Clinical and Experimental Experiences with Intravenous Vitamin C

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Clinical and Experimental Experiences with Intravenous Vitamin C

          Clinical and Experimental Experiences
                with Intravenous Vitamin C
       Neil H. Riordan, PA-C;1 Hugh D. Riordan, M.D.;1 Joseph P. Casciari, Ph.D.1

     For the purposes of this paper reference             ment. In particular we began testing for
to ascorbic acid or vitamin C refers to so-               toxicity of vitamin C toward cultured tumor
dium ascorbate. All in vitro studies de-                  cell lines using dense monolayers and hol-
scribed herein used sodium ascorbate. All                 low fiber tumor models to mimic the three
intravenous vitamin C references herein re-               dimensionality of tumors. We used human
fer to the use of vitamin C for injection pro-            sera as culture media to include the serum
duced by Steris Laboratories, or American                 inhibitory activity seen in previous assays.
Regent laboratories; both are ascorbic acid               Using these new culture conditions we
buffered to a pH range of 5.5 to 7.0 by so-               found that the cytotoxic concentration of
dium hydroxide and/or sodium bicarbonate.                 vitamin C for most human tumor cell lines
                                                          was indeed much higher than previously
Background                                                described. (Figure 1, p. 202).
      Vitamin C has potential as a chemo-
therapeutic agent. Rather than possessing                 Human Vitamin C Pharmacokinetics
adverse side effects as most chemotherapeu-                    Given the information that higher con-
tic drugs do, vitamin C has side benefits such            centrations of vitamin C were required to
as increasing collagen production, and en-                become cytotoxic to tumor cells, we needed
hancing immune function.                                  to learn more about the pharmacokinetics
      We began to study the effects of vita-              of vitamin C. There were no data on the
min C on cultured tumor cells in 1991. We                 concentrations of vitamin C that were
found that vitamin C was preferentially toxic             achievable in human beings after high-dose
to tumor cells–it killed tumor cells before               intravenous vitamin C. We therefore began
killing normal cells. This phenomenon first               a series of experiments to yield data for
came to our attention through the work of                 modeling pharmacokinetics of high doses
Benade et al in 1969.1 They theorized that                of vitamin C.
the preferential toxicity was due to the rela-                 We gave a series of vitamin C infusions
tive deficiency of catalase in tumor cells.               to a 72 year old male who was in excellent
This theory has since been validated by oth-              physical condition except for slowly pro-
ers.2 Our early findings on preferential vita-            gressing, non-metastatic carcinoma of the
min C toxicity were published in 1994.3 In                prostate. Before the infusions, and at in-
that paper we also described a so called “se-             tervals thereafter, blood was drawn from a
rum effect;” vitamin C’s toxicity was reduced             heparin lock (not the site of infusion). The
by the presence of human serum. Serum’s                   plasma was separated and analyzed for
inhibitory effects led us to the conclusion               plasma vitamin C concentration using a
that the concentrations of vitamin C which                microplate-based 2,6-dichlorophenol-indo-
were toxic to tumor cells in our early stud-              phenol assay. Some of the results are given
ies (5 to 50 mg/dL) would not necessarily                 in Figure 2, (p. 202). From this experiment
be toxic in vivo.                                         we observed that a 30 gram infusion was
      We therefore began a series of experi-              not adequate to raise plasma levels of vita-
ments in which we tried more closely to                   min C to a level that was toxic to tumor
mimic the in vivo tumor micro-environ-                    cells (>200 mg/dL for dense monolayers
                                                          and >400 mg/dL for hollow fiber models).
1. Bio-Communications Research Institute, 3100 N. Hill-
side Ave, Wichita, KS 67219.                              Infusion of 60 grams resulted in a brief (30

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Journal of Orthomolecular Medicine                                                                               Vol. 15, No. 4, 2000

                 Figure 1. Vitamin C toxicity toward human colon cancer cells in different models.

                                                                120

                                                                100
                                 Percent live cells remaining

                                                                80

                                                                60                                                                                                Dense Hollow Fiber
                                                                                                                                                                  Dense Monolayer
                                                                40                                                                                                Sparse Monolayer

                                                                20

                                                                 0

                                                                -20
                                                                       0             200         400              600           800               1000
                                                                                           Vitamin C (mg/dL)

                 Figure 2. Effects of 15, 30, 60, and 65 grams of ascorbate infused over various times on
                 plasma ascorbate concentration in a 72-year-old man.

                           540
                                                                                                                                                      6/4/97 30g in 80 min.
                           480
                                                                                                                                                      6/4/97 60g in 80 min.
                           420
Plasma Ascorbate (mg/dL)

                                                                                                                                                      6/25/97 60g first 60 min
                           360                                                                                                                        20g next 60 min.

                           300

                           240

                           180

                           120

                           60

                             0
                                         -60
                                                                -40
                                                                      -20

                                                                                20
                                                                                     40
                                                                                           60
                                                                                                80
                                                                            0

                                                                                                     100
                                                                                                           120
                                                                                                                  140
                                                                                                                        160
                                                                                                                              180
                                                                                                                                    200
                                                                                                                                          220
                                                                                                                                                240
                                                                                                                                                      260
                                                                                                                                                            280
                                                                                                                                                                  300
                                                                                                                                                                        320
                                                                                                                                                                              340
                                                                                                                                                                                    360
                                                                                                                                                                                          380
                                                                                                                                                                                                400

                                                                  IV started                         Time (min)

                                                                                                                   202
Clinical and Experimental Experiences with Intravenous Vitamin C

min) elevation of plasma levels of vitamin        all experiments are shown in Table 2 (p.
C above 400 mg/dL, while 60 grams infused         204) To see if there was any systematic
over 60 minutes immediately followed by           variation in Table 2 parameter values over
20 grams infused over the next 60 minutes         time, the parameter KX, and the ratio K2/
resulted in a 240 minute period in which          K 1 for each experiment were plotted
the vitamin C plasma concentration was            against time. The excretion constant, KX,
near or above 400 mg/dL.                          was remarkably uniform, as was the ratio
                                                  K2/K1 (Figure 4, p. 205). The tissue up-
Ascorbate Pharmacokinetics                        take rate constant, K1, did vary, but not in
     Using data from the above experi-            a systematic way. We use the ratio K2/K1
ments we designed a two-compartment               to point out that while K2 also varies, its
model with four adjustable parameters (VP,        variation merely compensates for varia-
KX, K1, K2) to fit the data. The model sche-      tions in K1. We conclude from this analy-
matic and the data fit are shown in the           sis that the pharmacokinetic parameters
accompanying Figure 3 (below). The pa-            of the subject did not change over a one
rameter KX represents the rate of excre-          month period of regular ascorbate infu-
tion of ascorbate out of the blood (renal         sions.
excretion), while parameter K1 represents
the rate of diffusion of ascorbate from the       Other Pharmacokinetic Studies
blood into tissue and K2 represents the dif-           We plotted data points from three re-
fusion rate for return of ascorbate to the        cent studies (over a three month period)
blood stream from the tissue compart-             against the theoretical curve obtained us-
ment.                                             ing the average parameter values given
     We used this two compartment                 above. The results are shown in (Figure 5,
model to obtain kinetic parameters from           p. 205). Clearly, there was excellent agree-
each of the in vivo vitamin C experiments         ment between the theoretical curve and
where sufficient time-concentration data          the recent data, suggesting the ascorbate
were obtained. We first fitted all four pa-       pharmacokinetics for this subject were the
rameters, then fixed the blood plasma             same over the three month treatment pe-
volume at 30 dL (near the average value           riod. This further supports the conclusion
for all experiments) and floated the three        that the ascorbate transport parameters
K values. Results are given in Table 1            for a given subject remain relatively con-
(p.204). The average parameter values for         stant during the time of treatment.

  Figure 3. Two compartment model.

                           Injection        Plasma           Injection
                              G(t)          VP, CP(t)            Kx

                                       K2               K1

                                            Tissue
                                             QT(t)

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Journal of Orthomolecular Medicine                 Vol. 15, No. 4, 2000

  Table 1. Ascorbate pharmacokinetics in vivo.

Date            5/29/97   6/4/97   6/5/97   6/11/97     6/12/97       6/18/97   6/19/97   6/25/97   6/26/97

Dose (g)          15        30      60         30           60           65       65        65        65

Infusion          45        80     160         40           80           60       60        60        60
min

Kx (min -1)     0.026     0.027    0.024    0.025       0.022         0.025     0.022     0.023     0.027
excretion

K1 (min-1)      0.195     0.214    0.653    0.307       0.124         0.447     0.200     0.150     0.884
tissue adsorb

K2 (min-1)      0.066     0.060    0.165    0.091       0.038         0.141     0.062     0.040     0.235
tissue efflux

K2/K1           0.337     0.279    0.253    0.296       0.302         0.317     0.310     0.265     0.266
efflux/adsorb

Max CP          125.7     186.1    285.3    233.3       417.8         458.4     495.0     472.8     397.2
mg/dL

Ave. (1-8hr) 37.3         70.6     150.1    76.0        165.4         167.6     185.4     221.5     151.9
CP mg/dL

   Table 2. Average parameter values.

                                   Parameter        Mean         SD
                                   Kx               0.025        0.002
                                   K1               0.353        0.261
                                   K2               0.100        0.067
                                   K2/K1            0.292        0.028

Computer Protocol Simulations                           A) 1 hour at 60 g/hr
    A program was then constructed to                   B) 2 hours at 60 g/hr
predict the plasma ascorbate levels in vari-            C) 1 hour at 60 g/hr, then 6 hours at 10 g/hr
ous protocols based on the pharmaco-ki-                      Predicted plasma ascorbate levels
netic parameters obtained above. Three                  for these protocols are shown in Figure 6
protocols were simulated:                               (p.206). Prolonged infusions at higher
                                                     204
Clinical and Experimental Experiences with Intravenous Vitamin C

 Figure 4. Pharmacokinetic variation in parameter values over time.

        Figure 5. Plotted data points from three recent studies against the
        theoretical curve based on figure four values.

                                    500
                                    450
                                    400                                          Cp(data)
         Plasma Ascorbate (mg/dL)

                                                                                 Cp (calc)
                                    350
                                    300
                                    250
                                    200
                                    150
                                    100
                                     50
                                      0
                                          0   60   120   180 240 300      360   420      480 540
                                                            Time (min)

doses obviously give the highest peak val-                        Effects of Human Serum Obtained from
ues, while a “trickle” infusion can be used                       Subject Receiving Intravenous Vitamin C
to maintain plasma levels at a desired level.                     on Tumor Cell Growth
     This computer simulation can be a                                 To study more closely the probability
useful tool for examining what plasma                             of in vivo cytotoxic effects of intravenous
levels we can expect from various                                 vitamin C we planned and performed the
protocols, once the pharmacokinetics for                          following experiment. Dense monolayers
a given subject are known from an ini-                            of human prostate tumor cells (PC-3 from
tial experiment.                                                  ATCC) were created in microplates. A pa-

                                                               205
Clinical and Experimental Experiences with Intravenous Vitamin C

 Figure 7. Effects of human serum removed from patient before and at intervals
 after intravenous infusion of vitamin C (60 grams) on cultured human
 prostate tumor cells.

                     120.00                                                                        700

                                                                                                   600
                     100.00

                                                                                                   500
                      80.00
 Survival % (bars)

                                                                                                   400
                      60.00
                                                                                                   300

                      40.00
                                                                                                   200

                      20.00                                                                        100

                       0.00                                                                          0
                              T=0     T=35    T=65   T=95      T=125   T=185    T=245    T=305

                                                       Time (min)

tient with carcinoma of the prostate was                     ter the beginning of the IV vitamin C. Dur-
given 65 grams of intravenous vitamin C                      ing those periods the serum concentration
(in 500 cc sterile water for injection) over                 was greater than 400 mg/dL. After that time
65 minutes. Serum separator blood tubes                      the toxicity decreased. The last sample
were drawn before the infusion and at in-                    taken (vitamin C concentration 213 mg/dL)
tervals thereafter from a heparin lock sepa-                 resulted in 64% inhibition compared to the
rate from the infusion site. The final blood                 controls.
draw was five hours after the infusion be-
gan. Some of the collected serum was then                    Potentiation of Preferential Toxicity of
tested for vitamin C concentration, and the                  Vitamin C
rest was heat-inactivated and used as cul-                        Because plasma concentrations of vita-
ture media for the prostate tumor cells. The                 min C of greater than 200 mg/dL are prob-
cells were incubated for five days when the                  lematic to maintain, we began looking for
numbers of viable tumor cells were deter-                    ways to increase the sensitivity of tumor cells
mined using a previously described                           to vitamin C. During experimentation we
carboxy-fluorescein diacetate/microplate                     found that lipoic acid (a water and lipid solu-
fluorometer viable cell determination                        ble antioxidant that recycles vitamin C) can
method. The results of the experiment are                    enhance the tumor toxic effects of vitamin
graphed in Figure 7 (p.207). Greater than                    C. Figure 8 (p.208) illustrates dose response
97% cytotoxicity was observed for the serum                  of tumor cells in a hollow fiber tumor model
samples taken at 35, 65, and 95 minutes af-                  exposed to vitamin C with and without lipoic

                                                         206
Journal of Orthomolecular Medicine                     Vol. 15, No. 4, 2000

  Figure 8. Effect of lipoic acid on ascorbate efficiency: SW620 human colon
  carcinoma cells grown as hollow fiber solid in vitro tumors exposed for 48 hours to
  sodium ascorbate alone or in combination with lipoic acid sodium (combo 10:1).

                              1.2

                              1.0

                              0.8
          Survival Fraction

                              0.6

                              0.4        Ascorbate
                                         Combo 10:1

                                    Ascorbate
                              0.2   LC50 = 700 mg/dL
                                    Combo (10:1)
                                    LC50 = 120 mg/dL
                               0
                                            10           102          103         104

acid. Lipoic acid decreased the dose of vita-               mented cultured tumor cells with vita-
min C required to kill 50% of the tumor cells               min C concentrations that are achievable
from 700 mg/dL to 120 mg/dL.                                with oral supplementation (2 and 4 mg/
                                                            dL) and measured the collagen produced
Effects of High-Dose Vitamin C on                           using a well-known method.5 We found
Tumor Cell Collagen Production                              that indeed, these concentrations of vi-
     It is well known that vitamin C is re-                 tamin C greatly increased the production
quired for the hydroxylation of proline, and                of collagen. Data are summarized in Fig-
that low levels of vitamin C can be a lim-                  ure 9, p.209. It is interesting to note that
iting factor in the production of colla-                    when we performed cytotoxicity assays
gen. Because many tumor cells produce                       of vitamin C against the PC-3 human
collagenase and other proteolytic en-                       prostate carcinoma cell lines using con-
zymes, we wanted to determine if vita-                      centrations as high as 300 mg/dL, we
min C supplementation would increase                        were unable to detach remaining live cells
collagen production by tumor cells,                         from the tissue culture f lasks using
thereby having a balancing effect on col-                   trypsin/EDTA. In some cases several
lagenase. In an experiment, we supple-                      days of treatement with high concentra-
                                                         207
Journal of Orthomolecular Medicine                     Vol. 15, No. 4, 2000

   Figure 6. Theoretical blood ascorbate levels.

                                     700
                                               A          1 hour at 60 g/hr
                                     600       B          2 hours at 60 g/hr
                                               C          1 hour at 60 g/hr
          Plasma Ascorbate (mg/dL)

                                     500                    then 6 hours at 10 g/hr

                                     400

                                     300

                                     200

                                     100

                                       0
                                           0   200               400                  600
                                                   Time (min)

tions of collagenase were required to                       Patients with Renal Cell Carcinoma
detach the cells. One of us remembers                       Treated with Intravenous Vitamin C
literally “chipping” cells off the plastic                       One of us (HDR) reported positive ef-
flasks. Prostate tumor cells are very re-                   fects of vitamin C therapy in a patient with
sistant to high doses of vitamin C. It may                  adenocarcinoma of the kidney in 1990.4
be that they are so rapidly using the vita-                 This report described a 70-year-old white
min C for collagen production that it                       male diagnosed with adenocarcinoma of
doesn’t have as much residence time as in                   his right kidney. Shortly after right ne-
other cell lines, and is therefore less toxic.              phrectomy, he developed metastatic le-
Of clinical note is that we have several pa-                sions in the liver and lung. The patient
tients diagnosed with prostate cancer who                   elected not to proceed with standard meth-
have taken continuous large oral doses of                   ods of treatment. Upon his request, he
vitamin C for many years and do not                         began intravenous vitamin C treatment,
progress to metastatic disease, despite a                   starting at 30 grams twice per week. Six
relatively large intracapsular tumor bur-                   weeks after initiation of therapy, reports
den. Perhaps their tumor cells are “gluing                  indicated that the patient was feeling well,
themselves” in place by high collagen pro-                  his exam was normal, and his metastases
duction.                                                    were shrinking. Fifteen months after ini-
                                                            tial therapy, the patient’s oncologist re-
Clinical Experiences                                        ported the patient was feeling well with ab-
    We have not observed toxic reactions                    solutely no signs of progressive cancer. The
to high-dose intravenous vitamin C. All                     patient remained cancer-free for 14 years.
patients are pre-screened for glucose-5-                    He died of congestive heart failure at the
phosphate dehydrogenase deficiency.                         age of 84. A second case study, published

                                                         208
Clinical and Experimental Experiences with Intravenous Vitamin C

                      Figure 9. Effects of Vitamin C supplementation on collagen production by
                      tumor cells.

                       30

                       25
 Collagen (ug/well)

                       20                                                                PC-3 pancreatic tumor
                                                                                         cells
                       15
                                                                                         Ovarian tumor cells
                       10

                        5

                        0
                                  0                   2                  4

                               Ascorbic Acid added to Culture Media (mg/dL)

in 1998,5 described another complete remis-                   nutritional supplement. A radiology report
sion in a patient with metastatic renal cell                  on a chest x-ray taken January 15, 1998, stated
carcinoma. The patient was a 52-year-old                      that no significant infiltrate was evident, and
white female from Wisconsin diagnosed                         there was resolution of the left upper lobe
with non-metastatic disease in September                      lung metastasis. In February, 1999 a chest x-
1995. In October 1996, eight metastatic                       ray showed no lung masses, and the patient
lung lesions were found: seven in the right                   reported being well at that time.
lung and one in the left (measuring be-
tween 1-3 cm). The patient chose not to                       Combined Intravenous Vitamin C and
undergo chemotherapy or radiation treat-                      Chemotherapy in a Patient with Stage IV
ments. The patient was started on intra-                      Colorectal Carcinoma
venous vitamin C and specific oral nutri-                          In April, 1997, a 51-year-old white male
ent supplements to correct diagnosed de-                      from Wichita, Kansas was first seen at our
ficiencies and a broad-spectrum oral nu-                      center. He was well other than having type
tritional supplement in October, 1996. The                    II diabetes until the previous fall when he
initial dose of intravenous vitamin C was                     developed painless bright red rectal bleed-
15 grams, subsequently increased to 65                        ing. A work-up demonstrated the presence
grams after two weeks. The patient was                        of a distal colon lesion. On December 31,
given two infusions per week. Intravenous                     1997 he underwent an anterior colon re-
vitamin C treatments were continued un-                       section and appendectomy at a local hos-
til June 6, 1997. An x-ray taken at that time                 pital. The colon tumor penetrated through
revealed resolution of all but one lung                       the bowel wall and into the surrounding
metastases. The patient discontinued intra-                   pericolonic adipose tissue. Two large he-
venous vitamin C infusions at that time and                   patic metastases were discovered at the
continued taking the broad-spectrum oral                      time of surgery; one was biopsied. Pathol-

                                                           209
Journal of Orthomolecular Medicine                         Vol. 15, No. 4, 2000

Figure 10. Patient with cancer of the pancreas.

                          8000

                          7000

                          6000
   CA-19-9 Tumor Marker

                          5000

                          4000

                          3000

                          2000

                          1000

                             0
                             12/1/96   3/11/97   6/19/97    9/27/97        1/5/98      4/15/98    7/24/98
                                                           Date

ogy revealed that the colon lesion was a                          from the stomach wall and liver. Segments
moderately differentiated adenocarcinoma,                         three and five both contained multiple nod-
and the liver biopsy was metastatic adeno-                        ules. His CEA was 9.8 post surgery. The
carcinoma. Following surgery he received                          Pittsburg University oncologist informed
chemotherapy with weekly 5-FU and leu-                            him his prognosis was very poor and that
covorin for twelve cycles with a decrease                         he should go home and begin chemotherapy
in his CEA from 90.2 to 67.7. The patient                         again. He and his wife asked this oncologist
and his wife, who is an R.N., asked the                           if he should use intravenous vitamin C. He
chemotherapist about getting intravenous                          responded, “I know of no studies which
vitamin C along with the chemotherapy.                            showed that this [vitamin C] would eradi-
The oncologist informed them that vitamin                         cate or delay progression of cancer.”
C would not be of any value.                                           In spite of the two no-confidence rec-
      The patient was then seen at Pittsburg                      ommendations for the use of intravenous
University hospital on May 13, 1997 where                         vitamin C, The patient returned to our
he underwent liver resection to segments                          center for infusions after recovering from
three and five. During surgery, the stom-                         surgery in June, 1997. He also began re-
ach was mobilized off the inferior surface                        ceiving weekly 5-FU (1100 mg) and Leu-
of the liver and a frozen section of this area                    covorin (1300 mg) treatments adminis-
was taken and confirmed metastatic ad-                            tered by his local oncologist. His first vita-
enocarcinoma. The pathology report                                min C infusion was 15 grams over one hour.
showed metastatic carcinoma consistent                            The dose was gradually increased during
with colon primary within the desmoplas-                          bi-weekly infusions. On September 9, 1997,
tic tissue and adjacent hepatic parenchyma                        a post-intravenous vitamin C (100 gram in

                                                             210
Clinical and Experimental Experiences with Intravenous Vitamin C

1000 cc sterile water infused over 2 hours)     disappeared upon reinstatement of vitamin
plasma concentration of vitamin C was 355       C infusions; and 4) For this patient intra-
mg/dL. He was then started on intrave-          venous vitamin C did not work against the
nous vitamin C, 100 grams, twice weekly. His    chemotherapy, as demonstrated by his
wife gave most of these infusions at home.      complete remission.
In addition to the vitamin C, he was given      Combined Intravenous Vitamin C and
recommendations for oral vitamin and min-       Chemotherapy in a Patient with Carcinoma
eral supplementation to increase levels of      of the Pancreas
nutrients that he was found to be low in.            In October 1997, a 70-year-old white
     He kept up his vitamin C infusions until   male from Southeastern Kansas was first
February, 1998 when he traveled to Florida      seen at our center. After exploratory sur-
for a vacation. While on vacation he con-       gery in December 1997 he had been diag-
tinued the 5-FU/Leucovorin injections. Af-      nosed with a low-grade mucinous carci-
ter a two weeks hiatus from the vitamin C       noma of the pancreas. During surgery there
infusions he began to experience nausea,        was found to be widely metastatic disease
diarrhea, stomach pain, and stomatitis; com-    affecting all intra-abdominal organs. In
mon side effects of 5-FU. The side effects      January 1997 he was started on Gemzar. He
stopped when he restarted intravenous vi-       had an allergic reaction to Gemzar and was
tamin C. He continued on chemotherapy           placed on weekly 5-FU for 9 weeks. He was
and 100 gm bi-weekly intravenous vitamin        placed back on Gemzar in June, 1997 along
C until April 1, 1998. Other than the brief     with Decadron to counteract his allergy. In
period of side-effects mentioned above, he      spite of chemotherapy his CA-19-9 contin-
had no other side effects during the year of    ued to elevate until he was seen at our
chemotherapy. He never experienced              center. At that time his CA 19-9 was 7400
leukopenia, thrombocytopenia, or anemia.        U/mL (normal
Journal of Orthomolecular Medicine         Vol. 15, No. 4, 2000

active again. The evidence also suggest            hood would have been curative. She also
that intravenous vitamin C was working             had a so-called recurrence of her lym-
independently of the chemotherapy given            phoma during intravenous vitamin C
the CA-19-9 level continued to decrease            therapy months after her radiation
after chemotherapy was discontinued.               therapy had ended. The possibility exists
This patient died at home on July 4th,             that the lymphoma cells in her lymph
1998.                                              nodes were there at the initial diagnosis
                                                   and the adenopathy occurred during im-
Resolution of non-Hodgkin’s Lym-                   mune recognition of those cells. Also of
phoma with Intravenous Vitamin C-2                 note is the fact that this patient received
Cases                                              only 15 grams of vitamin C per infusion.
     A 66 year old white female was diag-          According to our model, this in not a high
nosed with a large peri-spinal (L4-5) ma-          enough dose to achieve cytotoxic concen-
lignant, non-Hodgkin’s lymphoma (diffuse           trations of vitamin C in the blood. There-
large cleaved cell of B-cell lineage) in Janu-     fore, any effect of vitamin C could only be
ary, 1995. Her Oncologist recommended              attributed to its biological response modi-
localized radiation therapy and                    fication characteristics.
Adriamycin-based chemotherapy. She be-                  In Fall 1994 a 73-year-old white male
gan localized radiation therapy five days          farmer from Western Kansas was diagnosed
per week for five weeks on 1/17/95, but            with wide-spread non-Hodgkin’s lym-
refused chemotherapy. On 1/13/95 she               phoma. Biopsies and CT-scan revealed bi-
was started on intravenous vitamin C, 15           lateral tumor involvement in his anterior
grams in 250 cc Ringer’s Lactate two times         and posterior cervical, inguinal, axillary and
per week which she continued after com-            mediastinal lymph node beds. Bone mar-
pleting the radiation therapy. She also            row aspirate was negative for malignant
began taking several oral supplements to           cells. He was treated with chemotherapy for
replace those found to be deficient by             8 months that resulted in remission. In July,
laboratory testing, and empirical co-en-           1997 he began losing weight (30 lbs). He re-
zyme Q10, 200 mg BID. She was also suc-            turned to his oncologist and a CT-scan at
cessfully treated at that time for an intes-       that time showed recurrence. He was placed
tinal parasite. On May 6, 1995 she returned        on chemotherapy in September, 1997. In De-
to her oncologist with swelling and pain-          cember, 1997 he developed leukopenia and
ful supraclavicular lymph nodes. One               then extensive left sided Herpes Zoster. As
lymph node was removed and found to                a result the chemotherapy was stopped. In
contain malignant lymphoma cells. In               March, 1998 he became a patient at our
spite of recommendations for chemo-                Center and began receiving intravenous vi-
therapy and more radiation, she refused            tamin C and oral nutrient supplements in-
and continued with her intravenous vita-           cluding lipoic acid. His vitamin C dose was
min C and oral regimen. Within six weeks           escalated until he was receiving 50 grams
the supraclavicular nodes were barely no-          in 500 cc sterile water two times per week.
ticeable. She continued intravenous vita-          He continued on that dose for 11 months.
min C infusions until December 24, 1996.           Three months after beginning vitamin C
She has been followed with regular physi-          therapy a CT-scan showed no evidence to
cal exams and has had no recurrence.               malignancy. Another CT-scan in February,
During a telephone follow-up on 3/23/99            1999 was also clear and he was declared to
she was well without recurrence. Com-              be in complete remission by his oncologist.
ment: This case is rare–the patient re-            Also of note is that this patient was ad-
fused chemotherapy, which in all likeli-           dicted to sleeping pills when first seen at

                                                 212
Clinical and Experimental Experiences with Intravenous Vitamin C

our center. After three months of intrave-      plasma concentrations of vitamin C using
nous vitamin C therapy he replaced the          varied infusion protocols. Lipoic acid en-
sleeping pills with Kava tea.                   hances vitamin C induced tumor cell tox-
Intravenous Vitamin C in a Patient with         icity. Vitamin C in blood concentrations
End-Stage Metastatic Breast Carcinoma           achievable through oral supplementation is
      In 1995 a hospitalized 68 year old        capable of increasing collagen production
women with widely metastatic end-stage          by tumor cells. Vitamin C in doses up to 50
breast cancer was seen.6 Her latest bone        grams per day, infused slowly, are not toxic
scan showed metastases to “nearly every         to cancer patients. Some cancer patients
bone in her skeleton.” She was experienc-       have had complete remissions after high-
ing bone pain which was not controlled          dose intravenous vitamin C infusions. Con-
with narcotics. At the time of her first con-   centrations of vitamin C that kill most
sultation she had blood clots in both sub-      tumor cells are not achieved after infusion
clavian veins, and shortly thereafter con-      of 30 grams of vitamin C. Therefore, re-
tracted cellulitis in her left arm and hand     missions in patients treated with this dose
secondary to an errant arterial blood draw.     of vitamin C are likely to have occurred as
After the blood clots were treated with         a result of vitamin C induced biological
Activase R, she was placed on intravenous       response modification effects rather than
vitamin C, 30 grams per day intially, in-       its cytotoxic effects.
creasing to 100 grams per day over five
hours. Within one week, the once bed-           References
bound patient began walking the halls of        1. Benade L, Howard T, Burk D: Synergistic kill-
the hospital. Several hospital staff reported       ing of Ehrlich ascites carcinoma cells by ascor-
that she looked like a new person. Her cel-         bate and 3-amino-1, 2, 4-triazole. Oncology,
                                                    1969; 23: 33-43.
lulitis cleared, and she was discharged from    2. Maramag C, Menon M, Balaji KC, Reddy PG,
the hospital. At home she received 100              Laxmanan S: Effect of vitamin C on prostate
grams of intravenous vitamin C three times          cancer cells in vitro: effect on cell number, vi-
per week. Three months after starting the           ability, and DNA synthesis. Prostate, 1997; 32:
vitamin C therapy a bone scan revealed              188-95.
resolution of several skull metastases. Six     3. Riordan NH, et al: Intravenous ascorbate as a
                                                    tumor cytotoxic chemotherapeutic agent. Med
months after starting the vitamin C, she fell       Hypoth, 1994; 9: 207-213.
while shopping at a mall, and subsequently      4. Riordan HD, Jackson JA, Schultz M: Case study:
died of complications from pathological             High-dose intravenous vitamin C in the treat-
fractures.                                          ment of a patient with adenocarcinoma of the
                                                    kidney. J Orthomol Med, 1990; 5: 5-7.
                                                5. Riordan HD, Jackson JA, Riordan NH, Schultz
Conclusion                                          M: High-dose intravenous vitamin C in the
     We have presented evidence that vita-          treatment of a patient with renal cell carcinoma
min C may be useful in the treatment of             of the kidney. J Orthomol Med, 1998; 13: 72-73.
cancer. In particular we have produced the      6. Riordan N, Jackson JA, Riordan HD: Intravenous
following evidence: Vitamin C is toxic to           vitamin C in a terminal cancer patient. J
tumor cells. Concentrations of vitamin C            Orthomol Med, 1996; 11: 80-82.
that kill tumor cells can be achieved in
humans using intravenous vitamin C infu-
sions. Infusion of a bolus of vitamin C fol-
lowed by slow infusion can result in sus-
tained concentrations of vitamin C in hu-
man plasma. Modeling of vitamin C phar-
macokinetics can accurately predict

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