Blocking Carbohydrate Absorption and Weight Loss: A Clinical Trial Using Phase 2™ Brand Proprietary Fractionated White Bean Extract

Abstract

Phase 2' starch neutralizer brand bean extract product ("Phase 2") is a water-extract of a common white bean (Phaseolus vulgaris) that has been shown in vitro to inhibit the digestive enzyme alpha-amylase. Inhibiting this enzyme may prevent the digestion of complex carbohydrates, thus decreasing the number of carbohydrate calories absorbed and potentially promoting weight loss.
Fifty obese adults were screened to participate in a randomized, double-blind, placebo-controlled study evaluating the effects of treatment with Phase 2 versus placebo on weight loss. Participants were randomized to receive either 1500 mg Phase 2 or an identical placebo twice daily with meals. The active study period was eight weeks. Thirty-nine subjects completed the initial screening process and 27 subjects completed the study.
The results after eight weeks demonstrated the Phase 2 group lost an average of 3.79 lbs (average of 0.47 lb 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 129 percent (p=0.35). Triglyceride levels in the Phase 2 group were reduced an average of 26.3 mg/dL, more than three times greater a reduction than observed in the placebo group (8.2 mg/dL) (p=0.07). No adverse events during the study were attributed to the study medication.
Clinical trends were identified for weight loss and a decrease in triglycerides, although statistical significance was not reached. Phase 2 shows potential promise as an adjunct therapy in the treatment of obesity and hypertriglyceridemia and further studies with larger numbers of subjects are warranted to conclusively demonstrate effectiveness.

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Alternative Medicine Review
◆ Volume 9, Number 1 ◆ 2004 Page 63
Original Research White Bean Extract
Abstract
Background: Phase 2™ starch neutralizer
brand bean extract product (“Phase 2”) is a
water-extract of a common white bean
(Phaseolus vulgaris) that has been shown in
vitro to inhibit the digestive enzyme alpha-
amylase. Inhibiting this enzyme may prevent
the digestion of complex carbohydrates, thus
decreasing the number of carbohydrate
calories absorbed and potentially promoting
weight loss. Methods: Fifty obese adults were
screened to participate in a randomized,
double-blind, placebo-controlled study
evaluating the effects of treatment with Phase
2 versus placebo on weight loss. Participants
were randomized to receive either 1500 mg
Phase 2 or an identical placebo twice daily with
meals. The active study period was eight
weeks. Thirty-nine subjects completed the
initial screening process and 27 subjects
completed the study. Results: The results after
eight weeks demonstrated the Phase 2 group
lost an average of 3.79 lbs (average of 0.47 lb
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
129 percent (p=0.35). Triglyceride levels in the
Phase 2 group were reduced an average of 26.3
mg/dL, more than three times greater a
reduction than observed in the placebo group
(8.2 mg/dL) (p=0.07). No adverse events during
the study were attributed to the study
medication. Conclusion: Clinical trends were
identified for weight loss and a decrease in
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
triglycerides, although statistical significance
was not reached. Phase 2 shows potential
promise as an adjunct therapy in the treatment
of obesity and hypertriglyceridemia and further
studies with larger numbers of subjects are
warranted to conclusively demonstrate
effectiveness.
(Altern Med Rev 2004;9(1):63-69)
Introduction
Obesity is a dangerous and highly preva-
lent condition in the United States. Almost 61 per-
cent of the U.S. population is either overweight
(defined as a Body Mass Index (BMI) >25 kg/m
2
)
or obese (defined as a BMI >30 kg/m
2
). Obesity
increases the risk of several co-morbidities, includ-
ing degenerative arthritis, obstructive sleep apnea,
dyslipidemia, hypertension, diabetes mellitus, and
coronary artery disease. In addition to health risks,
obese individuals have lower quality of life evalu-
ation scores (SF12) than their non-obese counter-
parts.
1
Fortunately, obesity is treatable and there
is strong evidence that even modest weight loss
Jay Udani, MD – Assistant Clinical Professor, UCLA School
of Medicine; Medical Director, Integrative Medicine
Program, Northridge Hospital
Correspondence address: 18250 Roscoe Blvd, Suite 240,
Northridge, CA 91325
Email: Jay.Udani@CHW.edu
Mary Hardy, MD – Director, Cedars-Sinai Integrative
Medicine Medical Group; Assistant Clinical Professor, USC
School of Medicine
Damian C. Madsen, BA – Senior Clinical Research
Coordinator, California Neuroscience Research Medical
Group

Page 64 Alternative Medicine Review
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White Bean Extract Original Research
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(5% of body weight) significantly decreases the
risk of these diseases, especially diabetes and car-
diovascular disease.
Pharmacological treatments are currently
available for obesity, including serotoninergic agents
(dexfenfluramine, fluoxetine), noradrenergic agents
(sibutramine) and lipase inhibitors (orlistat). While
each of these drugs has been shown to be effective
as an adjunct to dietary modification and exercise,
their utility is limited by side effects that include car-
diac valvular disease, hypertension, seizures, sexual
dysfunction, and fecal incontinence.
2
The general public uses many other meth-
ods for weight loss, including non-prescription
weight loss products (herbs, vitamins, and nutritional
supplements) and meal replacement preparations.
Scientifically rigorous studies have not been per-
formed on these products, and in many cases safety
and efficacy take a back seat to marketing.
The Phase 2™ starch neutralizer brand bean
extract product (“Phase 2”) is a water extract of a
common white bean (Phaseolus vulgaris) that has
been shown in vitro to inhibit the digestive enzyme
alpha-amylase.
3-6
Phase 2 was previously sold as
Phaseolamin 2250, purportedly referring to 1 g of
the product blocking 2,250 starch calories. Alpha-
amylase, secreted in saliva and by the pancreas, is
responsible for breaking down starch to simple sug-
ars that are absorbed in the small intestine. Blocking
this digestive enzyme may prevent the digestion of
complex carbohydrates, allowing them to pass
through the digestive system. The end result of block-
ing alpha-amylase would logically be a decrease in
the number of calories absorbed, potentially promot-
ing weight loss.
Acute and chronic (90 day) animal toxicity
studies to date have demonstrated no clinical or patho-
logical toxicity associated with ingestion of Phase
2.
7,8
A 2003 double-blind, placebo-controlled
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
group after 30 days (p < 0.05). In addition, the ex-
perimental group demonstrated a 10.45-percent re-
duction of body fat.
9
An earlier controlled crossover study
(n=10) of Phase 2 versus placebo in
normoglycemic individuals measured pre- and
postprandial glucose levels.
10
The glucose levels
of the Phase 2 group returned to baseline 20 min-
utes earlier than the placebo group. In addition,
the area under the plasma glucose versus time
curve (a measure of glucose absorption and me-
tabolism) was 57-percent lower with Phase 2.
These results suggest less glucose is absorbed in
subjects taking Phase 2 and the absorbed glucose
is cleared from the bloodstream more rapidly.
Methods
Subjects
Fifty obese adults were screened for this
study. Randomized subjects (n=39; 35 females, 4
males) had a mean age of 36.5 years (range: 20-
69; SD 12.19) and mean weight of 193.1 lbs (range
148-256; SD 26.95). There were no significant
differences between the two groups. Entry crite-
ria included subjects older than 18, a BMI (weight
in kilograms divided by the square of height in
meters) of 30-43 kg/m
2
, adequate contraception
in women of childbearing potential, and absence
of any use of drugs to treat obesity. In addition,
subjects were excluded if they had active eating
disorders, history of seizures, or any significant
gastrointestinal (including malabsorption), car-
diac, renal, hepatic, psychiatric, or endocrine dis-
orders, or a history or presence of drug abuse or
excessive alcohol intake. Potential subjects whose
baseline laboratory levels were abnormal (serum
creatinine > 1.6 mg/dL; BUN > 28 mg/dL; AST >
57 IU/L (males), >39 IU/L (females); ALT > 72
IU/L (males), >52 IU/L (females); HbA1C > 6%)
were also excluded from the study.
Intervention
Subjects were randomly allocated
(using a random number generator at
www.randomizer.org) to receive either 1500 mg
Phase 2 or identical placebo twice daily with lunch
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

Alternative Medicine Review
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the study that provided 100-200 g of complex car-
bohydrate intake per day. Carbohydrate intake was
recommended for the subjects on the basis of es-
timated daily maintenance carbohydrate require-
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 taken. Dietary compliance was measured by
requiring a daily diet diary, which was reviewed
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.
Measures
Objective Measures
Each participant was given a physical ex-
amination. Weight and bioelectrical impedance for
body fat composition were also collected.
Subjective Measures
Each participant completed 10-point Likert
scales for hunger, energy, and appetite control.
Bioassays
Standard metabolic spectrophotometric
assays were run on a Hitachi model 717 for glu-
cose, triglycerides, total cholesterol, basic metabo-
lism, liver function, and kidney function (serum
creatinine and BUN). HBA1C, hematology, and
urinalyses were also conducted.
Apparati
Standard metabolic spectrophotometric as-
says were conducted on a Hitachi model 717. A Bio-
dynamics 310e Body Fat Analyzer was used to de-
termine body fat composition of study subjects.
11
Design and Procedure
A randomized, double-blind, placebo-
controlled study was conducted for eight weeks.
Subjects participated in five group visits over the
course of eight weeks; one baseline (week 0) and
four clinical visits (weeks 2, 4, 6, and 8). Each
subject signed a written, informed consent form
before entry into the trial.
Baseline Visit
The initial screening visit included a medi-
cal history, physical examination, body weight
evaluation, and fasting lab evaluations (see Bio-
assays section above).
Upon being determined eligible, subjects
were randomized and given medication instruc-
tions and diet instruction from a registered dieti-
cian. The following clinical visit was scheduled
two weeks from baseline.
Clinical Visits
Visit 2 (End of Week 2)
At the second visit, the weight of each
participant was measured and bioelectrical imped-
ance was performed for body fat composition. The
initial 10-point subjective scales for hunger, ap-
petite control, and energy were completed during
this visit.
Visit 3 (End of Week 4)
During the third visit, the participants
again had their weight measured and bioelectrical
impedance was performed for body fat composi-
tion. Blood samples were collected for triglycer-
ide and cholesterol analyses. Ten-point subjective
scales for hunger, appetite control, and energy
were again completed.
Visit 4 (End of Week 6)
The fourth visit involved weight measure-
ment, performance of bioelectrical impedance for
body fat composition, and completion of the 10-
point subjective scales for hunger, appetite con-
trol, and energy.
Visit 5 (End of Week 8)
At the concluding visit, each participant
had a final weight measurement and bioelectrical
impedance for body fat composition tested. Blood
samples were collected for basic metabolic panel,
HbA1C, liver function tests, triglyceride, and cho-
lesterol analyses, and the final 10-point subjec-
tive scales for hunger, appetite control, and en-
ergy were completed.

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White Bean Extract Original Research
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Results
Participation
Of a total of 50 subjects who initially were
screened, 39 subjects were randomized and 27
completed the study. Twenty randomized subjects
received Phase 2 and 19 received placebo. Four-
teen Phase 2 subjects and 13 placebo subjects com-
pleted the study. New subjects were not recruited
to replace dropouts and an intent-to-treat analysis
was performed.
Weight Loss
The study results after eight weeks dem-
onstrated the Phase 2 group lost an average of 3.79
lbs (an average of 0.47 lb per week) compared
with the placebo group, which lost an average of
1.65 lbs (an average of 0.21 lb per week) (Table
1). The difference is 129 percent with a two-tailed
p-value = 0.35. Similar trends were seen at two,
four, and six weeks.
Triglyceride Levels
Triglyceride levels in the
Phase 2 group decreased an aver-
age of 26.3 mg/dL, more than three
times greater a reduction than the
8.2 mg/dL drop observed in the pla-
cebo group (p=0.07) (Table 2).
Secondary Outcomes
Several sec-
ondary outcomes
were measured dur-
ing the study. For
each secondary mea-
sure, however, no
clinically or statisti-
cally significant dif-
ferences were identi-
fied between the ac-
tive and placebo
groups (Tables 3
and 4).
Adverse Events
No adverse events occurred that were be-
lieved to be due to the active product. Abdominal
pain, bloating, and gas were experienced by one
placebo subject, and one Phase 2 subject com-
plained of an increased incidence of tension head-
aches while in the active phase of the trial.
Safety Data
Safety data was obtained at time 0 and
week 8. These data included creatinine as a marker
of kidney function; electrolytes including sodium,
chloride, and calcium; carbon dioxide; and AST/
ALT as markers of liver function. There were no
clinically significant changes in any of these mark-
ers across either of the groups.
Discussion
The data from this study provides prelimi-
nary evidence through positive trends that Phase
2 may be effective in reducing both weight and
triglyceride levels. Positive secondary outcome
Table 1. Weight Loss in Pounds
Weight loss
Phase 2™
Placebo
Week 2
1.87
1.05
Week 4
1.93
0.14
Week 6
2.29
0.75
Week 8
3.79
1.65
Table 2. Triglyceride Levels (mg/dL)
Triglyceride level
Phase 2™
Placebo
Week 0
152.6
146.9
Week 4
145.3
144.6
Week 8
126.3
138.7
Change
26.3 (17.2%)
8.2 (5.6%)

Alternative Medicine Review
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Table 3. Secondary Outcomes
Outcome
Body Fat (%)
Energy Level
(10-pt scale)
Appetite
Control
(10-pt scale)
Hunger
(10-pt scale)
HbA1c
Total
Cholesterol
Phase 2™
baseline
38.7 %
4.8
4.7
4.8
5.54 mg/dL
194 mg/dL
Phase 2™
at eight
weeks
38.2 %
6.2
5.1
5.1
5.16 mg/ dL
200 mg/dL
Phase 2™
change
-0.5 %
+1.4
+0.4
+0.3
-0.38 mg/dL
+6.45 mg/dL
Placebo
baseline
41 %
6.0
5.7
5.4
5.47 mg/dL
194 mg/dL
Placebo
at eight
weeks
41 %
5.9
5.4
5.1
5.21 mg/dL
200 mg/dL
Placebo
change
0 %
-0.1
-
-0.3
-0.3
-0.26 mg/dL
+6.18 mg/dL
P Values
>0.05
>0.05
>0.05
>0.05
>0.05
>0.05
Table 4. Additional Secondary Outcomes – Waist and Hip Measurements
Changes from
Baseline (in)
Change in Waist
Measurements
Change in Hip
Measurements
Phase 2™
Placebo
p Values
Phase 2™
Placebo
p Values
2 weeks
-1.27 in
-0.85 in
>0.05
+0.32 in
-0.17 in
>0.05
4 weeks
-0.67 in
-0.96 in
>0.05
+0.43 in
-0.21 in
>0.05
6 weeks
-1.29 in
-1.08 in
>0.05
+0.32 in
-0.52 in
>0.05
8 weeks
-1.46 in
-1.08 in
>0.05
+ 0.32 in
-0.57 in
>0.05

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White Bean Extract Original Research
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trends, including an increase in energy and a de-
crease in body fat, were also seen. While none of
these trends reached statistical significance, they
are clinically relevant and provide a good frame-
work on which future research can be conducted.
While weight loss is an important end
point in obesity treatment, the primary concern in
the medical management of obesity is morbidity
and mortality risk reduction by improving the un-
derlying cardiovascular and metabolic risk factors,
including high blood pressure, atherogenic
dyslipidemia, and insulin resistance. A widely held
view is that modest (approximately 5%) inten-
tional weight loss is associated with significant
improvements in obesity-related cardiovascular
and metabolic abnormalities.
2,12-14
If the results
from this study can be replicated in the future, then
the Phase 2 product might play a role in this risk
factor reduction by assisting with modest weight
loss over time. A number of cardiovascular risk
factors were measured directly and it was found
the reduction of triglycerides by Phase 2 ap-
proached statistical significance (p=0.07). None
of the other secondary endpoints, including total
cholesterol and HbA1c, showed improvement.
There were several limitations of this
study. The first and foremost was the small sample
size, which occurred due to a combination of
factors. These include an effect size power
calculation based upon data from the only
available literature at the time – a study reporting
a striking difference between groups with a loss
of four-percent body weight after only 30 days.
Factors that may have contributed to the high
dropout rate include the requirements of multiple
blood draws and the slow weight loss effect of the
product. Many subjects have expectations of losing
several pounds a week. This study showed an
average of 0.47 lb per week in the active group
and 0.21 lb per week in the placebo group.
Regardless of the reason, the overall number of
completers was lower than hoped for. Given the
statistical rigor of the study design, statistical
significance was not reached. Future studies will
be needed to definitively test this product.
Preliminary calculations indicate a minimum of
150 completed subjects would be required to
demonstrate a statistically meaningful result. This
study can provide a good framework, however,
for future studies to demonstrate conclusively
whether Phase 2 can effectively contribute to the
treatment of obesity.
Disclosures
This research was made possible by a
grant from Pharmachem Laboratories, and was
presented as an abstract at the October 10, 2003
American Society of Bariatric Physicians Annual
Meeting. The corresponding author discloses that
he has ongoing research support from
Pharmachem Laboratories, the manufacturer of
Phase 2, and has provided consulting services to
Pharmachem Laboratories. The authors do not
have any financial interest in Pharmachem Labo-
ratories, the Phase 2 product, or any other com-
mercial product.
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