Evidence for, and Associated Risks with, the Human Chorionic Gonadotropin Supplemented Diet.

Trend diets can be commonplace amongst those who are trying to lose weight but in most cases there is some shred of evidence to suggest they might be of some benefit. Seldom is there a diet which is such a fad that it is not only completely unfounded but also potential harmful. The human chorionic gonadotropin or "hCG diet" is such a diet, which after half a century still has no evidence to support its efficacy; in fact all scientific publications subsequent to the original article counter these claims. In this short communication, we review the literature and present data on exactly what some of the hCG diet preparations actually contain and highlight that, based on current data, these may do more harm than good. It is worrying that more consideration is not given to the possible danger of administration of hCG preparations to individuals without an evidence-based rational.

B152 anti-hyperglycosylated human chorionic gonadotropin free ß-Subunit. A new, possible treatment for cancer.

OBJECTIVE: To investigate the ability of B152 to block cancer growth in cell lines in vivo and in nude mice in vitro. STUDY DESIGN: We examined JAR, JEG-3, and NTERA trophoblastic cancer cell lines and KLE, Hec-1A, SCaBER, and T24 nontrophoblastic cancer cell lines. JEG-3 cells were transplanted into 8 nude mice. Four nude mice were administered B152 antibody, and 4 were administered control non-specific IgG. Two studies were completed: first with antibody treatment started 2 weeks after cancer transplantation, and second with antibody treatment started at the time of transplantation. RESULTS: In 3 trophoblastic cancer lines and 4 non-trophoblastic cancer cell lines, B152 suppressed the growth of cancer cells, forcing cells into a state of regression. When B152 was administered to nude mice with tumor xenographs, the antibody blocked cancer cell growth and invoked oncostasis. When B152 was administered to nude mice starting at time of xenograph transplantation, the antibody prevented tumor growth completely. CONCLUSION: B152 suppresses tumor growth by seemingly blocking hyperglycosylated human chorionic gonadotropin (hCG) free ß-subunit effects. Thus, highly specific antibodies against hCG such as B152 may form part of a novel adjuvant treatment regimen against hCG-producing tumors in humans. This may form a new treatment for humans.

Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

INTRODUCTION: Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. METHODS: Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. RESULTS: Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). DISCUSSION: Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

Familial hCG syndrome: production of variable, degraded or mutant forms of hCG.

OBJECTIVE: To examine the properties of the unique degraded forms of hCG produced in familial hCG syndrome and to describe 15 cases referred to the USA hCG Reference Service. STUDY DESIGN: Total hCG was detected by Immulite total hCG assay. The molecules missing the beta-subunit C-terminal peptide were detected by the Centaur total hCG assay; the proportion of molecules missing the beta-subunit C-terminal peptide was determined as Immu-lite assay minus Centaur assay. Free beta-subunit was detected in the FBT11 free beta-subunit assay with 5008 anticore-hCGbeta tracer. RESULTS: In all cases the syndrome was confirmed by either a mother,father, or sibling exhibiting ectopic hCG production. Serum hCG ranges in cases from 1-216 mIU/mL and urine hCG from 1.5-527 mIU/mL. It was estimated that 48-100% of molecules were missing the beta-subunit C-terminal peptide. Serum hCG free beta-subunit was measured, accounting for 52-79% of the total hCG immunoreactivity. Molecules missing the C-terminal peptide and free beta-subunit mark this syndrome. Serial serum samples were examined in 4 cases; hCG concentrations varied widely with time from < 1 to 182 mIU/mL. CONCLUSION: The proportion of molecules missing the beta-subunit C-terminal peptide, 48-100%, is extraordinarily high. Epitope studies and gel filtration studies indicate that the C-terminal peptide may not actually be missing, suggesting that the beta-subunit may be a mutant blocking C-terminal peptide recognition.

Direct analysis of hCGßcf glycosylation in normal and aberrant pregnancy by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The analysis of human chorionic gonadotropin (hCG) in clinical chemistry laboratories by specific immunoassay is well established. However, changes in glycosylation are not as easily assayed and yet alterations in hCG glycosylation is associated with abnormal pregnancy. hCGß-core fragment (hCGßcf) was isolated from the urine of women, pregnant with normal, molar and hyperemesis gravidarum pregnancies. Each sample was subjected to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) analysis following dithiothreitol (DTT) reduction and fingerprint spectra of peptide hCGß 6-40 were analyzed. Samples were variably glycosylated, where most structures were small, core and largely mono-antennary. Larger single bi-antennary and mixtures of larger mono-antennary and bi-antennary moieties were also observed in some samples. Larger glycoforms were more abundant in the abnormal pregnancies and tri-antennary carbohydrate moieties were only observed in the samples from molar and hyperemesis gravidarum pregnancies. Given that such spectral profiling differences may be characteristic, development of small sample preparation for mass spectral analysis of hCG may lead to a simpler and faster approach to glycostructural analysis and potentially a novel clinical diagnostic test.

Hyperglycosylated hCG and pregnancy failures.

Considerable evidence indicates that one third of early pregnancy failures, spontaneous abortions and biochemical pregnancies, are due to chromosomal abnormalities, and two thirds are due to inappropriate implantation. These findings led us to investigate the role of hyperglycosylated hCG, an important pregnancy implantation signal, in pregnancy failures. We used urinary hCG determinations to evaluate a total of 127 pregnancies on the day of implantation, as marked by a positive urinary hCG. These included 81 normal term pregnancies, 18 spontaneous abortion pregnancies, and 28 biochemical pregnancies. Of the normal term pregnancies, the mean±standard deviation concentration of hyperglycosylated hCG was 5.4±4.3 mIU/ml equivalents, and the percentage of hyperglycosylated hCG was 88±17%. All term pregnancies produced hyperglycosylated hCG>51%. Of the 18 cases that spontaneously aborted, both the mean hyperglycosylated hCG (1.9±2.0 mIU/ml equivalents) and the percentage of hyperglycosylated hCG (41±33%) were significantly lower than in the normal pregnancy group. Only 4/18 spontaneously aborting pregnancies produced more than 51% hyperglycosylated hCG on the day of implantation. Similarly, of the 28 biochemical pregnancies, both the mean hyperglycosylated hCG (0.63±1.3 mIU/ml equivalents) and the percentage of hyperglycosylated hCG (21±29%) were significantly lower than in the normal pregnancy group. Only 4/28 pregnancies produced more than 51% hyperglycosylated hCG. Low hyperglycosylated hCG concentrations are associated with pregnancy failure. Whether this association is a primary cause of pregnancy failure or is simply a marker for an abnormal conceptus requires further investigation.

hCG, the wonder of today's science.

BACKGROUND: hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail. CONTENT: These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies. CONCLUSIONS: The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death.

hCG, five independent molecules.

INTRODUCTION: The hCG amino acid sequence supports 5 glycoproteins. All are called hCG forms. This review examines all 5 molecules, the hormone as produced by the placental syncytiotrophoblast cells, the sulfated hormone produced by the pituitary gonadotrope cells, the hyperglycosylated hCG autocrine made by placental cytotrophoblast cells, and the autocrine cancer promoters hyperglycosylated hCG, hCGß and hyperglycosylated hCGß as made by all malignancies. This review examines all the molecules and multiple proven functions, ranging from evolution to cancer promotion to hormone action. RESULTS AND DISCUSSION: hCG forms are critical super-growth factors in humans, with an exceptional wide range of functions.

HCG variants, the growth factors which drive human malignancies.

The term human chorionic gonadotropin (hCG) refers to a group of 5 molecules, each sharing the common amino acid sequence but each differing in meric structure and carbohydrate side chain structure. The 5 molecules are each produced by separate cells and each having separate biological functions. hCG and sulfated hCG are hormones produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells. Hyperglycosylated hCG is an autocrine produced by placental cytotrophoblast cells. Hyperglycosylated hCG drives malignancy in placental cancers, and in testicular and ovarian germ cell malignancies. hCGß and hyperglycosylated hCGß are autocrines produce by most advanced malignancies. These molecules, particularly the malignancy promoters are presented in this review on hCG and cancer. hCGß and hyperglycosylated hCGß are critical to the growth and invasion, or malignancy of most advanced cancers. In many ways, while hCG may appear like a nothing, a hormone associated with pregnancy, it is not, and may be at the center of cancer research.

Familial HCG syndrome.

An explanation is needed for why some men and women show positive in hCG screening tests when they are not pregnant, do not have cancer and are otherwise asymptomatic. In this study, a total of 10 families comprising 30 persons with a history of positive hCG tests were investigated. Total hCG was measured in serum and urine samples using the Siemens Immulite hCG test. Total hCG, C-terminal peptide determinant, and hCGß were measured in 96 well plate assays. Twenty-four of 30 family members produced only hCGß, and hCG or hCGß missing the ß-subunit C-terminal peptide, two rarely detected hCG degradation products as the only source of hCG immunoreactivity. In every one of the 10 families, hCG related molecules were detected first in one member and then later detected in other family members. In 8 of 10 families, all members produced comparable hCG concentration (Cases 1-8). All of the 10 original family members investigated were otherwise asymptomatic, and tested negative in ordered head and pelvis MRI scans and CT chest cancer tests. None had been administered hCG for dietary, anabolic or fertility reasons. Therefore Familial hCG Syndrome, a genetic defect, was indicated in each of the 10 families. In these cases of Familial hCG Syndrome only biologically inactive variants of hCG were detected. It is inferred that in Familial hCG Syndrome, hCG gene expression does not interfere with fertility.

Minimally-aggressive gestational trophoblastic neoplasms.

INTRODUCTION: We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. METHODS: Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, <40% of total hCG. It can also be identified by hCG doubling rate, with doubling time greater than 2 weeks. RESULTS: Nineteen new cases were identified as having minimally aggressive gestational trophoblastic disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. DISCUSSION: A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml.

The hCG assay or pregnancy test.

This review examines human chorionic gonadotropin (hCG) or pregnancy tests from multiple perspectives. It first investigates the molecule hCG and shows that the term represents five independent molecules differing in carbohydrate and meric structure that share a common amino acid sequence. The review goes on to show that multiple degradation produces also the need to be tested for an hCG or pregnancy test to be optimally efficient. The review then carefully examines the literature showing the sensitivity and specificity of automated laboratory tests. Point-of-care pregnancy tests are then investigated along with over-the-counter pregnancy tests. Appropriate detection of hyperglycosylated hCG, nicked hCG, nicked hCG missing the ß-subunit C-terminal peptide and nicked hyperglycosylated hCG is a limitation on all pregnancy tests. In the opinion of the author, just one automated laboratory test, the Siemen's Immulite, one point-of-care test, the Beckman-Coulter Icon 25, and one brand of over-the-counter device, First Response, are suitable for early pregnancy detection and possibly other applications.

Hyperglycosylated hCG, hCGß and Hyperglycosylated hCGß: interchangeable cancer promoters.

INTRODUCTION: Several groups are researching cancers, and showing that hCGß is a promoter of cancer growth and malignancy. Recent research shows that some hCGß is present as Hyperglycosylated hCGß. Other groups studied Hyperglycosylated hCG as a promoter of choriocarcinoma and germ cell malignancies. The question therefore arises, are Hyperglycosylated hCG, hCGß and Hyperglycosylated hCGß interrelated or interchangable promoters of cancer? METHODS: The actions of Hyperglycosylated hCGß, hCGß and Hyperglycosylated hCG are investigated in 7 cell lines, Jar and JEG-3 choriocarcinoma cell lines, NTERA germ cell cancer line, SCaBER and T24 bladder epithelial carcinoma lines, KLE and Hec-1-a endometrial adenocarcinoma and epithelial carcinoma cell lines. Actions of promoters on cell growth are investigated. RESULTS: The actions of Hyperglycosylated hCG, hCGß and Hyperglycosylated hCGß appear to be interchangeable in all cell lines investigated. DISCUSSION: All hCG-related cancer promoters seem interrelated, working through a similar mechanism, antagonism of apoptosis through know receptors such as TGFß receptors in all cancers studied.

Total hCG tests.

INTRODUCTION: There are 12 types of automated total hCG tests sold today, the Abbott Architect, Abbott AxSym, the Beckman Access 2. Beckman DxI 800, the Ortho Vitros EciQ, Roche Elecsys hCG+ß, Siemens ACS180, Siemens Centaur, Siemens Dimension, Siemens Immulite and Siemens Stratus, and the Tosoh A1A. All tests claim to be total hCG tests but do not define what total means. Total hCG test needs to detect all hCG variants in order to be used for all hCG test clinical applications. Here we assess this ability. METHODS: Coded samples of pure hCG, nicked hCG, hyperglycosylated hCG, nicked hCG missing C-terminal peptide, nicked hyperglycosylated hCG, asialo hCG, hCGß, nicked hCGß and ß-core fragment were tested blindly in serum and urine at 10 independent laboratories. RESULTS: While the Siemens Immulite total hCG test detected 8 of 9 hCG variant standards, other assays poorly detected important determinants such as nicked hCG missing the C-terminal peptide, ß-core fragment, hyperglycosylated hCG, nicked hCG, asialo hCG, and hCGß. Four assay appropriately detected 4 of 9 variants, 2 assays detected 3 of 9, 4 assays detected 2 of 9 and 1 assay only appropriately detected 1 of 7 hCG variants. DISCUSSION: Care is needed in selecting a total hCG test. The Siemens Immulite tests performed best at detecting all the hCG variants making it appropriate for all applications. Nine assays had limited applications, 3 of the assays were appropriate for advanced pregnancy testing only.

The utility of six over-the-counter (home) pregnancy tests.

BACKGROUND: The home pregnancy market is rapidly evolving. It has moved from detection of pregnancy on the day of missed menstrual bleeding, to detection claims 4 days prior. It is moving from all manual tests to digital tests, with a monitor reading the bands and informing women they are pregnant. A thorough study is needed to investigate the validity of claims and evolving usefulness of devices. METHODS: Studies were proposed to examine the sensitivity and specificity of home tests and their abilities to detect pregnancy. Methods examined the abilities of tests to detect human chorionic gonadotropin (hCG), hyperglycosylated hCG, free ß-subunit, a mixture of these antigens in 40 individual early pregnancy urines. RESULTS: Using a mixture of hCG, hyperglycosylated hCG and free ß-subunit typical for early pregnancy, the sensitivity of the First Response manual and digital tests was 5.5 mIU/mL, while the sensitivities of the EPT and ClearBlue brand manual and digital tests was 22 mIU/mL. On further evaluation, the First Response manual and digital tests both detected 97% of 120 pregnancies on the day of missed menstrual bleeding. The EPT manual and digital devices detected 54% and 67% of pregnancies, respectively, and the ClearBlue manual and digital devices detected 64% and 54% of pregnancies, respectively. CONCLUSIONS: First Response manual and digital claim >99% detection on the day of missed menses. The results here suggest similar sensitivity for these two tests. The EPT and ClearBlue manual and digital test make similar >99% claims, the data presented here disputes their elevated claim.

Individual deviations in human chorionic gonadotropin concentrations during pregnancy.

BACKGROUND: Serum and urine human chorionic gonadotropin (hCG) vary greatly during the course of pregnancy. We investigated the cause of this variation. STUDY DESIGN: Eighty-two women provided daily urine samples during the first 6 weeks of gestation. First-void urine samples were monitored for luteinizing hormone (LH) and hCG. RESULTS: Variation was wide when pregnancy hCG anchoring to the last menstrual period (variation 677 ± 786-fold) or to LH peak (variation 810 ± 936-fold). When pregnancy was anchored to the day of implantation (variation 187 ± 123-fold) variation was significantly reduced (P < .00005). Individual differences in the rate of hCG production were examined. hCG production ranged from 1.52-fold to 2.92-fold per day. Rate differences in hCG were also a major source of hCG variation. CONCLUSION: Two factors are responsible for the wide fluctuation in hCG concentrations, first dating pregnancies to the start of the last menstrual period rather than the timing of implantation and second, individual pregnancy differences in the rate of hCG production.

Biological functions of hCG and hCG-related molecules.

BACKGROUND: hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. RESULTS AND DISCUSSION: hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.

USA hCG reference service, 10-year report.

INTRODUCTION: The USA hCG Reference Service has been dealing with cases of persistent low levels of hCG and gestational trophoblastic diseases for 10years. Here we present the complete experience. METHODS: Total hCG in serum and urine was measured using the Siemen's Immulite 1000 assay. Hyperglycosylated hCG, nicked hCG, free ss-subunit and ss-core fragment were measured using microtiterplate assays with antibodies B152, B151, FBT11 and B210, respectively. RESULTS: The USA hCG Reference Service has identified 83 cases of false-positive hCG, 71 cases of aggressive gestational trophoblastic disease (GTD), 52 cases of minimally invasive GTD, 168 cases of quiescent GTD and 22 cases of placenta site trophoblastic tumor (PSTT). In addition, 103 cases of pituitary hCG have been identified, 60 cases of nontrophoblastic tumor, 4 cases of inherited hCG and 2 cases of Munchausen's syndrome. This is 565 cases total. Multiple new methods are described and tested for diagnosing all of these disorders. CONCLUSIONS: The USA hCG Reference Service experience shows new methods for detecting multiple hCG-related disorders and recommends new approaches for detecting these hCG-related disorders.

Inherited human chorionic gonadotropin.

OBJECTIVE: To investigate 405 cases of persistent low concentrations of human chorionic gonadotropin (hCG). STUDY DESIGN: The USA hCG Reference Service measured total regular hCG, follicle stimulating hormone and luteinizing hormone (LH) with the Siemens (New York, New York) Immulite 1000 assay. Hyperglycosylated hCG, nicked hCG, C-terminal peptide total hCG, intact regular hCG, free beta-subunit and beta-core fragment were measured in manual microtiter plate assays. RESULTS: Four cases of inherited hCG were identified, with similar hCG production recorded in first degree relatives. All cases produced primarily the regular hCG dimer. In 1 case hCG was detected only in the urine sample. CONCLUSION: Inherited hCG is disclosed as a source of persistent low concentrations ofhCG. It was assumed that this regular hCG is produced by the pituitary gland, either as excess pituitary production beyond that which occurs alongside the LH peak in every menstrual cycle or as a genetic disorder.