intravenous vitamin c therapy in japan - · pdf file01/06/2017 · 1 dr. atsuo...

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Dr.Atsuo YanagisawaPresident

JapaneseCollegeofIntravenousTherapyInternational SocietyforOrthomolecularMedicine

Intravenous Vitamin C TherapyIn Japan

■DirectorSPICSalonMedicalClinic

■PresidentJapanesecollegeofIntravenousTherapyInternationalSocietyfor

OrthomolecularMedicine■SpecialinterestsCertifiedChelationTherapy(ACAM,USA)MasterofIntravenousVitaminCTherapy(Japan)FellowofAmericanCollegeofCardiology(USA)

Dr.Atsuo Yanagisawa,MD,PhD

■ProfessorshipFormerProfessorofMedicine&CardiologyProfessorofGraduateSchoolofProjectDesign■Awarded2011OrthomolecularMedicineHallofFame(Canada)2014AwardofAntoineBéchamp (France)2014PearlMakerAwardofRiordanClinic(USA)

■BoardPresident,Int’lCongressofIntegrativeMedicine(2010)Board,InternationalSocietyofPersonalizedMedicineDirector,Int’lEducationalCenterforIntegrativeMedicine

Dr.Atsuo Yanagisawa,MD,PhD

SPICSalonMedicalClinicKamakuraCity,Japan

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Today’s topics

1.IntravenousHigh-doseVitaminCTherapyforCancerTreatmentinJapan

2.NutritionsupplementsalongwithIVCforcancerpatients

生存率

Breastcancer-100yearsago

BreastcancerStageIII&IV

024681012years

024681012years

%su

rvival

%su

rvival

%su

rvival

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Intravenous Vitamin CTherapyfor Cancer Treatment

<Subjects>:100patientswithterminalcancer

<Treatments>:i.v. VitaminC10g/dayfor10days+oralVitaminC10g

<Controlsubjects>:1,000patietns

<Results>:Survivalperiodwas4.2timeslongerinVitaminCtreatedpatients.

<

Drs.EwanCameron&LinusPauling

1976Volume73:3685-89,1976

10

Terminal Caner Patients treated with iv & oral

Vitamin C

survival time

% s

urvi

val

controls

Cameron E & and Pauling L:Volume 73:3685-89, 1976

ProcNatlAcadSciUSA75:4538-42September,1978

Breast

StomachColon

Lung

Ovary

RectumKidney

Bladder

Dr.Creagan andMoertel treatedterminalcancerpatientsusingonly2monthstreatmentoforalvitaminCwithoutIVCandshowednobenefit.ThemedicalscientistslostinterestaboutVitaminCforcancer,…but

MayoClinicStudies

Creagan etal,NEngl JMed301:687,1979Moertel etal,NEngl JMed312:137,1985

19791985

Volume 102:13604-13609 September 20, 2005

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues.

Qi Chen*†, Michael Graham Espey‡, Murali C. Krishna‡, James B. Mitchell‡, Christopher P. Corpe*, Garry R. Buettner§, Emily Shacter†, and Mark Levine*¶

National Institute of HealthNational Cancer InstituteFood & Drug Administration, U.S.A.

2005

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Volume 102:13604-13609 September 20, 2005

2005

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Copyright ©2007 by the National Academy of Sciences

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Copyright ©2007 by the National Academy of Sciences

Fig. 5. Pharmacologic ascorbic acid concentrations: mechanisms for selective cell deathMechanism of Vitamin C-induced selective cancer cell death

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Clinical Trial of IVC for Cancer - 1Lung Iowa University 2015, USA

Stomac Sun Yat-sen University 2016, China

Colon Jefferson University 2011, USA

Sun Yat-sen University 2017, China

Jefferson University 2009, USAKansas University 2011, USA

Pancreas CTA* in Philadelphia 2012, USABruckner Cancer Center 2014, USAIowa University 2014,USA

Liver Jefferson University 2012, USA

Breast CTA* in Chicago 2016, USA

Ovary Kansas University 2005, USA*CTA; Cancer Treatments for America

Prostate Copenhagen University 2010, DenmarkJohn’s Hopkins Universty 2015, USA

Lymphoma Jefferson University 2008, USATokai University 2008, JapanIowa University-phase 1 2013, USA

Brain Iowa University-phase 2 2015, USANeblaska University 2013, USA

Safety McGill University 2008, Canada

QOL JCIT 2010, Japan

Chemo resistant -McGill University 2010, Canada

Terminal solid tumor – CTA in Chicago 2006, USA

Clinical Trial of IVC for Cancer - 2

ScienceTranslationalMedicine.org2014; 6 : 222

High-Dose Parenteral Ascorbate EnhancedChemo-sensitivity of Ovarian Cancer and

Reduced Toxicity of Chemotherapy

Kansas University Medical CenterNational Institute of Health (USA)

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22ScienceTranslationalMedicine.org 2014; 6 : 222

Chemosensitizing effects of Vitamin C to carboplatin

VC: Vitamin CCp : Carboplatin

VC Cp CP+VC3.2mM 0.15mM

23ScienceTranslationalMedicine.org 2014; 6 : 222

Time to disease progressionor relapse for each subject.

(The bars represent median time)

spleen. Ascorbate alone or in combination with chemotherapy alsodid not cause any pathologic changes in the liver, kidney, or spleen(Fig. 3E).

Reduction of chemotherapy-associated toxicity by ascorbatein ovarian cancer patientsA pilot phase 1/2a clinical trial was conducted in patients with newlydiagnosed stage III or IV ovarian cancer. High-dose intravenous ascor-bate was added to conventional paclitaxel/carboplatin therapy, and tox-icity was assessed. Twenty-seven participants were randomized intoeither the standard Cp + Pax arm or theCp+Pax +AAarm. Cp+Pax chemothera-pywasadministered for the initial 6months,and AA treatment for 12 months. Partici-pants were followed for survival for 5 years.Two subjects in the Cp + Pax arm volun-tarily withdrew because they wanted intra-venous vitamin C, and they were excludedfrom data analysis. Data on 25 participants(12 inCp+Paxarmand13inCp+Pax+AAarm) were evaluated for untoward eventsusing the National Cancer Institute (NCI)CommonTerminologyCriteria forAdverseEventsversion3 (CTCAEv3).No treatment-related grade 5 toxicity (death) occurred.Ascorbate treatment did not increase the rateof grade 3 or 4 toxicity. Moreover, grade 1and 2 toxicities were substantially decreasedin theCp+Pax+AAgroupversus theCp+Pax group (Fig. 4A and tables S1 and S3).Compared with participants treated withCp + Pax, participants treated with Cp +Pax + AA had decreases in almost all thecategories of toxicity evaluated, includingneurotoxicity, bone marrow toxicity, in-fection, hepatobiliary/pancreatic toxicity,toxicities in the renal/genitourinary, pul-monary, and gastrointestinal systems, anddermatology (Fig. 4B and tables S1 andS4). Overall survival trended toward im-provementwith ascorbate addition to stan-dard chemotherapy (Fig. 4C and table S1),and themedian time fordiseaseprogression/relapse was 8.75 months longer in the Cp +Pax + AA arm than in the Cp + Pax arm(Fig. 4D and table S1), although neither oneachieved statistical significance becausethe trial was not statistically powered to de-tect efficacy. These results might also haveimproved with more frequent ascorbatedosing (13).

DISCUSSION

Conventional chemotherapies have littleimpact on the outcomes for relapsed andchemo-resistant ovarian cancers, but there

is potential to improve the treatment outcome using the CAM (comple-mentary and alternative medicine) regimen of high-dose intravenousascorbate as adjuvant. We investigated this possibility, and resultsshowed that ascorbate induced ovarian cancer cell death at concentra-tions easily achievable clinically by intravenous infusion (10–13, 21).Ascorbate worked synergistically in vitro and in vivo with the first-linechemotherapeutic drugs carboplatin and paclitaxel. In patients withadvanced ovarian cancer, treatment with ascorbate reduced toxicitiesassociated with chemotherapy. Because the study was not poweredfor detection of efficacy, statistical improvement in survival was not

Fig. 4. Reduction of toxicity in ovarian cancer patients after adding ascorbate to chemotherapy.Cp + Pax arm: participants received standard of care chemotherapy for 6 months. Cp + Pax + AA arm: inaddition to the Cp + Pax treatment, participants received intravenous AA using a dose-escalatingprotocol, with final dose of either 75 or 100 g per infusion depending on peak plasma concentration ofeach individual. The target peak plasma concentration of ascorbate was 350 to 400 mg/dl (20 to 23 mM).Once the dose was determined, participants received ascorbate infusion two times per week for a total of12 months. The first 6 months were in conjunction with the Cp + Pax chemotherapy. Fourteen subjectswere randomized to Cp + Pax arm. Two voluntarily withdrew before receiving any treatment and wereexcluded from data analysis. Thirteen subjects were randomized to the Cp + Pax + AA arm. Two werenoncompliant with tobacco use and were removed from the arm, and another one was removed afterin vitro assays detected that the subject was resistant to all chemotherapy. These three subjects receiveddoses of chemotherapy and ascorbate, so their adverse events were counted, but they were excludedfrom survival follow-up. (A) Average adverse events per encounter for all participants and all toxicitycategories. Any and all unwanted events were counted and graded for severity according to NCI CTCAEv3.Records for adverse events include patient interviews, emergency room visits, patients’ oncologist visits,and hospitalization records. The number of adverse events in each grade for each participant was dividedby the number of encounters of that participant, and then the adverse events per encounter were aver-aged in the Cp + Pax arm and the Cp + Pax + AA arm, respectively. (B) Percentage of participants who hadtoxicities in each arm. Toxicities were categorized by anatomic organ/system according to NCI CTCAEv3.All grades of toxicities were counted. More detailed data on patient toxicities are included in table S1. (C)Kaplan-Meier curves of overall survival at 60 months after diagnosis. (D) Time to disease progression orrelapse for each subject. The bars represent median time of each arm.

R E S EARCH ART I C L E

www.ScienceTranslationalMedicine.org 5 February 2014 Vol 6 Issue 222 222ra18 6

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VC: Vitamin CCp : CarboplatinPax: paclitaxel

VC (n = 10)

24ScienceTranslationalMedicine.org 2014; 6 : 222

VC: Vitamin CCp : CarboplatinPax: paclitaxel

Reduction of toxicity in ovarian cancer patients after adding Vitamin C to chemotherapy

VC (n = 13)

25ScienceTranslationalMedicine.org 2014; 6 : 222

(1) The combination of vitamin C with chemotherapeutic agents carboplatin and paclitaxel significantly inhibited ovarian cancer in mouse models.

(2)Intravenous vitamin C reduced chemotherapy-associated adverse effects in patients with ovarian cancer.

CONCLUSIONS

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EffectsofIVCinPtswithGlionlastoma

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HighDoseIntravenousVitaminCimproveQualityofLifeinCancerPatients.

MethodsOrganization JapaneseCollegeofIVTherapyParticipants 140 clinicsand5hospitalsSubjects 60CancerptswhohadnohistoryofIVC

QOL evaluation EORTCQLQ-C30

AdministrationofIVC

<RiordanIVCProtocol>PatientswereadministeredIVCtwiceaweek.

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EffectsofHighDoseIntravenousVitaminCTherapyonHealth-relatedQualityofLifeinCancerPatients.

Vitamin C (A.A.)# Grams (# cc) Diluent Type MgCl

AddedInfusion Time

(~0.5 gram/minute)Osmolality (calculated)

15 grams (30cc) 250cc Ringer's Lactate 1cc ~30 minutes* 827 mOsm/L

25 grams (50cc) 250cc Sterile Water 1cc ~50 minutes 800 mOsm/L

50 grams (100cc) 500cc Sterile Water 2cc ~100 minutes 900 mOsm/L

75 grams (150cc) 1000cc Sterile Water 2cc ~150 minutes 703 mOsm/L

100 grams (200cc) 1000cc Sterile Water 2cc ~200 minutes 893 mOsm/L

TheRiordanIVCProtocoldosingscheduledepictedabovehasservedasa“safestart”forcancerpatientsnewtoIVC.TheCenterfortheImprovementofHumanFunctioningInternationalinWichita,Kansas,since1990,has

administeredover30,000onsiteIVCinfusionsaccordingtothisprotocol.Zerofatalitiesandraresideeffectsatestamenttoitsremarkablesafety.

http://www.doctoryourself.com/RiordanIVC.pdf

Riordan IVC Standard Infusion ProtocolDeveloped and Typically Used at Center

PreviousanticancertherapySurgery 8Chemotherapy(CTx) 20Radiotherapy(RTx) 1Surgery+CTX 18CTx+RTx 3Surgery+CTx+RTx 1Nostandardtherapy 9

Total 60

EffectsofHighDoseIntravenousVitaminCTherapyonHealth-relatedQualityofLifeinCancerPatients.

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BeforeIVC 2 wks 4 wks

GlobalHealth&QOL 45+ 28 53+ 27* 61+ 24**

*p<0.05frombeforeIVC.**p<0.01frombeforeIVC.(Wilcoxon signedrankstest)

Results

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Functionalscale

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Functionalscales Before 2wks 4wks

Physical 74.0+ 27.7 78.3+ 23.7* 79.9+ 24.1*Role 64.2+ 33.0 71.2+ 31.1* 75.4+ 30.2**

Emotional 76.4+ 21.1 82.2+ 19.0* 87.4+ 15.3**Cognitive 74.3+ 26.1 81.6+ 23.9 84.2+ 22.1**Social 70.9+ 30.4 81.3+ 25.2* 82.4+ 21.7**

Valuesaremean+SD.*p<0.05and**p<0.01frombeforeIVC.(Wilcoxon signedrankstest)

Symptomscale

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Symptomscales Before 2wks 4wksFatigue 42.4+ 28.7 31.8+ 25.3** 28.4+ 25.7**Insomnia 31.1+ 32.1 23.2+ 27.2* 16.4+ 23.7**Pain 17.8+ 25.7 13.8+ 23.6 10.0+ 13.9*Constipation 21.1+ 31.3 13.6+ 22.4* 11.7+ 22.3*Financialdifficulties 34.5+ 32.1 26.4+ 29.8 26.2+ 28.2*Dyspnea 27.2+ 29.8 23.2+ 27.2 16.4+ 23.7Appetiteloss 26.1+ 36.4 30.5+ 32.9 20.5+ 28.0Nausea/vomiting 08.9+ 22.1 09.3+ 20.6 07.6+ 17.6

Diarrhea 10.7+ 24.3 09.2+ 19.5 10.1+ 20.0

Physician’sreport 2wks 4wksMarkedlyimproved 1(2%) 1(2%)

Moderatelyimproved 5(8%) 6(10%)Mildlyimproved 22(37%) 29(48%)

Unchanged 30(50%) 21(35%)Mildlyworsened 2(3%) 3(5%)

Moderatelyworsened 0(0%) 0(0%)Markedlyworsened 0(0%) 0(0%)

Physician’sevaluation

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47% 60%

Conclusions1 Theeffectsofhigh-doseIVConQOL in60cancer patientswerestudied using EORTICQLQ-30assessment.

2 Intheglobalhealth/qualityoflifescale,healthscoreimprovedfrom45±28to61±24at4weeksafterIVC(p<0.01).

3 Infunctionalscale,thepatientsreportedsignificantlyhigherscoresforphysical,role,emotional,cognitive,andsocialfunctionafterIVC(p<0.05).

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Conclusions4 Insymptomscale,patientsreportedsignifcantly

lowerscoresforfatigue,pain,insomnia,constipationandfinancialdifficultiesafteradministrationofvitaminC(p<0.05).

5 Physiciansreportedthat 60%oftheirpatientsimprovedQOLafterIVC,while35%wasunchanged,and5%worsened.

6 IVC canbeconsideredasasafeandeffectivetherapytoimproveQOLincancerpatients.

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Fromthe2016surveyof339doctorsinJapan

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Purposeofthestudy

Most of patients who are diagnosed with cancer mustchoose from limited options of standard therapy suggestedby their oncologist.

Among standard therapy options, chemotherapy hasstrong adverse reactions and drastically lowers QOL.Sometimes it is difficult for the patients to make decisionsbecause chemotherapy often fails to improve conditions, orcancer can recur even if the treatment works.

Therefore, we conducted a survey on doctors, who haverich knowledge of medicine, about choices they wouldmake if they were diagnosed cancer.

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Methods

(1)Wesentane-mailto650membersofTheJapaneseCollegeofIntra-venousTherapy(JCIT)andasktofilloutaquestionnairebuiltontheweb.

(2)WealsoasktoJCITmemberstolookfornon-memberfellowsofphysician/dentistwhorepliedthesamequestionnairesontheweb.

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