Original Research White Bean Extract Blocking Carbohydrate Absorption and Weight Loss: A Clinical Trial Using Phase 2™ Brand Proprietary Fractionated White Bean Extract Jay Udani, MD; Mary Hardy, MD; and Damian C. Madsen, BA Abstract triglycerides, although statistical significance Background: Phase 2™ starch neutralizer was not reached. Phase 2 shows potential brand bean extract product (“Phase 2”) is a promise as an adjunct therapy in the treatment water-extract of a common white bean of obesity and hypertriglyceridemia and further (Phaseolus vulgaris) that has been shown in studies with larger numbers of subjects are vitro to inhibit the digestive enzyme alpha- warranted to conclusively demonstrate amylase. Inhibiting this enzyme may prevent effectiveness. the digestion of complex carbohydrates, thus (Altern Med Rev 2004;9(1):63-69) decreasing the number of carbohydrate calories absorbed and potentially promoting Introduction weight loss. Methods: Fifty obese adults were screened to participate in a randomized,
lent condition in the United States. Almost 61 per-
double-blind, placebo-controlled study
cent of the U.S. population is either overweight
evaluating the effects of treatment with Phase
(defined as a Body Mass Index (BMI) >25 kg/m2)
2 versus placebo on weight loss. Participants
or obese (defined as a BMI >30 kg/m2). Obesity
were randomized to receive either 1500 mg
increases the risk of several co-morbidities, includ-
Phase 2 or an identical placebo twice daily with
ing degenerative arthritis, obstructive sleep apnea,
meals. The active study period was eight
dyslipidemia, hypertension, diabetes mellitus, and
weeks. Thirty-nine subjects completed the
coronary artery disease. In addition to health risks,
initial screening process and 27 subjects
obese individuals have lower quality of life evalu-
completed the study. Results: The results after
ation scores (SF12) than their non-obese counter-
eight weeks demonstrated the Phase 2 group
parts. 1 Fortunately, obesity is treatable and there
lost an average of 3.79 lbs (average of 0.47 lb
is strong evidence that even modest weight loss
per week) compared with the placebo group, which lost an average of 1.65 lbs (average of 0.21 lb per week), representing a difference of
Jay Udani, MD – Assistant Clinical Professor, UCLA Schoolof Medicine; Medical Director, Integrative Medicine
129 percent (p=0.35). Triglyceride levels in the Phase 2 group were reduced an average of 26.3
Correspondence address: 18250 Roscoe Blvd, Suite 240,Northridge, CA 91325
mg/dL, more than three times greater a reduction than observed in the placebo group
Mary Hardy, MD – Director, Cedars-Sinai Integrative
(8.2 mg/dL) (p=0.07). No adverse events during
Medicine Medical Group; Assistant Clinical Professor, USC
the study were attributed to the study medication. Conclusion: Clinical trends were
Damian C. Madsen, BA – Senior Clinical Research
identified for weight loss and a decrease in
Coordinator, California Neuroscience Research MedicalGroup
Alternative Medicine Review ◆ Volume 9, Number 1 ◆ 2004 Page 63
Copyright2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
White Bean Extract Original Research
(5% of body weight) significantly decreases the
risk of these diseases, especially diabetes and car-
normoglycemic individuals measured pre- and
postprandial glucose levels.10 The glucose levels
available for obesity, including serotoninergic agents
of the Phase 2 group returned to baseline 20 min-
(dexfenfluramine, fluoxetine), noradrenergic agents
utes earlier than the placebo group. In addition,
(sibutramine) and lipase inhibitors (orlistat). While
the area under the plasma glucose versus time
each of these drugs has been shown to be effective
curve (a measure of glucose absorption and me-
as an adjunct to dietary modification and exercise,
tabolism) was 57-percent lower with Phase 2.
their utility is limited by side effects that include car-
These results suggest less glucose is absorbed in
diac valvular disease, hypertension, seizures, sexual
subjects taking Phase 2 and the absorbed glucose
is cleared from the bloodstream more rapidly.
ods for weight loss, including non-prescription
weight loss products (herbs, vitamins, and nutritional
Subjects
supplements) and meal replacement preparations.
Fifty obese adults were screened for this
Scientifically rigorous studies have not been per-
study. Randomized subjects (n=39; 35 females, 4
formed on these products, and in many cases safety
males) had a mean age of 36.5 years (range: 20-
and efficacy take a back seat to marketing.
69; SD 12.19) and mean weight of 193.1 lbs (range
The Phase 2™ starch neutralizer brand bean
148-256; SD 26.95). There were no significant
extract product (“Phase 2”) is a water extract of a
differences between the two groups. Entry crite-
common white bean (Phaseolus vulgaris) that has
ria included subjects older than 18, a BMI (weight
been shown in vitro to inhibit the digestive enzyme
in kilograms divided by the square of height in
alpha-amylase.3-6 Phase 2 was previously sold as
meters) of 30-43 kg/m2, adequate contraception
Phaseolamin 2250, purportedly referring to 1 g of
in women of childbearing potential, and absence
the product blocking 2,250 starch calories. Alpha-
of any use of drugs to treat obesity. In addition,
amylase, secreted in saliva and by the pancreas, is
subjects were excluded if they had active eating
responsible for breaking down starch to simple sug-
disorders, history of seizures, or any significant
ars that are absorbed in the small intestine. Blocking
gastrointestinal (including malabsorption), car-
this digestive enzyme may prevent the digestion of
diac, renal, hepatic, psychiatric, or endocrine dis-
complex carbohydrates, allowing them to pass
orders, or a history or presence of drug abuse or
through the digestive system. The end result of block-
excessive alcohol intake. Potential subjects whose
ing alpha-amylase would logically be a decrease in
baseline laboratory levels were abnormal (serum
the number of calories absorbed, potentially promot-
creatinine > 1.6 mg/dL; BUN > 28 mg/dL; AST >
57 IU/L (males), >39 IU/L (females); ALT > 72
Acute and chronic (90 day) animal toxicity
IU/L (males), >52 IU/L (females); HbA1C > 6%)
studies to date have demonstrated no clinical or patho-
logical toxicity associated with ingestion of Phase2.7,8
Intervention
clinical trial (n=60) of Phase 2 versus placebo for
weight loss documented a 4.0-percent loss of body
weight compared with 0.47 percent in the placebo
www.randomizer.org) to receive either 1500 mg
group after 30 days (p < 0.05). In addition, the ex-
Phase 2 or identical placebo twice daily with lunch
perimental group demonstrated a 10.45-percent re-
and dinner for eight weeks. The product was taken
with at least 8 oz of water. Subjects began a con-trolled high-fiber/low-fat diet at the beginning of
Page 64 Alternative Medicine Review ◆ Volume 9, Number 1 ◆ 2004
Copyright2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
Original Research White Bean Extract
the study that provided 100-200 g of complex car-
Baseline Visit
bohydrate intake per day. Carbohydrate intake was
The initial screening visit included a medi-
recommended for the subjects on the basis of es-
cal history, physical examination, body weight
timated daily maintenance carbohydrate require-
evaluation, and fasting lab evaluations (see Bio-
ment. Subjects were instructed to eat the majority
of carbohydrates during lunch and dinner since
those were the meals at which Phase 2 or placebo
were randomized and given medication instruc-
were taken. Dietary compliance was measured by
tions and diet instruction from a registered dieti-
requiring a daily diet diary, which was reviewed
cian. The following clinical visit was scheduled
at each visit. Use of any drugs, herbs, or other non-
prescription preparations for obesity were discon-tinued prior to the start of the study. Clinical Visits Visit 2 (End of Week 2) Measures Objective Measures
participant was measured and bioelectrical imped-
Each participant was given a physical ex-
ance was performed for body fat composition. The
amination. Weight and bioelectrical impedance for
initial 10-point subjective scales for hunger, ap-
body fat composition were also collected.
petite control, and energy were completed duringthis visit. Subjective Measures
Each participant completed 10-point Likert
Visit 3 (End of Week 4)
scales for hunger, energy, and appetite control.
again had their weight measured and bioelectrical
Bioassays
impedance was performed for body fat composi-
tion. Blood samples were collected for triglycer-
assays were run on a Hitachi model 717 for glu-
ide and cholesterol analyses. Ten-point subjective
cose, triglycerides, total cholesterol, basic metabo-
scales for hunger, appetite control, and energy
lism, liver function, and kidney function (serum
creatinine and BUN). HBA1C, hematology, andurinalyses were also conducted. Visit 4 (End of Week 6)
The fourth visit involved weight measure-
Apparati
ment, performance of bioelectrical impedance for
Standard metabolic spectrophotometric as-
body fat composition, and completion of the 10-
says were conducted on a Hitachi model 717. A Bio-
point subjective scales for hunger, appetite con-
dynamics 310e Body Fat Analyzer was used to de-
termine body fat composition of study subjects.11
Visit 5 (End of Week 8) Design and Procedure
At the concluding visit, each participant
had a final weight measurement and bioelectrical
impedance for body fat composition tested. Blood
controlled study was conducted for eight weeks.
samples were collected for basic metabolic panel,
Subjects participated in five group visits over the
HbA1C, liver function tests, triglyceride, and cho-
course of eight weeks; one baseline (week 0) and
lesterol analyses, and the final 10-point subjec-
four clinical visits (weeks 2, 4, 6, and 8). Each
tive scales for hunger, appetite control, and en-
subject signed a written, informed consent form
Alternative Medicine Review ◆ Volume 9, Number 1 ◆ 2004 Page 65
Copyright2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
White Bean Extract Original Research Triglyceride Levels Table 1. Weight Loss in Pounds
Phase 2 group decreased an aver-age of 26.3 mg/dL, more than three
Weight loss
8.2 mg/dL drop observed in the pla-cebo group (p=0.07) (Table 2). Secondary Outcomes
ondary outcomeswere measured dur-ing the study. Foreach secondary mea-
Table 2. Triglyceride Levels (mg/dL) Triglyceride level
cally significant dif-ferences were identi-
tive and placebogroups (Tables 3and 4). Adverse Events Participation
Of a total of 50 subjects who initially were
lieved to be due to the active product. Abdominal
screened, 39 subjects were randomized and 27
pain, bloating, and gas were experienced by one
completed the study. Twenty randomized subjects
placebo subject, and one Phase 2 subject com-
received Phase 2 and 19 received placebo. Four-
plained of an increased incidence of tension head-
teen Phase 2 subjects and 13 placebo subjects com-
aches while in the active phase of the trial.
pleted the study. New subjects were not recruitedto replace dropouts and an intent-to-treat analysiswas performed. Safety Data Weight Loss
week 8. These data included creatinine as a markerof kidney function; electrolytes including sodium,
chloride, and calcium; carbon dioxide; and AST/
onstrated the Phase 2 group lost an average of 3.79
ALT as markers of liver function. There were no
lbs (an average of 0.47 lb per week) compared
clinically significant changes in any of these mark-
with the placebo group, which lost an average of
1.65 lbs (an average of 0.21 lb per week) (Table1). The difference is 129 percent with a two-tailedp-value = 0.35. Similar trends were seen at two,
Discussion
The data from this study provides prelimi-
nary evidence through positive trends that Phase2 may be effective in reducing both weight andtriglyceride levels. Positive secondary outcome
Page 66 Alternative Medicine Review ◆ Volume 9, Number 1 ◆ 2004
Copyright2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
Original Research White Bean Extract Table 3. Secondary Outcomes Phase 2™ Phase 2™ Phase 2™ baseline baseline
5.54 mg/dL 5.16 mg/ dL -0.38 mg/dL 5.47 mg/dL 5.21 mg/dL -0.26 mg/dL >0.05
+6.45 mg/dL 194 mg/dL 200 mg/dL +6.18 mg/dL >0.05
Table 4. Additional Secondary Outcomes – Waist and Hip Measurements Changes from Baseline (in) Alternative Medicine Review ◆ Volume 9, Number 1 ◆ 2004 Page 67
Copyright2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
White Bean Extract Original Research
trends, including an increase in energy and a de-
demonstrate a statistically meaningful result. This
crease in body fat, were also seen. While none of
study can provide a good framework, however,
these trends reached statistical significance, they
for future studies to demonstrate conclusively
are clinically relevant and provide a good frame-
whether Phase 2 can effectively contribute to the
work on which future research can be conducted.
point in obesity treatment, the primary concern in
Disclosures
the medical management of obesity is morbidity
and mortality risk reduction by improving the un-
grant from Pharmachem Laboratories, and was
derlying cardiovascular and metabolic risk factors,
presented as an abstract at the October 10, 2003
including high blood pressure, atherogenic
American Society of Bariatric Physicians Annual
dyslipidemia, and insulin resistance. A widely held
Meeting. The corresponding author discloses that
view is that modest (approximately 5%) inten-
tional weight loss is associated with significant
Pharmachem Laboratories, the manufacturer of
improvements in obesity-related cardiovascular
Phase 2, and has provided consulting services to
and metabolic abnormalities.2,12-14 If the results
Pharmachem Laboratories. The authors do not
from this study can be replicated in the future, then
have any financial interest in Pharmachem Labo-
the Phase 2 product might play a role in this risk
ratories, the Phase 2 product, or any other com-
factor reduction by assisting with modest weight
loss over time. A number of cardiovascular riskfactors were measured directly and it was foundthe reduction of triglycerides by Phase 2 ap-
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Original Research White Bean Extract
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Figure 2. Adapted from: Hagiwara K, Kataoka S, Yamanaka H, et al. Detection ofcytokines in bovine colostrum. Vet Immunol Immunopathol 2000;76:183-190. Alternative Medicine Review ◆ Volume 9, Number 1 ◆ 2004 Page 69
Copyright2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
Sur T K et a l / Acta Pharmac ol Sin 20 03 Feb; 2 4 (2): 18 7-192Chine se Academ y of Sci encesht tp:/ /www.Chi naPh ar.c omAnti-inflammatory and anti-platelet aggregation activitySUR Tapas Kumar, BISWAS Tuhin Kanti2, ALI Liaquat3, MUKHERJEE Biswapati4 Department of Pharmacology; 2SN Pradhan Centre for Neurosciences, Dr BC Roy Postgraduate Institute of Basic Medical Sciences 244B, Acharya
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