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HCG Fat Loss
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Dr. Simeons HCG Protocol
> Dr. A.T.W. Simeons >
HCG For Weight Loss - A Double-Blind Study
Abstract
Female obese volunteers participating in a double blind study, and submitted
to the administration of a presentation of hCG (Human Choriogonadotropin) plus
a VLCD (Very Low Calorie Diet), decreased specific body circumferences and
skinfold thickness from conspicuous body areas more efficiently than Placebo +
VLCD-treated subjects.
Since a significant fat proportion from total body fat is subcutaneously
located (50 to 65 percent, depending on sex and fat distribution), this hCG
metabolic activity would result in a reduction of the total body fat mass, the
main cause for obesity. We suggested that the combination of a VLCD and hCG
could not only trigger clinically significant changes in subcutaneous fat
stores but simultaneously decrease body weight and modelate body contour.
hCG administration proved to be a safe and effective procedure on obese
treated volunteers. No side effects were
observed during the study. There are no reports in the literature regarding
this administration route to compare our findings.
Compared to placebo treated subjects, volunteers who were managed with an administration of hCG coped more efficiently with daily irritating situations,
were in a better mood, and handled home conflicts without stepping up family
discussions.
Keywords: Gonadotropin(s), Chorionic; Obesity; Adipose tissue metabolism; fat
; overweight; beta-endorphin; lypolisis; lipogenesis.
Introduction
Quite few substances have been so neglected and misunderstood regarding its
potential therapeutic actions as hCG, the acronym for Human Chorionic
Gonadotropin.
First discovered by Ascheim and Zondek as back as 1927 in the urine from
pregnant women, thousands of articles were published regarding its action
on gonads, but comparatively quite a few investigated its vast therapeutics
potentialities, encompassing Kaposi sarcoma, asthma, psychoses, artheriopaties, thalassemia, osteopenia,
glaucoma.
hCG is the glycoproteic hormone normally secreted by trophoblastic cells of
the placenta during pregnancy. It consists of two dissimilar, separately, but
most presumably coordinately translated chains, called the alpha and beta
subunits.
The three pituitary hormones LH (Luteinising Hormone), FSH (Follicle
Stimulating Hormone) and TSH (Thyroid Stimulating Hormone) are closely related
to hCG in that all fours are glycosilated and have a dimeric structure
comprising the alpha and beta chains as well.
The aminoacid sequence of alpha chain of all four human glycoproteic hormones
is nearly identical. The aminoacid sequence of the Beta subunits differs and
account for by the unique immunological and biological activities of each
glycoproteic hormone. Beta hCG contains a carboxylic residue of 30
aminoacids characteristic to hCG.
Its denomination (Human Chorionic Gonadotropin) dates back from the early
days, when it was found hCG rendered mature the infantile sex glands in
experimentation animals (Gonadotropin) and it was secreted by the placentary
chorion (Chorionic).
However, recent data suggest both terms can be misleading: normal human
tissues from non-pregnant subjects (88,74,48,86,87), trophoblastic and non-trophoblastic
tumors, bacteria, and plants express hCG or a hCG-like
substance.
The first report on hCG and obesity was published back as 1954 in The Lancet,
by a British born physician, graduated in Germany,
Dr. A.T.W. Simeons.
Dr. Simeons was born in London in 1900 and graduated in medicine at the
University of Heidelberg. After further studies in Germany and Switzerland he
moved to Dresden where he was appointed to a large surgical Hospital.
He got very involved in tropical diseases and joined the school of Tropical
Medicine in Hamburg. He later moved to work in Africa for a while. Later he
went to India (1931) he became fascinated with the country and its health
problems and stayed there for 18 years. In 1949 he moved to Rome where he
continued his work on psychosomatic disorders at the Salvatore Mundii
Hospital.
After its publication, hCG was advocated for several years as an useful
approach to obesity. The pendulum of its popularity swinged back and forth
until a serial of studies but three concluded hCG was
of no use to manage the disease
According to basic pharmacological postulates, the administration route may
influence the biological activity of a drug. All previous studies were
performed with a hCG preparation administered by injections. One of the
authors of this study (DB) theorized that an increase in dose and a shifting
in hCG administration to a sublingual-enteral route may modify the
pharmacological activity of hCG.
The purpose of this study was to assess the utility of a presentation hCG for the management of obesity.
Materials and
Methods
The study design was of the double-blind type: neither treating physician nor
patient knowing who was receiving hCG, or an inert substance (placebo). Female
patients for the study were selected, since the clinic where the study was
performed specializes in the diagnosis and treatment of gynecologic disorders.
Details of the protocol were explained to eighty-three volunteers, who were
solicited through a written announcement. Before being entered the study they
signed an informed consent in front of a neutral witness.
Inclusion
Criteria
We required selected volunteers to meet the following criteria: being at least
25 % BMI (Body Mass Index) overweight, and in general healthy condition. If
taking medication for obesity, such as anorectics or amphetamines, they should
discontinue the medication at least one month prior the initiation of the
study.
Drugs to control their clinical diseases (hypertension, hypothyroidism, etc.)
were allowed. No patients under steroid, diuretics or hormones were entered
the study. During the study, volunteers were also asked about starting the use
of medical prescribed drugs or pharmaceutical preparations during the trial
period.
Exclusion Criteria
No teenagers and patients over 75 y.o were admitted to the study. No patients
with severe and/or uncontrolled clinical diseases (cancer, IDDM, heart
attacks, infarcts sequelae) were accepted. After applying the
inclusion/exclusion criteria, we counted on 70 subjects to divide in treatment
groups.
These women were randomly assigned to groups Placebo or hCG by a simple randomized sampling method. This latter group was in turn splitted
in two subgroups: G1 and G2, according to the hCG dose administered.
Procedures
Patients were Caucasic, ages ranging from 23 to 73 years old, a range of heights of 1.62 cm. to 1.81
cm, and overweight ranging from 25 to 49.9 on BMI Tables.
Since there were no published reports on the use of hCG, group G2 was
administered twice the dose of G1, to assess if hCG concentration may affect
obtained results.
The pharmacist prepared two types of vials: one containing saline solution, and the other containing a diluted and buffered solution of
standardized hCG .
Vials were randomly labeled, each number corresponding with a patient. The
pharmacist kept the codes in a sealed envelope. They were opened after
completing the protocol.
Diet Plan
The same Very-Low-Calorie-Diet (VLCD), specific and detailed, was prescribed
to all groups.
Breakfast: tea or coffee in any quantity without sugar. Only one tablespoonful
of milk allowed in 24 hr. Saccharin or other sweeteners could be used.
Lunch: 100 grams. of veal, beef, chicken breast, fresh white fish, lobster,
crab or shrimp. All visible fat was carefully removed before cooking, and the
meat weighed raw. Salmon, tuna fish, herring, dried or pickled fish was not
allowed.
The chicken breast was removed raw from the bird. One type of vegetable could
be only chosen from the following: spinach, chard, chicory, beet-greens, green
salad, tomatoes, celery, fennel, onions, red radishes, cucumbers, asparagus,
and cabbage. One breadstick (grissini) or one Melba toast was allowed, and an
apple or an orange, or a handful of strawberries or one-half grapefruit.
For dinner: The same four choices as lunch.
The juice of only one lemon daily was allowed for all purposes. Salt, pepper,
vinegar, mustard power, garlic, sweet basil, parsley, thyme, marjoram, etc.,
could be used for seasoning, but no oil, butter or dressing. Tea, coffee,
plain water, mineral water were the only drinks allowed, but they could be
taken in any quantity and always.
Clinicometric
Controls
Volunteers assisted twice weekly at the clinic to be controlled and weighed.
The following evaluations were completed once a week:
I. Height and Weight, performed on a medical scale. Volunteers were weighed
using normal underwear
II. Body circumferences. Using a flexible, non elastic metric tape, the
following anatomic areas were assessed:
Wrist, at the level of flexion fold (wrist-forearm);
Breast, submammary fold;
Waist: at the hypogastric region level;
Abdominal, at the navel level;
Hips: pubic line;
Thighs: 8 cm. below pubic line;
Suprapatelar, at the patella upper border;
Ankle, at the flexion fold (peroneal protuberance).
III. Skinfold thickness. Using a Lange Skinfold Caliper (Cambridge Scientific
Industries, Cambridge, Maryland), the following folds were examined:
Tricipital, arm midline, posterior region and tricipital muscle zone;
Anterior Axilar line, at the fold created when pinching the skin region
at the level of the pectoralis muscle extending to the arm;
Subscapular: inferior scapular spine;
Thoracic: at the fold created when pinching the region located
immediately below the ribs, at the level of an imaginary line extending from
anterior axilar line;
Suprailiac, at the fold created 4 cm above the anterior superior iliac
spine;
Supraumbilical, 3 cm above navel;
Infraumbilical, 3 cm below navel;
Thighs, internal aspect of thighs, eight cm below the pubic area;
Patellar area, at the fold created when pinching the region located 6 cm
medial to the internal patellar border.
IV. Bioelectrical impedance. Using Tetrapolar Bioelectrical Impedance with a body fat analyzer Maltron, model BF-905 (Maltron International Ltd.,
Rayleigh, Essex).
Volunteers voided previous to the evaluation, placed on supine position , and
allowed to rest half an hour before determination. Self-adhering electrodes
were placed on extremities. Every determination was performed with a separate
set of electrodes, discarded after single use.
The following TBI determinations were assessed:
1. Fat weight
2. Lean weight
3. Water weight
4. Calories
V. b-hCG determinations: all subjects enrolled in the trial were studied for
plasmatic b-hCG levels by an ELISA test on 0-15-30 study days.
VI. Mood questionnaire: from the first study week on, patients were given
weekly self-administered questionnaires to be completed at home. It consisted
of twenty-four questions related to their mood changes in the course of the
study, plus four questions related to adverse drug effects. They returned the
data at the time of the subsequent visit to the clinic.
Data Analysis
Variables were splitted as follows for a better data processing and
statistical results presentation:
· Category I, BW plus four bioelectrical impedance records.
· Category II, eight anthropometrical measurement.
· Category III, nine skinfold assessments (see long names and definitions for the studied variables at
the beginning of this section).
Each set was analyzed with a two-way multivariate analysis of variance,
comparing the obtained Wilks-lambda' F with the corresponding critical value.
TREATMENT (VLCD diet plus group-specific pharmacological intervention) was
considered the between-subject factor with three levels, and WEEK
of clinicometric control served as an additional within-subject factor with
six levels: weeks 0 to 5.
To estimate how the differences between treatment' groups depended on the
trial time elapsed since week zero (comparison of pattern trend changes in
function of treatment time) we obtained the MANOVA result for the effect of
the INTERACTION (also displayed in the text as TREATMENT x WEEK).
Moreover, to prevent any possible influence of acute effects specifically
associated to any VLCD program in the adaptation phase (first 5-7 days), we
additionally evaluated with separate MANOVA analyses the differences between
groups and within subjects in the course of the last four treatment's weeks.
After obtaining a statistically significant multivariate test for a particular
main effect or interaction, we further examined the univariate F tests for
each dependent variable. When parameters from these tests displayed
significant modifications, data were further analyzed to ascertain which group was the responsible for the previous p values obtained.
We also compared data basal values from each group against those obtained in
subsequent weeks (e.g., records of week 0 against week 1, thereafter against
week 2, and so on). These pairwise comparisons were statistically assessed
applying a post hoc Scheffé F tests.
Questionnaire responses were converted into percentages and submitted to a
chi-square (2c) test to compare between-groups and within-groups (pairing off
final vs. initial data) statistic results.
To attenuate the natural source of within-subject variation, inherent to all
assessments of subjective symptoms, we averaged data results from identical
questionnaires completed weekly during the initial first two study weeks.
Thus, we obtained a more precise "initial questionnaire" (avoiding the
potential "adaptation effect" common to any VLCD regime in the first treatment
week).
To obtain the final mood behavior results over the last two treatment weeks,
they were averaged using the same schema as detailed before.
Results
All volunteers were submitted to the same VLCD schedule lasting five weeks.
The objective of this study was to gather data on the potential synergism
between hCG administration and a VLCD plan.
At the end of the study we counted a total of 4.3 % missing data due to the
absence of subjects in control days (no one absent in more than two
opportunities) because personal situations not associated with the
experimental conditions.
No statistic differences were obtained among Placebo and hCG groups regarding
missing data.
1. Regarding weight loss, similar results (with/without hCG administration)
were obtained. Bioelectrical impedance exhibited discrete modifications in
tested groups.
As expected, for all types of clinicometric assessments, significant results
were obtained through MANOVA analysis on factor WEEK.
Figure 1 and
Figure 2
(bioelectrical impedance and anthropometrical data, respectively) show that
the time-dependent changes were uniformly present in all tested groups.
We therefore estimated that the decreasing observed patterns were the
consequence of VLCD acting on overweight patients. However, regarding skinfold
thickness findings (Figure 3 and Figure 4), we detected in P group a noticeable
tendency to attenuation of the within-subject variation during the last (third
to fifth) study weeks.
The data suggested us that this latter period might be the focus of our
interest (see detailed analysis below).
Figure 1 shows data patterns resulting in all groups from three representative
variables (BW, FW and LW) of the variable category I. The MANOVA analysis
revealed nearly significant differences for the INTERACTION (TREATMENT x WEEK)
without statistical significance on analysis of TREATMENT as main effect.
When all groups were submitted to multivariate and univariate analyses taking
exclusively data from weeks 2-5, we observed no significant difference result
for the INTERACTION among group P and hCG-treated groups. This finding could
be related to differences in mean basal body weights and treatment-dependent
responses to the acute effects of VLCD during former weeks.
When post hoc Scheffé test was applied to compare the result from each weekly
record (weeks 1-5) to it's corresponding basal value (week zero), we found
similar patterns for all groups concerning analysis of BW and TBI records
(compare P vs. hCG-treated groups in every panel of Figure 1).
However, regarding the analysis of FW and BW data, we detected significant
differences for the effect of the INTERACTION. Comparing FW patterns from groups P and G1. For the comparison P vs. G2, (BW and FW data), we obtained:
respectively.
2. hCG + diet decreased more significantly waist and abdominal circumferences
than diet alone.
Figure 2
shows the results for three (category II) body circumference assessments. MANOVA analysis showed significant differences
for factor TREATMENT as main effect, which we do not
consider relevant due to the presence of higher basal records in group G2 when
compared to the rest of the studied groups.
As a whole, the effect of the INTERACTION did not reveal statistical
significance.
Nevertheless, significant differences were obtained after further analysis for
the effect of the INTERACTION on variable WAT.
Data assessments from other circumferences did not show statistical
differences for this effect among groups.
When the records of weeks 0-1 were subtracted from MANOVA analysis, almost all
p values were slightly affected. WAT and ABD measurements demonstrated to be
still more affected by the INTERACTION.
3. Weak effects of hCG on a series of skinfold thickness reduction patterns.
Figure 3 and
Figure 4 show results from subcutaneous fat evaluations, as assessed by skinfold thickness, on nine selected skinfolds.
Figure 3
presents three representative folds out of five that demonstrated to be
slightly affected by the pharmacological treatment. Analyzing skinfold data
from weeks 0 to 5, the main effect TREATMENT showed statistical significance.
MANOVA analysis run on weeks 2-5 data resulted in a significance increase for
TREATMENT as main effect. In addition, the
INTERACTION was enhanced on data from SCA (l) assessment: by comparing data
from groups P and G2 during weeks 2 to 5.
4. Higher response rates in a different skinfold series by treatment with hCG
plus a VLCD.
In
Figure 4 we display skinfold thickness results obtained from another series
of four examined skinfolds. MANOVA analysis
resulted in a nearly significant INTERACTION without statistical significance
for TREATMENT as main effect.
When the specific effect of the INTERACTION was evaluated for each skinfold,
highly significant differences were found.
When we restricted the data analysis from weeks 2 to 5, we found nearly
significant results for factor TREATMENT as main effect and for the effect of
the INTERACTION.
From the obtained data, it becomes clear that skinfolds determinations in G2
subjects showed a differential response to VLCD schedule with respect to that
of P controls (for INTERACTION, in these points of skinfold assessment).
5. Selective response of some skinfolds to hCG was dependent on dose.
The experimental design of this investigation was not intended to determine
the dose-response curve for hCG acting on diet-induced effects.
However, the effects of hCG on some of these skinfolds seemed to be dependent
on dose, since it was found significant differences for the effect of the
INTERACTION after the comparison between G1 vs. G2 groups, and a nearly
significant p value.
Figure 4 also displays the percentages of skinfold thickness reduction from
the beginning to the end of the clinical trial. We found skinfolds decreases
for group G1 ranging from over 22% and up to over 115%
over respective decreases in P group.
These differences were still higher when G2-subjects were compared to P
controls: by computing the ratio between decrease percentages, G2 had over
twice to over four-fold the skinfold records drops observed in group P (see each actual percentage, group
by group, in
Figure 4).
Most of the differences among hCG-treated subjects and P controls regarding
skinfold reduction rates were enhanced when data corresponding to week five
was compared to records of week two instead week zero (data not shown).
6. Improvement in mood-related parameters by hCG.
In Figure 5 we display the responses to four representative questions asking
about the occurrence frequency for specific mood-related events, according to
a multiple choice designed questionnaire completed every treatment week by all
the subjects enrolled in the trial.
Panels A to D display the initial and final questionnaire results, expressed
as percentages for each optional response (covering a four-option frequency
scale from never to frequent).
Using this procedure, we expected to find in tested volunteers skewness
towards either sense concerning their behaviors and feelings in response to a
diet and a pharmacological intervention.
For all these questions, and compared to control subjects, hCG-treated
volunteers (G1+G2) showed a trend to improvement of interpersonal contacts and
mood control when confronting upsetting or conflicting situations.
Pairing off final (f) vs. initial (i) distribution of percentages for optional
responses, we particularly found statistical significance in two of these
questions in group G.
P group-subjects did not present temporal differences (see panel A), or were
adversely affected in their mood during the trial.
Furthermore, group P exhibited in other two questions certain skewness to the
impairment of its mood; for group G
we obtained the 2c3 values 1.51 and 3.98, respectively, showing the
absence of temporal mood changes.
For all other mood-related questions, no statistical significant difference
among groups was found (data not shown).
We also included some questions intended to evaluate the potential occurrence
of treatment-dependent clinical anomalies regarding hormonal, physiological or
metabolic disorders. We found no significant difference after final vs.
initial records' comparison (data not shown).
7. No detectable b-hCG plasmatic levels in all tested groups.
On treatment days 0, 15 and 30 we have tested all volunteers, screening for
the presence of plasmatic b-hCG. Concentrations were undetectable in all cases
(data not shown).
Discussion
Concerning hCG and its utility for the management of obesity, this study
introduces two new aspects:
I) This is the first report assessing variables not included in previous
reports;
II) We have detected mood changes in hCG treated patients, regarding a better
confrontation of daily emotionally conflicting situations.
These assertions will be separately discussed:
I) Skinfold thickness (SKF) and Tetrapolar Bioelectric Impedance (TBI)
records.
Both approaches have been extensively discussed in the literature. It was
shown that the correlation between the values obtained with the two methods to
be linear and highly significant for both sexes.
There is general agreement that skinfolds calipers are particularly useful in
the clinical setting, particularly in view of the fact that measurement of
subcutaneous body fat at different body sites is becoming increasingly
important for the characterization of risk of certain disease states.
When comparing skinfolds assessments to body circumference estimates, despite
some data suggest that the latter approach appears to be more sensitive in the
determination of subcutaneous body fat, this procedure is in our opinion
subjected to clinical variables (bloating syndrome after a meal, premenstrual
water retention, etc.) that may affect negatively on the final estimates
results.
Also, when comparing SKF to body contour assessments, some data suggest that
the pattern of fat thickness body distribution measured over several specific
sites by one method of measurement is unlikely to be duplicated by of the
other method on the same individual.
Adipose tissue patterns show great variability, showing the importance of
using skinfold caliper readings from a variety of different anatomic sites
including upper limbs, lower limbs and trunk.
According to the above conclusions from several authors,
we would like to suggest that former studies on hCG and obesity lacked of
sufficient data to estimate accurately modifications of adipose tissue
distribution in tested volunteers. Consequently we designed the study to
assess as many as possible variables.
As far as our study concerns, we subjected each volunteer enrolled in the
trial to four bioelectrical impedance, eight anthropometrical plus nine SKF
evaluations. Performing this multiple site determinations, our results show
that specific SKF are highly responsive to hCG pharmacological intervention
(upper and lower umbilical).
The greater response was obtained in those regions where the corresponding
circumference assessments resulted in nearly significant or significant
decreases through the trial period (see waist and abdomen records in Fig. 2
and the above detailed description of statistical results for the effect of
the interaction).
II) Volunteers treated with hCG coped better with daily irritating
situations.
As can be seen on Figure 5, hCG-treated groups handled better their
irritability, their mood at home, and were less prone to episodes of extreme
nervousness capable of provoking violent discussions . Several reports
proposed hCG might be used for the treatment of psychoses or neurosis. Our study appears to corroborate these proposals.
To conclude, this study poses several still unanswered questions:
1. hCG plasmatic levels. We have tested all volunteers, screening for the b-hCG
in plasma. Concentrations were undetectable in all cases.
Therefore, which hCG fraction is responsible for the pharmacological activity
observed in our study? hCG molecular size makes highly improbable that the entire molecule has been
absorbed. Our hypothesis is that only a fraction of the entire hCG molecule is
absorbed through this administration route .
2. hCG and lipid metabolism. We do not know precisely how hCG acts on adipose
tissue metabolism. However, some reports suggest hCG possesses
a metabolic activity on adipose tissue (i.e. decrease lipogenesis). These
actions are not directly exerted on adipocytes, since fat cell membranes have
no receptors for hCG.
3. hCG and mood. A stable mood and lack of attrition characterized the hCG-treated
group.
It is well known that VLCD's are associated with mood changes, particularly
attrition during the dieting period. In one study, disinhibition and
hunger were significantly related to anxiety and depression while restraint
was not. Another study concluded that elevated levels of anxiety persist
in female patients throughout a VLCD course of treatment.
Also many patients complain about fatigue during a VLCD.
Conversely, our data suggest that hCG-treated volunteers rather improved their
attitude towards their environment, in the sense of an enhanced well-being,
less irritability and lack of fatigue. Since commercial preparations of hCG
contains b-endorphin and this neuropeptide has been demonstrated to
affect the function of limbic-emotional circuits, we hypothesized
that the b-endorphin fraction present in commercial preparations of hCG might
account for the activity observed regarding mood control.
Additional studies remain to be performed to test the validity of this
hypothesis.
Conclusions
1. Female obese volunteers participating in a double blind study, and
submitted to the administration of a presentation of hCG plus a VLCD,
decreased specific body circumferences and skinfold thickness from conspicuous
body areas more efficiently than Placebo + VLCD-treated subjects.
Since a significant fat proportion from total body fat is subcutaneously
located (50 to 65 percent, depending on sex and fat distribution), this hCG
metabolic activity would result in a reduction of the total body fat mass, the
main cause for obesity. We suggested that the combination of a VLCD and hCG could not only trigger clinically significant changes in subcutaneous fat
stores but simultaneously decrease body weight and modelate body contour.
2. hCG administration proved to be a safe and effective procedure on
obese treated volunteers. No side effects were observed during the study.
There are no reports in the literature regarding this administration route to
compare our findings.
3. Compared to placebo treated subjects, volunteers managed with an administration of hCG coped more efficiently with daily irritating situations,
were in a better mood, and handled home conflicts without stepping up family
discussions.
This study appears to contradict former conclusions on the issue of hCG and
obesity. We attribute those differences to a different approach, including
variables not assessed in former publications.
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