Illicit use of hCG in dietary programs and to promote anabolism

[madman]

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Illicit use of hCG in dietary programs and to promote anabolism (2022)

The most common therapeutic use of hCG is not to promote ovulation or to promote progesterone production and maintain pregnancy. It is the illicit use of hCG in dietary programs which we first reviewed in 2016 [1]. There are currently thousands of websites, books, newspaper advertisements, and TV advertisements selling diets with these ridiculous claims. Some athletes even give themselves regular shots of hCG to promote testosterone and anabolism for muscle and bone growth. These uses inspire us to ask, why? This chapter discusses the pros and cons of illicit hCG uses and misuse of hCG administration. Finally, this chapter considers the dangers of any hCG variant administration.




Dietary programs

Advertisements trying to sell prescription hCG and novel diets come from medical clinics, doctors’ offices, and pharmacies all over the world. These advertisements are in newspapers and even presented by medical correspondents on major TV shows (KSL5 Utah, Fox Morning Show, Mike & Juliet Show, and others). This story starts with one very small study performed in England in the early 1950s. Dr. Simeons conducted a nonblinded, noncontrolled study in which participants were restricted to 500 kcal/day and administered 125 IU supplements of urine-origin hCG [2]. The study had amazing results and led to weight loss. According to Dr. Simeons [2]. hCG must mobilize stored fat all over the body and suppresses the appetite. If you search the Internet, there are literally thousands of advertisements for the hCG-based diet of Dr. Simeons.

In 1959, Sohar [3] argued that it was solely the 500-kcal diet that led to the weight loss and that the hCG supplements do absolutely nothing. In the 1960s, Craig et al. [4] and Frank [5] each conducted their own study regarding the Simeons diet. The two separate experiments both agreed that there is no possible or even conceivable relationship between hCG administration and loss of weight or hunger. In the years that followed, physicians profiting from the dietary administration of hCG began performing double-blind studies. These small, inappropriately controlled studies claimed to somehow confirmed that the Simeons diet worked [6,7]

Then, in the 1970s, several double-blind studies were independently performed by Young et al. [8], Stein et al. [9], Greenway and Bray [10], and Shetty and Kalkoff [11]. They all reached the same conclusion as Sohar did in 1959—that hCG has absolutely nothing to do with hunger and fat mobilization and does not promote weight loss. In the 1980s, Richer and Runnebaum [12] reached the same conclusion. In the 1990s, the high-standard controlled studies of Bosch et al. [13] and Lijesen et al. [14] once again confirmed that an hCG diet simply does not work and could not work.

The amount of medical evidence that began accumulating was overwhelming. Countless studies used clean, double-blind, and carefully controlled data to disprove the claims of Simeons’ hCG-based diet. It simply does not work [15,16]. It should be noted that in 2007, the USA Federal Trade Commission charged Kevin Trudeau with misrepresentation for writing a book praising the hCG diet [17].

Today, the CV Rao Laboratory [18–20] world experts on hCG biological function, have identified hCG receptors in numerous sites associated with pregnancy, the uterus, the placenta, the fetus, and the brain. The laboratory has not, however, ever found evidence for a receptor in the digestive tract, in the liver, or in adipose tissues that could explain how hCG mobilizes stored fat and suppresses hunger. Thus, Simeons’ 1954 results are seemingly false and were apparently contrived to support a new enterprise. Nevertheless, Simeons started a dietary fad, and even after 59 years, his diet is still sold throughout the world. Dr. Simeons even published a support book for followers of his diet. Somehow, Simeons became a public and scientific hero for this nonsense diet. After the accumulation of all this evidence, how and why there are still clinics, doctors’ offices, and pharmacies completely sold on the hCG diet defies all logic, unless they are falsely led by money.

Yes, hCG will promote emesis or nausea and vomiting. Is this the secret to the diet’s claims of exceptional weight loss—extreme hyperemesis or nausea and constant vomiting?

Today, clinics and pharmacies give patients a choice of injectable hCG, hCG drops that one places under the tongue, or hCG-green tea pill [17,21–23]. They claim that each works as well as the other, but there is no evidence, yes absolutely no evidence, to support that hCG can mobilize fats, suppress hunger, or induce euphoria, as claimed.

Surely, the digestive tract destroys this large 37,000 molecular weight glycoprotein hormone before it is absorbed into the circulation. Pills comprising hCG are a fraud. Injectable hCG preparations range from partially purified human pregnancy urine extracts called Profasi, Pregnyl, Novarel, Chorex, and Follotein to super-pure Chinese hamster ovary cell-line recombinant hCG called Ovidrel. All are misused for dietary purposes with claims of great weight loss. It is one thing for a woman to be sold by crazy advertisements about some miracle diet, but it is another to consider the consequence of hCG administration, cessation of menstrual periods, infertility, and hyperemesis gravidarum.





hCG and anabolism promotion

Unquestionably, hCG as a super-potent luteinizing hormone replacement promotes testicular testosterone that acts on muscles and bones to promote growth and anabolism in men. Interestingly, injections of hCG do not promote significant testosterone production in women [24], but rather promote progesterone and androstenedione production [24]. As such, the other illicit use of hCG is in athletics, particularly in major professional sports and world sports such as the Olympic Games. The hormone is also sold on the Internet and in magazine advertisements, purporting to make people strong like Mr. Universe by aiding muscle growth.

Agencies such as the World Anti-Doping Agency (WADA) and the U.S. Anti-Doping Agency (USADA) started to test the urine of Olympic and other international athletes. In the United States, all major athletic associations perform random urine tests that detect testosterone, growth hormone, and the hormone hCG, including the National College Athletic Association, National Football League, National Hockey League, National Basketball League, National League Baseball, and the American League Baseball.

As shown by Stenman et al. [25], hCG can circulate for 7-11 days after injection. The USA hCG Reference Service has shown WADA and USADA that during this period, hCG is gradually degraded to a free subunit, to nicked hCG, to nicked molecules missing the β-subunit C-terminal peptide, and finally to β-core fragment. Thus, it is important to measure each of these molecules in urine tests.

Today, most sporting agencies test urine using the Siemens Immulite assay, which is the only automated hCG test that detects all of these degradation products [26,27]. Laidler et al. [28] measured hCG in 1400 men and statistically determined that a 5-mIU/ml cutoff was very acceptable in terms of total hCG concentration present in urine. Delbenke et al. [29] examined 5663 men and found background hCG in men reaching 2.28 mIU/ml. They also supported the 5-mIU/ml sensitivity limit. This is now used as the cutoff in doping studies by WADA and USADA.




hCG variants as dangerous substances

Research presented in this book clearly demonstrates and confirms that hCG variants, most notably hyperglycosylated hCG, hyperglycosylated hCG free β-subunit, extravillous cytotrophoblast hCG and its free β-subunit, are the principal drivers, the malignancy factor of most human cancers (see Chapter 30). These promoters, but not regular hCG, function by binding and antagonizing a TGFβ type II receptor [30–32]. Expression of the molecules and their TGFβ pathways appear to be a major part of carcinogenesis or human cancer transformation. These agents probably start and maintain all cancers.

These four molecules, hyperglycosylated hCG, hyperglycosylated hCG free β-subunit, extravillous cytotrophoblast hCG and its free β-subunit, appear to transfer cells into malignant cells by driving growth, blocking apoptosis, and driving invasion (see Chapter 30). As such, if a person has damaged tissues, pre-cancerous tissue, or immune-suppressed cancer tissue in their body, then that person is likely to have that tissue transformed into cancer tissue by the presence of these molecules. Looking at pregnancy urine hCG as discussed in Chapters 5 and 6, it is an average of 84.5% hormone hCG, 1.9% hyperglycosylated hCG, and 13.7% extravillous cytotrophoblast hCG. So all urinary concentrates of pregnancy hCG must contain the cancer molecules. We gave not studied 100s or 1000s of cases that have received these mixtures but I am sure that a significant number of them eventually developed cancer.

As shown in Table 29.1, most common prescription commercial hCG preparations are contaminated with these molecules. This is probably particularly true regarding hCG pills and hCG nasal drops sold on the Internet. It is inferred that these urinary-derived hCG preparations are highly carcinogenic or very dangerous substances.

One hCG preparation, Serono Ovidrel, is a recombinant form of hCG made with Chinese hamster ovary cells. It is an absolutely pure hormone hCG containing no hyperglycosylated hCG or extravillous cytotrophoblast hCG. This is seemingly the safest form of hCG to use. It still is very slowly or partially dissociated into hCG free β-subunit, one of the cancer promoters [33], so it is not completely harmless. If one has to administer hCG to oneself, then this expensive preparation, Serono Ovidrel, is clearly the only form to use. Ideally, however, one should stay away from all forms of hCG.

 

[madman]

Table 29.1 Commercial preparation of hCG and its variants

 

[testiculus]

"It is inferred that these urinary-derived hCG preparations are highly carcinogenic"

This is a very strongly worded conclusion, that is pretty concerning. The referenced research papers are dealing with HCG secreting tumors which is a different problem than using exogenous HCG. However the authors of this book (who are also the authors of number of the referenced papers on HCG secreting tumors) seems to have reached the conclusion that uniary derived HCG exhibits the same metastatic cancer promoting properties as the HCG secreted by these tumors. Is anyone familiar with this line of research? I've started reading some of the papers, but there is a fair bit to untangle here. If this is true, everyone should stop using HCG.

 

[madman]

Give you further insight as to where Cole is coming from.


CHAPTER 30

Cancer hCG, hyperglycosylated hCG, extravillous cytotrophoblastic hCG, and TGFb receptor 2

One gonadotropin, extravillous cytotrophoblast hCG, is an apparent centerpiece of cancer. It is in fact stolen by cancers, from pregnancy, to drive malignancy. Extravillous cytotrophoblast hCG emerges from human evolution as a super acidic, super potent TGFß agonist [1–3]. Super acidic and super potent as a result of the evolution of an increasingly acidic hCG pathway (see Chapter 2) [1–3].

The story of hCG and cancer is a personal one and much of the research described below was performed in my own research groups or with collaborators [4–6]. It started by looking at hCG as a tumor marker testing a total of 2,508 non-trophoblastic cancers (Including bladder cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, gastric cancer, hepatic cancer, lung cancer, intestinal cancer, lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, uterine cancer, and vulvar cancer) in first-morning urine samples. We also studied 91 trophoblastic cancers (choriocarcinoma, ovarian germ cell cancer, and testicular germ cell cancer) using first-morning urine samples and the B204 beta core fragment and nicked free ß-subunit assay (Table 30.1).

The 2,167 non-trophoblastic cancer patient urines and 91 trophoblastic cancer patient urine were tested in the B204 assay, with a 3.0 pmol/ml cancer cut-off. All 91 trophoblastic cancers were positive, 100% detection, yet only 949 of 2,167 non-trophoblastic cancer urines were positive, with 44% detection (Table 30.1). It was concluded that a more sensitive B204 assay was needed for non-trophoblastic cancers.

A more sensitive assay was generated using 125I-tracer antibody and 1/12,000 rather than 1/4,000 capture antibody. The more sensitive assay had a cut-off for cancer of 0.1 pmol/ml. Using this assay, all 341 non-trophoblastic cancers were positive, with 100% detection. It was concluded that trophoblastic cancers produce larger amounts of detectable material, 3.5-2,398,000 pmol/ml or 1.3–880,000 mIU/ml, and that non-trophoblastic cancers produce tiny concentrations of detectable material, 0.2-340 pmol/ml or 0.074-124 mIU/ml. We also concluded that all cancers produce one form of hCG or another.

But what form of hCG do cancers produce? Different hCG variants were measured using different assays: total hCG using the Siemens Immulite 1000 assay, hyperglycosylated hCG and extravillous cytotrophoblast hCG using the B152 assay, and all free ß-subunit using the FBT11 assay (Table 30.2).

As shown in Table 30.2, 51 of 51 non-trophoblastic neoplasms serum samples, 100%, were positive in the Siemens Immulite assay, in the B152 (102 ± 6.5% of total hCG) and in the FBT11 assay (99 ± 8.8% of total hCG). This indicated that 51 of 51 cases were producing hyperglycosylated hCG or extravillous cytotrophoblast hCG free ß-subunit. Concanavalin A-Sepharose affinity chromatography (not shown) showed that the free ß-subunit had triantennary oligosaccharides or were extravillous cytotrophoblast free ß-subunit. Similarly, the total hCG and B152 immunoassays and the Concanavalin A-Sepharose test (not shown) indicated that 32 of 32 trophoblastic cancers were producing extravillous cytotrophoblast hCG. It was concluded that trophoblastic cancer only (100%, no exceptions seen) produces extravillous cytotrophoblast hCG dimer and that non-trophoblastic cancer only (100%, no exceptions seen) produces extravillous cytotrophoblast hCG free ß-subunit.

Why were all non-trophoblastic cancers producing only beta subunit of hCG but all trophoblastic cancers were producing extravillous cytotrophoblast hCG? This question is best answered by a paper by Beebe et al [7]. In pregnancy, ß-subunit of hCG receives 6 disulfide bridges, and α-subunit of hCG receives 5 disulfide bridges. The last two disulfide bridges on ß-subunit, ß93-100 and ß26-110 are completed by a placental enzyme, placental disulfide isomerase. If hCG is produced by another cell other than a trophoblast cell, this enzyme is not present, and the disulfide bridges are not made. Without these disulfide bridges the ß-subunit just forms a free ß-subunit and does not combine with α-subunit to form αß dimer [7]. This was seemingly the case with cancer-free ß-subunit.

Other authors have shown that the hCG molecules produced by cancer cells drove malignancy-like functions in cancer cells [8–15] (Table 30.3). Based on the studies described above, this must be extravillous cytotrophoblast hCG or its free ß-subunit. In 1996 Gillott et al. [8] showed that the ß-subunit produced by T24, ScaBER, and RT112 bladder cancer cell line drove cancer cell line growth and blocked apoptosis in. In 2000 this was confirmed by Butler et al. [9] using ScaBER bladder cancer cell line and its ß-subunit. In 2002 Devi et al. [10] tested DU145 prostate carcinoma cell line and showed that the ß-subunit drove cancer cell line growth. Then, in 2006 our laboratory [11] used Jar and JEG-III choriocarcinoma cell line and showed that invasive cytotrophoblast hCG drove cancer growth and drove cancer cell invasion of others. Then, in 2008 Jankowska et al. [12] showed with tissue from 12 patients with planoepithelial cervical cancer, with one patient with glossy cell cervical cancer, one patient with basaloid cell cervical cancer, one patient with intraepitheliate cervical cancer, and 15 patients with endometrial cancer that the ß-subunit blocked apoptosis. In 2008 Li et al. [13] showed with tissue from 81 patients with uterine cervical cancer that the ß-subunit blocked apoptosis and in 2011 Guo et al. [14] looked at T29 and T80 epithelial ovarian cancer cell lines and tissue from 15 patients with ovarian carcinoma and showed that the ß-subunit produced by the cancers promoted cell growth and blocked apoptosis. Finally, and most recently, Kawamata et al. [15] examined tissue from 80 patients with colorectal cancer, examined Caco-2, LoVo, HCA-7, WiDr, and T84 colorectal cancer cell lines, and showed with them all that ß-subunit drove cancer growth and drove cell-cell invasion of other tissues. All of these studies are summarized in Table 30.3.

We went on to examine 10 different cancer cell lines, from choriocarcinoma, testicular germ cell cancer, endometrial adenocarcinoma, squamous bladder cancer, epithelial bladder carcinoma, epithelial lung cancer, Hodgkin’s lymphoma, and cervical carcinoma (Table 30.4). Again all 10 cancers produced extravillous cytotrophoblast hCG and its free ß-subunit and vast cancer cell growth. It was concluded from these results (Tables 30.3 and 30.4), that extravillous cytotrophoblast hCG and its free ß-subunit seemingly drove malignancy in all or most cancers.

After the development of monoclonal antibody B152 (a monoclonal antibody raised against extravillous cytotrophoblast hCG and hyperglycosylated hCG and their free ß-subunit which did not bind the hormone hCG [16]), it was possible to immobilize extravillous cytotrophoblast hCG and its free ß-subunit as produced by cancer cell lines. As shown in Table 30.5 treatment with B152, 2.0 µg/ml, took the malignancy out of the cancer so that it did not grow at all over 24 hours. Two conclusions were made. Firstly, this confirmed and proved that extravillous cytotrophoblast hCG and its free ß-subunit controlled malignancy in all or most cancers. Secondly, that this confirms that extravillous cytotrophoblast hCG and its free ß-subunit are the primary drivers of malignancy in cancer cells.

Furthermore, eight nude mice were transplanted subcutaneously with JEG-III human choriocarcinoma cells and 8 nude mice were transplanted subcutaneously with Caski human cervical carcinoma cells. In each transplant, 10 million cancer cells total were transplanted into 6 skin sites on nude mice. After two weeks, multiple metastases were present on the skin of animals, tumors as large as 2 cm in diameter in size. Athymic mice were then given either antibody B152 (2 × 4 mice) or control mouse immunoglobulin G (IgG) (2 × 4 mice), 0.3 mg intraperitoneally injected twice weekly for two weeks or until 4 weeks cancer time. The tumor cross-section area was measured weekly with calipers before every treatment according to the formula: length x width x π x 4. Termination was mandatory at 4 weeks for the University of New Mexico Health Science Center Animal Resource Center.

As shown in Fig. 30.1, IgG did nothing but let both cancers continue to grow and metastasize to >300% of two weeks' size. B152 immediately blocked the cancers, blocking all cancer malignancies. After 4 weeks the choriocarcinoma was if anything 76% the size of the cancer at 2 weeks cancer time, and the cervical cancer was if anything 91% of the size of the cancer at 2 weeks.

In conclusion, B152 antibody treatment eliminated the malignancy of the human choriocarcinoma (Fig. 30.2A) and of the human cervical carcinoma (Fig. 30.2B) in athymic mice, deactivated the cancer.

Extravillous cytotrophoblast hCG and its free ß-subunit blocks apoptosis in human cancer cases (Table 30.3) and blocks immune response to the cancer. If B152 was humanized by established DNA technology [17–19], B152 would possibly be an effective cure for cancer, blocking malignancy and without extravillous cytotrophoblast hCG or its free ß-subunit apoptosis and the immune system would destroy all remnant cancer tissue. Alternatively put, B152 could be a cure for all or most human cancers, and removing these forms of hCG from the circulation could present a very interesting therapy for treating cancers that produce these molecules [20] and that specific antibody therapies will need to take into consideration glycovariation on hCG to ensure effectiveness [21].

We know that the production of hCG is linked to the growth and invasion in cancer cells but what is the mode of action? Multiple authors have shown that the ß-subunit of hyperglycosylated hCG and extravillous cytotrophoblast hCG and free ß-subunit act on TGFß receptor 2. It is through this receptor that hCG can block apoptosis, promote cell growth and promote invasion by promoting metalloproteinases and promoting collagenases [9, 22, 23].

Interestingly, Butler and colleagues [9] who tested TGFß receptor 2 activity in bladder cancer cells claim that hCG free ß-subunit are antagonists and can be specifically competed out. Berndt and colleagues [22] used LHCGR mouse aortic ring cells and insist that it is an agonist. Ahmad and colleagues found that overall hCG ß-subunit formed a special previously unknown link with TGFß that changed everything. Whatever this previously unknown link may be, it allows the hCG ß-subunit to take control of the TGFß receptor.

A model of hyperglycosylated hCG, hyperglycosylated hCG free β-subunit, or hCG free β-subunit antagonizing cytotrophoblast cells in blastocyst implantation or cancer malignancies is shown in Fig. 30.1. As illustrated, TGFβ-II receptors act through SMAD and cAMP intermediates, which permit nuclear penetration. SMADs have been demonstrated in the response of TGFβ receptor 2 to hyperglycosylated hCG [22]. Angiogenesis has also been demonstrated in response to hyperglycosylated hCG [23] and that hyperglycosylated hCG and hyperglycosylated hCG free β-subunit are interchangeable promoters with similar potency have also been demonstrated [24].

Lustabader et al., Lapthorn et al., and Wu et al. [25–28] have demonstrated a common cystine knot structure in hCG (on hCG α-subunit and β-subunit) linking the structure of hCG and TGFβ. That the hCG amino acid sequence with different glycosylation (hyperglycosylation) can bind the LH/hCG hormone receptor and the TGFβ-II autocrine receptor is rather unusual, giving the molecule two distinctly different functions (hCG and hyperglycosylated hCG) and two distinct sets of actions. These mechanisms and actions of hCGβ in epithelial cancer were proposed almost twenty years ago [29] and have since been discussed in detail by Butler and collaborators [30,31].




Table 30.1 Urine B204 assay (cancer cut-off 3.0 pmol/ml) and super-sensitive B204 assay (cancer cut-off 0.1 pmol/ml), detects ß-core fragment, free ß-subunit, hyperglycosylated hCG free ß-subunit and nicked free ß-subunit.

Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay.

Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay.

Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay. (Cont.)

Table 30.3 Eight independent reports that hyperglycosylated hCG and hCG ß-subunit promote cancer cell malignancy (10-17).

 

[madman]

Table 30.4 Promotion of cancer cell 24 h growth at 70% confluency by C5 extravillous cytotrophoblast hCG. All experiments carried out in quadruplicate. Sixteen T75 flask of each cancer cell line grown to approximately 70% confluent. Four flasks rejected to prevent 70% confluence imbalance, 4 flask used for 70% confluence cell count. No additive flask results (-70% count) considered as blank and subtracted from all results. In case of Jar choriocarcinoma cells, for instance, mean no additive result 100,360 cells, mean 70% confluency result 128,880 cells, blank = 128880-100360 = 28,520 cells, blank = 100%. 20ng extravillous cytotrophoblast hCG mean result 158540 cells, 158540-blank = 130020 cells, 130020/100360 x 100 = 130%. (Cont.)

Table 30.4 Promotion of cancer cell 24 h growth at 70% confluency by C5 extravillous cytotrophoblast hCG. All experiments carried out in quadruplicate. Sixteen T75 flask of each cancer cell line grown to approximately 70% confluent. Four flasks rejected to prevent 70% confluence imbalance, 4 flask used for 70% confluence cell count. No additive flask results (-70% count) considered as blank and subtracted from all results. In case of Jar choriocarcinoma cells, for instance, mean no additive result 100,360 cells, mean 70% confluency result 128,880 cells, blank = 128880-100360 = 28,520 cells, blank = 100%. 20ng extravillous cytotrophoblast hCG mean result 158540 cells, 158540-blank = 130020 cells, 130020/100360 x 100 = 130%. (Cont.)

Table 30.5 Cancer cells cultured to 70% flask confluency, then cultured 24 h with antibody B152 in quadruplicate and cells counted. B152 is monoclonal antibody B152 Values are percent change from 70% confluency. The 70% confluency column lists the percentage cells and the cell count ± standard deviation, all other columns just list percentage cells ± standard deviation.

FIGURE 30.1 Action of hyperglycosylated hCG, hyperglycosylated hCG free β-subunit, and hCG free β-subunit on TGFβ receptor 2.

FIGURE 30.2 Eight nude mice transplanted with 10,000,000 cells JEG-III human choriocarcinoma cells (A), and 8 nude mice transplanted with 10,000,000 cells CaSki cervical carcinoma (B). 2 weeks later half of each 8 treated with antibody B152 and half treated with non-specific immunoglobulin G (IgG).

 

[madman]

PREGNYL hCG by MERCK CANADA

PREGNYL® (chorionic gonadotropin for injection, USP) 10,000 units/vial Human Gonadotropin Merck Canada Inc. 16750 route Transcanadienne Kirkland QC Canada H9H 4M7 The action of human chorionic gonadotropin (hCG) is virtually identical to that of pituitary LH, although hCG appears to have a...

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Still using urinary-derived hCG!