Riordan Clinic IVC Academy 5 · 6/5/2018 · Pharmacokinetics of Oral Vitamin C using Liposomal...
Transcript of Riordan Clinic IVC Academy 5 · 6/5/2018 · Pharmacokinetics of Oral Vitamin C using Liposomal...
O
5IVC History, Cancer Research
(slides 41 - 80)
Riordan Clinic IVC Academy
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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depleted subjects.”*Hickey, Roberts, and Miller (unpublished)
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220mM/L
70mM/L
Phase 2
Phase 1AA is actively reabsorbed
AA is rapidly excreted
Phase 3 ????mM/L
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36 Grams of Liposomal C (Two Subjects) Is This “Phase 3” of Vitamin C?
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Phase 137-120 “ref. range”
(BioCenter Lab – 6634 plasma C levels - only 50 > 120 mmol/L)
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220mM/L
70mM/L
Phase 2
Phase 1AA is actively reabsorbed
AA is rapidly excreted
Phase 3 450mM/L
Bowel tolerance dosing or frequent liposomal packs
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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 half-life is about 30 minutes… x 5 = 2.5 hours
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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
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Phase 1 – AA is actively reabsorbed
Phase 2 – AA is actively excreted
Phase 3 – Dynamic Flow Oral Dosing220 – 450 mm/L
Phase 5 – High Dose Intermittent IVCTargeting 10,000 – 30,000 mm/L
Phase 4 – Mid-Dose Continuous IVCTarget range of 1000 – 2000 mm/L
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1 square = growth in 1 week
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High dose IVC kills tumor cells each treatment. But surviving “chemo-resistant cells” grow back stronger each time.
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Low dose, continuous IVC solves the problem of “resistant cancer cell” selection with intermittent high dose IVC
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The Yellow Line = continuous recovery. Intermittent IVC “controls” cancer, but often does not “defeat” cancer.
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Mid-Dose-Continuous-IVC can also be AUGMENTED with standard Riordan Protocol Dosage infusions. “Hybrid IVC”
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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.
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Mid-Dose-Continuous IVC will spark a continuously positive rate of chronic illness recovery by imitating the way ascorbate is made in injured animals
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Tumor Inhibition by Vitamin C (animal studies)
Survival time of sarcoma bearing mice control and treated with IP ascorbate 700 mg/kg
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Clin Cancer Res. 2010 January 15; 16(2): 509–520
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Effect of Ascorbic Acid on AngiogenesisAscorbic 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
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Corrects scurvy in cancer patients (less fatigue)Supports detoxification systems in the bodyRelieves pain and promotes well-beingBoosts cellular immunity (to prevent secondary infections)Stimulates collagen formation (to wall off tumor)Inhibits hyaluronidase (to retard metastasis)
Relieves cellular hypoxia/restores aerobic metabolismRestores mitochondrial functioning, improves apoptosisInhibits angiogenesis and reduces tumor nutrient supplyPotentiates chemotherapy and radiationReduces side effects & toxicity of conventional therapy
Plausible oncologic adjunct in cancer patient care
Ascorbic Acid is Amazing…dosing is crucial!
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Effects of IVC on Inflammation
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Inflammation and CancerInflammation 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
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The Seven Hallmarks of Cancer1. Self-sufficiency of growth signals2. Insensitivity to antigrowth signals3. Evasion of apoptosis4. Unlimited proliferation potential5. Enhanced angiogenesis6. Tissue invasion and metastasis7. Inflammatory microenvironment
Molecular Cancer Research; 4(4). April 2006
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Cytokines, inflammation and tumor growthTumors 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.
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• 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
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Inflammation: a driving force of cancer metastasisInflammatory cells produce TNFα, TGFβ, IL-6, IL-1activate NFκB STAT3 pathways induce epithelial-to-mesenchymal transition (EMT) and metastasis.
Wu Y et al. Cell Cycle 8:20, 3267-3273; October 15, 2009
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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
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CRP a Prognostic IndicatorCRP Predicts Cancer Survival in
• Ovarian Ca• Renal Ca• Pancreatic Ca• GI Cancers• Prostate ca
• Multiple myeloma
• Melanoma• Lymphoma
Mahmoud FA, Rivera NI. Current Oncology Report 2002;4:250–5
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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
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CRP values before and after IVC treatments
Most of the cancer patients,
70 ± 13 % showed a reduction in CRP
during IVC therapy.
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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
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The Effects of IVC on PSA
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The effects of IVC therapy on PSA
70 % of patients showed reduced PSA levels
during IVC treatment.
Mikirova et al. 2015
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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.
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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.
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Changes of the rate of PSA progression during IVC treatment
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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.
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2637ALP (U/L)PSA (ng/ml)Vitamin C (grams-IVC)Vitamin C (grams - Chelation)
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Effect of IVC on Bone Regeneration
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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
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Effect of IVC on Cell Signaling
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DamageRepair
Signaling
AdaptedeOs – External Oxidative Stress
iOs – internal Oxidative Stress
Reserves
Chemical
AOS
ROS
Structural
Depletion
Unified TheoryOf
SustainedIllness
DNAMembranes
GeneticExpression
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Cellular Injury Inadequate nutrient reserves
The damage cannot be repaired Cytokine signaling intensifiesthe inflammatory response
Cytokine Signaling
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