Volume 7-6

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- References
proached statistical significance (p=0.07). None of the other secondary endpoints, including total management. Postgrad Med Special Report2001;June:3-9.
cholesterol and HbA1c, showed improvement.
Hensrud DD. Pharmacotherapy for obesity.
Med Clin North Am 2000;84:463-476.
study. The first and foremost was the small sample Layer P, Zinsmeister AR, Di Magno EP.
size, which occurred due to a combination of Effects of decreasing intraluminal amylase factors. These include an effect size power activity on starch digestion and postprandial calculation based upon data from the only gastrointestinal function in humans. Gastroen- available literature at the time – a study reporting a striking difference between groups with a loss Layer P, Rizza RA, Zinsmeister AR, et al.
of four-percent body weight after only 30 days.
Effect of a purified amylase inhibitor on Factors that may have contributed to the high carbohydrate tolerance in normal subjects andpatients with diabetes mellitus. Mayo Clin dropout rate include the requirements of multiple blood draws and the slow weight loss effect of the product. Many subjects have expectations of losing Fordtran JS. Starch-blockers – their effect on several pounds a week. This study showed an calorie absorption from a high-starch meal. N average of 0.47 lb per week in the active group Engl J Med 1982;307:1413-1416.
and 0.21 lb per week in the placebo group.
Hollenbeck CB, Coulston AM, Quan R, et al.
Regardless of the reason, the overall number of completers was lower than hoped for. Given the preparation on carbohydrate digestion and statistical rigor of the study design, statistical absorption: in vivo and in vitro studies. Am JClin Nutr 1983;38:498-503.
significance was not reached. Future studies willbe needed to definitively test this product.
Preliminary calculations indicate a minimum of150 completed subjects would be required to Page 68 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
Jensen N, Everone C, Rosenberg M. A study of Lewy VD, Danadian K, Arslanian S. Determi- the survival, body weights, health status, and food consumption of mice when given varying American children: validation of bioelectrical extract which contain Phaseolamin. Unpub- absorptiometry. J Pediatr Endocrinol Metab Maheshwari R, Srimal R, Kuttan R. Chronic toxicity studies of Phaseolamin 2250. Unpub- tendamistate (an alpha amylase inhibitor). S Meiss DE, Ballerini R. Effectiveness of Phase 2™, a natural alpha-amylase inhibitor, for Anonymous. Clinically studied Phaseolamin 2250 for non-stimulant carb control. http:// placebo-controlled study. Presented at Scripps www.phaseolamin2250.com/catalog7.htm.
Clinic Natural Supplements in Evidence-Based Practice Conference. January 18, 2003.
Goldstein DJ. Beneficial health effects of Vinson J. Investigation on the efficacy of modest weight loss. Int J Obes Relat Metab Phaseolamin 2250, a purified bean extract from Pharmachem Laboratories. UnpublishedData. University of Scranton. 2001.
Corrections to Bovine Colostrums: A Review of Clinical
Uses; Alternative Medicine Review 2003;8(4):378-394.
The following credits were inadvertently omitted:
Figure 1.
Adapted from: Ebina T, Sato A, Umezu K, et al. Treatment of multiple
sclerosis with anti-measles cow colostrum. Med Microbiol Immunol
(Berl1984;173:87-93.
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
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