In vivo effectiveness of a starch absorption
blocker in a double-blind placebo-controlled study with normal
subjects.
Joe A. Vinson, PhD, Donna M. Shuta, BS and Hassan Al Kharrat, MS
Department of Chemistry
University of Scranton
Scranton, PA 18510
Analysis data were obtained from the first study
done reported on September 6, 2001 and the second study on November,
20, 2001. The total subjects from both studies numbered 20. Nine
were excluded who did not furnish all blood samples or who had a
negative area for the plasma glucose-time curve and were therefore
poor absorbers.
Of the 11 subjects, 8 were female and 3 were male, ranging in age
from 21 to 57. The Phase 2® group had significantly lower plasma
glucose at 60 minutes and almost significantly lower glucose at 45
minutes. The area of the curve (area above the baseline which is 0
to 62 minutes for Phase 2® and 0 to 80 minutes for the control),
which represents glucose absorption and metabolism, was 66% smaller
with Phase 2® .
This product shows effectiveness in both sedentary college-age
subjects and physically active adults.
Clinical Studie 2.
November 20 - In vivo effectiveness of a
starch absorption blocker in a double-blind placebo-controlled study
with normal college-age subjects.
Joe A. Vinson, PhD and
Donna M. Shuta, BS
Department of Chemistry
University of Scranton
Scranton, PA 18510
Inhibition of carbohydrate metabolism or absorption
is one mechanism to reduce hyperglycemia in normal and especially in
diabetic subjects. Another possible benefit is the decrease in
calorie intake after eating carbohydrates for obesity and weight
loss. In the 1980's there were several reports of in vitro and in
vivo effectiveness of a natural starch blocker that worked by
inactivating the enzyme amylase. We investigated this hypothesis
with an initial pilot study. After this initial study with subjects
who were physically active during the study, we did a second study
to confirm the results. In this second study, again there was a
double-blind placebo-controlled crossover trial with ten subjects
(five males and five females aged 21 to 27) who participated with
informed consent. After an overnight fast the subjects appeared in
the morning and were given in a random fashion either 1) placebo
consisting of 4 slices of white bread (60 g of carbohydrate), 42 g
of soybean oil margarine, and 4 g of Sweet N'Low; 2) experimental
comprising the control plus 1.5 g of Phase 2® (Pharmachem
Laboratories). The subjects rested between blood drawings. Plasma
glucose was measured from blood sample drawn at baseline and every
15 minutes for 1 hour, then every 20 minutes for the second hour.
Two subjects did not complete the study and 4 subjects were
poor/non-absorbers as the area under the glucose-time curve was
negative. Therefore the data of the remaining 4 subjects was used.
As expected the control bread produced an increase in glucose in the
normal subjects that reached a broad peak after 45 minutes. The peak
glucose for the Phase 2® group occurred at 30 minutes. This dose of
Phase 2® produced a smaller increase than the control from 15 to 80
minutes, with an almost significant difference (p < 0.1) at 45 and
60 minutes. The glucose cleared from the plasma about 30 minutes
earlier with the Phaseolamin™ compared to the control. The area
under the plasma glucose-time curve (a measure of glucose absorption
and metabolism) was 85% lower with the Phase 2® , p < 0.05. Thus
only 15% of the glucose in the bread compared to the control found
its way into the body in the presence of Phase 2® . These results
show the effectiveness of the product in decreasing the absorption
of glucose from complex carbohydrates from this group of subjects.
Clinical Studie 3.
Phase 2® ™ Demonstrates Efficacy When Taken
With a Mixed Full Meal
University of Scranton researcher, Prof. Joe A.
Vinson, reports that Phase 2® reduced starch absorption by 28% when
0.75 grams of the ingredient was mixed with a full meal and served
to participants in a random, blinded fashion. Three previous human
pilot trials conducted by Vinson confirmed that 1.5 grams of Phase
2® were effective in reducing starch calories (an average of 66%)
when study participants were fed a high carbohydrate, high fat meal
of bread and margarine.
"This study is important because it shows that half the amount of
Phase 2® can be effective in a full meal containing carbohydrates,
proteins and fat," said Vinson. "It is also consistent with previous
studies. An even more significant difference in starch absorption
may occur if respondents are given a higher dose of Phase 2® ."
The study involved seven participants who consumed a microwaved
control meal consisting of Hungry-Man Frozen Country Fried Beef
Steak, along with 240 ml of water. The meal contained 630 calories
with 64 grams of carbohydrates, 29 grams of protein, and 29 grams of
fat in the form of breaded sirloin beef patties, mashed potatoes
with gravy, mushrooms, green beans, and cherry-apple crumb cake. The
control group received only the meal, while the other group received
the meal with 0.75 grams of Phase 2® mixed in with the mashed
potatoes.
KEARNY, NJ, DEC. 10, 2002—Patients who took a
concentrated starch neutralizer extracted from the white kidney
bean, lost nearly a half pound per week (3.8 lbs. over eight weeks),
on average, or better than 200% more than those on placebo. Patients
on the starch neutralizer also lost 1.5 inches around their waists,
on average, or 43% more than those on placebo.
“The results are encouraging, and look very promising,” said
chief researcher, Jay Udani, M.D., Medical Director, Integrative
Medicine Program, Northridge Hospital Medical Center, Los Angeles,
CA.
“One of the most surprising results of the study was the impact
that the starch neutralizer had on triglycerides, a form of bad
cholesterol,” said Udani. “There was a dramatic, 26-point drop in
triglyceride levels, on average, for patients taking the starch
neutralizer, while those on placebo averaged only an 8 point drop in
triglyceride levels. The difference between the two groups was more
than 300%.
“The ability of this product to reduce triglycerides may be an
important adjunct in maintaining a good cardiac profile.”
Another surprising result, according to Udani, was the effect of
the starch neutralizer on energy levels.
“Those patients on the starch neutralizer reported a 13% increase
in energy, while those on placebo reported no improvement in this
area. This is important because the starch neutralizer is not a
stimulant.”
No significant adverse effects from the starch neutralizer were
reported by any of the patients participating in the study.
Pharmachem laboratories, Kearny, NJ, is the supplier of Phase 2®
starch neutralizer. The company develops, supplies and manufactures
a variety of high-quality, efficacious food supplements standardized
for specific potency, solubility, direct compression and
disintegration characteristics. The Company operates four processing
and manufacturing facilities in Northern New Jersey, including the
H. Reisman Corporation. Pharmachem also owns American Ingredients,
Anaheim, CA.
Clinical Studie 5.
Investigation of the efficacy of Phase 2® ,
a purified bean extract from Pharmachem Laboratories
Joe
A. Vinson, Ph.D.
Department of Chemistry
University of Scranton
Background
Amylase is a digestive tract enzyme, which breaks down starch into
small units capable of being further degraded to glucose, which is
used for fuel for normal metabolism and body homeostasis. Clinical
use of inhibitors of amylase activity has widespread appeal because
a controlled reduction of starch digestion could influence
carbohydrate uptake in diabetes and obesity, the latter of which is
a current problem with 20% of the US population. Of course obesity
is also linked to a greater risk of diabetes. A search in the
National Library of Medicine Database reveals that there are 1098
articles concerning amylase inhibition. About 15 years ago there
were a number of articles concerning the use of commercial
bean-derived extracts. Also there were several articles indicating
that some of these products, which were good in vitro inhibitors,
were not effective when given to humans. Possible reasons for this
failure were 1) insufficient activity; 2) destruction in the
gastrointestinal tract; 3) suboptimal pH conditions; and 3)
different gastric emptying rates of starch and inhibitor. A
comprehensive experimental investigation by a group at the Mayo
Clinic in 1985 found that the major reason commercial bean amylase
inhibitors have failed to influence starch digestion in humans is
their low antiamylase activity. Some inhibitors also have side
effects such as diarrhea and an increase in intestinal gas. We have
investigated the effectiveness of a new commercial bean extract
(Phase 2® ) prepared by Pharmachem Laboratories using normal human
subjects.
Protocol Five males and five females (ages 21 to 57) participated in
a double-blind placebo controlled crossover study with informed
consent. All subjects were employees at a commercial clinical
laboratory and went about their duties as secretaries and
technicians during the study. After an overnight fast, the
participants were sampled for blood and then given in a random
manner either 1) placebo consisting of 4 slices of white bread (60
grams of carbohydrate), 42 grams of soybean oil margarine and 4
grams of Sweet N'Low spread on the bread; 2) experimental comprising
the placebo plus 1.5 grams of Phase 2® prepared by Pharmachem
Laboratories. Plasma glucose wasmeasured, by a commercial enzyme kit
(Sigma Chemical Company), from blood drawn at baseline every 30
minutes for 4 hours. After 1 week the regimen was repeated with the
other supplement.
Results and Discussion The subjects were normoglycemic as measured by fasting
glucose concentration, which averaged 98 mg/dl for the placebo and
104 for the Phase 2® . From 60 to 120 minutes (as seen in the
accompanying figure) the change in plasma glucose of the Phaseolamin™
group from the baseline was ½ to 1/3 of the level of the placebo
group. Phaseolamin™ consumption caused the plasma glucose to return
to baseline values 20 minutes earlier than the placebo without
Phaseolamin™. The average area under the plasma glucose-time curve
from 0 to 150 minutes, which is a measure of absorption and
metabolism, was 57% lower with Phaseolamin™. Plotting the average
change in glucose concentration from 30 minutes to 210 minutes, the
area under the curve was positive for the placebo but negative for
Phase 2® . This indicates that very little of the glucose from the
starch in the bread was absorbed when co-ingested with Phase 2® and
the glucose was cleared very rapidly. No side effects were observed
with this product. The promising positive preliminary results of
this single dose pilot study need to be confirmed. More control of
physical activity is required to decrease the variability of plasma
glucose between subjects. Ingestion of Phase 2® with a conventional
meal should be examined. Other groups such as diabetic and obese
should be studied with a single dose and also in a long-term
supplementation study.
Clinical Studie 6.
Summary of clinical study evaluating
effectiveness of Phase 2® .
Dr. R. Ballerini,
Managing Director of Pharmeceutical Development and Service srl.
Milano, Italy
Summary
A study on 60 human healthy volunteers, males and females, aged
20-45 years, which had been characterized by a 5 - 15 kg. overweight
for at least 6 months was conducted to evaluate safety and efficacy
of a food supplement intended to help weight loss by reducing
absorption of calories from carbohydrates, comparing such a product
vs. a placebo. The study was performed upon request from Consorzio
RTC - Ricorche e Tecnologie Cosmetologiche.
The considered
products were identified as Blockal batch D106B and Blockal batch
1600301.
An envelope containing qualitative and quantitative formulations
of the samples and the key for the identification of the products
was given to the Study Responsible and, if necessary was available
for the researchers during all the study. At the end of the study
the envelope was opened, and products and formulations identified in
front of the Study Responsible and of a RTC delegate.
To highlight the activity claimed by the considered product,
volunteers were asked to take a tablet before a meal rich of complex
carbohydrates.
In this sense, 30 days before starting the test (t-30) each
subject was controlled by a Dietician, that gave him/her a table
with nutritional suggestions, recommending the daily assumption of
complex carbohydrates during one of principal meals, so that they
could get used to this regimen.
All volunteers undertook to take the Dietician's advice and their
weight was registered after 10, 20 and 30 days. Only 60 volunteers
whose weight remained stable in such a period were recruited for the
study.
A 30-day double blind test for home use of the food supplement,
with LAB control, was then performed.
Volunteers were divided in two homogenous groups (sex, age,
weight) and took 1 tablet a day of the considered products, in the
correspondence of the meal with complex carbohydrate high content,
for 30 days as follows:
Group 1: Blockal batch D106B
Group 2: Blockal batch 1600301
Volunteers undertook to maintain their regular habits (such as
sport, or any other habits that could affect the study) and to
follow the Dietician's nutritional advises.
At the beginning (t0) and at the end of the study (t30), weight
of each subject was measured. Fat body mass and lean body mass were
calculated (bioelectric impedance measure method).
At the same time (t0 and t30) a cutaneous echographia was
performed on each subject to determine adipose membrane thickness.
Such an evaluation was performed at trochanter zone in women and at
abdominal zone in men. Waistline, hips circumference and thigh
circumferences were also measured.
Furthermore, at the end of the study, volunteers' opinions
concerning tolerability and efficacy of the products were
considered.
Results
Group 1: (Blockal batch D106B) At the end of the study (t30) results highlighted that the
product determined a weight loss of kg 2,933 (corresponding to 3.90%
of total body weight). Such a weight loss also determined a 10.45%
reduction of fat body mass, without significant modifications of
lean body mass.
Results also highlighted that the product determined a 11.63%
reduction of adipose membrane (by echography), a 3.44% reduction of
waistline, a 1.39% reduction of hips circumference and a 1.44%
reduction of thigh circumference.
Personal evaluation also highlighted a good tolerability and a
good efficacy of the considered product.
Group 2: (Blockal batch 1600031) At the end of the study (t30) results highlighted that the
product determined a weight loss of kg 0.348 (corresponding to 0.47%
of total body weight) without significant modifications of fat body
mass and of lean body mass.
Results also highlighted that the product determined a 1.30%
reduction of adipose membrane (by echography), a 0.53% reduction of
waistline, a 0.10% reduction of hips circumference and a 0.39%
reduction of thigh circumference.
Personal evaluation also highlighted a good tolerability and a
low efficacy of the considered product.
At the end of the study, the Study Responsible compared the
formulations of considered product that resulted as follows:
Blockal batch D106B (Group 1): food supplements containing active
ingredients inhibiting carbohydrate absorption (includes 500mg of
Phase 2® )
Blockal batch 1600031 (Group 2): placebo
Conclusions Results suggest that Blockal batch 1600031 (placebo) did
not determine significant modifications of the considered
parameters, while Blockal batch D106B demonstrated a good efficacy
in reduction of calories intake form complex carbohydrates for an
easier, correct and balanced weight loss (calculated by impedance
measure), with reduction of adipose membrane thickness (echography)
and a reduction of waistline, hips circumference and thigh
circumference.
Such results have to be correlated with the specific composition
of the product that contains a vegetal glycoprotein capable of
inhibiting pancreatic a-amylase. Such a protein (weight 49,000
Daltons) demonstrated in vitro an inhibition corresponding to 14.638
units per gram).
It should also be stressed that in this study, food supplement
was administered in correspondence of a complex carbohydrate high
content meal, and that complex carbohydrates can be absorbed only
after enzymatic parting trough pancreatic amylases.
Weight loss, particularly of fat body mass, can be reconducted to
a lower absorption of complex carbohydrates, due to the activity of
the vegetal glycorprotein included in the food supplement taken
before the meal.
The study demonstrated the real capability of the considered
product to determine in vitro weight loss trough fat body mass
reduction via a reduced absorption of complex carbohydrates, that
represent a relevant, or even excessive, part of calories intake.
Clinical Studie 7.
Chronic Toxicity Study Confirms Safety of
Phase 2® Ingredient
KEARNY, NJ, NOV. 5, 2002--Pharmachem Laboratories,
Inc., today announced that a Chronic Toxicity Study (L.D.50)
demonstrated that Phase 2 Starch Neutralizer™, the first
standardized white bean extract used in a variety of weight loss
supplements, is safe and non-toxic.
“Phase 2® showed no signs of chronic toxicity at doses up to 1.0
gm/kg body weight for up to 90 days,” said Ramadasan Kuttan, Ph.D.,
director, Amala Cancer Research Center, Thrissur, India, who
conducted the study along with R. C. Srimal, M.D. “The data
indicates that administration of Phase 2® for 90 days did not
produce any adverse reaction as seen from the organ weight,
necropsy, haematological values and biochemical values.”
Additional findings of the study were as follows:
• There was no significant weight changes in any of the animals.
• Food consumption in the Phase 2® groups (1 gm and 5 gm) was found
to be decreased significantly, especially after two months of
treatment, compared to controls.
• Liver function tests indicated that chronic administration of
Phase 2® at the doses given did not produce any change in the liver
function tests such as GOT, GPT, ALP, Bilirubin, total protein and
Albumin/Globulin ratio.
• Chronic administration of the Phase 2® did not produce any change
in the renal function as indicated from serum urea, creatinine and
electrolyte levels.
• Chronic administration of Phase 2® did not produce any change in
the haematological parameters such as total WBC, differential count
and platelets.
• There was no change in necroscopy of the animals and organ weight
of the animals such as liver, kidney, spleen were unchanged.
• There was no significant change in the lipid profile of animals
treated with Phase 2®
• Histopathology of liver and kidney of the Phase 2® -treated groups
was normal and similar to controls.
An LD 50 study for acute toxicity, conducted earlier this year,
also confirmed that Phase 2® is “safe and non-toxic.”
