ORAL HCG™ METHOD

The hCG Method for the treatment of obesity:
Overcoming the "test of time"

Author: Daniel Oscar Belluscio, MD

"A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it."
Max Planck 1858-1947. German Theoretical Physicist

A. The pharmacological nature of hCG
B. A word of caution for those interested in the hCG method for obesity treatment.
C. Proposed mechanisms of action
D. An interesting combined procedure: hCG protocol plus selective local adrenergic modulation of adipose tissue metabolism
E. Oral hCG (Human Choriogonadotropin) for the management of obesity: a Double-Blind study

Note: The number in bold and between brackets refer to the bibliographical references included in the double-blind study.

A. The pharmacological nature of hCG

hCG is a glycoproteic hormone, normally secreted by trophoblastic cells of the placenta. It consists of two dissimilar, separately but coordinately translated chains called the Alfa and beta subunits (46-93-160-231-369-415-483-484).

The three pituitary hormones LH (Luteinising Hormone) are closely related to hCG in that all four are glycosilated and have a dimeric structure comprising an Alpha and Beta chain as well.

The aminoacid sequences of the Alfa chain of all four human glycoproteic hormones are nearly identical.

Aminoacid sequences of the beta subunits differ because of the unique immunological and biological activities of each glycoproteic hormone. Beta -hCG contains a carboxylic residue of 30 aminoacids characteristic to hCG (44-45-216-395).

When it was discovered by Ascheim and Zondek by 1927 they found out that hCG matured the infantile sex glands of experimental animals, and it was secreted by the human placenta. From there its denomination: Chorionic Gonadotrophin (25-519).

However, recent data suggest that both terms can be quite misleading: normal human tissues (231-464) plasma from non pregnant subjects (62-353-516), trophoblastic and non-trophoblastic tumors (83 -106- 110- 226-345- 400-401-444), bacteria (3- 4- 28- 301- 312-436) and plants (138-168) express hCG or a hCG- like material.

After the first report on hCG use for obesity treatment, an innumerable amount Physicians all over the world visited Dr. Simeons in Italy, to learn from first hand the hCG original protocol.

Many of them attempted to recreate the standard procedure without success, or obtaining undesirable results. TOP

B. A word of caution to those interested in performing the method.

After many years of experience on the use of hCG for the management of obesity, we would like to stress the following

• hCG is not a magic wand
It does not cure or eradicate obesity, but weight losses are rapid, comfortable, and the maintenance period after treatment runs a smoother course.

• There is no difference regarding weight loss between hCG-treated and
non-treated patients

Obesity might not be only a matter of overweight. Dieting per se is not a treatment for obesity. Rather, it is an ancillary procedure.

Unless we try to act upon the basic diencephalic disturbance, any dietetic procedure will be condemned to failure.

We cannot improve diabetes just by dieting, and obesity cannot be effectively treated without some sort of medical intervention in the diencephalon.

Anorectics point in that direction, and were for many years an unsuccessful approach to obesity because their side-effects.

Dr. Simeons never sustained that weight loss under hCG was more important than without hCG-treated cases. What he suggested was that hCG, acting at hypothalamic level, might correct the basic hypothalamic disorder, and consequently adipose tissue metabolism.

If this turns out to be the case, hCG could be an excellent adjuvant procedure in the management of the disease.

The vast majority of publications concluded hCG has no action on weight loss, rendering no better results than a current Hypocaloric diet, except for classical Asher and Harper report concluding that weight losses under hCG were superior to placebo. TOP

C. Proposed mechanisms of action

• hCG displays a metabolic action on adipose tissue metabolism

Throughout these years, hCG has been reported to exert its actions on several tissues other than gonadal: Kaposi sarcoma, asthma, psychoses, artheriopaties, thalassemia, osteopenia and glaucoma. Therefore, we are not dealing with a "pure" sex hormone

Available data would indicate that hCG might also improve lypolisis in human adipose tissue, via an inhibitory effect on lipogenesis.

• hCG actions on adipose tissue metabolism (161-382)

Fleigelman concluded that the administration of hCG in rats decreased the activity of alfa-glycerophosphate dehydrogenase and glucose-6-phosphate dehydrogenase from the liver and adipose tissue, suggesting a decreased lipogenic activity in both tissues under hCG (161) .

Yanagihara reported that hCG accelerates "not only the mobilization of fat from fat deposits, but also its utilization in peripheral tissues. hCG increased the metabolism of injected fat emulsions, suggesting the acceleration not only of fat oxidation, but also increased ketone production in the liver and its utilization in peripheral tissues" (514).

Romer reported that hCG intensifies the metabolism of rat brown adipose tissue (391).

Administration of hCG to humans appears to increase the release of fatty acids that varies with the age of the subject. Melichar demonstrated that hCG causes a marked FFA release in newborn infants (317).

In adults, a single dose of hCG caused a marked FFA release by p > 0.05 when compared to placebo-treated subjects.

Consequently we hypothesize, that hCG might act upon adipose tissue metabolism through some mediators secreted at hypothalamic level.

• The diencephalic region and hCG

One of the most valuable hypotheses on the genesis of obesity sustains that the basic metabolic disorder lies in the hypothalamic region: like in any other clinical disorder, we have to find out who is the villain in this story. For example: the pancreas in diabetes, the thyroid in hypothyroidism. the adrenal glands in Addison disease.

The organ more frequently incriminated in the genesis of fat accumulation seems to be the hypothalamus. A considerable body of evidences points in that direction.

Interestingly, exogenous administered hCG accumulates in hypothalamic region, particularly in Ventromedial and Lateral Hypothalamus. It is not therefore unreasonable to suppose that the target organ for hCG metabolic actions might be the diencephalon. (178-513)

hCG may act at diencephalic level, probably modifying some neuropeptide metabolic pathways, which in turn act whether on Ventromedial or Lateral hypothalamic Nucleus, or via Hypothalamus hypophisis (30-209).

Summary

There are no age or sex limits, and hardly any contraindications (211) to use the hCG method for the treatment of obesity. Tolerance to the treatment is excellent, and many patients willingly submit to a second treatment.

Weight loss is safe and comfortable for patients, provided that they meticulously follow the prescribed diet. Any deviation from the protocol is apt to yield poor results. Even minor deviations may cause unwanted setbacks.

The hCG protocol is an appropriate approach to the treatment of obesity that also includes a behavior modification program as well as pharmacological and dietetic aspects. When properly managed, the result is rapid weight loss and improved body shape after treatment. Clinical complications and unfavorable results are related to unsafe modifications of the protocol.

Evidence suggest that hCG promotes lipolytic activity. Since hCG does not mobilize in vitro lipids from the fat cell, it was hypothesized that the hypothalamic region might be the intermediate organ in hCG lipolytic action.

The hCG method includes patients' follow-up (daily visits to the doctor to be weighed and injected), helping patients with their behavior modification program. There are some similarities between the behavioral program included in the hCG protocol and a current behavior modification program for obesity treatment.

The 500 Kcal-diet as prescribed in the original treatment proved to be safe and effective. Results are not surpassed by any other modality of obesity therapy. Reshaping of body contour is more noticeable in those patients displaying the so-called gynoid types (fat located in buttocks and hips area). TOP

D. An interesting combined procedure: hCG protocol plus selective local adrenergic modulation of adipose tissue metabolism

• Introduction

The subject of adipose tissue membrane receptors has been a subject of great interest in recent years.

Human fat cells possess both Alpha and Beta membrane adrenoreceptors, acting differently on adipose tissue metabolism (500).

The major function of adrenoreceptors in white fat cells is to regulate the breakdown of triglycerides to free fatty acids and glycerol through lipolysis. Functions and mechanisms of action of adrenoreceptors in white fat cells are as follows:(16-17-18-19-20-21-22).

1. Beta l.2.3. receptors increase lipolysis rate.

2. Alpha 2 decrease lipolysis rate.

Human adipose tissue is an extremely metabolic active organ: Depending on where it is localized, it shows a different response to drug intervention. Visceral fat cells are more responsive than abdominal subcutaneous fat cells (gluteal or femoral) to the lipolytic actions of catecholamines.

There are also sex differences: A higher Alpha2-receptor affinity has been reported in peripheral male subcutaneous fat cells than in the abdominal, which may explain why the regional variation in catecholamines-induced lipolysis within the subcutaneous adipose tissue is more pronounced in men than in women.

Fasting also modifies the regional sensitivity of adipose tissue: It is associated with a decrease in catecholamines-induced lipolysis rate in peripheral, but not abdominal, subcutaneous adipose tissue. This may further promote the development of gynoid obesity.

During fasting, Alpha activity (antilipolytic) increases and Beta action (lipolytic) decreases in female thighs region (351-352).

An increase of Alpha activity is related to a decreased lipolysis, whereas a diminution of beta adrenergic activity provokes the same effect (366).

Therefore, it has been suggested that the combination of both activities might explain why the female thigh region is more resistant to dietetic procedures.

Abdominal adipocytes are more responsive to the lipolytic action of Beta-1 adrenergic agonists, while gluteal adipocytes are more responsive to the antilipolytic action of Alpha-2-adrenergic agonists.

In lean and obese adults, gluteal subcutaneous adipose tissue was strikingly more responsive to antilipolytic alpha-adrenergic stimulation, and less responsive to lipolytic beta-adrenergic stimulation compared to abdominal tissue (394).

This would explain why gluteal and femoral fat pads are more resistant to dietary interventions.

Taken together, these results seem to suggest that it should be possible to locally modulate the activity of Alpha and Beta adrenoreceptors through the administration of Beta-adrenergic or Alfa-Blockers agents. Beta Stimulation and/or Alpha blocking of adipocytes membrane receptors might increase lipolysis in those areas.

Thus, a reasonable combination would be the prescription of a Very Low Calorie Diet (such as indicated in the hCG Protocol) plus the local administration of Alpha Blockers or Beta stimulating agents.