been
identified, including leptin, resistin, TNF-.alpha., and IL-6, that
may contribute to obesity-linked metabolic abnormalities (Kern et
Ranganathan, 2001; McTernan et al., 2002). Since plasma leptin
level is closely correlated with the weight of adipose tissue
(Friedman et Halaas, 1998), and reports (Uygun et al. 2000) state
that a continuous weight gain may result in increased serum leptin,
the decreased plasma leptin level associated with IGOB131 treatment
may be attributable to the decrease of adipose tissue induced as a
consequence of weight loss.
[0045] Adipose tissue plays a prominent role in both insulin
resistance and the clinical expression of metabolic syndrome, most
likely mediated by the increased release and peripheral tissue
action of non-esterified fatty acid and by the dysregulated
production of adipocyte-secreted proteins, including leptin,
adiponectin, resistin, TNF-.alpha., and IL-6 (Hotamisligil et
Spiegelman, 1994, Matsuzawa et al., 1999, McTernan et al., 2002).
Adiponectin, which is exclusively expressed in adipose tissue and
abundant in human plasma, appears to be decreased in individuals
with obesity, type 2 diabetes, and coronary heart disease (Weyer et
al., 2002; Kumada et al., 2003). Although its physiological role is
still unclear, adiponectin may possess insulin-sensitizing, as well
as anti-inflammatory and anti-atherogenic properties (Okamoto et
al., 2000; Yamauchi et al., 2001; Okamoto et al., 2002; Matsuzawa
et al., 2002).
[0046] Adiponectin has recently been shown to increase hepatic
insulin sensitivity (Combs et al., 2001), to stimulate fatty acid
oxidation in liver and skeletal muscle, and to have protective
effects on cardiovascular functions (Hu et al., 1996; Yamauchi et
al., 2001). There are several reports suggesting that adiponectin
directly modulates glucose tolerance and peripheral tissue insulin
sensitivity, possibly through AMP kinase activation (Yamauchi et
al., 2002; Tomas et al., 2002). Moreover, different modalities of
weight loss--as well as peroxisome proliferator-activated
receptor-.gamma. (PPAR-.gamma.) agonist therapy--have been shown to
increase adiponectin levels longitudinally (Yang et al., 2001; Yu
et al., 2002). Another study demonstrated that moderate acute
weight loss of 5-7% in obese subjects with metabolic syndrome is
associated with dramatic improvement in all aspects of the
condition, although the individuals remained markedly obese (Case
et al., 2002).
[0047] The study, which specifically assessed, among other things,
adipocytokine variations in a group of obese subjects with
metabolic syndrome after a ten week IGOB131 treatment, showed a
marked improvement in glucose associated with a significant change
in adiponectin levels. In general, expression of adiponectin in
plasma correlates well with expression in adipose tissue.
[0048] The study also measured the anti-metabolic syndrome effects
of IGOB131 via body weight, abdominal fat mass, plasma lipids,
adiponectin, C-reactive proteins, and leptin levels in obese
participants. The extract's efficacy may be a result of the
synergistic effects of combining dietary fiber, albumin proteins,
and antioxidants in sufficient amounts. The involvement of the
soluble fiber fraction with an unstirred water layer present along
the luminal surface of mucosa intestinal cells increases the
thickness of that layer, thereby forming a physical barrier to the
cholesterol absorption (Kritchevsky, 1988; Roberfroid, 1993).
[0049] The effectiveness of the IGOB131 extract may also be
attributed to the albumin fraction. Earlier human studies on the
effect of plant protein revealed that the administration of soy
protein to female volunteers with normal lipids levels induced a
significant reduction in serum levels of blood lipids. A 1981 study
(Wolfe et al., 1981) showed a reduction of both total cholesterol
and triglycerides levels in a hypercholesterolemic man who was fed
a plant protein diet.
[0050] Other studies, similar to the plant albumin ones, have shown
the metabolic syndrome-preventive activity of antioxidant
components (i.e., vitamin C, polyphenols). Antioxidants, especially
epigallocatechin gallate, had antiobesity activity and apparently
improved metabolic disorders via modulation of adipokines and
growth factors (Kao et al., 2000; Ashida et al., 2004), especially
suppression of leptin concentrations (Kao et al., 2000; Ashida et
al., 2004; Sayama et al., 2000).
[0051] In sum, Irvingia gabonensis extract (IGOB131) administered
twice a day to healthy, overweight, and obese individuals resulted
in weight reduction (body weight, body fat, waist size) and an
improvement in the symptoms associated with metabolic syndrome. The
extract showed efficacy in the control and lowering of serum total
cholesterol, LDL-cholesterol, and serum leptin levels, while the
serum adiponectin was higher than in the placebo group. These
results suggest that IGOB131 may be used to manage metabolic
syndrome through control of obesity and lipid profile.
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[0132] Tables
TABLE-US-00001 TABLE 1 Body weight: effectiveness of IGOB131 Weight
change (%) Body weight (mean kg) 4 Weeks- 8 Weeks- 10 Weeks-
Initial 4 weeks 8 weeks 10 weeks Initial Initial Initial Placebo
96.4 .+-. 12.3 95.8 .+-. 8.2.sup. 95.1 .+-. 10.6 95.7 .+-. 15.2
-0.62 -1.35 -0.73 IGOB131 97.9 .+-. 9.1 94.3 .+-. 5.5.sup.a .sup.
89.7 .+-. 4.7.sup.a .sup. 85.1 .+-. 3.1.sup.b -3.68
-8.38.sup..dagger. -13.07.sup..dagger-dbl. .sup.ap < 0.05;
.sup.bp < 0.01 compared with Placebo .sup..dagger.p < 0.05;
.sup..dagger-dbl.p < 0.01 compared with Initial; intra-group
analysis
TABLE-US-00002 TABLE 2 Body fat: effectiveness of IGOB131 Fat
reduction (%) Body fat (mean %) 4 Weeks- 8 Weeks- 10 Weeks- Initial
4 weeks 8 weeks 10 weeks Initial Initial Initial Placebo 34.72 .+-.
8.60 33.31 .+-. 10.86 32.99 .+-. 11.93 32.73 .+-. 15.71 -4.06 -4.98
-5.73 IGOB131 34.17 .+-. 7.96 .sup. 31.61 .+-. 5.42.sup.a .sup.
28.19 .+-. 6.63.sup.a .sup. 27.88 .+-. 5.51.sup.a
-7.49.sup..dagger. -17.50.sup..dagger. -18.41.sup..dagger. .sup.ap
< 0.05; .sup.bp < 0.01 compared with Placebo .sup..dagger.p
< 0.05; .sup..dagger-dbl.p < 0.01 compared with Initial;
intra-group analysis
TABLE-US-00003 TABLE 3 Waist size: effectiveness of IGOB131 Waist
Change (%) Waist (mean cm) 4 Weeks- 8 Weeks- 10 Weeks- Initial 4
weeks 8 weeks 10 weeks Initial Initial Initial Placebo 106.40 .+-.
10.83 102.73 .+-. 10.63.sup. 101.10 .+-. 14.89.sup. 101.11 .+-.
15.86 -3.45 -4.98 -4.97 IGOB131 105.11 .+-. 6.38 98.01 .+-.
8.44.sup.a 90.11 .+-. 8.70.sup.a .sup. 88.10 .+-. 7.6.sup.b
-6.75.sup..dagger. -14.27.sup..dagger. -16.18.sup..dagger-dbl.
.sup.ap < 0.05; .sup.bp < 0.01 compared with Placebo
.sup..dagger.p < 0.05; .sup..dagger-dbl.p < 0.01 compared
with Initial; intra-group analysis
TABLE-US-00004 TABLE 4 Plasma total cholesterol level:
effectiveness of IGOB131 Change (%) Total cholesterol (mean mg/dL)
4 Weeks- 8 Weeks 10 Weeks- Initial 4 weeks 8 weeks 10 weeks Initial
Initial Initial Placebo 145.28 .+-. 22.40 143.94 .+-. 12.21.sup.
142.11 .+-. 13.66.sup. 142.47 .+-. 12.17 -0.92 -2.18 -1.93 IGOB131
151.74 .+-. 18.52 133.74 .+-. 16.63.sup.a 120.18 .+-. 11.97.sup.a
.sup. 111.92 .+-. 5.83.sup.a -11.86.sup..dagger.
-20.80.sup..dagger. -26.24.sup..dagger. .sup.ap < 0.05; .sup.bp
< 0.01 compared with Placebo .sup..dagger.p < 0.05;
.sup..dagger-dbl.p < 0.01 compared with Initial; intra-group
analysis
TABLE-US-00005 TABLE 5 Plasma LDL cholesterol level: effectiveness
of IGOB131 Change (%) LDL cholesterol (mean mg/dL) 4 Weeks- 8
Weeks- 10 Weeks- Initial 4 weeks 8 weeks 10 weeks Initial Initial
Initial Placebo 77.42 .+-. 9.19 76.46 .+-. 8.93.sup. 74.11 .+-.
9.29.sup. 73.67 .+-. 8.25.sup. -1.24 -4.28 -4.84 IGOB131 82.21 .+-.
8.06 71.81 .+-. 5.92.sup.b 64.73 .+-. 8.91.sup.b 59.77 .+-.
4.98.sup.b -12.65.sup..dagger-dbl. -21.26.sup..dagger-dbl.
-27.30.sup..dagger-dbl. .sup.ap < 0.05; .sup.bp < 0.01
compared with Placebo .sup..dagger.p < 0.05; .sup..dagger-dbl.p
< 0.01 compared with Initial; intra-group analysis
TABLE-US-00006 TABLE 6 Fasting blood glucose levels: effectiveness
of IGOB131 Change (%) Blood glucose (mean mg/dL) 4 Weeks- 8 Weeks-
10 Weeks- Initial 4 weeks 8 weeks 10 weeks Initial Initial Initial
Placebo 81.42 .+-. 9.63 79.49 .+-. 10.10.sup. 77.81 .+-. 9.41.sup.
77.12 .+-. 7.80.sup. -2.37 -4.43 -5.28 IGOB131 85.55 .+-. 5.59
76.64 .+-. 10.29.sup.a 68.74 .+-. 9.25.sup.a 66.30 .+-. 4.93.sup.a
-10.41.sup..dagger. -19.65.sup..dagger. -22.50.sup..dagger. .sup.ap
< 0.05; .sup.bp < 0.01 compared with Placebo .sup..dagger.p
< 0.05; .sup..dagger-dbl.p < 0.01 compared with Initial;
intra-group analysis
TABLE-US-00007 TABLE 7 C-reactive protein levels: effectiveness of
IGOB131 Change (%) (mean mg/dL) 4 Weeks- 8 Weeks- 10 Weeks- Initial
4 weeks 8 weeks 10 weeks Initial Initial Initial Placebo 1.462 .+-.
0.045 1.455 .+-. 0.041.sup. 1.445 .+-. 0.032.sup. 1.445 .+-.
0.049.sup. 0.48 1.16 1.16 IGOB131 1.490 .+-. 0.041 0.911 .+-.
0.049.sup.a 0.712 .+-. 0.044.sup.b 0.715 .+-. 0.049.sup.b
38.86.sup..dagger. 52.21.sup..dagger-dbl. 52.01.sup..dagger-dbl.
.sup.ap < 0.05; .sup.bp < 0.01 compared with Placebo
.sup..dagger.p < 0.05; .sup..dagger-dbl.p < 0.01 compared
with Initial; intra-group analysis
TABLE-US-00008 TABLE 8 Adiponectin levels: effectiveness of IGOB131
Change (%) Blood adiponectin (mean mg/l) 4 Weeks- 8 Weeks- 10
Weeks- Initial 4 weeks 8 weeks 10 weeks Initial Initial Initial
Placebo 12.11 .+-. 3.21 15.18 .+-. 3.50.sup. 14.63 .+-. 3.47.sup.
14.94 .+-. 3.92.sup. 25.35 20.81 23.37 IGOB131 12.16 .+-. 3.04
24.84 .+-. 3.81.sup.a 30.95 .+-. 3.96.sup.b 31.59 .+-. 3.85.sup.a
104.28.sup..dagger. 154.52.sup..dagger-dbl. 159.79.sup..dagger.
.sup.ap < 0.05; .sup.bp < 0.01 compared with Placebo
.sup..dagger.p < 0.05; .sup..dagger-dbl.p < 0.01 compared
with Initial; intra-group analysis
TABLE-US-00009 TABLE 9 Leptin levels: effectiveness of IGOB131
Change (%) Serum leptin (mean ng/ml) 4 Weeks- 8 Weeks- 10 Weeks-
Initial 4 weeks 8 weeks 10 weeks Initial Initial Initial Placebo
31.39 .+-. 1.83 29.39 .+-. 1.39.sup. 28.18 .+-. 1.84.sup. 28.45
.+-. 1.86.sup. 6.37 10.23 9.37 IGOB131 32.96 .+-. 1.63 18.12 .+-.
1.38.sup.a 16.84 .+-. 1.25.sup.a 16.91 .+-. 1.36.sup.b
45.02.sup..dagger. 48.91.sup..dagger. 48.70.sup..dagger-dbl.
.sup.ap < 0.05; .sup.bp < 0.01 compared with Placebo
.sup..dagger.p < 0.05; .sup..dagger-dbl.p < 0.01 compared
with Initial; intra-group analysis
* * * * *