Controversies over Concurrent UseControversies over Concurrent Useof Supplements and Foods of Supplements and Foods

DuringDuringChemotherapy and RadiotherapyChemotherapy and Radiotherapy

Dr. Tom Archie, MD, DABFP, DABMA

Wood River Cancer Guides - Hailey, IDUpdated as of 2006

www.drtomsalchemy.com

AntioxidantsAntioxidants

The main area of controversy deals with the The main area of controversy deals with the concurrent use of Antioxidantsconcurrent use of Antioxidants Reduce oxidative stress (stealth of electrons from a stable Reduce oxidative stress (stealth of electrons from a stable

molecule to an oxidizing substance)molecule to an oxidizing substance) Increases availability of unstable “free radicals”Increases availability of unstable “free radicals” Damage nearby DNA, increase inflammation and Damage nearby DNA, increase inflammation and

mutationsmutations

Not all foods and supplements have antioxidant Not all foods and supplements have antioxidant propertiesproperties

Important not to confuse antioxidants with all Important not to confuse antioxidants with all supplements and foods, although many foods have supplements and foods, although many foods have some antioxidant properties (many fruits/veggies)some antioxidant properties (many fruits/veggies)

AntioxidantsAntioxidants

Vitamins A, C, EVitamins A, C, E Beta-caroteneBeta-carotene LuteinLutein SeleniumSelenium ZincZinc LycopeneLycopene CoQ10CoQ10

Colored vegetables and fruitsColored vegetables and fruits

Richest FoodRichest Food Sources of Antioxidants Sources of Antioxidants

Small red beans (dried)Small red beans (dried) Wild blueberriesWild blueberries Red kidney beansRed kidney beans Pinto beansPinto beans Blueberries (cultivated)Blueberries (cultivated) CranberriesCranberries Artichokes (cooked)Artichokes (cooked) BlackberriesBlackberries PrunesPrunes RaspberriesRaspberries Dark ChocolateDark Chocolate

StrawberriesStrawberries Red delicious applesRed delicious apples Granny Smith applesGranny Smith apples PecansPecans Sweet cherriesSweet cherries Black plumsBlack plums Russet potatoes Russet potatoes

(cooked)(cooked) Black beans (dried)Black beans (dried) PlumsPlums Gala applesGala apples

Avoid Antioxidants?Avoid Antioxidants?

Avoid Antioxidants?Avoid Antioxidants?

R Salganik, MD, PHD UNC-Chapel HillR Salganik, MD, PHD UNC-Chapel Hill Argues for studying AO-depleted diet in Argues for studying AO-depleted diet in

humanshumans Mice w/ brain tumors fed normal diet vs. Mice w/ brain tumors fed normal diet vs.

AO-depleted dietsAO-depleted diets AO-depleted diets assoc w/ higher ROS AO-depleted diets assoc w/ higher ROS

(reactive oxygen species), more apoptosis of (reactive oxygen species), more apoptosis of cancer cells (vs. normal), and smaller tumorscancer cells (vs. normal), and smaller tumors

No study of survival changes (malnutrition No study of survival changes (malnutrition risk?)risk?)

Pre-Chemo/RadPre-Chemo/RadOxidative Stress Oxidative Stress

Screening?Screening?

R Salganik, MD, PHD UNC-Chapel HillR Salganik, MD, PHD UNC-Chapel Hill Argues for screening populations for ROS Argues for screening populations for ROS

(reactive oxygen species) (reactive oxygen species) Argues that some level of ROS is necessaryArgues that some level of ROS is necessary

Hyper-producers of ROSHyper-producers of ROS Higher CA risk (and coronary dz, dementia, etc)Higher CA risk (and coronary dz, dementia, etc) Better use of AOBetter use of AO

Hypo-producers of ROSHypo-producers of ROS Lower CA riskLower CA risk Use of AO possibly unnecessary or at worst harmfulUse of AO possibly unnecessary or at worst harmful

Pre-Chemo/RadPre-Chemo/RadOxidative Stress Oxidative Stress

Screening?Screening?

Hypo-producers of ROS with high Hypo-producers of ROS with high carcinogenic exposure (smoker, carcinogenic exposure (smoker, industrial chemicals) industrial chemicals)

AO might prevent apoptosis of CA cells AO might prevent apoptosis of CA cells (smokers and beta-carotene)(smokers and beta-carotene)

Salganik. JACN. Salganik. JACN. 2001;20(5):464S2001;20(5):464S

This assumes thatThis assumes that

antioxidants protect cancer cellsantioxidants protect cancer cells

from apoptosis.from apoptosis.

Is that, in fact, the truth?Is that, in fact, the truth?

9/05 D’Andrea Article in9/05 D’Andrea Article in CA: A Cancer Journal for CliniciansCA: A Cancer Journal for Clinicians

““Use of Antioxidants During Use of Antioxidants During Chemotherapy and Radiotherapy Chemotherapy and Radiotherapy Should Be Avoided”Should Be Avoided”

Poor and biased reviewPoor and biased review Basis for D’Andrea’s argumentBasis for D’Andrea’s argument

Theory of antioxidant mechanism vs Theory of antioxidant mechanism vs “therapeutic” oxidative stress by chemo/rad“therapeutic” oxidative stress by chemo/rad

Selective group of trials re: negative interactionSelective group of trials re: negative interaction Studies against antioxidant efficacy in general Studies against antioxidant efficacy in general

but having nothing to do with concurrent usebut having nothing to do with concurrent use

AgreementAgreement

Absence of adequate RCT evidence Absence of adequate RCT evidence on concurrent useon concurrent use

Use or non-use could be harmfulUse or non-use could be harmful Cancer patients should not self-Cancer patients should not self-

medicate with antioxidantsmedicate with antioxidants Cancer not a self-help diseaseCancer not a self-help disease

Not all antioxidants likely to be Not all antioxidants likely to be beneficial beneficial

Some may interfere with chemotherapy or Some may interfere with chemotherapy or radiotherapyradiotherapy

Vitamin CVitamin C Moertel Studies Moertel Studies

D’Andrea: Neither study showed improvement vs D’Andrea: Neither study showed improvement vs placebo and possibly worse survival in Vit C groupplacebo and possibly worse survival in Vit C group

11stst Study Study Patients had chemo first, followed by oral Vit CPatients had chemo first, followed by oral Vit C Vit C given to immunocompromised pts (Vit C given to immunocompromised pts (NOT NOT

CONCURRENTCONCURRENT and not even Vit C as initial therapeutic and not even Vit C as initial therapeutic trial vs cancer)trial vs cancer)

22ndnd Study Study No Chemo – No Chemo – NOT A CONCURRENT STUDYNOT A CONCURRENT STUDY Vit C 10 grams oral (no IV Vit C – Pauling had shown Vit C 10 grams oral (no IV Vit C – Pauling had shown

efficacy of IV Vit C)efficacy of IV Vit C) NIH’s Levine: “Efficacy of Vit C cannot be judged from NIH’s Levine: “Efficacy of Vit C cannot be judged from

clinical trials that use only oral dosing.”clinical trials that use only oral dosing.”

Vitamin CVitamin C

D’Andrea speculates on Golde’s findingsD’Andrea speculates on Golde’s findings Vit C enters cancer cells via glucose Vit C enters cancer cells via glucose

transporterstransporters Assumes that this Vit C “feeds” cancer cellAssumes that this Vit C “feeds” cancer cell Assumes Vit C interferes with chemo/radAssumes Vit C interferes with chemo/rad

Levine at NIH proved (vs. speculation)Levine at NIH proved (vs. speculation) IV Vit C selectively kills variety of CA cellsIV Vit C selectively kills variety of CA cells ““By acting as a pro-drug to deliver By acting as a pro-drug to deliver

hydrogen peroxide to malignant tissues”hydrogen peroxide to malignant tissues”

Lesperance StudyLesperance Study

90 women early-stage breast cancer90 women early-stage breast cancer Standard therapy with or withoutStandard therapy with or without

B-carotene, niacin, Vit C, selenium, CoQ10, zincB-carotene, niacin, Vit C, selenium, CoQ10, zinc NOT RCTNOT RCT

Retrospective review matched cases from one physician’s Retrospective review matched cases from one physician’s practice (Dr. Adam Hoffer, MD, PhD)practice (Dr. Adam Hoffer, MD, PhD)

Patients took 3-6 supplementsPatients took 3-6 supplements Doses varied widelyDoses varied widely

CoQ10 – does never recordedCoQ10 – does never recorded Selenium 1-750 mcgSelenium 1-750 mcg Zinc 0-50 mgZinc 0-50 mg Vit C 1-24 gramsVit C 1-24 grams

AO group had lower disease-free survival, breast AO group had lower disease-free survival, breast cancer-specific survival, but same overall survival cancer-specific survival, but same overall survival rate as non-AO grouprate as non-AO group

D’Andrea:D’Andrea: ““Although many confounding factors may explain Although many confounding factors may explain

these differences in survival, the data should concern these differences in survival, the data should concern any oncologist who has patients considering any oncologist who has patients considering antioxidant therapy.”antioxidant therapy.”

Archie: Archie: The data should concern any oncologist that the data The data should concern any oncologist that the data

are meaningless.are meaningless. D’Andrea should be careful not to inappropriately D’Andrea should be careful not to inappropriately

bias the readership of bias the readership of CA: A Cancer Journal for CA: A Cancer Journal for CliniciansClinicians against supplements which may actually be against supplements which may actually be helpful and not harmful.helpful and not harmful.

Lesperance Study Lesperance Study What does it mean?What does it mean?

Vitamin C and Vitamin C and RadiationRadiation

Radiation for variety of cancersRadiation for variety of cancers 50 patients randomized 50 patients randomized

+/- Vit C 1 gram orally 5x per day+/- Vit C 1 gram orally 5x per day 4 month follow-up (meaningful?)4 month follow-up (meaningful?)

63% vs. 45% complete remission63% vs. 45% complete remission Fewer side effectsFewer side effects

Hanck. Prog Clin Biol Res. Hanck. Prog Clin Biol Res. 1988;259:3071988;259:307

CoQ10 andCoQ10 and Breast Cancer Breast Cancer

Blocks COX-2Blocks COX-2 High dose of CoQ10 associated with High dose of CoQ10 associated with

fewer deaths in women with fewer deaths in women with metastatic breast cancer metastatic breast cancer

Lockwood, Biochem Biophys Res Lockwood, Biochem Biophys Res Commun 1995 July 6;212(1):172Commun 1995 July 6;212(1):172

CoQ10 and TamoxifenCoQ10 and Tamoxifen

May 2005 Study. Rats with mammary May 2005 Study. Rats with mammary tumors were given tamoxifen, coenzyme tumors were given tamoxifen, coenzyme Q10, tamoxifen plus coenzyme Q10, or no Q10, tamoxifen plus coenzyme Q10, or no therapy. therapy. Addition of CoQ10 increased the susceptibility of Addition of CoQ10 increased the susceptibility of

cancer cells to tamoxifen.cancer cells to tamoxifen.Perumal et al. Mol Cell Biochem. 2005 May;273(1-Perumal et al. Mol Cell Biochem. 2005 May;273(1-

2):151-60. 2):151-60.

February 2005 study: mammary tumor February 2005 study: mammary tumor proliferation in rats was prevented by the proliferation in rats was prevented by the administration of tamoxifen plus CoQ10, administration of tamoxifen plus CoQ10, niacin, and riboflavin.niacin, and riboflavin. Perumal et al. Chem Biol Interact. 2005 Feb 28;152(1):49-58 Perumal et al. Chem Biol Interact. 2005 Feb 28;152(1):49-58

Co Q10 and Co Q10 and AdriamycinAdriamycin

Doxorubicin (Adriamycin)Doxorubicin (Adriamycin) Increased risk for congestive heart Increased risk for congestive heart

failure failure CoQ10 protects against this risk CoQ10 protects against this risk

without interfering with the cytotoxic without interfering with the cytotoxic effect of the drugeffect of the drug

Konklin. J Nutr. Konklin. J Nutr. 134(11) 3201S.134(11) 3201S.

CoQ10 and CoQ10 and RadiationRadiation

No interference with radiation in No interference with radiation in mouse studies at 10mg/kg dosemouse studies at 10mg/kg dose There was interference at 40mg/kg, but There was interference at 40mg/kg, but

a standard “high dose” human dose is a standard “high dose” human dose is 400mg (about 5-8mg/kg in human adult)400mg (about 5-8mg/kg in human adult)

Lund. Folia Lund. Folia Microbiol. 1998;43:505Microbiol. 1998;43:505

Vitamin A andVitamin A andChemotherapyChemotherapy

Small Cell Lung Cancer Small Cell Lung Cancer efficacy of etoposide in vitroefficacy of etoposide in vitro efficacy of doxorubicin in vitroefficacy of doxorubicin in vitro

SarcomaSarcoma efficacy of doxorubicin, cisplatin, efficacy of doxorubicin, cisplatin,

vincristinevincristine Head and Neck cancerHead and Neck cancer

Synergistic with cisplatinSynergistic with cisplatin

Vitamin A andVitamin A andChemotherapyChemotherapy

Pancreatic Cancer Vitamin A palmitate 50,000 iu orally twice

per day plus b-interferon and combined chemotherapy (epirubicin, mitomycin C, and 5-fluorouracil)

Prolonged symptom palliation in 35%pts Fairly toxic combination, however only

toxic effect attributed to Vit A was hepatic Also helpful in non-lymphocytic

leukemia

Vitamin A andVitamin A andRadiationRadiation

Radiotherapy +/- Vit A 150,000iu or Radiotherapy +/- Vit A 150,000iu or beta-carotene 90mg/kg in mice with beta-carotene 90mg/kg in mice with xenografted breast cancerxenografted breast cancer survivalsurvival tumor sizetumor size

Adv squamous cell CA mouth Adv squamous cell CA mouth (human)(human) mucositismucositis No change in survival (no interference)No change in survival (no interference)

Beta-CaroteneBeta-Carotene

Decreased efficacy of Decreased efficacy of antimetabolitesantimetabolites 5-FU5-FU MethotrexateMethotrexate

Increased efficacy of radiotherapyIncreased efficacy of radiotherapy Increased efficacy of some Increased efficacy of some

chemotherapychemotherapy Alkylating (cyclophosphamide, ifosamide)Alkylating (cyclophosphamide, ifosamide) Anthracycline (Adriamycin, bleomycin)Anthracycline (Adriamycin, bleomycin) Platinum-containing (cisplatin)Platinum-containing (cisplatin)

Melatonin andMelatonin andChemotherapyChemotherapy

100 people with metastatic Non-small cell 100 people with metastatic Non-small cell Lung cancer randomized to chemo alone vs. Lung cancer randomized to chemo alone vs. chemo plus melatonin 20mg/daychemo plus melatonin 20mg/day 5-year survival higher in melatonin group 5-year survival higher in melatonin group (6% vs. 0%)(6% vs. 0%) Chemotherapy better tolerated in melatonin Chemotherapy better tolerated in melatonin

group.group. Similar effects seen in RCTs of colorectal Similar effects seen in RCTs of colorectal

cancer and effective vs cancer-related cancer and effective vs cancer-related thrombocytopeniathrombocytopenia

Lissoni. J Pineal Res 2003;35:12Lissoni. J Pineal Res 2003;35:12

Cerea et al. Anticancer Res.2003;23:1951Cerea et al. Anticancer Res.2003;23:1951Lissoni et al. J Pineal Res 2001;30:123Lissoni et al. J Pineal Res 2001;30:123

Melatonin andMelatonin andRadiationRadiation

RCT Glioblastoma RCT Glioblastoma Radiation +/- melatonin 20mgRadiation +/- melatonin 20mg Increased 1 year survival in Increased 1 year survival in

melatonin groupmelatonin group 6/14 vs 1/14 still alive6/14 vs 1/14 still alive

Fewer side effects in melatonin groupFewer side effects in melatonin groupLissoni. Onc. 1996;53:43Lissoni. Onc. 1996;53:43

N-acetylcysteineN-acetylcysteine

efficacy of anthracycline-type drugs in animal efficacy of anthracycline-type drugs in animal studiesstudies Doxorubicin (Adriamycin)Doxorubicin (Adriamycin) BleomycinBleomycin

No known reduction of Adriamycin-associated No known reduction of Adriamycin-associated cardiotoxicitycardiotoxicity

No effect on alkylating agentsNo effect on alkylating agents CyclophosphamideCyclophosphamide hematuria associated with cyclophosphamidehematuria associated with cyclophosphamide

efficacy of cisplatin vs bladder cancer cells in efficacy of cisplatin vs bladder cancer cells in vitrovitro But NAC is used to treat cisplatin-associated renal failure But NAC is used to treat cisplatin-associated renal failure

Glutatione, CisplatinGlutatione, Cisplatin and Neurotoxicity and Neurotoxicity

Fear: Thiol-containing antioxidants Fear: Thiol-containing antioxidants might interfere with platinum-might interfere with platinum-containing drugscontaining drugs N-acetylcysteine blunts efficacy of N-acetylcysteine blunts efficacy of

cisplatin vs. bladder cancer cells in vitrocisplatin vs. bladder cancer cells in vitro Glutatione is a thiol-containing Glutatione is a thiol-containing

substancesubstance Glutathione does not interfere with Glutathione does not interfere with

cisplatincisplatin

Glutathione, Cisplatin and Glutathione, Cisplatin and Neurotoxicity Neurotoxicity

Glutathione found in Phase 3 clinical trials to Glutathione found in Phase 3 clinical trials to decrease adverse effects of cisplatindecrease adverse effects of cisplatin Gastric, ovarian, colorectal, NSCCLung, head/neckGastric, ovarian, colorectal, NSCCLung, head/neck Neurotoxicity, need for transfusion, hair loss, Neurotoxicity, need for transfusion, hair loss,

difficulty concentrating, anemia, thrombocytopeniadifficulty concentrating, anemia, thrombocytopenia No decrease in efficacy of cisplatin Patients able to tolerate more cisplatin treatmentsPatients able to tolerate more cisplatin treatments Same effects seen for oxilaplatinSame effects seen for oxilaplatin

Smyth et al. Ann Oncol. 1997;8:569Smyth et al. Ann Oncol. 1997;8:569Cascinu et al. J Clin Oncol. 1995;13:26-32Cascinu et al. J Clin Oncol. 1995;13:26-32Cascinu et al. J Clin Oncol. 2002;20:3478-83Cascinu et al. J Clin Oncol. 2002;20:3478-83Smidinger et al. Wien Klin Wochenschr. Smidinger et al. Wien Klin Wochenschr.

2000;112:617-232000;112:617-23

GlutamineGlutamine

Protects GI tract vs. radiation and Protects GI tract vs. radiation and chemotherapy toxcitychemotherapy toxcity

Preserves glutathione levelsPreserves glutathione levels Prevents Adriamycin cardiac toxcicityPrevents Adriamycin cardiac toxcicity

Cao. J Surg Res. 1999;85:178Cao. J Surg Res. 1999;85:178

Decker-Baumann. Eur J Decker-Baumann. Eur J Cancer. 1999;35:202Cancer. 1999;35:202

Jensen et al. Ann Surg Oncol. Jensen et al. Ann Surg Oncol. 1994;1:1571994;1:157

Some studies fail to replicate thisSome studies fail to replicate thisBozzetti et al. Nutr. Bozzetti et al. Nutr.

1997;13:7481997;13:748

TangeretinTangeretin

Flavanoid found in citrus fruitFlavanoid found in citrus fruit efficacy of platinum drugs efficacy of platinum drugs

(cisplatin, carboplatin)(cisplatin, carboplatin) efficacy of hormonal agent efficacy of hormonal agent

tamoxifentamoxifen Bracke et al. J Natl Cancer Inst. 1999;91:354.Bracke et al. J Natl Cancer Inst. 1999;91:354.

Green TeaGreen Tea

concentration of Adriamycin in two concentration of Adriamycin in two tumor types but not in normal tissuetumor types but not in normal tissue

anti-tumor efficacy by 2.5x vs. anti-tumor efficacy by 2.5x vs. ovarian sarcomasovarian sarcomas

Sadzuka. Clin Cancer Res. Sadzuka. Clin Cancer Res. 1998;4:153.1998;4:153.

Sugyama. Cancer Letter. Sugyama. Cancer Letter. 1998;133:19.1998;133:19.

MalnutritionMalnutrition

NCI website:NCI website:““Side effects of cancer and cancer treatments Side effects of cancer and cancer treatments

make it difficult to eat well…Malnutrition can result, make it difficult to eat well…Malnutrition can result, causing the patient to be weak, tired, and unable to causing the patient to be weak, tired, and unable to resist infections or withstand cancer therapies.”resist infections or withstand cancer therapies.”

Yale UniversityYale University “In addition to weight lost prior to the diagnosis of “In addition to weight lost prior to the diagnosis of head head and neck cancer, the patient may lose an additional and neck cancer, the patient may lose an additional 10% of10% of pre-therapy body weight during radiotherapy or pre-therapy body weight during radiotherapy or combined-combined- modality treatment.”modality treatment.”

““A reduction of greater than 20% of total body weight A reduction of greater than 20% of total body weight results in an increase in toxicity and mortality.”results in an increase in toxicity and mortality.”

Colasanto et al. Onc. Colasanto et al. Onc.

2005;19:3712005;19:371

ImmunosuppressionImmunosuppression

One of the most common dose-One of the most common dose-limiting complications of limiting complications of chemotherapychemotherapy

Melatonin Melatonin Improved WBC and platelet counts in Improved WBC and platelet counts in

NSCCLung with etoposide and cisplatinNSCCLung with etoposide and cisplatin AstragalusAstragalus

Cochrane Collaborative Cochrane Collaborative leukopenia, nausea, vomiting and overall leukopenia, nausea, vomiting and overall

side effects of chemotherapyside effects of chemotherapy

Chinese MedicineChinese Medicineand Radiationand Radiation

Fu-Zheng pattern (correct predisposing Fu-Zheng pattern (correct predisposing patterns of deficiency and stagnation)patterns of deficiency and stagnation) Symptom management and increase in Symptom management and increase in

survivalsurvival 197 pts Stage III and IV ENT cancers 197 pts Stage III and IV ENT cancers

randomized to radiation with or without randomized to radiation with or without TCM herbs (Yi Qi Yang Yin Tang). 3-year TCM herbs (Yi Qi Yang Yin Tang). 3-year survival 67% vs. 33%.survival 67% vs. 33%.

Sun. Rec Results in Cancer Research 1988:108:327Sun. Rec Results in Cancer Research 1988:108:327

Chinese MedicineChinese Medicineand Chemotherapyand Chemotherapy

303 patients with Stage III and 63 with Stage IV 303 patients with Stage III and 63 with Stage IV gastric cancer with chemo randomized to additional gastric cancer with chemo randomized to additional Pishen Fang herbal formula or to control group.Pishen Fang herbal formula or to control group. 5yr survival 53% Stage III with herbs and 10% Stage IV with 5yr survival 53% Stage III with herbs and 10% Stage IV with

herbsherbs 10yr survival 47% Stage III with herbs10yr survival 47% Stage III with herbs

Yu. J Trad Chin Med Yu. J Trad Chin Med 1993;13(1):31.1993;13(1):31.

2001 first US FDA-approved clinical study of extract 2001 first US FDA-approved clinical study of extract of Coix lachryma-jobi called Kanglaite for refractory of Coix lachryma-jobi called Kanglaite for refractory solid tumors (Lung CA mentioned). Study ongoing. solid tumors (Lung CA mentioned). Study ongoing.

Previous Chinese studies show inhibition of mitosis of tumour cells during Previous Chinese studies show inhibition of mitosis of tumour cells during G2/M phase of the cell cycle, tumor cell apoptosis, increased gene G2/M phase of the cell cycle, tumor cell apoptosis, increased gene expression of FAS and Apo-1, inhibits angiogenesisexpression of FAS and Apo-1, inhibits angiogenesis

www.clinicaltrials.gov/ct/show/NCT00031031?order=1 www.clinicaltrials.gov/ct/show/NCT00031031?order=1 www.annieappleseedproject.org/kanglaite.htmlwww.annieappleseedproject.org/kanglaite.html

Concurrent Use –Concurrent Use – Both Chemo and Rad Both Chemo and Rad

Finish study SCCLung with chemo and Finish study SCCLung with chemo and radiation +/- antioxidant supplementradiation +/- antioxidant supplement Concurrent antioxidants survivalConcurrent antioxidants survival Vit A 15,000 IU, B-carotene 10,000 IU,

a-tocopherol 300 IU, Vit C 2000mg, and selenium 800mcg

2yr survival >33% vs <15% historical controls Non-randomized study of 18 people compared Non-randomized study of 18 people compared

to historical controlsto historical controls (Not much unlike the Lesperance study, except (Not much unlike the Lesperance study, except

that the doses were the same for each person)that the doses were the same for each person)Jaakkola. Anticancer Research. 1992;12:599.Jaakkola. Anticancer Research. 1992;12:599.

Whole FoodWhole Foodvs. Syntheticvs. Synthetic

Juice Plus is first supplement endorsed by Juice Plus is first supplement endorsed by the Center for Advancement in Cancer the Center for Advancement in Cancer Education (CACE)Education (CACE)

1. apples, oranges, pineapple, cranberries, peaches, acerola 1. apples, oranges, pineapple, cranberries, peaches, acerola cherries, papayacherries, papaya

2. carrots, parsley, beets, kale, broccoli, cabbage, spinach, 2. carrots, parsley, beets, kale, broccoli, cabbage, spinach, tomatoes, barley, oat fiberstomatoes, barley, oat fibers

3. blueberries, blackberries, bilberries, raspberries, cranberries, 3. blueberries, blackberries, bilberries, raspberries, cranberries, elderberries, black currants, red currants, and Concord grapeselderberries, black currants, red currants, and Concord grapes

oxidative stress, DNA damage, oxidative stress, DNA damage,

homocysteine, immune function markershomocysteine, immune function markers

Silymarin, Glycine, Ginger

VEGFR

EGCG, silymarin, quercetin, resveratrol, soy isoflavones, curcumin, EPA

Cu antagonists

VEGF, AKs, bFGF, IL8, MMPs,

TNF-1, heparinases, collagenases

curcmin, artemsia, mistletoe, ginger scutellaria, resveratrol, grapeseed extract, green tea, gingko, squalamine, Vit D silymarin, glycine,

ginger artemsia mistletoe curcumin scutellaria

curcmin, scutellaria, cartilege, silymarin, green tea

bFGFR and TNF-1:

Cu antagonists

Multifocal Angiostatic

Therapy

Growth FactorsNFkBCOX-2

Anti GFs: green tea quercetin magnolia resveratrol, soy, curcumin holy basil rosemary ganoderma licorice Vit E

Anti- NFkB: poria, coriolus, ginger, resveratrol, green tea, artemsia, quercetin, carnosol, panax ginseng, silymarin, salicylates, curcumin, picentannol, basil, Cu antagonists rosemary

Anti-COX-2: quercetin, scutellaria, EPA/DHA, licorice, ginger, resveratrol, grapeseed extract, curcumin, salicylates, garlic, green tea, panax ginseng, silymarin, bilberry, antioxidants, boswellia, aloe

We’ve all been waiting, wondering, Will we ever know the truth?

What it’s like washing windows

When you know that there are pigeons on the roof?