Pharmacological Dose Vitamin C and Interrupted Oral Bromocriptine
A Synergistic Effect
So why do we here discuss these two agents in combination? The reason is that some combinations exhibit characteristics not noted with either agent alone. Such a cooperative effect is known in pharmacology as “synergy”.
A perceived synergy of the ascorbate / bromocriptine was recognized in the late 1980′s at the Mississippi Baptist Medical Center in Jackson, Mississippi, where patients placed on high dose vitamin C and bromocriptine experienced improvement in strength and stamina much greater than that noted with either agent alone. This was perceived as a possible major advance.
In quality of life analyses of subjectively perceived problems in advanced cancer patients, the three worst problems are:
loss of physical strength
loss of stamina
Deficits of strength and stamina, as perceived by the patients, are usually not addressed by the conventional physician, and there is no standard of care intervention for these problems. Patients are, however, pleased if the physician or his staff exhibits sufficient concern to define the extent of these problems, and possess sufficient therapeutic knowledge that these symptoms may be successfully treated. It is essential to remember the delay to effective of 1 to 8 weeks onset described in “bromocriptine” applies here.
A suppressor T-lymphocyte blocker
For reasons that are unclear, cancer patients experience a marked overgrowth of a population of lymphocytes known as suppressor T-lymphocytes. These cells act to prevent or obstruct immune mediated cancer offensives: these cells are “breaks” in the immune system. Abundantly documented in the experimental literature is a much improved immune function in patients and experimental animals who have been given Cimetidine (Tagamet).
While this effect is well proven by numerous reports in the scientific literature, this effect is not marketed by drug companies because of the expense involved to get FDA approval. Use of cimetidine by physicians for immune restoration in cancer patients is an “off label use”. Off label use of FDA approved medications by physicians is both legal and ethical.
Cimetidine has many drug interactions. However, no other drug in its class has an investigational literature documenting comparable enhancement of immune function. Furthermore, a sizable literature of extraordinary remissions and apparent cures in cases of apparently incurable cancer have been reported with cimetidine in both animals (cimetidine is used in veterinary practice) and people.
Cyclical Gonadal Hormones
Induction of Menstrual Cycle Associated Natural Killer Cell Surges
A female, after puberty, is almost immune to cancer before reaching the age of 40. Exceptions include a few breast cancers, some lymphomas, and a small diversity of other cancers. During reproductive years, (age 13 – 40) female physiology is characterized by ovulatory (menstrual) cycles and numerous other rhythmical cycles, such as puberty itself, diurnal cycles (sleep at night, awake during day), respirations, heart beat, brain waves, etc. During menstrual cycles, the maximum resistance to cancer occurs mid cycle after 12 – 14 days of estrogen, around the time of ovulation.
William J. M. Hrushesky, M.D., has studied and described in several peer reviewed papers and in a book* marked fluctuation in natural killer (NK) cell activity and resistance to breast cancer during menstrual cycles of the premenopausal women.
Hrushesky has also reported a marked difference in survival of breast cancer patients as a function of the time of the menstrual cycle when breast cancer resection was carried out.
Dr. Hrushesky has not, however, documented the mechanism of causation for the synchrony and covarience of immune surveillance peaks and ovulation which he has observed. Remaining unanswered is the mechanistic question, “Is this covarience a co-dependence on some common central cause, or, in the alternative, is the NK spike substantially derivative of the ovarian hormonal secretions: i.e. do the hormones associated with the menstrual cycle induce, at the time of ovulation, the clinically documented NK lymphocyte surge.
How are these cycles created? The brain is an elaborate computer. The command to the human brain to precipitate ovulation is 12 – 14 days of estrogen, a hormone secreted by the ovary under the inducement of the brain. NK peaks are associated with high serum peaks of estrogen and follicle stimulation hormone (FSH), and a cyclical high in luteinizing hormone (estrogen induced LH spike). LH, like growth hormone (GH), has been documented to be a powerful stimulant of NK cells.
Thus the brain is a computer that regulates immune surveillance (the normal ability to destroy early cancer), among its many many other non-conscious cyclical functions. What Dr. Smith has observed is that clinical employment of hormones made by the ovary, estrogen and progesterone, is able to induce cyclical fluctuations in NK count, strongly supporting the conclusion that these two hormones in youthful otherwise normal premenopausal females cause or are a major contributing cause of the cyclical intensifications of immune surveillance observed during menstrual cycles.
For an operative immune resistance to cancer, a patient must have three distinct systems intact:
A recognition “spotter” function
This function provides the mechanism whereby cancer cells may be discriminated from normal tissues. Basic research indicates such a function to be present in three types of cells: B-lymphocytes, dendritic cells, and macrophages.
Macrophages are scavenger cells capable of consuming dead cells, recognizing “spotting” foreign antigen (cancer) and presenting this foreign tumor antigen to the lymphocytes in an acceptably formatted manner. The B-lymphocytes which are presented foreign antigen — that part of the cancer cell that “looks” different from normal cell — then facilitate the immune surveillance process by the manufacture of tumor specific antibody based on the information (prepared tumor antigen) arriving directly or indirectly from the macrophages. Cancer specific antibody, once produced by the B-cells, then circulates through the body until it contacts cancer cells where it becomes attached. This antibody serves as a recognizable label on the foreign enemy cancer cells which, for attack purposes, have been “designated” or “targeted” for destruction by the natural killer and antibody activated killer cells.
A destroy “killer” function
This activity appears to operate by way of natural killer lymphocytes (NK cell) and related lymphocytes. NK cells are enabled or empowered to perform effectively by growth hormone (GH) and luteinizing hormone (LH):
(a) The command for the brain to produce an LH surge is 10 days to two weeks of estrogen. In pre-menopausal women this surge causes (1) ovulation and, (2) a large increase in NK lymphocyte counts and host mediated cancer resistance.
(b) Estrogen is a NK function suppressor; therefore when employed as an immune stimulant, estrogen should not be given for more than two weeks at a time.
(c) Progesterone, the hormone secreted by the ovary after ovulation, if administered immediately after the estrogen induced LH surge, induces a further increase in LH secretion, and is, therefore, a useful tool in interventions designed to augement / restore immune surveillance. Medroxyprogesterone acetate (Provera) for 10 days, and initiated after the end of an initial 14 day Premarin cycle, completes simulation of the Hrushesky circadian gonadal hormone cycle wherein large NK surges and large cancer resistance surges are well documented in the youthful female and in experimental animals.
(d) In cancer patients over the age of 40, estrogen typically induces prolactin secretion, whereas in early adulthood, estrogen is a direct GH secretagogue. Prolactin, secreted in large amounts during pregnancey, causes breast enlargement and immune suppression. Unborn babies are “tumors” and immune suppression to neoplasms is part of the essential physiology of pregnancy. Bromocriptine is a powerful regulator of the cell population that produces prolactin and GH. Bromocriptine (Parlodel) blocks prolactin secretion and stimulates GH secretion.
An Administrative, Management, and Regulatory System
This system is substantially the province of the helper T-lymphocytes. Helper lymphocytes are the cells known to decline in AIDS, and the AIDS related decline is associated with greatly increased susceptibility to infection and cancer. The entire lymphocyte series is substantially controlled by the thymus gland and its hormones. The thymus is subject to enabling restriction without growth hormone (GH). Bromocriptine (Parlodel) and pharmacological doses of vitamin C typically induce, over time, an increase in strength and stamina. This effect appears to arise from the ability of this combination to stimulate GH and is associated with rises in helper T-lymphocyte counts.
* Circadian Cancer Therapy, William J.M. Hrushesky, editor, CRC Press, 1994, 292 pages. At the time this book was published, Dr. Hrushesky was the Senior Attending Oncologist at the Stratten Department of Veterans Affairs Medical Center and Professor of Medicine at Albany Medical College. Dr. Hrushesky’s bibliography includes more than 200 scientific papers.
Adenocarcinoma of the Lung with Multiple Brain Metastases
Read more about patient Arnold Ashley:
Low Dose Bromocriptine (Parlodel™)
Reprogramming hormone assembly lines
Based on research literature and clinical experience, bromocriptine may be used to restore strength and stamina in many cancer patients. Bromocriptine may benefit cancer patients in more than one way.
Prolactin is spontaneously overly secreted in some lung cancer patients. This excess secretion causes breast tenderness and enlargement. Premarin may cause breast tenderness and breast enlargement in men, but this effect is mediated by way of prolactin. If prolactin is blocked with bromocriptine, estrogen may be employed for its immune enhancing effects without fear of feminizing or prolactogenic effects in either sex.
A cell population, the somatomammatrophs, in the master gland, the hypophysis, has a pleuripotential capability to secrete either prolactin, or somatotropin, or both. The relative ratio of the production and secretion of these two hormones appears to have frequent marked clinical consequences.
In old age and cancer, somatomammatrophs secrete mostly prolactin. Prolactin is the hormone secreted in pregnancy. It helps establish a state where the mother’s immune system tolerates the progressive growth of the baby. Somatotropin is the trophic (nourishing) hormone of the thymus gland, the master gland of immunity.
Loss of somatotropin secretion leads to loss of physical strength and stamina. There is an actual decrease in muscle mass. Patients get flabby and indolent. Their sense of well being may be very seriously compromised by weakness and loss of stamina.
Based on extensive observation of strength and energy restoration in cancer and autoimmune patients, bromocriptine is capable of restoring the youthful ratio of bromocriptine / prolactin secretion, providing in cancer patients a return of the lost vigor of months or even years earlier. Not surprising from the known effects of bromocriptine as a stimulant of growth hormone secretion, objective evidence of improved surface labeling (maturation) of lymphocytes is frequently observed in cancer patients to whom bromocriptine is prescribed.
CD2, CD3, CD4 (helper cells) and CD56 (natural killer cells) frequently increase.
A pharmacological effect of bromocriptine seems to be a reprogramming of hormone assembly lines inside the somatomammotroph. These hormone assembly lines, which are capable of assembling either prolactin or somatotropin, require a conversion time from prolactin to somatotropin of one to eight weeks, typically 1 1/2 weeks (10 days) to a month (30 days). In many very weak cancer patients, the Center encourages a clinical trial of bromocriptine lasting two months, as a typical experience of no benefit at 10 days frequently converts to significant benefit by 8 weeks.
Bromocriptine is begun slowly. The worst common side effects of bromocriptine are light headedness with standing (orthostatic hypotension) and nausea. Either of these symptoms, if present, usually resolves spontaneously within three or four days.
Linked to immune decline
Melatonin is a naturally occurring hormone which, in a normal person, has its source in the thymus gland. Melatonin secretion declines steadily throughout life. Melatonin decline occurring in old age correlates with and appears causally related to the immune decline of old age. Melatonin decline is clearly not the only cause of the loss of immune surveillance in old age, but the decline in melatonin appears to contribute significantly.
Melatonin is intimately related to sleep, NK cell function, and emotional state. There are hundreds of research papers in the scientific literature related to the effect of melatonin on immunity and cancer.
Reports in the Italian medical literature suggest melatonin and IL-2 are synergistic if given together at or around early sleep. A beneficial consequence of this synergy is that IL-2 benefits may be seen at sufficiently low doses of this expensive cytokine to be more easily affordable by cancer victims.
Proleukin TR – Chiron Pharmaceuticals
The youthful person normally has an ongoing search and destroy mechanism working constantly against cancer. This process is known as “immune surveillance”. The natural killer lymphocyte (NK cell) is the killing effector (hit man) of the immune surveillance mechanism. IL-2 is a direct stimulant of NK cells. NK cells may decline in old age or cancer. During treatment with IL-2, assays for NK cells as a percentage of total lymphocytes will usually rise.
Dr. Steven Rosenberg at the National Cancer Institute has employed large doses of IL-2 in successfully inducing sustained remissions and apparent cures in patients with metastatic melanoma and renal cell carcinoma, two types of cancer notoriously resistent to radiotherapy and chemotherapy. IL-2 has produced a very significant lengthening of median and mean survival with apparent cures. Cure in the treated patients is suggested by a flat survival curve.
An editorial appeared in the same issue of the Journal of the American Medical Association as Rosenberg’s paper on IL-2 . In this editorial, Samuel Helman states:
” What then have we learned from this clinical experiment? The initial hypothesis was that it was possible to stimulate the host immune response to become an effective antitumor agent. The report by Rosenberg in this issue of THE JOURNAL clearly supports this hypothesis and is best regarded as a ‘proof of principle’. Interleukin-2 has no direct antitumor activity. It appears to act by causing the production of lymphokine activated killer cells and expanding the population of T-cells that can destroy target cells. Rosenberg, et al. have demonstrated that IL-2 treatment has resulted in clear, and in some cases dramatic, tumor regression. ……We are impressed with the duration of the complete responses. …..We should conclude that this study represents a significant advance in cancer therapy because of the novel mechanism of action of IL-2 and the long duration of complete responses.”
Interferon Beta-1b (IF-b)
Betaseron TR – Berlex Pharmaceuticals
As part of the normal body cells’ genetic programming, each cell exhibits samples of the proteins being employed within the cell as exhibits on the cell surface. As such display is of no direct benefit to the individual cell in question, this universal characteristic undoubtedly is part of the evolutionary endowment of cells which facilitates immune surveillance functions. Tens of thousands of clonally different lymphocytes, each programmed for an amino acid sequence alien to normal cells, constantly patrol the environment of all cells. If any one of these thousands of different lymphocytes encounters a cell displaying foreign amino acid sequences, the lymphocyte attaches itself to the foreign cell and undergoes profound stimulation. The clonal proliferation or the rapid exponential growth of enough lymphocytes to initiate the extermination of cancer cells may rapidly occur when such foreign sequences are recognized.
But for reasons poorly understood, some cancer cells do not express their foreign protein content in a manner detectable to the lymphocytes. Beta- interferon has the capability to induce cells to markedly increase their surface display of intracellular protein amino acid sequences. This increase in display in turn greatly facilitates recognition of cancer cells as foreign by the lymphocytes programmed to recognize such differences or by NK cells on patrol. The cancer cells are thus forced by IF- b to abandon a behavior characteristic that may have protected them from host attack.
Researchers at the Roswell Park Cancer Institute in New York state carried out a phase 1-2 clinical trial of IF-b in non small-cell lung cancer patients receiving radiotherapy as standard and conventional treatment. The patients receiving IF-b did markedly better compared with patients receiving radiotherapy alone.
At the American College of Radiology and Radiation Therapy Oncology Group (RTOG) meeting on clinical trials in Boston, Massachusetts on September 8, 1995, the discussant on lung cancer, in describing a current phase 3 clinical trial at Roswell Park, stated, “It looks like they are hitting a home run up there.” The result, to be released, may very well make IF-beta competitive with chemotherapy as an adjuvant tool.
IF-b is better tolerated than IL-2, although flu-like symptoms and mild malaise may also occur. Elderly and debilitated cancer victims seem to tolerate IF-b well and with minimal difficulty.
A a non-specific immune stimulant
Selenium is a naturally occurring mineral which has been shown:
(a) to be higher in the soils of geographical locations in the U.S. with low overall cancer incidence
(b) to be higher in the soil of countries of the world with low cancer incidence
(c) to be lower in patients with a higher risk of developing cancer over time
(d) to be higher in cancer patients who live a long time after the diagnosis of cancer
(e) to stimulate a heightened immune reaction in animals in a variety of experimental settings
(f) to induce a person or an animal to increase endogenous production of glutathione peroxidase, a powerful, naturally occurring, antioxidant enzyme
A mild anticoagulant, non specific immune stimulant, and regenerator of down regulated antioxidant function
Vitamin E has several documented anticancer properties:
(a) Cancer rather regularly induces an altered blood coagulation tendency with a heightened tendency to clot. Unexplained venous clotting (thrombosis) in an older patient frequently signals an undetected cancer. Seymore Ochsner, M.D. at the Ochsner Clinic in New Orleans, LA, popularized the use of vitamin E to prevent the vein thrombosis following surgery. Post surgical thrombosis may lead to deadly pulmonary emboli or other severe complications of major surgery.
Cancer colonies may protect themselves from phagocytosis by macrophages or attack by NK cells by spinning a cocoon-like coat of coagulated protein around themselves, much as hive moth larvae protect themselves from bee attacks as they burrow through the cells of a honey bee hive destroying everything in their path. Vitamin C or E, by decreasing the predisposition of blood to clot, “leans against” the pathophysiologic adaptation of the cancer colony.
(b) Vitamin E is the principle antioxidant of the fatty components (“lipid compartment”) of the body. The body’s own synthesized antioxidant defenses (catalase, glutathione peroxidase, etc.) appear to be simultaneously down regulated in old age by a major regulatory gene known as a codon. Pharmacological doses of vitamin E “leans against” this deficiency by external (“exogenous”) replacement of lost free radical defenses.
(c) In a large clinical and investigational literature, vitamin E has been clearly and unequivocally documented to improve immune function. The effect is common to most plant origin (phytochemical) antioxidants