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

© Riordan Clinic 2018

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depleted subjects.”*Hickey, Roberts, and Miller (unpublished)


220mM/L

70mM/L

Phase 2

Phase 1AA is actively reabsorbed

AA is rapidly excreted

Phase 3 ????mM/L


36 Grams of Liposomal C (Two Subjects) Is This “Phase 3” of Vitamin C?

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{{{

Phase 3

Phase 2

Phase 137-120 “ref. range”

(BioCenter Lab – 6634 plasma C levels - only 50 > 120 mmol/L)


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


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


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 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


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

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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.

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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


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


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


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!


Effects of IVC on Inflammation


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


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


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.


• 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 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


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 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


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.

© Riordan Clinic 2018© Riordan Clinic 2018

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.


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


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


DamageRepair

Signaling

AdaptedeOs – External Oxidative Stress

iOs – internal Oxidative Stress

Reserves

Chemical

AOS

ROS

Structural

Depletion

Unified TheoryOf

SustainedIllness

DNAMembranes

GeneticExpression


Cellular Injury Inadequate nutrient reserves

The damage cannot be repaired Cytokine signaling intensifiesthe inflammatory response

Cytokine Signaling


riordan clinic ivc academy 5 · 6/5/2018 · pharmacokinetics of oral vitamin c using liposomal...

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