Intravenous Ascorbate as agent of modification of the quimioterapéutica and biological answer

by the center for the improvement of Human Functioning, International, Inc., institute of investigation of the biocomunicaciones. Reprinted with the permission.

(emphasis added by editor Andrew Saul of

By more than 15 years we have studied intravenous ascorbic acid of the high dose (IAA) as therapy adjunctive for the patients of the cancer. Initially, the 15 doses of g by the infusion were used, once or twice for week. Sense of this improved patient dose of the well-being, the reduced pain, and in many cases of life prolonged beyond prognoses of oncologists.

Twelve years ago, we used infusions of 30 grams of intravenous ascorbic acid, twice per week, and found that the injuries metastatic in the lung and the liver of a man with primary a renal carcinoma of the cell disappeared in a question of weeks (1). In that one ‘age we thought that IAA was useful for the patients with the cancer only through two biological mechanisms of the modificante of the answer: increasing production of extracellular collagen (“masonry’ of the tumor according to proposed by Cameron and Pauling) and of the enhancement of the immune function. We later disclose a case of the resolution of the metastases of the bone in a patient with the cancer of primary chest (1A) that used infusions of 100 grams, once or twice for the week (2).

In a recent publication (3) we presented evidence that the ascorbic acid and its salts (AA) could more be than modificantes biological of the answer. We find that the ascorbic acid is preferential toxic to the cells of the tumor that they suggest could be useful as quimioterapéutico agent. The preferential toxicity happened test-tube in multiple types of the cell of the tumor. Also we presented the data that suggested them concentrations of the plasma of ascorbate required for the cells of the tumor of the slaughter were attainable in human beings. Others have described to toxicity in vivo in the multiple types and the animal models (4-8) of the tumor.

Here we wished to summarize our experience using IAA for approximately 50 patients with the cancer. We include our protocol, precautions, and studies of case of two patients treated for the renal carcinoma metastatic of the cell.

Reasoned analysis of the treatment
Of our studies (3) we concluded that:

 The cells of the tumor are more susceptible for the purposes of the high-dose, products ascorbate-induced of peroxidation due to a relative deficiency of catalase; and, 

 The concentrations of ascorbate above to kill enough to the cells of the tumor can be probably reached in human beings. 

We later prove samples of the human serum of the patients who received IAA, and confirmed that the concentrations of the AA can reach the levels that are cytotoxic to the cells of the tumor in vitro. Using dense it populated monolayers, three-dimensional models of the tumor of the hollow-fiber, and human serum as half of the growth of fence to the imitator what it happens in vivo, we found that a concentration of the 400 AA of mg/decilitro kills with effectiveness to the majority of the types of the cell of the tumor. We disclose originally that a concentration of 40 mg/decilitro was (3) suitable. Those early data were generated of Ines studies vitro using monolayers of little cell populated and standard growth medium with the fine weave

The picture 1 (that can be considered in the original paper fixed to demonstrates to the answers to the doses of increase of ascorbate of four human lines of the cell of the tumor dense swellings in monolayers in means of the human serum.

Picture 1 Subtitle:
The answer to ascorbate of the sodium (half of 12 samples) of the cell of the tumor aligns Mia PaCa-2 (human pancreatic carcinoma). SK-MEL-28 (human melanoma), SW-620 (human carcinoma of both points), and U-2-OS (human sarcoma osteogenic), everything of ATCC, Rockville, Md. The results reflect total the viable cells. The means of the maintenance were growth medium of the DMEM High-glucose (Irvine Sci.) wf 10% heat-did inactive serum + fetal antibiotics + Fungizone of the yearling calf, dampened incubator CO2 of 5% in 37 degrees of Experimental C. that the means were human serum of patients with diagnosis of respective human tumors. Cultivated by 3 days after the suplementación of ascorbate. Cultivated field with 24,000 celIs Avell in the plates of the culture 96-well (Nune). The absolute quantification of cells cheers was determined with the method previously described of fluorómetro of microplate (16).

Picture 2 Subtitle:
Concentrations of ascorbate of the plasma during the infusion of 65 grams of ascorbic acid in 500 ml of sterile water in an index of a gram AA per minute. The whole blood was taken via a lock from heparin of the antecubital vein from the contraleral arm to the arm that received the infusion of the intravenous one. The concentrations of the AA of the plasma were determined using the liquid of the high performance chromatograpy. Patient I was a man 74-year-old that had a diagnosis of the carcinoma non-metastatic of the prostate, that had received more than 30 infusions of IAA in both years before the study. Patient 2 was a man 50-year-old with a diagnosis of the lymphoma of non-Hodgkin that had received infusions of l6 IAA before the study. Patient 3 was an old man of 69 years with a diagnosis of the carcinoma metastatic of the jejunum that had received 16 infusions of IAA before the study.

Picture 2 represents the levels of ascorbate of the plasma of three representative patients given 65 grams of ascorbate on 65 minutes. Patient 1 with the located cancer of the prostate was clinical good and had received IAA in the past; he reached a maximum concentration of the plasma of 702 mg/decilitro. Patients 2 and 3, had diagnosis of the lymphoma of non-Hodgkin, and carcinoma metastatic of the jejunum, respectively. Both had received several infusions of IAA at the time of study, they had reached lower concentrations of the AA of the plasma of 309 mg/decilitro (patient 3), and of 396 yet mg/decilitro (patient 2).

Of the data in both pictures 1 and 2, one can see that the required concentrations to kill to the cells of the tumor can be reached at least briefly in human plasma. Picture 2 suggests it necessity to measure concentrations of ascorbate of the plasma of the post-IAA to determine if the patients are reaching what we hoped are the suitable concentrations.

Protocol Of the Infusion

Option of the treatment
The treatment of the cancer with IAA is due to never consider to replace an effective, proven treatment. It must be only considered in: 

Cases of the lack of the treatment using proven cases of the methods without known effective treatments; and, 

Cases in which it is used as proven treatments of an associate. 

Because the IAA treatment is experimental a form informed appropriate into the consent is due to read, to understand, and to sign by the patient.

Precautions and side effects
The side effects of IAA in our experience are rare. Nevertheless, there are potential contraindications and side effects that will be considered.

1. Although it has been disclosed only once in Literature, the necrosis of the tumor, the hemorrhage, and the subsequent death after a single intravenous dose of 10 grams of the AA, according to the disclosed thing by Campbell and Gato (10), must be the preoccupation of the highest priority by the security of IAA for the patients of the cancer. Therefore, we always began with a small dose (it see the infusion).

2. Another report described nephropathy acute of oxalate in a patient with the bilateral obstruction ureteric and the renal shortage that received 60 grams IAA (11). Also we have heard a report of the case of a patient with carcinoma of both points, receiving IAA daily, that developed nausea and to vomit and was hospitalized for the dehydration (12). Both cases demonstrate the necessity to make sure that the patients have the suitable renal function, the hidración, and capacity that urinary annuls. To these ends, our laboratory tests of the basic line include a profile and a urinalysis of the chemistry of the serum.

3. The hemolysis can happen in patients with a red deficiency of dehydrogenase of the cell glucose-6-phosphate (G6PD). Therefore we proved G6PD in all the patients before beginning IAA infusions.

4. The pain located in the site the infusion can happen if the tariff of the infusion is too high. This is corrected generally slowing down the tariff.

5. Because ascorbate is an agent chelating, some individuals can experiment to sacudarir due to calcium under the serum. This is dealed with by (1 cc per minute) a slow intravenous push of 10 cc gluconate of calcium.

6. The rivers (13) disclosed that contraindicated in the renal shortage, patient of chronic hemodialyses, unusual forms of overload of the iron is high dose IAA, and formers of stone of oxalate. Nevertheless, the stone formation of oxalate can be considered a contraindication relative. Two groups of the investigators (14.15) demonstrated that the oxide of magnesium (300 rng/d oral) and the B6 vitamin (10 mg/d oral) inhibited the stone formation of oxalate in formers of stone.

7. Given the amount of liquid that is used as vehicle for ascorbate and bicarbonate of sodium hydroxide/sodium fit the pH, any condition that could on the contrary be affected by the liquid or increasing sodium is contraindicated relatively. For example: congestive cardiac arrest, ascitis, oedema, etc.

8. As with any intravenous site, the infiltration is always possible.

9. Ascorbate is due to only give by the intravenous dripping. Push of the intravenous one must never be given, because the osmolalidad of high doses is able of peripheral veins sclerosing, nor must intramuscular or subcutaneous he be given. There is always a compensation between the fluid volume and the osmolalidad. We have found a osmolalidad of less than 1200 milliOsmal than it will be tolerated well by the majority of the patients (table 1, that can be seen in the original paper). 

The basic line works - for above
Before administering great amounts of ascorbate, we compiled the following information for a basic line and as way to supervise therapy: 

 Profile of the chemistry of the serum with electrolytes 
 The account of blood with differential finishes 
 Red cell of blood G6PD 
 Patient weight 
 Tumor type/staging 
 Appropriate markers of the tumor of the serum 
 CT, MRL, explorations of the bone, and appropriate projection of image of the x-ray

Subtitle Of Table 1:
Osmolalidad of several amounts of acid of sodium ascorbate/ascorbic in the sterile lactate of the water and the bell founder (mOsm; = mOsm isotónico 300). The hypotonic mixtures are emphasized: the useful mixtures of isotónico to mOsm 1200 are in elm. An equal volume of the solution of the intravenous one takes off of the purse or the bottle, before adding the acid solution concentrated of sodium ascorbate/ascorbic (500 mg/mL).

Solution of the infusion
In therapy of ascorbate of the high-dose, many intravenous solutions are hypertonic. This does not look like to present a problem while it is the tariff of the infusion under enough and the tonicity does not exceed 1200 milliOsmal (mOsm). We instill generally the AA mixed with the solution of the lactate of the bell founder (RL) for the amounts of the AA up to 15 grams, and in the sterile water for greater amounts of AA. We at the moment use an acid mixture of sodium ascorbate/ascorbic that 0,91 sodium awkward person contains by the awkward person of ascorbate (500 AA/mL magnesium, range 5.5-7.0 of the pH, pharmaceuticals of the merit, Los Angeles, California, and pharmaceuticals of Maclaskey, Wichita, Kansas). Table I demonstrates the osmolalidades of solutions commonly prepared.

According to the indicated thing in the precautions, a dose that begins small of 15 grams AA in 250 ml RL on 1 hour is recommended. They look at the patient of fence for any injurious effect. The dose can then be increased gradually in a certain term. The tariff of the infusion does not have to exceed 1 gram AA per minute; 0.5 gram/mm is tolerated well by the majority of the patients. Although there is variability due to programming and to tolerance, a typical protocol will consist of the following infusions: 

Week 1: infusion of 1 of 15 xs g by the day, 2-3 per week 
Week 2: infusion of 1 of 30 xs g by the day, 2-3 per week 
Week 3: infusion of 1 of 65 xs g by the day, 2-3 per week 

The dose then adjusts to reach 400 the transitory concentrations of mg/decilitro, 2-3 infusions of the plasma per week.

According to our hypothesis of operation, the goal of the infusions is to raise to the concentration of ascorbate of the plasma on the level tumor-citoto'xico for so of length as it is possible. Because he is ascorbate cleared so easily by the kidney, the optimal tariff of the infusion will give rise at levels tumor-citoto'xicos of the plasma of ascorbate for the longest periods -- and hopefully, maximum slaughter of the cell of the tumor.

We advise to patients to replace oral with 4 grams of ascorbate daily, especially in the days when one does not become any infusions, to help to prevent a “possible effect scorbutic with the bounce.”

Histories of the case
We have seen patients with almost each type of solid tumor in our clinic. Much of them has received IAA, with several degrees of success. Our cases include to patient with cancer of head of pancreas on which IAA lived by 3,5 years with as therapy only, resolution of metastasis of bone in patients with cancer of chest, many patients with lymphoma of non-Hodgkin (none of whom they have died of his disease), the resolution of the primary tumors of the carcinoma of the liver, the resolution and the downsizing of the injuries metastatic of the carcinoma of both points, and of the resolution of injuries metastatic and the survival of three years of the surplus in patients with ovarian carcinoma extensively metastatic. We glide to present a complete compilation of cases in another communication.

We have only seen two cases of renal carcinoma metastatic of the cell, considered a uniformly untreatable disease. Because the results were so dramatic, people with this disease could potentially benefit the majority from the IAA treatment. 

The following are those two cases.

Case 1
52-year-old that saw the white female with a history of the renal carcinoma of the cell in our clinic for the first time inside October, 1996.In September of 1995, shortly after diagnosis of a primary tumor in its left kidney, a nefrectomía was realised. The histology confirmed renal carcinoma of the cell. Was not any evidence of metastasis in that one ‘age. In 1996 march, the metastases to the lungs were found in the film of the x-ray of the chest. In September of 1996, a film of the x-ray of the chest revealed 4 1 to the 3-centi'metros masses in its lungs. A month advanced more were 8 1 to the 3-centi'metros masses in its lungs (7 in right lung, 1 in new doctor of left). No, the radiation, or the surgical therapies were realised before their visit to our clinic in October of 1996, when she began IAA therapy. Its initial dose era 15 g, that increased to 65 g after 2 weeks, two per week. Ignition also began it: cysteine of the N-acetyl (products of the investigation of the vitamin, city of Carson, nanovoltio), 500 p.o of magnesium 1, QD; they glucan of beta-1,3 (a stimulator of the macrophage, NSC-24, Nutrition Supply Corp., city of Carson, nanovoltio), 2,5 magnesium 3 p.o. QD; oil of the fish (Wonderful, pharmaceuticals of Bronson, St Louis, MONTH; acid docosahexaenoic of magnesium 300 acid eicosatetraenoic of magnesium, 200), 1 p.o. TID; vitamin C, 9 g p.o. QD; betacaroteno (carotene beta 25, Miller Pharmacal Group, Inc., current of carol, IL), 25,000 lU. 1 p.o. SUPPLY; L-l-threonine (Solgar Vitamin Co, Inc., Lynbrook, NY), 500 magnesium p.o. QD (for a revealed deficiency laboratory test of the serum); Bacillus laterosporus (Lateroflora, See-saw-Tech international the USA, San Marcos, CA), 280 magnesiums, 2 p.o. QD for intestinal icans of the candida a/b, complex of hexaniacinate of inositol (Niaplex, Karuna Corp. , Novice, CA; 500 niacin of magnesium, chromium of 100 magnetocardiogramas) 2 p.o. QD, and a diet of no-refining-azu'car.

It continued IAA treatments until June of 1997 when another film of the x-ray of the chest revealed the resolution of 7 of the 8 masses, and the reduction in the size of 8vo. According to the medical report of the image projection, “the nodular one infiltrates sight in the right lung previously and covering the heart it is evident a not more length and the nodular ones infiltrate sight in field left superior of the lung have demonstrated to the marked diminution of the size interval and only the vague suggestion of a density of approximately I centimeter.”

The patient continued treatments of IAA in June of 1997. It has continued in a program of oral nutritional help from that time, and in this writing (December of 1997) she is well without the evidence of the progression.

Case 2
In December of 1985, a mass that occupied the post more under the right kidney was discovered in a man of the target of the years 70-. The pathology of the mass after a radical nefrectomía confirmed renal carcinoma of the cell. Oncologist in another clinic it followed it. Approximately three months after the surgery, of the film of x-ray of the patient and the exploration of CT demonstrated “multiple pulmonary injuries and injuries in several areas of its liver which was lymphadenopathy abnormal and periaortic.”

In march 1986 they saw the patient in our clinic (1). He decided not to experiment 
chemotherapy. It competes solicitd and it was begun in IAA, 30 g twice per week. In April of 1986, six weeks after the studies of the film of x-ray and the exploration of CT, the report of oncologist indicated, 

“… the patient returns the good sensation. Its examination is totally normal. Its x-ray of the chest demonstrates a dramatic improvement in the compared pulmonary nodules does to six weeks. Lymphadenopathy periaortic is solved totally…, any it has had a viral infection with the pulmonary injuries with lymphadenopathy that has solved or (2) it really had cancer appellant of the kidney that is responding to its therapy of vitamin C.” 

The report of oncology in July 1996 indicated, “is evidence of the progressive no cancer. He looks well. the x-ray of the chest is today totally normal. The pulmonary nodules go away totally. There is evidence of the no metastasis of the lung, of the metastasis of the liver or the metastasis of the lymph node today, any.”

In 1986 the received patient 30 time-weekly infusions of g two by 7 months. The treatments then were reduced to once by the week by 8 more months. For the 6 additional months it received the weekly magazine, 15 infusions of g IAA. During and after treatments, the patient did not disclose any toxicity, and their profiles of the chemistry of the blood and studies of the urine were normal.  They saw the patient continued well, and periodically in our clinic until the beginning of 1997 when he died, ca'ncer-free one, in age 82, 12 years after the diagnosis.

We think that IAA has potential as quimioterapéutico agent. We hope our protocols to mix itself and the infusion of IAA, precautions that will be taken before and during from their use, and the clinical information of the case will justify additional clinical tests and the investigation with IAA for the patients with disease metastatic. We do not think that it is a treatment for all the cancers. Although it demonstrates promise whereas a unique therapy, particularly in renal carcinoma of the cell, he is due to use mainly as associate to other effective therapies.

Our investigation is only funded with donations of individuals. Neither we have looked for nor received funding of the agencies of state. We animate to readers who support our investigation. All our 501 donations to (c) 3 organization are impose-deductible.

Neil H. Riordan, the CAP
Hugh D. Riordan, M.D.
Ronald E. Hunninghake, M.D.

The center for the improvement of the human, international, Inc. operation.
Avenue Of 3100 N. Hillside, Wichita, Kansas 67219

We would want to thank for the scientific personnel of the institute of investigation of the biocomunicaciones that contributed to this investigation: Neil Riordan, P.A. - C., Xiaolong Meng, Megabyte.; Tailor De Paul, B.S.; Jei Zhong, Megabyte.; Kevin Alliston, MS; and José Casciari, Ph.D. We is thankful puts to R. Davis, Ph.D., to correct this manuscript.

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