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If obesity is always due to one very specific diencephalic deficiency, it follows that the only way to cure it is to correct this deficiency. At first this seemed an utterly hopeless undertaking. The greatest obstacle was that one could hardly hope to correct an inherited trait localized deep inside the brain, and while we did possess a number of drugs whose point of action was believed to be in the diencephalons, none of them had the slightest effect on the fat-center. There was not even a pointer showing a direction in which pharmacological research could move to find a drug that had such a specific action. The closest approach wee the appetite-reducing drugs – the amphetamines—– but these cured nothing.
A Curious Observation
Mulling over this depressing situation, I remembered a rather curious observation made many years ago in India. At that time we knew very little about the function of the diencephalon, and my interest centered round the pituitary gland. Proehlich had described cases of extreme obesity and sexual underdevelopment in youths suffering from a new growth of the anterior pituitary lobe, producing what then became known as Froehlich’s disease. However, it was very soon discovered that the identical syndrome, though running a less fulminating course, was quite common in patients whose pituitary gland was perfectly normal. These are the so-called “fat boys” with long, slender hands, breasts any flat-chested maiden would be proud to posses, large hips, buttocks and thighs with striation, knock-knees and underdeveloped genitals, often with undescended testicles.
It also became known that in these cases the sex organs could he developed by giving the patients injections of a substance extracted from the urine of pregnant women, it having been shown that when this substance was injected into sexually immature rats it made them precociously mature. The amount of substance which produced this effect in one rat was called one International Unit, and the purified extract was accordingly called “Human Chorionic Gonadotrophin” whereby chorionic signifies that it is produced in the placenta and gonadotropin that its action is sex gland directed.
The usual way of treating “fat boys” with underdeveloped genitals is to inject several hundred international Units twice a week. Human Chorionic Gonadotrophin which we shall henceforth simply call HCG is expensive and as “fat boys” are fairly common among Indians I tried to establish the smallest effective dose. In the course of this study three interesting things emerged. The first was that when fresh pregnancy-urine from the female ward was given in quantities of about 300 cc. by retention enema, as good results could be obtained as by injecting the pure substance. The second was that small daily doses appeared to be just as effective as much larger ones given twice a week. Thirdly, and that is the observation that concerns us here, when such patients were given small daily doses they seemed to lose their ravenous appetite though they neither gained nor lost weight. Strangely enough however, their shape did change. Though they were not restricted in diet, there was a distinct decrease in the circumference of their hips.
Fat on the Move
Remembering this, it occurred to me that the change in shape could only be explained by a movement of fat away from abnormal deposits on the hips, and if that were so there was just a chance that while such fat was in transition it might be available to the body as fuel. This was easy to find out, as in that case, fat on the move would be able to replace food. It should then he possible to keep a “fat boy” on a severely restricted diet without a feeling of hunger, in spite of a rapid loss of weight. When I tried this in typical cases of Froehlich’s syndrome, I found that as long as such patients were given small daily doses of HCG they could comfortably go about their usual occupations on a diet of only 500 Calories daily and lose an average of about one pound per day. It was also perfectly evident that only abnormal fat was being consumed, as there were no signs of any depletion of normal fat. Their skin remained fresh and turgid, and gradually their figures became entirely normal. The daily administration of HCG appeared to have no side-effects other than beneficial ones.
From this point it was a small step to try the same method in all other forms of obesity. It took a few hundred cases to establish beyond reasonable doubt that the mechanism operates in exactly the same way and seemingly without exception in every case of obesity. I found that, though most patients were treated in the outpatients department, gross dietary errors rarely occurred. On the contrary, most patients complained that the two meals of 250 calories each were more than they could manage, as they continually had a feeling of just having had a large meal.
Pregnancy and Obesity
Once this trail was opened, further observations seemed to fall into line. It is well known that during pregnancy an obese woman can very easily lose weight. She can drastically reduce her diet without feeling hunger or discomfort and lose weight without in any way harming the child in her womb. It is also surprising to what extent a woman can suffer from pregnancy-vomiting without coming to any real harm.
Pregnancy is an obese woman’s one great chance to reduce her excess weight. That she so rarely makes use of this opportunity is due to the erroneous notion, usually fostered by her elder relations, that she now has “two mouths to feed” and must “keep up her strength for the coming event. All modern obstetricians know that this is nonsense and that the more superfluous fat is lost the less difficult will be the confinement, though some still hesitate to prescribe a diet sufficiently low in calories to bring about a drastic reduction.
A woman may gain weight during pregnancy, but she never becomes obese in the strict sense of the word. Under the influence of the HCG which circulates in enormous quantities in her body during pregnancy, her diencephalic banking capacity seems to be unlimited, and abnormal fixed deposits are never formed. At confinement she is suddenly deprived of HCG, and her diencephalic fat-center reverts to its normal capacity. It is only then that the abnormally accumulated fat is locked away again in a fixed deposit. From that moment on she is again suffering from obesity and is subject to all its consequences.
Pregnancy seems to be the only normal human condition in which the dicncephalic fat banking capacity is unlimited. It is only during pregnancy that fixed fat deposits can be transferred back into the normal current account and freely drawn upon to make up for any nutritional deficit. During pregnancy, every ounce of reserve fat is placed at the disposal of the growing fetus. Were this not so, an obese woman, whose normal reserves are already depleted, would have the greatest difficulties in bringing her pregnancy to full term. There is considerable evidence to suggest that it is the HCG produced in large quantities in the placenta which brings about this diencephalic change.
Though we may be able to increase the dieneephalic fat banking capacity by injecting HCG, this does not in itself affect the weight, just as transferring monetary funds from a fixed deposit into a current account does not make a man any poorer; to become poorer it is also necessary that he freely spends the money which thus becomes available. In pregnancy the needs of the growing embryo take care of this to some extent, but in the treatment of obesity there is no embryo, and so a very severe dietary restriction must take its place for the duration of treatment.
Only when the fat which is in transit under the effect of HCG is actually consumed can more fat be withdrawn from the fixed deposits. In pregnancy it would be most undesirable if the fetus were offered ample food only when there is a high influx from the intestinal tract. Ideal nutritional conditions for the fetus can only be achieved when the mother’s blood is continually saturated with food, regardless of whether she eats or not, as otherwise a period of starvation might hamper the steady growth of the embryo. It seems that HCG brings about this continual saturation of the blood, which is the reason why obese patients under treatment with HCG never feel hungry in spite of their drastically reduced food intake.
The Nature of Human Chorionic Gonadotropin
HCG is never found in the human body except during pregnancy and in those rare cases in which a residue of placental tissue continues to grow in the womb in what is known as a chorionic epithelioma. It is never found in the male. The human type of chorionic gonadotrophin is found only during the pregnancy of women and the great apes. It is produced in enormous quantities, so that during certain phases of her pregnancy a woman may excrete as much as one million International Units per day in her urine – enough to render a million infantile rats precociously mature. Other mammals make use of a different hormone, which can be extracted from their blood serum but not from their urine. Their placenta differs in this and other respects from that of man and the great apes. This animal chorionic gonadotrophin is much less rapidly broken down in the human body than HCG, and it is also less suitable for the treatment of obesity.
As often happens in medicine, much confusion has been caused by giving HCG its name before its true mode of action was understood. It has been explained that gonadotrophin literally means a sex-gland directed substance or hormone, and this is quite misleading. It dates from the early days when it was first found that HCG is able to render infantile sex glands mature, whereby it was entirely overlooked that it has no stimulating effect whatsoever on normally developed and normally functioning sex-glands. No amount of HCG is ever able to increase a normal sex function. It can only improve an abnormal one and in the young hasten the onset of puberty. However, this is no direct effect. HCG acts exclusively at a diencephalic level and there brings about a considerable increase in the functional capacity of all those centers which are working at maximum capacity.
The Real Gonadotrophins
Two hormones known in the female as follicle stimulating hormone (FSH) and corpus luteum stimulating hormone (LSH) are secreted by the anterior lobe of the pituitary gland. These hormones are real gonadotropilins because they directly govern the function of the ovaries. The anterior pituitary is in turn governed by the diencephalon, and so when there is an ovarian deficiency the diencephalic center concerned is hard put to correct matters by increasing the secretion from the anterior pituitary of FSH or LSH, as the case may be. When sexual deficiency is clinically present, this is a sign that the diencephalic center concerned is unable, in spite of maximal exertion, to cope with the demand for anterior pituitary stimulation. When then the administration of HCG increases the functional capacity of the diencephalon, all demands can be fully satisfied and the sex deficiency is corrected.
That this is the true mechanism underlying the presumed gonadotrophic action of HCG is confirmed by the fact that when the pituitary gland of infantile rats is removed before they are given HCG, the latter has no effect on their sex-glands. HCG cannot therefore have a direct sex gland stimulating action like that of the anterior pituitary gonadotrophins, as FSH and LSH are justly called. The latter are entirely different substances from that which can be extracted from pregnancy urine and which, unfortunately, is called chorionic gonadotrophin. It would be no more clumsy, and certainly far more appropriate, if HCG were henceforth called chorionic dienccphalotrophin.
HCG no Sex Hormone
It cannot he sufficiently emphasized that HCG is not sex-hormone, that its action is identical in men, women, children and in those cases in which the sex-glands no longer function owing to old age or their surgical removal. The only sexual change it can bring about after puberty is an improvement of a pre-existing deficiency. But never stimulation beyond the normal.. In an indirect way via the anterior pituitary, HCG regulates menstruation and facilitates conception, but it never virilizes a woman or feminizes a man. It neither makes men grow breasts nor does it interfere with their virility, though where this was deficient it may improve it. It never makes women grow a beard or develop a gruff voice. I have stressed this point only for the sake of my lay readers, because, it is our daily experience that when patients hear the word hormone they immediately jump to the conclusion that this must have something to do with the sex- sphere. They are not accustomed as we are, to think thyroid, insulin, cortisone, adrenalin etc, as hormones.
Importance and Potency of HCG
Owing to the fact that HCG has no direct action on any endocrine gland, its enormous importance in pregnancy has been overlooked and its potency underestimated. Though a pregnant woman can produce as much as one million units per day, we find that the injection of only 125 units per day is ample to reduce weight at the rate of roughly one pound per day, even in a colossus weighing 400 pounds, when associated with a 500-calorie diet. It is no exaggeration to say that the flooding of the female body with HCG is by far the most spectacular hormonal event in pregnancy. It has an enormous protective importance for mother and child, and I even go so far as to say that no woman, and certainly not an obese one, could carry her pregnancy to term without it.
If I can be forgiven for comparing my fellow-endocrinologists with wicked Godmothers, HCG has certainly been their Cinderella, and I can only romantically hope that its extraordinary effect on abnormal fat will prove to be its Fairy Godmother.
HCG has been known for over half a century. It is the substance which Aschheim and Zondek so brilliantly used to diagnose early pregnancy out of the urine. Apart from that, the only thing it did in the experimental laboratory was to produce precocious rats, and that was not particularly stimulating to further research at a time when much more thrilling endocrinological discoveries were pouring in from all sides, sweeping, HCG into the stiller back waters.
Some complicating disorders are often associated with obesity, and these we must briefly discuss. The most important associated disorders and the ones in which obesity seems to play a precipitating or at least an aggravating role are the following: the stable type of diabetes, gout, rheumatism and arthritis, high blood pressure and hardening of the arteries, coronary disease and cerebral hemorrhage.
Apart from the fact that they are often – though not necessarily – associated with obesity, these disorders have two things in common. In all of them, modern research is becoming more and more inclined to believe that diencephalic regulations play a dominant role in their causation. The other common factor is that they either improve or do not occur during pregnancy. In the latter respect they are joined by many other disorders not necessarily associated with obesity. Such disorders are, for instance, colitis, duodenal or gastric ulcers, certain allergies, psoriasis, loss of hair, brittle fingernails, migraine, etc.
If HCG + diet does in the obese bring about those diencephalic changes which are characteristic of pregnancy, one would expect to see an improvement in all these conditions comparable to that seen in real pregnancy. The administration of HCG does in fact do this in a remarkable way.
In an obese patient suffering from a fairly advanced case of stable diabetes of many years duration in which the blood sugar may range from 300-400 mg, it is often possible to stop all anti-diabetes medication after the first few days of treatment. The blood sugar continues to drop from day to day and often reaches normal values in 2-3 weeks. As in pregnancy, this phenomenon is not observed in the brittle type of diabetes, and as some cases that are predominantly stable may have a small brittle factor in their clinical makeup, all obese diabetics have to be kept under a very careful and expert watch.
A brittle case of diabetes is primarily due to the inability of the pancreas to produce sufficient insulin, while in the stable type, diencephalic regulations seem to be of greater importance. That is possibly the reason why the stable form responds so well to the HCG method of treating obesity, whereas the brittle type does not. Obese patients are generally suffering from the stable type, but a stable type may gradually change into a brittle one, which is usually associated with a loss of weight. Thus, when an obese diabetic finds that he is losing weight without diet or treatment, he should at once have his diabetes expertly attended to. There is some evidence to suggest that the change from stable to brittle is more liable to occur in patients who are taking insulin for their stable diabetes.
All rheumatic pains, even those associated with demonstrable bony lesions, improve subjectively within a few days of treatment, and often require neither cortisone nor salicylates. Again this is a well known phenomenon in pregnancy, and while under treatment with HCG + diet the effect is no less dramatic. As it does not after pregnancy, the pain of deformed joints returns after treatment, but smaller doses of pain-relieving drugs seem able to control it satisfactorily after weight reduction. In any case, the HCG method makes it possible in obese arthritic patients to interrupt prolonged cortisone treatment without a recurrence of pain. This in itself is most welcome, but there is the added advantage that the treatment stimulates the secretion of ACTH in a physiological manner and that this regenerates the adrenal cortex, which is apt to suffer under prolonged cortisone treatment.
The exact extent to which the blood cholesterol is involved in hardening of the arteries, high blood pressure and coronary disease is not as yet known, but it is now widely admitted that the blood cholesterol level is governed by diencephalic mechanisms. The behavior of circulating cholesterol is therefore of particular interest during the treatment of obesity with HCG. Cholesterol circulates in two forms, which we call free and esterified. Normally these fractions are present in a proportion of about 25% free to 75% esterified cholesterol, and it is the latter fraction which damages the walls of the arteries. In pregnancy this proportion is reversed and it may he taken for granted that arteriosclerosis never gets worse during pregnancy for this very reason.
To my knowledge, the only other condition in which the proportion of free to esterified cholesterol is reversed is during the treatment of obesity with HCG + diet, when exactly the same phenomenon takes place. This seems an important indication of how closely a patient under HCG treatment resembles a pregnant woman in diencephalic behavior.
When the total amount of circulating cholesterol is normal before treatment, this absolute amount is neither significantly increased nor decreased. But when an obese patient with an abnormally high cholesterol and already showing signs of arteriosclerosis is treated with HCG, his blood pressure drops and his coronary circulation seems to improve, and yet his total blood cholesterol may soar to heights never before reached.
At first this greatly alarmed us. But when we saw that the patients came to no harm even if treatment was continued and we found the same in follow-up examinations undertaken some months after treatment was continued as we found in examinations undertaken some months before treatment. As the increase is mostly in the form of the not dangerous form of the free cholesterol, we gradually came to welcome the phenomenon. Today we believe that the rise is entirely due to the liberation of recent cholesterol deposits that have not yet undergone calcification in the arterial wall and is therefore highly beneficial.
An identical behavior is found in the blood uric acid level of patients suffering from gout. Predictably such patients get an acute and often severe attack after the first few days of HCG treatment but then remain entirely free of pain, in spite of the fact that their blood uric acid often shows a marked increase which may persist for several months after treatment. Those patients who have regained their normal weight remain free of symptoms regardless of what they eat, while those that require a second course of treatment get another attack of gout as soon as the second course is initiated. We do not yet know what dioncephalic mechanisms are involved in gout; possibly emotional factors play a role, and it is worth remembering that the disease does not occur in women of childbearing age. We now give 2 tablets daily of ZYLORIC to all patients who give a history of gout and have a high blood uric acid level. In this way we can completely avoid attacks during treatment.
Patients who have brought themselves to the brink of malnutrition by exaggerated dieting, laxatives etc, often have an abnormally low blood pressure. In these cases the blood pressure rises to normal values at the beginning of treatment and then very gradually drops, as it always does in patients with a normal blood pressure. Normal values are always regained a few days after the treatment is over. Of this lowering of the blood pressure during treatment the patients are not aware. When the blood pressure is abnormally high, and provided there are no detectable renal lesions, the pressure drops, as it usually does in pregnancy. The drop is often very rapid, so rapid in fact that it sometimes is advisable to slow down the process with pressure sustaining medication until the circulation has had a few days time to adjust itself to the new situation. On the other hand, among the thousands of cases treated, we have never seen any incident which could be attributed to the rather sudden drop in high blond pressure.
When a woman suffering from high blood pressure becomes pregnant her blood pressure very soon drops, but after her confinement it may gradually rise back to its former level. Similarly, a high blood pressure present before HCG treatment tends to rise again after the treatment is over, though this is not always the case. But the former high levels are rarely reached, and we have gathered the impression that such relapses respond better to orthodox drugs such as Reserpine than before treatment.
In our cases of obesity with gastric or duodenal ulcers we have noticed a surprising subjective improvement in spite of a diet which would generally be considered most inappropriate for an ulcer patient. Here, too, there is a similarity with pregnancy, in which peptic ulcers hardly ever occur. However we have seen two cases with a previous history of several hemorrhages in which a bleeding occurred within 2 weeks of the end of treatment.
Psoriasis, Fingernails, Hair Varicose Ulcers
As in pregnancy, psoriasis greatly improves during treatment but may relapse when the treatment is over. Most patients spontaneously report a marked improvement in the condition of brittle fingernails. The loss of hair not infrequently associated with obesity is temporarily arrested, though in very rare cases an increased loss of hair has been reported. I remember a case in which a patient developed a patchy baldness – so called alopecia areata – after a severe emotional shock, just before she was about to start an HCG treatment. Our dermatologist diagnosed the case as a particularly severe one, predicting that all the hair would be lost. He counseled against the reducing treatment, but in view of my previous experience and as the patient was very anxious not to postpone reducing, I discussed the matter with the dermatologist and it was agreed that, having fully acquainted the patient with the situation, the treatment should be started. During the treatment, which lasted four weeks, the further development of the bald patches was almost, if not quite, arrested; however, within a week of having finished the course of HCG, all the remaining hair fell out as predicted by the dermatologist. The interesting point is that the treatment was able to postpone this result but not to prevent it. The patient has now grown a new shock of hair of which she is justly proud. In obese patients with large varicose ulcers we were surprised to find that these ulcers heal rapidly under treatment with HCG. We have since treated non obese patients suffering from varicose ulcers with daily injections of HCG on normal diet with equally good results.
The “Pregnant” Male
When a male patient hears that he is about to be put into a condition which in some respects resembles pregnancy, he is usually shocked and horrified. The physician must therefore carefully explain that this does not mean that he will be feminized and that HCG in no way interferes with his sex. He must be made to understand that in the interest of the propagation of the species nature provides for a perfect functioning of the regulatory headquarters in the diencephalun during pregnancy and that we are merely using this natural safeguard as a means of correcting the dicncephalic disorder which is responsible for his overweight.