Intravenous Ascorbate as a Chemotherapeutic and Biologic Response Modifying
by The Center for the Improvement of Human Functioning, International, Inc.,
Bio-Communications Research Institute
. Reprinted with permission.
(Emphasis added by DoctorYourself.com editor Andrew Saul)
Additional research papers may be read at
For over 15 years we
have studied high dose intravenous ascorbic acid (IAA) as an adjunctive therapy
for cancer patients. Initially, doses of 15 g per infusion were used, once or
twice per week. These doses improved patient's sense of well being, reduced
pain, and in many cases prolonged life beyond prognostications of
Twelve years ago, we used infusions of 30 grams of intravenous ascorbic
acid, twice per week, and found that metastatic lesions in the lung and liver of
a man with a primary renal cell carcinoma disappeared in a matter of weeks
(1). At that time we believed IAA was useful for patients with cancer solely
through two biological response modifier mechanisms: increased production of
extracellular collagen ("walling off' the tumor as proposed by Cameron and
Pauling) and enhancement of immune function. We subsequently reported a case of
resolution of bone metastases in a patient with primary breast cancer (1A)
using infusions of 100 grams, once or twice per week (2).
In a recent publication (3) we presented evidence that ascorbic acid and its
salts (AA) could be more than biological response modifiers. We found that
ascorbic acid is preferentially toxic to tumor cells suggesting that it
could be useful as a chemotherapeutic agent. Preferential toxicity occurred in
vitro in multiple tumor cell types. We also presented data suggesting that
plasma concentrations of ascorbate required for killing tumor cells were
achievable in humans. Others have described in vivo toxicity in multiple tumor
types and animal models (4-8).
Here we wish to summarize our experience using IAA for approximately 50
patients with cancer. We include our protocol, precautions, and case studies of
two patients treated for metastatic renal cell carcinoma.
studies (3) we concluded that:
Tumor cells are more susceptible to the effects of high-dose,
ascorbate-induced peroxidation products because of a relative catalase
Concentrations of ascorbate high enough to kill tumor cells likely can
be achieved in humans.
Subsequently we tested samples of human serum from patients receiving IAA,
and confirmed that AA concentrations can reach levels that are cytotoxic to
tumor cells in vitro. Using densely populated monolayers, three-dimensional
hollow-fiber tumor models, and human serum as a growth medium to closely mimic
what occurs in vivo, we found that an AA concentration of 400 mg/dL effectively
kills most tumor cell types. Originally we reported that a concentration of 40
mg/dL was adequate (3). Those early data were generated from in vitro studies
using sparsely populated cell monolayers and standard tissue culture
Figure 1 (which may be seen in the original paper posted at
http://brightspot.org/cresearch/intravenousc2.shtml) shows the responses to increasing doses of ascorbate of
four human tumor cell lines grown in dense monolayers in a medium of human
Figure 1 Caption:
sodium ascorbate (mean of 12 samples) of tumor cell lines Mia PaCa-2 (human
pancreatic carcinoma). SK-MEL-28 (human melanoma), SW-620 (human colon
carcinoma), and U-2-OS (human osteogenic sarcoma), all from ATCC, Rockville, MD.
Results reflect total viable cells. Maintenance medium was DMEM High-glucose
culture medium (Irvine Sci.) wf 10% heat-inactivated fetal calf serum +
antibiotics + Fungizone, 5% CO2 humidified incubator at 37 degrees C.
Experimental medium was human serum from patients with diagnoses of respective
human tumors. Cultured for 3 days after supplementation of ascorbate. Seeded
with 24,000 celIs Avell in 96-well culture plates (Nune). Absolute quantitation
of live cells determined using previously described microplate fluorometer
Figure 2 Caption:
concentrations during infusion of 65 grams ascorbic acid in 500 ml sterile water
at a rate of one gram AA per minute. Whole blood was taken via a heparin lock
from the antecubital vein of the arm contraleral to the arm receiving the IV
infusion. Plasma AA concentrations were determined using high performance liquid
chromatograpy. Patient I was a 74-year-old male who had a diagnosis of
non-metastatic prostate carcinoma, who had received more than 30 IAA infusions
in the two years prior to the study. Patient 2 was a 50-year-old male with a
diagnosis of non-Hodgkin's lymphoma who had received l6 IAA infusions prior to
study. Patient 3 was a 69 year old male with a diagnosis of metastatic carcinoma
of the jejunum who had received 16 IAA infusions prior to study.
Figure 2 depicts plasma ascorbate levels of three representative patients
given 65 grams of ascorbate over 65 minutes. Patient 1 with localized prostate
cancer was clinically well and had received IAA in the past; he achieved a peak
plasma concentration of 702 mg/dL. Patients 2 and 3, had diagnoses of
non-Hodgkin's lymphoma, and metastatic carcinoma of the jejunum, respectively.
Both had received several IAA infusions at the time of study, yet achieved lower
plasma AA concentrations of 309 mg/dL (patient 3), and 396 mg/dL (patient
From the data in both Figures 1 and 2, one can see that the concentrations
required to kill tumor cells can be achieved at least briefly in human plasma.
Figure 2 suggests the need to measure post-IAA plasma ascorbate concentrations
to determine if patients are achieving what we expect are adequate
cancer with IAA should never be considered to replace an effective, proven
treatment. It should only be considered in:
Cases of treatment failure using proven methods cases with no known effective
Cases in which it is used as an adjunct to proven treatments.
Because IAA treatment is experimental an appropriate informed consent form
should be read, understood, and signed by the patient.
Precautions and side effects
The side effects of IAA in our experience are rare.
However, there are contraindications and potential side effects to be
1. Although it has been reported only once in the literature, tumor necrosis,
hemorrhage, and subsequent death after a single intravenous 10 gram dose of AA,
as reported by Campbell and Jack (10), should be the highest priority concern
for the safety of IAA for cancer patients. For this reason, we always
begin with a small dose (see Infusion).
2. Another report described acute oxalate nephropathy in a patient with
bilateral ureteric obstruction and renal insufficiency who received 60 gram IAA
(11). We have also heard one case report of a patient with colon carcinoma,
receiving daily IAA, who developed nausea and vomiting and was hospitalized for
dehydration (12). Both cases show the need to ensure that patients have adequate
renal function, hydration, and urinary voiding capacity. To these ends, our
baseline lab tests include a serum chemistry profile and urinalysis.
3. Hemolysis can occur in patients with a red cell glucose-6-phosphate
dehydrogenase (G6PD) deficiency. We therefore test G6PD on all patients before
beginning IAA infusions.
4. Localized pain at the infusion site can occur if the infusion rate is too
high. This is usually corrected by slowing the rate.
5. Because ascorbate is a chelating agent, some individuals may experience
shaking due to low serum calcium. This is treated by a slow (1 cc per minute)
intravenous push of 10 cc's of calcium gluconate.
6. Rivers (13) reported that high dose IAA is contraindicated in renal
insufficiency, chronic hemodialysis patients, unusual forms of iron overload,
and oxalate stone formers. However, oxalate stone formation may be considered a
relative contraindication. Two groups of researchers (14,15) demonstrated that
magnesium oxide (300 rng/d orally) and vitamin B6 (10 mg/d orally) inhibited
oxalate stone formation in stone formers.
7. Given the amount of fluid which is used as a vehicle for the ascorbate and
the sodium hydroxide/sodium bicarbonate used to adjust the pH, any condition
which could be adversely affected by increased fluid or sodium is relatively
contraindicated. For example: congestive heart failure, ascites, edema,
8. As with any intravenous site, infiltration is always possible.
9. Ascorbate should only be given by intravenous drip. It should never be
given IV push, as the osmolality of high doses are capable of sclerosing
peripheral veins, nor should it be given intramuscularly or subcutaneously.
There is always a trade-off between fluid volume and osmolality. We have found
an osmolality of less than 1200 milliOsmal to be tolerated well by most patients
(Table 1, which may be seen in the original paper).
administering large quantities of ascorbate, we gather the following information
for a baseline and as a way to monitor therapy:
Serum chemistry profile with electrolytes
Complete blood count with differential
Red blood cell G6PD
Appropriate serum tumor markers
Appropriate CT, MRL, bone scans, and x-ray
Table 1 Caption:
Osmolality of various
amounts of sodium ascorbate/ascorbic acid in sterile water and Ringer's Lactate
(mOsm; isotonic = 300 mOsm). Hypotonic mixtures are underlined: useful mixtures
from isotonic to 1200 mOsm are in bold. An equal volume of IV solution is
removed from the bag or bottle, prior to adding concentrated sodium
ascorbate/ascorbic acid solution (500 mg/mL).
ascorbate therapy, many intravenous solutions are hypertonic. This does not seem
to present a problem as long as the infusion rate is low enough and the tonicity
does not exceed 1200 milliOsmal (mOsm). We generally infuse AA mixed with
Ringer's lactate (RL) solution for AA amounts up to 15 gram, and in sterile
water for larger amounts of AA. We presently use a sodium ascorbate/ascorbic
acid mixture Containing 0.91 moles of sodium per mole of ascorbate (500 mg
AA/mL, pH range 5.5-7.0, Merit Pharmaceuticals, Los Angeles, California, and
Maclaskey Pharmaceuticals, Wichita, Kansas). Table I shows the osmolalities of
commonly prepared solutions.
As indicated in the
precautions, a small starting dose of 15 gram AA in 250 mL RL over 1 hr is
recommended. The patient is watched closely for any adverse effects. The dose
can then be gradually increased over time. The infusion rate should not exceed 1
gram AA per minute; 0.5 gram/mm is well tolerated by most patients. Although
there is variability due to scheduling and tolerance, a typical protocol will
consist of the following infusions:
Week 1: 1 x 15 g infusion per day, 2-3 per week
Week 2: 1 x 30 g infusion per day, 2-3 per week
Week 3: 1 x 65 g infusion per day, 2-3 per
The dose is then adjusted to achieve transient plasma concentrations of 400
mg/dL, 2-3 infusions per week.
According to our working hypothesis, the goal of the infusions is to raise
plasma ascorbate concentration above the tumor-cytotoxic level for as long as
possible. Because the ascorbate is so readily cleared by the kidney, the optimal
infusion rate will result in tumor-cytotoxic plasma levels of ascorbate for the
longest time periods--and hopefully, maximum tumor cell killing.
We advise patients to orally supplement with 4 grams ascorbate daily,
especially on the days when no infusions are made, to help prevent a possible
scorbutic "rebound effect."
We have seen
patients with almost every type of solid tumor in our clinic. Many of them have
received IAA, with various degrees of success. Our cases include a patient with
cancer of the head of the pancreas who lived for 3.5 years with IAA as sole
therapy, resolution of bone metastases in patients with breast cancer, many
patients with non-Hodgkin's lymphoma (none of whom have died from their
disease), resolution of primary liver carcinoma tumors, resolution of and
reduction in size of metastatic colon carcinoma lesions, and resolution of
metastatic lesions and over 3-year survival in patients with widely metastatic
ovarian carcinoma. We plan to present a full compilation of cases in another
We have seen only two cases of metastatic renal cell carcinoma, considered a
uniformly untreatable disease. Because the results were so dramatic, people with
this disease could potentially benefit the most from IAA treatment.
Following are those two cases.
A 52-year-old white
female with a history of renal cell carcinoma was seen in our clinic for the
first time in October, 1996.In September 1995, shortly after diagnosis of a
primary tumor in her left kidney, a nephrectomy was performed. Histology
confirmed renal cell carcinoma. No evidence of metastases was found at that
time. In March 1996, metastases to the lungs were found on chest x-ray film. In
September 1996, a chest x-ray film revealed 4 1- to 3-cm masses in her lungs.
One month later there were 8 1- to 3-cm masses in her lungs (7 in right lung, 1
in left).No new medical, radiation, or surgical therapies were performed prior
to her visit to our clinic in October 1996, when she began IAA therapy. Her
initial dose was 15 g, which increased to 65 g after 2 weeks, two per
week. She was also started on: N-acetyl cysteine (Vitamin Research Products,
Carson City, NV), 500 mg 1 p.o., QD; beta-1,3- glucan (a macrophage stimulator,
NSC-24, Nutrition Supply Corp., Carson City, NV), 2.5 mg 3 p.o. QD; fish oil
(Super-EPA, Bronson Pharmaceuticals, St. Louis, MO; 300 mg eicosatetraenoic
acid, 200 mg docosahexaenoic acid), 1 p.o. TID; vitamin C, 9 g p.o. QD;
beta-carotene (Beta Carotene 25, Miller Pharmacal Group, Inc., Carol Stream,
IL), 25,000 lU. 1 p.o. BID; L-threonine (The Solgar Vitamin Co, Inc., Lynbrook,
NY), 500 mg p.o. QD (for a deficiency revealed by laboratory testing of serum);
Bacillus laterosporus (Lateroflora, International Bio-Tech U.S.A., San Marcos,
CA), 280 mg, 2 p.o. QD for intestinal Candida a/b icans, inositol hexaniacinate
complex (Niaplex, Karuna Corp., Novato, CA; 500 mg niacin, 100 mcg chromium) 2
p.o. QD, and a no-refined-sugar diet.
She continued IAA treatments until June 1997 when another chest x-ray film
revealed resolution of 7 of the 8 masses, and reduction in the size of the 8th.
According to the medical imaging report, "The nodular infiltrates seen
previously in the right lung and overlying the heart are no longer evident and
the nodular infiltrate seen in left upper lung field has shown marked Interval
decrease in size and only vague suggestion of an approximately I cm
The patient discontinued IAA treatments in June 1997. She has continued on an
oral nutritional support program since that time, and at this writing (December
1997) is well with no evidence of progression.
In December 1985, a mass
occupying the lower pole of the right kidney was discovered in a 70- year-old
white male. Pathology of the mass after a radical nephrectomy confirmed renal
cell carcinoma. He was followed by an oncologist at another clinic.
Approximately three months after surgery, the patient's x-ray film and CT scan
showed "multiple pulmonary lesions and lesions in several areas of his liver
which were abnormal and periaortic lymphadenopathy."
In March 1986 the patient was seen in our clinic (1). He decided not to
chemotherapy. Vie requested and
was started on IAA, 30 g twice per week. In April 1986, six weeks after the
x-ray film and CT scan studies, the oncologist's report stated,
". . . the patient returns feeling well. His exam is totally normal. His
chest x-ray shows a dramatic improvement in pulmonary nodules compared to six
weeks ago. The periaortic lymphadenopathy is completely resolved..., either he
has had a viral infection with pulmonary lesions with lymphadenopathy that has
resolved or (2) he really did have recurrent kidney cancer which is responding
to your vitamin C therapy."
The oncology report in July 1996 stated, "there is no evidence of
progressive cancer. He looks well . . . chest x-ray today is totally normal. The
pulmonary nodules are completely gone. There is no evidence of lung metastasis,
liver metastasis or lymph node metastasis today, whatsoever."
In 1986 the patient received 30 g infusions twice-weekly for 7 months. The
treatments were then reduced to once per week for 8 more months. For an
additional 6 months he received weekly, 15 g IAA infusions. During and after
treatments, the patient reported no toxicities, and his blood chemistry profiles
and urine studies were normal. The patient continued well, and was seen
periodically at our clinic until early 1997 when he died, cancer-free, at age
82, 12 years after diagnosis.
We believe that IAA has
potential as a chemotherapeutic agent. We hope our protocols for mixing and
infusion of IAA, precautions to be taken before and during its use, and clinical
case reports will justify further clinical trials and research with IAA for
patients with metastatic disease. We do not believe it is a cure for all
cancers. Although it shows promise as a sole therapy, particularly in renal cell
carcinoma, it should be used primarily as an adjunct to other effective
Our research is funded
solely through donations from individuals. We have neither sought nor received
funding from government agencies. We encourage readers to support our research.
All donations to our 501 (C) 3 organization are tax-deductible.
Neil H. Riordan, PA-C
Hugh D. Riordan,
Ronald E. Hunninghake, M.D.
The Center for the Improvement of Human Functioning, International,
3100 N. Hillside Ave., Wichita,
We would like to
thank the Bio-Communications Research Institute scientific staff who contributed
to this research: Neil Riordan, P.A.-C., Xiaolong Meng, MB.; Paul Taylor, B.S.;
Jei Zhong, MB.; Kevin Alliston, MS.; and Joseph Casciari, Ph.D. We thank Don R.
Davis, Ph.D., for editing this manuscript.
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Reprinted with the kind permission of Dr. Hugh D. Riordan and the
Bio-Communications Research Institute.