Riordan Clinic IVC Academy 5 IVC History, Cancer Research O (slides 41-80)
Pharmacokinetics of Oral Vitamin C using Liposomal Form* To test whether plasma vitamin C levels, following oral doses in supplemented volunteers are tightly controlled and subject to a maximum in the region of 220 mm/l, as suggested by previous researchers for depleted subjects. *Hickey, Roberts, and Miller (unpublished)
??? mm/l Phase 3? 220 mm/l Phase 2 AA is rapidly excreted 70 mm/l Phase 1 AA is actively reabsorbed
36 Grams of Liposomal C (Two Subjects) Is This Phase 3 of Vitamin C? (BioCenter Lab 6634 plasma C levels - only 50 > 120 mmol/l) 450 { 400 350 300 250 Phase 3 200 { 150 100 50 0{ Phase 2 37-120 ref. range Phase 1 0 60 120 180 240 300 360 420 36grL 36grL2
450 mm/l Phase 3 Bowel tolerance dosing or frequent liposomal packs 220 mm/l Phase 2 AA is rapidly excreted 70 mm/l Phase 1 AA is actively reabsorbed
Dynamic Flow Definition repeated Ascorbic Acid doses, at an interval of less than 5 half-lives, produce a high, steady-state value in blood plasma. Hickey, Roberts, Cathcart J Orthomol Med 2005; 20:237-244 Note: Phase 2 Ascorbic Acid halflife is about 30 minutes x 5 = 2.5 hours
Applied Dynamic Flow (over extended time) Irwin Stone 1982 letter to Albert Szent- Gyorgyi Nobel Prize winner Joe Kieninger achieved a plasma level of 1817 mm/l 32 mg/dl (USA units) Note: 1000 3000 mm/l is Mid-Dose Joe built up to 80 grams of AA/day over a 2½ year period
Phase 5 High Dose Intermittent IVC Targeting 10,000 30,000 mm/l Phase 4 Mid-Dose Continuous IVC Target range of 1000 2000 mm/l Phase 3 Dynamic Flow Oral Dosing 220 450 mm/l Phase 2 AA is actively excreted Phase 1 AA is actively reabsorbed
1 square = growth in 1 week
High dose IVC kills tumor cells each treatment. But surviving chemo-resistant cells grow back stronger each time.
Low dose, continuous IVC solves the problem of resistant cancer cell selection with intermittent high dose IVC
The Yellow Line = continuous recovery. Intermittent IVC controls cancer, but often does not defeat cancer.
Mid-Dose-Continuous-IVC can also be AUGMENTED with standard Riordan Protocol Dosage infusions. Hybrid IVC high dose mid
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. 120.00 700 100.00 600 Survival % (bars) 80.00 60.00 40.00 500 400 300 200 Serum ascorbate (mg/dl) (line) 20.00 100 0.00 T=0 T=35 T=65 T=95 T=125 T=185 T=245 T=305 Time (minutes) 0
Mid-Dose-Continuous IVC will spark a continuously positive rate of chronic illness recovery by imitating the way ascorbate is made in injured animals
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
Effect of Ascorbic Acid on Angiogenesis Ascorbic acid inhibits migration and angiogenesis of the endothelial cells. AA at 1-3 mg/ml caused the reduction of the growth of sprouts from aortic rings. Mikirova NA, Casciari JJ, Riordan NH. Ascorbate inhibition of angiogenesis in aortic rings ex vivo and subcutaneous Matrigel plugs in vivo. Journal of Angiogenesis Research 2010, 2:2
Ascorbic Acid is Amazing dosing is crucial! Corrects scurvy in cancer patients (less fatigue) Supports detoxification systems in the body Relieves pain and promotes well-being Boosts cellular immunity (to prevent secondary infections) Stimulates collagen formation (to wall off tumor) Inhibits hyaluronidase (to retard metastasis) Relieves cellular hypoxia/restores aerobic metabolism Restores mitochondrial functioning, improves apoptosis Inhibits angiogenesis and reduces tumor nutrient supply Potentiates chemotherapy and radiation Reduces side effects & toxicity of conventional therapy Plausible oncologic adjunct in cancer patient care
Effects of IVC on Inflammation
Inflammation and Cancer Inflammation is a critical component of tumor progression. Cancers arise from sites of chronic injury. Inflammatory component is present and contributes to tumor proliferation angiogenesis metastasis resistance to chemotherapy. Nature. 2002 December 19; 420, 6917
The Seven Hallmarks of Cancer 1. Self-sufficiency of growth signals 2. Insensitivity to antigrowth signals 3. Evasion of apoptosis 4. Unlimited proliferation potential 5. Enhanced angiogenesis 6. Tissue invasion and metastasis 7. Inflammatory microenvironment Molecular Cancer Research; 4(4). April 2006
Cytokines, inflammation and tumor growth Tumors that produce little or no cytokines induce limited inflammatory and vascular responses, resulting in constrained tumor growth. In contrast, production of an abundance of pro-inflammatory cytokines potentiates angiogenesis, thus favoring neoplastic growth. Nature. 2002 December 19; 420(6917), Coussens et al.
Effect of high-dose intravenous vitamin C on inflammation in cancer patients. The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. Modulation of inflammation by IVC correlated with decreases in tumor marker levels. Mikirova et al. Journal of Translational Medicine 2012, 10:189
Inflammation: a driving force of cancer metastasis Inflammatory cells produce TNFα, TGFβ, IL-6, IL-1 activate NFκB STAT3 pathways induce epithelial-to-mesenchymal transition (EMT) and metastasis. Wu Y et al. Cell Cycle 8:20, 3267-3273; October 15, 2009
CRP in Inflammation and Cancer Patients with increased CRP had a higher risk of dying from cancer than from other causes independent of acute infection. The relation of CRP to cancer death was stronger than to vascular death. Clinical Chemistry 54:2, 343 349, 2008, Claudia Marsik et al
CRP a Prognostic Indicator CRP Predicts Cancer Survival in Multiple myeloma Melanoma Lymphoma Ovarian Ca Renal Ca Pancreatic Ca GI Cancers Prostate ca Mahmoud FA, Rivera NI. Current Oncology Report 2002;4:250 5
Does high dose IVC therapy suppress inflammation in cancer patients? Patients followed the Riordan IVC Protocol IVC doses ranged from 7.5 g 50 g Median follow-up time was 7.2 years CRP and tumor markers were measured as a routine analysis Pro-inflammatory cytokines were measured before and after IVC
CRP values before and after IVC treatments Most of the cancer patients, 70 ± 13 % showed a reduction in CRP during IVC therapy.
Serum C-Reactive Protein as Independent Prognostic Variable Kaplan-Meier curves for overall survival of patients with ovarian cancer broken down by serum CRP. Hefer et al. Clin Cancer Res 2008;14(3): 210
The Effects of IVC on PSA
The effects of IVC therapy on PSA 70 % of patients showed reduced PSA levels during IVC treatment. Mikirova et al. 2015
Tracking of PSA levels over time in subjects with prostate cancer Subject A: initial Gleason score =6; treatments given weekly or twice weekly at doses of 25 g; PSA levels decreased from initial values of 60 ng/ml to final values in the normal range. Subject B: Gleason score = 6 9; treatments typically given weekly at doses of either 7.5 g or 25 g (40 IVC); PSA levels decreased from maximum values of 1500 ng/ml to a final value of 7 ng/ml.
Tracking of PSA levels over time in subjects with prostate cancer Subject A: initial Gleason score =6; treatments given weekly or twice weekly at doses of 25 g; PSA levels decreased from initial values of 60 ng/ml to final values in the normal range. Subject B: Gleason score = 6 9; treatments typically given weekly at doses of either 7.5 g or 25 g (40 IVC); PSA levels decreased from maximum values of 1500 ng/ml to a final value of 7 ng/ml.
PSA IVC (grams C) Changes of the rate of PSA progression during IVC treatment 12 11126 PSA IVC (grams C) 60 200 0.25 PSA frequency IVC ra te of change 0.6 10659 IVC 55 10 50 150 0.2 0.15 0.1 0.5 0.4 0.3 0.2 50 45 8 6 4 2 0.1 0.08 0.06 0.04 0.02 0 frequency of IVC rate of chang e 0.01 0.005 0-0.005-0.01-0.015-0.02 40 30 20 PSA 100 50 0.1 0.05 0 0-0.1-0.0 5 0 500 1000 1500-0.2 2000 days 40 IVC 35 30 25 0-0.02-0.025 100 200 300 400 500 600 700 800 900 d ays 0 10 0 200 400 600 800 DAYS 20 0 500 1000 1500 2000 days
The effect of IVC on the suppression of ALP As ALP is a marker of bone formation and the most often site of metastasis for prostate cancer patients is bone, the analysis of the ALP may be helpful tools to evaluate the effectiveness of the IVC therapy on metastatic site. 140 ALP PSA IVC 60 700 2637 ALP (U/L) PSA (ng/ml) Vitamin C (grams-ivc) Vitamin C (grams - Chelation) 120 50 600 500 40 ALP 100 30 PSA ALP 400 80 300 20 60 10 200 100 40 0 500 1000 1500 2000 2500 3000 3500 days 0 1900 1950 2000 2050 DAYS 2100 2150 2200
Effect of IVC on Bone Regeneration
Effect of vitamin C on bone regeneration AA deficiency inhibits bone formation osteoblasts differentiation bone matrix growth Immunohistochemical analyses of collagen I (a, b), and osteoblast cells. Urban et al. Head & Face Medicine 2012, 8:25
Effect of IVC on Cell Signaling
Unified Theory Of Sustained Reserves Illness Depletion Adapted eos External Oxidative Stress ios internal Oxidative Stress Genetic Expression Repair Damage DNA Membranes AOS Structural ROS Signaling Chemical
Cellular Injury Inadequate nutrient reserves The damage cannot be repaired Cytokine Signaling Cytokine signaling intensifies the inflammatory response