Riordan Clinic IVC Academy 5 IVC History, Cancer Research O (slides 1 40) Riordan Clinic 2018
High Dose Vitamin C Adjunctive Care for Cancer Patients IVC and Cancer Research Overview History & Research Nina Mikirova, PhD, Director of Research Ron Hunninghake, MD Chief Medical Officer IVC Academy Tokyo, 2017
Hugh D. Riordan, M.D. Riordan Clinic Founder
Medical Mavericks Download for free: riordanclinic.org/books/
Orthomolecular means "the right molecule." Dr. Linus Pauling
Vitamin C: The Electron Exchanger Albert Szent-Gyorgyi, M.D., Ph.D. 1937 Nobel Prize winner in Medicine Awarded for the discovery of vitamin C, in connection with biological respiration one of the primary substances assuring that a vigorous, continuing electron exchange takes place among the body s tissues and molecules.
Dr. Thomas Levy Curing the Incurable One definition of life a state in which an optimal degree of electron interchange among cells can take place.
Optimum Dosing of Vitamin C in Humans? Humans lost the ability to make vitamin C due to a genetic mutation GLO coverts glucose into vitamin C L-Gulonolactone Oxidase mutated
Comparing Vitamin C Synthesis to Predicted Oral Consumption mg/kg/d Human equivalent humans 1 60 mg/d dog 3 200 mg/d pig 8 500 mg/d monkey* 100 7,000 mg/d goat 190 14,000 mg/d sick goat ~1300 100,000 mg/d
the chronic underdosing of vitamin C from minimal or no supplementation and from eating depleted food will facilitate the development of nearly all the chronic degenerative disease that affect man. Irwin Stone The Healing Factor
Selective Cytotoxicity 140 120 Mia PaCa-2 Survival % 100 80 60 40 20 0 SK-MEL-28 SW-620 U-2-OS 0 100 200 300 400 500 600 700 800 900 Redox Cycling Ascorbate (mg/dl)
In Vitro vs. In Vivo
Tumor Inhibition by Vitamin C (animal studies) 10 Clin Cancer Res. 2010 January 15; 16(2): 509 520 Surviving Animals 8 6 4 2 Ascorbate Control 0 25 30 35 40 45 50 55 60 65 Time (days) Survival time of sarcoma bearing mice control and treated with IP ascorbate 700 mg/kg
In Vivo / In Vitro Steps 120.00 700 1. Human serum 2. Taken from cancer pt. 3. Before and at 30 minute intervals 4. After IVC 60,000 mg 5. IVC treated serum 6. Applied to human cancer cells 7. That had been previously cultured from an actual prostate tumor Survival % (bars) 100.00 80.00 60.00 40.00 20.00 0.00 T=0 T=35 T=65 T=95 T=125 T=185 T=245 T=305 Time (minutes) 600 500 400 300 200 100 0 Serum ascorbate (mg/dl) (line)
the chronic underdosing of vitamin C from minimal or no supplementation and from eating depleted food will facilitate the development of nearly all the chronic degenerative disease that affect man. Irwin Stone The Healing Factor
IVC Treatment of Cancer Patients at Riordan Clinic 63% Zero Low Norm High Serum C Level µm Scurvy <10 Low <30 Normal <100 High >100 23% 14% 18% 45%
Plasma Vitamin C Concentrations After IVC Plasma Ascorbate (mm) 28 24 20 16 12 8 4 0 y = 1.01 x 0.7 A ; r = 0.95 0 20 40 60 80 100 IVC Dosage (g) IVC 100x higher plasma C than highest tolerated oral dose A Plasma ascorbate (mm) 24 20 16 Two Compartment Pharmacokinetic Model Injection G(t) Plasma Excretion V C (t) P P K E 12 60 g 80 min K 1 K 2 8 Q (t) T Tissue 4 30 g 0 80 min 0 4 8 12 16 Time (hr) 20 24
High Dose Vitamin C PharmAscorb Antitumor Mechanisms
Vitamin C Antitumor Mechanisms 1. Generation of H 2 O 2 2. Anti-angiogenesis 3. Anti-inflammatory 4. Apoptosis 5. Cell Cycle Arrest 6. Genetic mal-adaptations 7. Metabolic modifications cell proliferation angiogenesis regression to glycolysis HIF reduction of maladaptive response NF-kB - antiinflammation VEGF activation Nrf2 induction of antioxidant programming
Selective Cytotoxicity on cultured tumor cell lines Pharmacologic ascorbic acid concentrations selectively kill cancer cells. 1.0 Data replicated by National Institutes of Health Surviving fraction 0.8 0.6 0.4 0.2 0.0 Ascorbate LC 50 =20 mm Combo LC 50 =4 mm Additive (Theoretical) 0 10-1 10 0 10 1 10 2 Ascorbate concentration (mm) Casciari et al. British Journal of Cancer (2001) 84(11), 1544 1550
Ascorbic Acid Vitamin C Acting as an Antioxidant Free Radicals are harmful oxidants 2FR 2FR AA 2e - DHA Dehydroascorbate (oxidized vitamin C)
Dehydroascorbic Acid Oxidized Vitamin C (DHA) Is Not Reabsorbed Two ferric ions are reduced to the ferrous state 2Fe 2Fe 3 + 2 + AA 2e - DHA kidneys
Pro-oxidant Effect of Vitamin C in the Presence of Iron and Oxygen Fe 3+ +2H + Fe 3+ AA 2e - Fe 2+ 2O 2 e - H 2 O 2 2O 2 + O 2 Fe 2+ AA e -
Proposed mechanism: IVC antitumor effects OHNO, S. Anticancer Research 29: 809-816 (2009) Pharm-Ascorb: Selective Cytotoxicity towards Catalasedeficient cancer cells
Toxicity of vitamin C to tumor cells derives from high GLUT1 expression by tumor cells Vitamin C may alter intracellular metabolism in cancer cells by disrupting the redox balance. High-dose vitamin C blocked the energy flux in glycolysis and the Kreb s Cycle ATP production is inhibited Science. 2015, 350: 1391
Cytotoxic effect of pharmacological vitamin C concentrations on tumor and normal cells OHNO, S. ANTICANCER RESEARCH 29: 809-816 (2009)
Mid-Dose Continuous IVC Ron Hunninghake, M.D. Chief Medical Officer Riordan Clinic Wichita, Kansas
Riordan Clinic riordanclinic.org
Cameron and Pauling 10 grams of IVC daily for 10 days followed by 10 grams orally in terminal cancer patients 1976 paper in Proc. Natl. Acad. Sci. Unclear if 10 gram oral C dose was single or divided 4-fold increase in life expectancy They speculated that larger amounts than 10 gr/d might have a greater effect. New Discovery! The 10 gram IVC was by 24 hour CONTINUOUS INFUSION
Mortel, et al Two randomized, double blind, placebo-controlled studies at Mayo Clinic 10 grams of oral C once daily in 200 late stage cancer patients No statistical benefit (but the study was not an actual replication of Cameron, Pauling s work) The Mayo studies were taken as definitive by the oncologic community
Oral mmole/l Intravenous mmole/l Predicted plasma vitamin C concentrations in healthy persons after administration of vitamin C. Padayatty, S. J. et. al. Ann Intern Med 2004;140:533-537
Vitamin C Pharmacokinetics: Implications for Oral & IV Use Ann Intern Med. 2004;140:533-537 Padayatty, Riordan, Levine, et al 0.015 to 1.25 gr of ORAL and IV Ascorbate Plasma C level measured after administration After 1.25 gr. ORAL 135 mm/l After 1.25 gr. IV 885 mm/l NOTE Acute Sepsis Rx Dose = 1.5 gr q6hr
Dual-Phase Ascorbic Acid Pharmacokinetics Phase 1 low plasma levels of AA < 70 mm/l < 1.2 mg/dl (USA units) renal transporters actively reabsorb AA oxidized ascorbate (DHA) is NOT reabsorbed
Dual-Phase Ascorbic Acid Pharmacokinetics Phase 2 high plasma levels of ascorbate >70 mm/l < 220 mm/l 1.2 3.9 mg/dl AA is rapidly excreted similar to small, water-soluble molecules
Dual-Phase Ascorbic Acid 220 Pharmacokinetics mm/l Phase 2 AA is rapidly excreted 70 mm/l Phase 1 AA is actively reabsorbed
220 Ascorbic Acid Half-life mm/l 70 mm/l Phase 2 AA is rapidly excreted 30 minutes Phase 1 AA is actively reabsorbed 8 40 days if intake is deficient!
Reference Range of Ascorbic Acid at the BioCenter Laboratory 220 120 37 mm/l 70 mm/l Phase 2 AA is rapidly excreted Phase 1 AA is actively reabsorbed BioCenter Lab 6634 fasting plasma C levels only 50 > 120 mmol/l
Dynamic Flow vs. Saturation NIH computer models predict plasma saturation of vitamin C after 200 mg of oral C This ignores the effect of repeat dosing of standard C and newer liposomal C preparations With a Phase 2 half-life of 30 minutes, frequent dosing of C q3-4 hrs will result in plasma levels that can readily exceed the 220 mm/l prediction (as demonstrated in observations noted above)
5gr of Standard C and 5gr Liposomal 4.5 C (in the same subject) 4 3.5 3 2.5 2 1.5 1 0.5 0 220 Phase 2 plasma levels 1.2 3.9 mg/dl 70 Phase 1 plasma levels < 1.2 mg/dl 0 35 60 90 150 210 270 360 420 5gr S 5gr L