Jeanne M. Wallace, PhD, CNC

Nutritional Solutionswww.nutritional-solutions.net

Integrative NutritionTo Complement Cancer Care

ModulatingOncometabolicSyndrome

Disclosure Information

Wallace, PhD, CNC, Jeanne

Indicated no relevant affiliations or financial interests.

Speaker has not presented any promotional talks to any pharmaceutical companies within the past 12 months.

Speaker will not discuss off-label or investigational drug use.

Learning Objectives•Describe integrative nutrition protocols targeting Oncometabolic Syndrome (a cluster of metabolic factors that influence the growth and progression of cancer)

•Choose standard lab testing to assess nutritional factors that may influence cancer outcomes, tailor a protocol to an individual's unique needs, and evaluate the efficacy of the nutrition intervention in modulating these factors. 

• Apply a diet to down regulate "Oncogenic Potential" via:a. Phytonutrient modulation of gene expression

b. Dietary & lifestyle guidelines to address insulin resistance

c. Strategies to modulate inflammatory eicosanoids

d. Dietary strategies for anti-angiogenesis

BestCaseSeries SurvivalComparison

GBM IV

4Intl J Radiat Onc Biol Physiol, 2003:57:S135–6.

0%

25%

50%

75%

100%

1 yr 3 yr 5 yr

➤ N=341 consecutive cases GBM IV (1997-2004) from NCI NCCAM Best Case Series submission

➤ Published survival rates for GBM IV [Shaw et al., 2003]

5

Other CancersSurvival Data Selected Cases 1999-2009

Sex Age Dx Survival

F 58 IV > 9 yr, 5 mo

M 36 II 9 yr, 5 mo

M 49 IV > 6 yr, 9 mo

F 61 IV 6 yr, 9 mo

F 46 IV 5 yr

M 76 III > 4 yr, 9 mo

M 46 IV 4 yr, 3 moCol

orec

tal

Age Dx Survival

55 IV > 14 yr, 2 mo

57 IIIc > 11 yr, 8 mo

54 IIIc > 10 yr, 5 mo

55 IIIc > 9 yr, 11 mo

57 IIc+BrCa > 9 yr, 2 mo

38 IIIc > 7 yr, 10 mo

67 IIIc > 6 yr, 4 mo

47 IIIc 6 yr, 1 mo

53 IIIc 6 yr

70 IV 5 yr, 9 mo

Ova

rian

Sex Age Dx Survival

M 70 III 4 yr, 1 mo

F 50 IV > 3 yr, 10 mo

M 66 IV > 3 yr, 3 mo

F 59 I > 3 yr, 2 mo

F 64 IV > 2 yr, 11 mo

M 54 IV 2 yr, 9 mo

M 58 III 2 yr, 3 mo

Pan

crea

tic

Oncology’s New Paradigm

SO

IL

Why doaphids ‘attack’ plants?

EC

OS

YS

TE

M

6

COX-2CRP

LOX-5

estrogen

leptin

adiponectinVEGF

IGF-1

↑NFkß5-HETE

cortisol

VEGF

bFGF

IL-6

TNF-α

↓ SHBG

↑ Copper

IL-10

fibrin

↓ Antioxidants

insulin

PDGF

↑ Iron

↓ Vit D↓ Zinc

They are influenced by factors in their environment.Cancer cells do not exist in isolation...

7

Oncometabolic Milieu

COX-2CRP

LOX-5

estrogen

leptin

adiponectinVEGF

IGF-1

↑NFkß5-HETE

cortisol

VEGF

bFGF

IL-6

TNF-α

↓ SHBG

↑ Copper

IL-10

fibrin

↓ Antioxidants

insulin

PDGF

↑ Iron

Hyper-coagulability

SystemicInflammation

InsulinResistance

HormoneImbalance

NutrientImbalances

ImmuneIncompetence

Angiogenesis

↓ Vit D↓ Zinc

8

Modulating

Gene Expression

Base pairsLetters

Chromosome Encyclopedia

GeneRecipe

DNAWord

Understanding GENETICS

10

“Give me the coding sequences of a chimpanzee and the regulatory mechanisms of a mouse,

and I’ll give you a mouse.”—Susumu Ohno

Evolutionary Geneticist

Understanding Epigenetics

Microbiome

Ecosystem ➠ Gene Expression

PositiveEmotions

Stress

Toxins

Oxidation

Radiation

Infection

Diet

Disease Health

Carcinogens CircadianRhythm

HealthyLifestyle

12

13

NFkßCancer’s MasterSwitch

Curr Allergy Asthma Rep, 2013;13: 44–9. • Curr Signal Transduc Ther, 2006:1:25-52. • Cancer Res, Feb 15, 2007;13(4):1076-82.

TRIGGERS carcinogensoxidationviral infectioninflammationradiationchemotherapy

NF

kß

NFkß Activates 400+ Genes

14Exp Biol Med (Maywood), 2008;233(1):21-31. • Curr Signal Transduc Ther, 2006:1:25-52.

AngiogenesisVEGF, TNF, IL-8

InflammationIL-6, COX-2,

TNF, chemokines

Survival/Anti-apoptosisbcl/bax, survivin

Proliferationmyc, IL-6,

Metastasis5-LOX, CAMs

NF

kß

Spices Inhibit NFkß

Ann NY Acad Sci, Dec 2004;1030:434-41.

anise

basil

black pepper

caraway

cardamom

chili pepper

cinnamon

clove

coriander

cumin

fennel

fenugreek

flaxseed

garlic

ginger

Holy basil

lemongrass

licorice

mint

mustard seed

nutmeg

oregano

parsley

rosemary

saffron

tamarind

turmeric

15

Modifying

Gene Expression

Histone modifiers UNWRAP the DNA strand

Methyl groups prevent the DNA strand from being

UNZIPPED

17Epigenomics, 2011;3(4):503-18. • Ann Rev Nutr, 2008;28:347-66.

Histone ModifiersHistone Acetyl-

Transferase

HAT

Histone D-Acetylase

HDAC

Genisteinsoy

Curcuminturmeric, curry

EGCGgreen tea

Seleniumbrazil nuts

Sulforaphanecruciferous veggies

Resveratrolgrapes, wine

Allyl mercaptangarlic

Wrapped

Unwrapped

HDACs

HATs

➠

➡➡➡

➡➡➡

➡➡➡

Epigenomics, 2011;3(4):503-18. • Ann Rev Nutr, 2008;28:347-66.

Methylation Modifiers

Methylation Support

DNMTInhibitors

FolateVitamin B12Vitamin B6

BetaineCholine

MagnesiumZinc

SeleniumSulforaphane

EGCGResveratrolGenistein

18

Once a gene is unwrapped & unzipped, its proteins can be assembled...or blocked by miRNA

19

mRNA

miRNA

microRNA

blocks

protein

assembly

Green tea EGCGCurcuminSoy foodsCruciferous veggies

Genes Nutr, 2011;6(2):93–108. • Pharm Res, 2010 Jun;27(6):1027-41. 20

NFkßswitch off

ModifyHistones

wrap/unwrapMethylation

zip/unzipmicroRNA

veto

spicesturmeric

basilmint

rosemarygarlic

parsleythymesage

saffron

green teacurcumin

cruciferous vegsoy foods berries

red/purple grapescitrusgarlic

brazil nutsbutyrate

leafy greens beets

green teacruciferous veg.

brazil nuts

green teacurcumin

cruciferous vegsoy foods

Biochem Pharmacol, 2010;80(12):1771–92. • Genes Nutr, 2011;6(2):93–108. 21

✤ Prostate cancer patients not electing surgery, radiation, hormone therapy

✤ Gene expression compared after 3 months on diet

✤ Expression of 500+ genes changed

✤Oncogenes were down-regulated

PNAS, 2008 Jun 17;105(24):8369-74.

Diet Alters Gene Expression B

EFO

RE

AFT

ER

22

NFkß & Diet Patternin Colorectal Cancer Patients

Clin Nutr, 2010 Feb;29(1):42-6.

High NFkßHigh histological aggressiveness

Low NFkßLow histological aggressiveness

↑ refined carbs↑ omega 6:3 ratio

(≅26:1)↑ alcohol

↑ omega 6:3 ratio (≅6:1)

↑ fiber↑ selenium↑ vitamin E↑ flavonoids↑ β-carotene↑ isoflavones

23

InsulinResistance &

Cancer

Hyperglycemia & Brain Tumor Survival

4

8

11

15

65-93 94-137 ≥ 138

25

50

75

100

5-Yr OS DFS PFS

NormoglycemicHyperglycemic

Neurol Res, 2010 May;32(4):442-8. J Clin Oncol, 2009 Mar 1;27(7):1082-6.25

Breast3-fold ↑ riskrecurrence over 5 yrs

Int J Cancer, 2006 Jul

1;119(1):236-8.

Ovarian 60% shorter median survival

Gynecol Oncol, 2011 Apr;

121(1):106-11.

Lung(NSCLC)

69% ↑ risk mortality if fasting

glucose ≥ 126

Lung Cancer, 2012 May;

76(2):242-7.

Prostate↑ 2-fold increase risk recurrence (meta-analysis)

J Exp Clin Cancer Res, 2013 Feb 13;32(1):9.

MetSx & Cancer Outcomes

26

Post-OpComplications

40% vs 11% with 11 vs 8 days

hospitalized

Dis Colon Rectum, 2010

Feb;53(2):186-91.

ImmuneSuppression

↑ risk infection during chemo

Diabetes Care, 2008 Oct;

31(10):1972-7.

Increased Estrogen

↑ aromatase activity, ↓ SHBG

production

Obes Rev, 2007 Sep;8(5):395-408.

MetSx correlates with...

27

Exp Diabetes Res, 2012:789174. • Am J Pathol, 2006 Nov;169(5):1505-22. 28

INDICATOR TARGET*Waist-Hip Ratio women < 0.8, men <1.0

Waist Circumference

women ≤ 35, men ≤ 40”

A1c < 5.0-5.2%

Triglycerides < 110 mg/dL

HDL cholesterol > 50-55 mg/dL

Blood pressure < 120/80

Glucose fasting < 60-90 mg/dL post-prandial < 120 mg/dL

Uric Acid < 5.5 mg/dL

*Based on optimal, Functional Medicine ranges and/or cut-off points associated with improved prognosis in cancer patients (not standard diagnostic criteria).

AssessingBiomarkers of

InsulinResistance

29

Insulin Resistance in Cancer Patients✤ DIET

✤ POOR DIGESTION

✤ STRESS

✤ LACK OF EXERCISE weak-ness, ↓ muscle mass, ↑ adiposity

✤ NUTRIENT DEFICIENCIES vitamin D, chromium, carnitine, CLA magnesium, biotin, vanadium, zinc

✤ TREATMENT EFFECT Beware! These wholesome-appearing foods may be problematic Oncol Nurs Forum, 2012 May;39(3):E275-87.

J Clin Oncol, 2001 May 1;19(9):2381-9. 30

SubstitutionsINSTEAD OF THIS...INSTEAD OF THIS... TRY THIS...TRY THIS...

Food (1 cup)

Glycemic

LOADFood(1 cup)

Glycemic

LOAD

White flour

Whole wheat

76

44

Almond Flour 0White flour

Whole wheat

76

44 Coconut Flour 0

Sandwich bun 18Portobello mushroom 3

Sandwich bun 18Romaine lettuce “wrap” 0

Brown rice 22 Cauliflower “rice” 2

Pasta noodles 22Zucchini “noodles” 1

Pasta noodles 22Miracle Noodles 0

Mashed Potatoes 16 Mashed Cauliflower 4

31

CinnamonBerries: blueberries, goji, blk currantChamomile teaAlliums: garlic, onions, leeks, chivesParsleyAvocadoOlive oilFlaxseed meal / Oat bran (soluble fiber)Lemon

Top Foods to Aid Glycemic Control

Diab Metabol Syndr: Clin Res Rev, 2010;4(1):21-40.Diab Care, 2003 Apr;26(4):1277-94. 32

InflammationPromotesCancer

Chronic systemicInflammationhas emerged as a

Hallmarkof Cancer

Proliferation Angiogenesis

Immune Evasion Chemoresistance

Radioresistance

Invasion

Metastasis

InflammationPredictsCancerSurvival

Nutr Cancer, 2001;41(1-2):64-9.

0%

20%

40%

60%

80%

100%

0 200 400 600 800 1000

% patientssurviving

Time (in days)

Low CRP

High CRP

35

TreatmentEfficacy

50% ↓ CRP predicts response to chemo

in NSCLC

J Med Assoc Thai, 2012 Feb;95

Suppl 2:S199-207.

TreatmentToxicity

more severe low blood counts

Ann Oncol, 2003;14:36-41.

Cachexia↓ appetite

↑ muscle wasting↑ weight loss

Lung Cancer, Jun 2003;40(3):295-9.

QOL ↑ fatigueCancer, 2012

Dec 1;118(23):6005-11.

hsCRP correlates with...

36

Dietary Fats & Inflammation

OMEGA-6 FATS✤ Commercially-raised

meat, poultry, dairy, eggs✤ Most nuts & seeds✤ Vegetable oils—corn, soy,

safflower, grapeseed oil (not olive oil)

ANTI-INFLAMMATORYInhibit tumor growth & progressionAnti-angiogenesis Complement radiation & chemo

PRO-INFLAMMATORYFoster tumor growth & progressionPromote angiogenesisSuppress immune function

PGE₂ LTB₄ PGE₃TXA₂ 5-HETE LTB₅

OMEGA-3 FATS✤Pasture-raised meat,

poultry, dairy, eggs✤Wild cold-water fish✤ Black walnuts, flaxseeds✤Oils of flax, hemp & canola

(unstable/not advisable)

Δ6-Desaturase

↑ Insulin

COX & LOX

PGE₁

37

Comprehensive Anti-Inflammatory Plan

*Annu Rev Pharmacol Toxicol, 2011 Feb 10;51:311-36.

Inhibit NFκßample culinary spices

↓ Lipid Peroxidationhigh ORAC diet

Shift Substratesimprove n-6:3 ratio

COX-2 Inhibitorsapigenin, berberine,

bromelain, curcumin, ginger, quercetin, resveratrol

Optimize Desaturase Function↓ hydrogenated+trans fats, provide cofactors (Zn, Mag,

vitamins C, B3, B6)

5-LOX Inhibitorsallicin, baicalein, berberine, boswellic acid, caffeic acid, curcumin, EGCG, galangin

Improve Insulin Sensitivity

↑ Prostaglandin Clearance

vitamin D*

38

Spices (esp. curry, ginger, garlic, parsley)

Wild, cold-water fish

Pastured-raised meat, dairy, eggs

Hot peppers

Olive oil

Leafy green veggies (spinach, chard, kale)

Cruciferous vegetables

Pumpkin, butternut squash, yam, carrot

Dark chocolate (flavanols)

Berries (blueberries, cherries, raspberries)

Top Foods to QuenchInflammation

39

AngiogenesisCancer& Copper

Copper & Cancer Outcomes

Clin Cancer Res, 2000 Jan;6(1):1-10. • Acta Med Okayama. 1986 Apr;40(2):103-5. • J Surg Oncol. 1991 Mar;46(3):178-81. • JNCI, 1981 Aug;67(2):263-75. • J Gastroenterol, 2003;38(1):45-51. • Ann Thorac Surg, Aug 2008;86(2):383-9. • Clin Cancer Res, 2003

May;9(5):1666-72. • Indian J Pathol Microbiol, 1990 Apr;33(2):171-4. • Ann Oncol, 2013 Feb: PMID: 23406736. • Biol Trace Elem Res, 2001;82(1-3):1-8. 

✤ Cancer pts have ↑ serum Cu levels (or Cu:Zn ratio) vs healthy controls

✤ Serum Cu and/or Cp correlates with tumor burden, advanced disease, and survival

✤ Cu levels rise during active disease and fall to normal in remission

✤ Cu depletion ↓circulating endothelial progenitor cells in BrCa pts

✤ Clinical trials of Cu chelation show activity in stabilizing disease

41

Contributors to Elevated Copper✤ Dietary supplements

✤ Vegetarian or vegan diet

✤ Adrenal hypofunction

✤ Zinc deficiency

✤ Gluten intolerance

✤ Estrogen dominance

✤ Inflammation (local or systemic)

Significant Food Sources of Copper

Food (100-gm/serving) mg

Liver, veal 15

Paté 15

Liver, beef 10

Oyster 8

Liver, duck 6

Soy flour 5

Shiitake, dried 5

Cocoa powder, unswt 4

Lobster, 6oz 4

www.NutritionData.com

42

Spices (esp. curry, ginger, garlic, parsley)

Berries (all types)

Green tea

Parsley, peppermint, thyme (apigenin)

Curry (turmeric, coriander, cumin)

Garlic

Brazil nuts (selenium)

Cold-water fish / Grass-fed meat (omega-3)

Traditional soy foods

Peanuts/boiled, red grapes (resveratrol)

Top Foods to Suppress Angiogenesis

J Physiol Pharmacol. 2005 Mar;56 Suppl 1:51-67. 43

Vitamin D &

Cancer

J Steroid Biochem Mol Biol, 2006 Dec;102(1-5):156-62. • J Steroid Biochem Mol Biol, 2010 Jul;121(1-2):343-8. • Ann Rev Pharmacol Toxicol, 2011 Feb 10;51:311-36. • Nutr Res Rev, 2009 Jun;22(1):82-92. • Biochem J, 2012 Jan 1;441(1):61-76.

Vitamin D and Cancer✤ Induces differentiation (more normal phenotype)

✤ Promotes apoptosis (programmed cell death)

✤ Inhibits invasion, angiogenesis and metastasis

✤ Inhibits estrogen synthesis & signaling (↓ expression of aromatase, down-regulates expression of ER-α)

✤ Plays a role in blood sugar regulation and insulin sensitivity

✤ Anti-inflammatory (prostaglandin dehydrogenase)

45

✤Breast Cancer - deficiency associated with worse prognostic markers (ER- and triple-negative tumors), ↑ recurrence risk (Oncotype scores), ↓ survival

✤Colorectal Cancer - high pre-Dx vitamin D3 associated with ↑ survival

✤Brain Tumor - 27% of pts treated with vit D had tumor regression or remission

✤Prostate Cancer - 30% response rate (≥50% ↓ PSA x median 4 months) in pts treated with vit D (up to 5,000iu/day)

Cancer Epidemiol Biomark Prev. 2011;20(4):717. •  J Clin Oncol. 2009 Aug 10;27(23):3757-63. •  J Clin Oncol. 2008 Jun;26(18):2984-91. •  J Neuro-oncol. 2001 Jan;51(1):57-66. • ASCO Annual Meeting, San Francisco, CA. 2010 Mar 5: #228.

Vitamin D and Cancer

46

ACTIONS D₃ A K₂Differentiation (revert to healthy phenotype) ✔ ✔

Apoptosis (cancer cell suicide) ✔ ✔ ✔

Anti-angiogenesis ✔ ✔

Inhibit invasion / metastasis ✔ ✔ ✔

Improve insulin sensitivity ✔ ✔

Reduce estrogen (block aromatase, ↓ ER) ✔ ✔

47

Fat-Soluble Vitamins & Cancer: Emerging Picture of Synergy

IndividualizingNutritionPlans

SimilarCases:Divergent Outcomes

Susan

Dx OvCa IIIc

Age 48

Ht/Wt 5’4” • 140 lbs

BMI 24

S/P TAH, T/C x 6

Labs WNL

Hx N/C

Sally

49

TEST TARGETCRP

high sensitivity or cardio-C-reactive protein

≤ 0.8-1.0 mg/L

A1c& insulin resistance panel

≤ 5.0-5.2%

Vitamin D325-OH-cholecalciferol

50-75 μg/dL

Free Copperserum Copper minus (3 x Ceruloplasmin)

≤ 10-15

Fibrinogen 200-325 mg/dL

Assessing OncometabolicParameters

50

hs-CRPInflammation ✘

✘ A1cInsulin Resistance

✘ Vitamin D₃Differentiation ✘

Copper & Ceruloplasmin

Angiogenesis✘

✘ FibrinogenBlood Viscosity

Different Stories Emerge

Susan Sally

51

Individualized Nutrition Support

Screen for interactions/contraindications.

hs-CRP

Copper

Vitamin D₃

A1c

Fibrinogen

Vitamin D₃

Bromelain ✔

Curcumin ✔

Quercetin ✔

✔ Fish oil ✔

✔ Blood Sugar Support

✔ Ginkgo biloba

✔ Vitamin D3 ✔

Molybdenum ✔

Zinc ✔

Susan Sally

52

Hyper-coagulability

ChronicInflammation

InsulinResistance

HormoneImbalance

NutrientImbalances

ImmuneIncompetence

Angiogenesis

53

✤ Individualize nutrition protocols ✤ Prioritize self-care strategies✤ Navigate nutrition controversies

Use model to guide choices

melatoninleptin

IGF-1

cortisol

↑ Copper

insulinInsulinResistance

HormoneImbalance

↓ Vit D↓ Zinc

COX-2

CRP LOX-5↑NFkß

VEGF

Inflammation

BloodViscosity

Angiogenesis

ImmuneCompetence

IL-10

HIF1-αFBG

54

Food is Powerful Medicine“Three times a day,

day after day, we are eating foods

that can influence our genes and help

us fight cancer...”—David Servan-Schreiber, MD

www.Nutritional-Solutions.netJeanne M. Wallace, PhD, CNC

Michelle Gerencser, MS • Patrice Surley, MH, NC

FrequentlyAsked Questions

Vegetarian/Vegan DietVegetarian/Vegan Diet Omnivore/Paleo DietOmnivore/Paleo DietPRO’s CON’s PRO’s CON’s

↑ Phytonutrients

↑ Fiber

↓ nitrates, HCAs & PAHs

↓ Toxins?*

↑ Copper / ↓ Zinc

↓ Protein

↑ Insulin

↓ CLA

↓ Omega-3s

↓ Vit A (retinol)

↓ Copper / ↑ Zinc

↑ Protein

↓ Glycemic

↑ Omega-3

↑ CLA

↑ Vit A (retinol)

↑ Tocotrienols, carotenoids, folate

Excess Omega-6s (if ≠grass-fed sources)

↑ Nitrates, HCAs & PAHs (carcinogens in processed, grilled/charred meats)

↑ Toxins? *

Crowd Out Phyto’s (if ↓ fruit/veggie intake)

Iron Excess?

*Mean DDT residues: vegetarian diet 239µg/person (range 124-288); non-vegetarians 225µg (range 138-263). Sci Total Environ. 1988;76:139–46.*Mean DDT residues: vegetarian diet 239µg/person (range 124-288); non-vegetarians 225µg (range 138-263). Sci Total Environ. 1988;76:139–46.*Mean DDT residues: vegetarian diet 239µg/person (range 124-288); non-vegetarians 225µg (range 138-263). Sci Total Environ. 1988;76:139–46.*Mean DDT residues: vegetarian diet 239µg/person (range 124-288); non-vegetarians 225µg (range 138-263). Sci Total Environ. 1988;76:139–46.

✤ Not estrogen, rather SERM - in vivo competes with estrogen and xenoestrogens

✤ Modulates estrogen via many pathways - ↑ SHBG, ↓ circulating estrogen, ↑ 2:16-OH estrogen ratio

✤ Rodents metabolize soy differently - lower isoflavone conjugation leads to 20-150-fold ↑ circulating levels than in humans

FAQ: Is SOY safe forER+ breast cancer?

Population Findings ReferenceMeta-Analysis:

9,514 US & Asian BrCa pts over

~7.5 yrs

↓Risk of recurrence in those eating soy foods

Am J Clin Nutr. 2012 Jul;96(1):123-32.

3,088 U.S. BrCa pts followed 5 yrs

↓ mortality with increasing intake soy

isoflavones

Cancer Epidemiol Biomark & Prev.  2011;20(5):854-8.

5,042 Asian BrCa pts, followed 5 yrs

↓ risk mortality and ↓ recurrence in those

with higher soy intake

JAMA. 2009 Dec 9;302(22):2437-43.

1,954 U.S. BrCa pts, followed 6 yrs

60% ↓ rate of recurrence with high isoflavone intake in

post-menopausal pts on Tamoxifen

Breast Cancer Res Treat. 2009 Nov;118(2):395-405.

50 human clinical trialsn = 8,521 pts (>5,000 given antioxidants during treatment)No evidence of interferenceEnhanced cytotoxic efficacy of chemotherapyIncreased survival time

Review

Alt Ther Health Med, 2007 Mar-Apr;13(2):40-7.

FAQ: Do antioxidants interfere with cancer treatment?✤ Differential uptake - ↑ intake in cancer cells,

results in pro-oxidant effect

✤ ↑ Oxidation leads to ↑ gene instability - excessive oxidation fosters more aggressive tumor behavior

✤ ↑ Oxidation leads to ↓ cell proliferation - but cytotoxic treatment targets rapidly dividing cells

✤ ↑ Oxidation activates NFkß - which confers radioresistance and chemoresistance

✤ Foods vs supplements - foods have much ↑ORAC (antioxidant effect) than supplements!

80% ↓ risk of progression and 87% ↓ risk of mortality in pts with BOTH ↑ antioxidant status and ↑ biomarkers of oxidation

Oxidation vs Antioxidants: It’s

not a war....

BMC Cancer 2009;9:458-69.