As medical professionals we are all too familiar with the obesity epidemic facing our nation. I would not insult your intelligence to go on some long-winded diatribe informing you of the problem. Of course it’s a problem. The factors at play from a research perspective, looking into the evidence-based rationale of genetic, hormonal and socioeconomic factors in a complex dance does not begin to describe our current understanding of obesity. With our greater understanding the complex mechanisms of insulin resistance, adipose storage and hormonal factors we do now know that obesity is not a premise based on the number of calories ingested and the number of calories expended but a complex interplay of hormonal mechanisms, molecular biology and of course, human behavior. In speaking to the relationship of HCG and its implications in weight loss and change in body composition I believe it’s important to relate the groundwork in order to understand where the formative research began in this regard, before looking forward. In the 1950’s a British Physician, A.T. Simeon, who had long pondered the mechanisms of obesity for some time, noted the findings of a fellow physician who quite unexpectedly, while running a research trial on young boys with Froehlich’s Disease, which was marked by ravenous hunger and obesity and adipose deposits at characteristically “female” sites, such as the hips, buttocks and thighs. These patients also suffered symptoms of gynecomastia and underdeveloped testicles, due to disease of the anterior pituitary gland. The treatment consisted of biweekly therapeutic injections of HCG, as this was noted to induce precocious puberty in laboratory models. These patient’s despite having no caloric restriction, noted a marked reduction in appetite, and as an unanticipated finding, the patients lost significant amounts of weight as well as decrease in hip circumference. Dr. Simeon was so moved by these findings that he felt there must be a correlation between HCG and weight reduction and began his own trials which were published in the acclaimed Lancet, in 1954(1). Several clinical trials have attempted to follow in his footsteps, but only one double blind placebo controlled study has achieved the dramatic results Simeon and legions of faithful patients have been describing for decades.
In the aforementioned DBPC study, patients were randomly assigned to receive 125 iu of HCG or placebo via subcutaneous injection 6 days/week for 6 weeks, and placed on a monitored 500-550 kcal/day die. A mean weight loss of 18 lbs was reported upon completion of the study. Patients were also queried daily on their degree of satiety. The majority of patients reported “no feelings of hunger”.(1) They were also queried as to the status of their general state of well-being and again the majority reported feeling “good” to “excellent”.(2) Why do we not have a multitude of randomized clinical trials to provide us with the evidence-based medicine we long for, and use as our true north, in navigating the often rough seas one must face in daily decision making as a physicians. Don’t we all desire these guideposts upon which to lean? Yes. But, we also desire results for the patient. And, we all know that before we have evidence-based data, we have correlative data. Now of course all that correlates does not surmount to be true. However, much of it does. Given we do know about HCG dietary therapy is that we have significant number of very satisfied patients who have lost a dramatic amount of weight. In physician practices who maintain patients on HCG longer than the induction phase of 6 weeks, they are able to maintain or continue on in their weight reduction.
Let’s refresh our memories on the molecular structure and bio-activity of HCG and you will see that some provocative hypotheses exist as to the postulated mechanisms of action. Firstly, HCG is present in both sexes, obviously in minuscule amounts in males, and in pregnant females in large quantities. There are actually many faces to HCG from a molecular and bio-active standpoint, with 4 primary sub-groups. First off, we have Intact HCG which is produced by the placenta and keeps serum progesterone levels high to support and maintain the pregnancy. Intact HCG is comprised of an alpha and beta sub-units, which come together to form the intact HCG molecule. While the beta sub-unit is unique to HCG; however, the alpha sub-unit has cross reactivity with three completely different hormones FSH, LH and TSH. Now the progesterone of the intact HCG acts on receptors in the maternal brain causing the nausea and decreased appetite associated with pregnancy and, in extreme cases, hyperemesis gravidarum. This raises some possible hypotheses as to the mechanism by which HCG causes weight loss. There certainly could be an argument raised for a decrease in appetite due to the effects of mild nausea. Research demonstrates a known correlation between pregnancy and hyperthyroid states due to the cross reactivity of the alpha sub-unit of the HCG molecule’s interaction with thyroid stimulating hormone and resultant hyperthyroidism (3). This increase in metabolic rate could account also for weight loss, when looked at through the lens of one seeking novel approaches to weight loss.
Secondly, we have hyperglycosylated HCG which is similar to the intact HCG molecular structure but, with even more carbohydrate molecules attached. It predominates in early pregnancy. I doubt it has any worthy mention in relationship to weight loss.
Thirdly, we have the HCG free beta sub-unit which is produced by trophoblastic as well as non-trophoblastic malignancies (4). Pancreatic cancer, transitional cell carcinoma of the bladder and ovarian cancers are among them (5). In Ovarian cancer 41% of ovarian malignancies expressed genetic mutations, coded for HCG and the beta sub-unit fragment further delineated into subgroups HCG1 and HCG2 (6)interestingly, in the wasting syndromes seen in malignancy we note three uniform characteristics: decrease in fat mass, increased response to insulin and weight loss (7) HCG is a tumor marker, obviously in germ cell tumors such as testicular cancer or neuroblastoma. But the HCG beta sub-unit also serves as a tumor marker and for prognostic value, in other malignancies as well (6). In studies the HCG beta sub-unit was detected in pancreatic cancer as well as the CA-19-9, more commonly referenced and recognized as the tumor marker for pancreatic cancer.(8) Oncologists agree that pancreatic, as well as perhaps gastric cancer (for obvious reasons) has the most marked and rapid weight loss of all malignancies. Perhaps via some, as yet undetermined phenomenon HCG triggers a cascade on a cellular level, in which the end result is weight loss, much as we see in the mechanisms of malignancy induced cachexia I have alluded to. There is still much fodder for research to determine the exact mechanism, but it begs the question. Why is pancreatic cancer, positive for HCG? And, it just so happens to trigger the greatest amount of weight loss of all malignancies in a very short period of time. What is the correlation? As yet we do not know. The fodder for further study of this molecule abound. if the intellectual curiosity of the scientific community is not aroused, we will never determine the mechanism by which we are seeing such compelling results to those who have used this modality to lose weight and change the composition of their bodies via HCG therapy.
For completeness sake, lastly, we have pituitary HCG, which is produced at low levels during the menstrual cycle and seems to mimic the activity of LH. I am not proposing any hypothesis related to weight loss, for this transient bump in HCG seen in normal females. It is my hope that I have ignited your intellectual curiosity. There have been many studies over the years but in meta-analysis it was determined these studies were largely flawed. The meta-analysis was conducted to determine it HCG was a valuable adjunct in weight loss, fat redistribution, hunger and a sense of well –being, and the conclusions drawn were that largely every study was of poor methodology. HCG therapy has been a pathway for success to so many in their journey a weight reduction and ultimately a healthy lifestyle. A patient that sees results is more apt to continue on a diet with a low glycemic index and a reasonable aerobic exercise plan than one who does not. Don’t you owe your patient’s every tool in your arsenal to combat obesity? I don’t know why exactly the HCG diet works, but, I feel that there are some very thought provoking questions that are raised when one examines the nature of the molecule and its relationship to weight loss. Maybe, just maybe, Dr. Simeon, and the thousands of physicians he has trained over the decades, since he was first published in the Lancet, maybe he knows to count on the results seen with HCG diet therapy.
Citations:
1. Simeon A.T. The action of chorionic gonadotropin in the obese The Lancet 1954 (6845) 946-947.
2. Ascher W.L. Harper H. The effect of chorionic gonadotropin on weight loss, hunger and feeling of well- being. American Journal of Clinical Nutrition Feb 1973;26 (2) 211-218
3. Tan, Jackie, Loh Keh, Yeo George. Transient hyperthyroidism in women with hyperemesis gravidarum. International Journal of Obstetrics and Gynecology June 2002; 109 (6) 683-688
4. Cole, L Biological functions for the HCG and HCG related molecules. Reproductive Biology and Endocrinology 2010; August 8 (102) doi: 1186/1477-7827-8-102
5. Hotakainer K, Haflund C, Paju A. HCG beta subunit and core fragment in bladder banker: mRNA and protein expression in urine, serum and tissue. European Journal of Urology June 2002; 441 (6) 667-685.
6. Kubiczak M, Walkowiak GP, Nowak E. Human chorionic gonadotropin beta subunit genes CGB1 and CGB2 are transcriptionally active on ovarian cancer. International Journal of Molecular Science 2013 June (6) 12650-12660.
7. Kumar R.T Cachexia. Molecular Endocrinology 1999, 13 851-851-856 8. SEER Training Modules; Tumor Markers. U.S. Department of Health and Human Services, National Institute of Health and the National Cancer Institute, last updated 2015.
