Health Studies Collegium Predictive Biomarkers Master · Health Studies Collegium Predictive Biomarkers Master 1 ... Health Studies Collegium Predictive Biomarkers Master 2 ... 1st

Health Studies CollegiumPredictive Biomarkers Master

1

Health Studies Collegium Foundation

Rethink Health: Stop Fighting Disease-Start Restorative Health

Biological Detoxification

FASCP, FACN, FACAAI,

FOCIS, FAMLI, FRSMSenior Fellow, Health Studies Collegium

Founder and Chairman,

PERQUE™ Integrative Health,

ELISA/ACT™ Biotechnologies,

RMJH Rx

Russell Jaffe, MD, PhD, [email protected] ; drrusselljaffe.com

• What “stop fighting disease” means

• How ‘stop fighting & start healing’ focuses on…

o CAUSES not symptom consequences

o OPPORTUNITIES for fuller recovery

o PREDICTIVE GOAL VALUES not statistical ranges

o BIOLOGICAL DETOXIFICATION

o NATURE, NURTURE, & WHOLENESS

• Successful outcomes

Today’s Insights and Epiphanies

Let’s Rethink Health together!

Conventional view of Health is…

Absence of disease or infirmity

WHO defines Health as…

“highest attainable state of physical,

mental, & social well-being.”

Yet Health evolving…

Lancet, 2009; 373(9666): 781, 7 March.

“WHO definitions of health do not

work in an era marked by new

understandings of disease at

molecular, individual, and societal

levels.”


2

Predictive Biomarker Goals

• Predictive markers to guide therapy

• Goal values for evidence based care

• Add life to years & years to life

• Improve health, improve outcomes, lower costs

and risks

Let’s Rethink Health together! A portmanteau of “biological

marker,” refers to a broad

subcategory of medical signs – i.e.,

objective indications of medical

state observed from outside the

patient – which can be measured

accurately and reproducibly.

Kyle Strimbu & Jorge A. Tavel, M.D. What are Biomarkers? Curr Opin HIV AIDS. 2010; 5(6): 463–466.

Biomarker:

A “predictive biological marker” is a

specific subcategory of analytic

observations, i.e., objective

indications of medical state

observed from outside the patient

that can be measured accurately and

reproducibly while predicting 10

year survival & QoLY.

Modified by Jaffe from Kyle Strimbu & Jorge A. Tavel, M.D. What are Biomarkers? Curr Opin HIV AIDS. 2010; 5(6): 463–466.

Predictive Biomarker:

‘Normal’ Values Predictive Goal Values

Hbg A1c4-6%

Therapy Goal: <7%<5%

hsCRP 1-3 mg/L <0.5 mg/L

Homocysteine 4-17 µmoles/L<6 µmoles/L

LRA NA Immune Tolerance

1st AM urine pH 4.6-8 6.5-7.5

Vitamin D 20-40 ng/mL 50-80 ng/mL

Omega 3 index ND >8%

8 OH dGuanisine4.6-19.2 ng/mg (11.9+/-

7.3 ng/mg)<5ng/mg creatinine

Values: ‘Normal’ vs Predictive Goal

Epigenetics,

Metabolomics &

Microbiomics

High sensitivity / hsAll cause

morbidity &

mortality

Compare therapy

outcomes

Therapeutic

Biomarkers

hsPB


3

High Sensitivity Predictive Biomarkers (hsPB)

Personalized, Evidence-Based, Comparative

hsHgb A1c:

Sugar, insulin… AGEs

hsCRP:

Inflammation, repair

disease

8 oxo-guanine:

Oxidative stress… ALEs

hsHomocysteine:

Methylation, detox…Sulfur

Omega 3:6; EFAs

Omega 3 Index:

Immune Tolerance

hsLRA

Cell talk & adhesion

Vitamin D:

cell acidosis risk

1st AM urine pH:

Jaffe R, Predictive Biomarkers Provide

Evidence for Comparative Effectiveness

Research, HSC 90_13:01 Advisory on

Predictive Medicine & Health

Promotion.

Gruenewald TL, Seeman TE, Ryff CD,

Karlamangla A, Singer BH.

Combinations of Biomarkers Predictive

of Later Life Mortality. PNAS, 2006;

103 (38): 14158-14163.

Chronic Diseases Continue to Rise…

Global Burden of Disease Study 2010. Global Burden of Disease Study 2010 (GBD 2010) Results by Cause 1990-2010 -

Country Level. Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2013.

Chronic

Ill-health

Average

decline

Years of Life

An

y P

hys

iolo

gic

Fu

nc

tio

n

20 40 60 80 100

Maintain life-long repair

Averages deceive; individuals choose

Stop Fighting

Start Healing

Causes rather than Consequences

Sustainable health…

We are what we eat and drink, think and do

Epigenetic health bank account…

replenish or deplete by choices & habits

Start Restorative Healing

Central to health and being well

• Homeostasis

• Essential nutrients to meet individual needs

• Detoxification competences

• Reduce environmental toxin exposures

Eat what you can digest, assimilate, and eliminate without immune burden.


4

Stop Fighting Disease

Start Healing; Identify Opportunity

• Immune system tolerance & delayed allergies

o Inflammation is repair deficit

• Correct individual nutrient deficits

o Predictive Biomarkers and Self Assessments

o Personalize supplement & lifestyle programs

• Safer toxin removal (3 phases)

• Alkaline Way: Nature, Nurture, & Wholeness

Remove obstacles to recovery;

Evoke human healing responses

Predictive Biomarkers (PB) for

Better Clinical Care


PB tests & functional assessments include all

epigenetic risks

Least risk-highest gain goal values rather than

normal lab values

High sensitivity predictive biomarkers =

personalized and higher quality clinical care.

Test Name Test Descriptions Predictive Goal Values

hsHgb A1c

(hsHemoglobin A1c)

Sugar / insulin / energy…

AGE <5%

hsCRP

(hsC-Reactive Protein)

Repair, inflammation

immune status <0.5 mg/L

hsHCY

(hsHomocysteine)

Detox, epigenetic,

methylation… Sulfur < 6 µmol/L

hsLRA

(hsLymphocyte Response

Assay)

Immune memory /

repair tolerance

No delayed

reactions

Essential Predictive Biomarkers

to Determine Functional Age

Predictive Biomarker Tests

to Determine Your Functional Age

Test

Name

Test

Descriptions

Predictive Goal

Values

hsHgb A1c

(hsHemoglobin A1c)

Sugar/insulin/energy… AGE<5%

hsCRP(hsC reactive protein) Repair & inflammation immune status <0.5 mg/L

hsHCY

(hsHomocysteine)

Detox, epigenetic, methylation… Sulfur < 6 µmol/L

hsLRA

(hslymphocyte response assay)Immune memory/immune tolerance No reactions

Ur pH >6º rest

(1st AM Urine pH)

Mineral status &

cell acid/alkaline balance6.5 – 7.5

Vitamin D(25-Hydroxy-cholecalciferol)

Cell communication status50 – 80

ng/mL

Omega-3 Index

(Omega 3/6 EFA ratio)Omega 3:6 ratio; EFAs

>8%

8-OHdG

(8-Oxo-Guanine)Oxidative stress/antioxidant nucleus status

<5 ng/mg

creatinine

Lifetime Health: 92% choices

Modified from: Baccarelli A, et al., Cardiovascular Epigenetics Basic Concepts and Results From Animal

and Human Studies. Circulation: Cardiovascular Genetics. 2010; 3: 567-573.

Jaffe R, Nash R, Ash R, Schwartz N, Corish R, Born T, Lazarus H. An Equation of Health: Role of

Transparency and Opacity in Developing Healthcare Efficacy Measures and Metrics.

J Management Development 2007; 26 (5): 441-458.

Jaffe R. The Alkaline Way: Integrative Management of Rheumatoid Arthritis and Other Autoimmune

Conditions. In: Watson RR, Preedy V, Eds. Bioactive Food as Interventions for Arthritis and Related

Inflammatory Diseases. Academic Press, 2013. p 97-112.

Predictive Biomarker 1

hsHemoglobin A1c =

hsHgb A1c = hsHbA1c


5

Insulin & Blood Sugar Control

Muscle: Fat from sugar

(as energy store);

receptors can be resistant Pancreatic

Islet Cells

Blood

Glucose Insulin

Liver

Highest Quality

of Life

Hgb A1c <5 is Predictive Biomarker

Lowest Quality

of Life

Hinzmann R, Schlaeger C, Tran C T. What Do We Need Beyond Hemoglobin A1c to Get the Complete Picture of Glycemia in People With Diabetes?

Int. J. Med. Sci. 2012; 9: 665-681

Hgb A1c Predicts AG

(Average Glucose; Blood Sugar)

400

AG

(m

g/d

l)

350

300

250

200

150

100

50

03 5 7 9 11 13

Hgb A1c(%)

8%

Hgb A1c / HgA1c Predicts Survival

Bunn HF, Haney DN, Gabbay KH, Gallop PM. Further Identification of the Nature and Linkage of the Carbohydrate in Hemoglobin A1c.

Biochem Biophys Res Commun. 1975; 67(1): 103-109.

Luevano-Contreras C et al, Dietary Advanced Glycation End-Products and Aging. Nutrients 2010; 2: 1247-1265.

Hinzmann R, Schlaeger C, Tran C T. What Do We Need Beyond Hemoglobin A1c to Get the Complete Picture of Glycemia in People with

Diabetes? Int J Med Sci 2012; 9(8):665-681. doi:10.7150/ijms.4520

Gruenewald TL, Seeman TE, Ryff CD, Karlamangla A, Singer BH. Combinations of Biomarkers Predictive of Later Life Mortality. PNAS, 2006;

103 (38): 14158-14163.

5%

6%

7%

9%10%

11%

12%

5.4

7.0

8.610.2 11.8 13.4

14.9

16.5

Blood Glucose

(mmol/L)

Excellent Poor

Hgb A1c >5%, Life Habit Solutions

• Immunotolerant Diet

• 40 Component Super Multi

40+ g Fiber

Hyman M, Mani J, Jaffe R. Diabetes and Insulin Resistance, Food and Nutrients in Primary Care. In: Kohlstadt I, Ed. Advancing Medicine with Food

and Nutrients, 2nd Ed., CRC Press, 2012, p 373-390.

Jaffe, R. Diabetes as an Immune Dysfunction Syndrome. In: Watson RR, Preedy VR, Eds. Bioactive Food as Dietary Interventions for Diabetes,

Academic Press, 2013, p 41-52.

40+ Bn live Probiotics

Hgb A1c >5%, Manage AGEs

Hyman M, Mani J, Jaffe R. Diabetes and Insulin Resistance, Food and Nutrients in Primary Care. In: Kohlstadt I, Ed. Advancing Medicine with Food and

Nutrients, 2nd Ed., CRC Press, 2012. p 373-390.

Jaffe, R. Diabetes as an Immune Dysfunction Syndrome. In: Watson RR, Preedy VR, Eds.

Bioactive Food as Dietary Interventions for Diabetes, Academic Press, 2013. p 41-52.

Herbal symbiotic glucose/sugar regulators

more active forms then micellized for 3X greater uptake

• Standardized corosolic acid, 50 mg*

• Chromium as citrate, 250 mcg*

• Vanadium as ascorbate, 250 mcg*

• French lilac, 150 mg*

• Bitter Melon / Marah, 150 mg*

• Huckleberry / Bilberry, 100 mg*

• Phosphatidylcholine, 71 mcg*

Dose based on

Hgb A1c or

Blood Sugar results


6


High Sensitivity

C Reactive Protein

= hsCRP

31

Chronic Inflammation = Chronic

Disease = Chronic Repair Deficit

Yet Two Americans die

every minute

of avoidablecoronary events

550,000/year

ReThink Systemic Inflammation

Arthritis

Pulmonary

Diseases

Cardio

Diseases

AlzheimerDiabetesAuto-

immune

Disease

Neuro-

logical

Disease

Prion

Diseases

Cancer

Inflammation

Grundy SM, Cleeman JI, Daniels SR, Donato KA et. al., Diagnosis and management of the metabolic syndrome:

An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation, 2005;112(17):2735-2752.

Kahn R, Buse J, Ferrannini E, Stern M et. al., The Metabolic Syndrome: Time for a Critical Appraisal: joint statement from the American Diabetes Association and

the European Association for the Study of Diabetes. Diabetes Care. 2005 Sep;28(9):2289-2304.

Jaffe R, Mani J. Rethink Health: Inflammation Is Actually Repair Deficit: Using Physiology First to Achieve Better Outcomes, Part 1: Value and Importance of

Understanding Inflammation as Repair Deficit. Townsend Letter for Doctors and Patients. 2013, Jun (359): 68-74.

Chronic Inflammation = Chronic

Disease = Chronic Repair Deficit (cont’d)

2015 US:

40 MM diabetics

100 MM pre-diabetics

By 2025:

65 MM Diabetics &

130 MM pre-diabetics

hsCRP is Body’s Cry For Repair

Adapted from Zwaka TP,, et al. Circulation 2001; 103; 1194-1197.

Silva D, Pais de Lacerda A. High-sensitivity C-reactive Protein as a Biomarker of Risk in Coronary Artery

Disease, Rev Port Cardiol. 2012; 31: 733-745

CRP-Mediated Uptake of LDL by Macrophages

ARIC, Circulation 2004;109:837-842

Interaction of CRP & Lp-PLA2 CHD Risk

in ARIC Study

C M Ballantyne, R C Hoogeveen, H Bang, J Coresh, A R Folsom, G Heiss, A R Sharrett, Lipoprotein-Associated Phospholipase A2, High-Sensitivity C-

Reactive Protein, and Risk for Incident Coronary Heart Disease in Middle-Aged Men and Women in the Atherosclerosis Risk in Communities (ARIC) Study

Circulation. 2004; 109: 837-842.

Multiply

risk when

Lp-PLA2

and CRP

levels

increase

Low risk

when

Lp-PLA2

levels

are low

3X

Rela

tive R

isk f

or

CH

D

3

2.5

2

1.5

1

.5

0

Low-Medium LpPLA2

High LpPLA2


7

JUPITER Trial: Rosuvastatin 20 mg in Older,

Normolipidemic Subjects w/ ↑ hsCRP, N=17,802

Predictive Value of Multiple Biomarkers

• Men >50, women >60 years old CVD/DM (mean 66)

• LDL <130 (TC 186, LDL 108, HDL 49, TG 118)

• hsCRP >2 mg/L (mean 4.3)

• BMI 28, BP 134/80, FBG 94, Hgb-A1C 5.7%

• Metabolic syndrome 41%

• 13.6% 10-yr CV risk with placebo (intermediate)

• Study stopped early (1.9 years)*

* Ridker PM, The JUPITER Trial Results, Controversies, and Implications for Prevention

Circulation: Cardiovascular Quality and Outcomes. 2009; 2: 279-285

hsCRP <0.5 is Predictive Biomarker

Ridker PM, Wilson PWF, Grundy SM. Circulation 2004; 109; 2818-2925

Calculated Framingham 10-Year Risk

Actual Cardiovascular Events

Compared with Framingham Estimate

Card

iovascu

lar

Even

ts

+ hs-CRP in the WHS

0%

5%

10%

15%

20%

25%

30%

0-1% 2-4% 5-9% >10

<1.0

1.0-3.0

>3.0

2X

Ridker PM et al, N Engl J Med, 2002;347:1557

2.2X

1.3X1.9X

hsCRP Measures Repair Need

Inflammation in pathology =

Repair deficit in physiology

Healthy body repairs w/o hsCRP… ‘cry for help’

Vavuranakis M, Kariori MG, Kalogeras KI, Vrachatis DA, Moldovan C, Tousoulis D, Stefanadis C. Biomarkers as a Guide of Medical Treatment in

Cardiovascular Diseases. Curr Med Chem. 2012; 19(16): 2485-2496.

Silva D, Pais de Lacerda A. High-sensitivity C-Reactive Protein as a Biomarker of Risk in Coronary Artery Disease, Rev Port Cardiol. 2012; 31: 733-745.



ReThink Systemic Inflammation

Arthritis

Pulmonary

Diseases

Cardio

Diseases

AlzheimerDiabetesAuto-

immune

Disease

Neuro-

logical

Disease

Prion

Diseases

Cancer

Inflammation

Grundy SM, Cleeman JI, Daniels SR, Donato KA et. al., Diagnosis and management of the metabolic syndrome:

An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation, 2005;112(17):2735-2752.

Kahn R, Buse J, Ferrannini E, Stern M et. al., The Metabolic Syndrome: Time for a Critical Appraisal: joint statement from the American Diabetes Association and

the European Association for the Study of Diabetes. Diabetes Care. 2005 Sep;28(9):2289-2304.



High Sensitivity C-Reactive Protein

(hs-CRP)

Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. New Engl J

Med. 1997; 337(4): 230-236.

Calc

ula

ted

Fra

min

gh

am

10-Y

ear

Ris

k S

co

re 10-20

5-10

<5

<0.5 20 40 60 >80

Pro

bab

ility o

f Liv

ing

10 Y

ears

>20

80%

99%

hs-CRP mg/L

Inflammation vs Probability of Living 10

Years

60%

20%

40%


8

Oxidation Markers as

Predictive Biomarkers

43

Middleton E, et. al. The Effects of Plant Flavonoids on Mammalian Cells: Implications for Inflammation,

Heart Disease and Cancer. Pharmacol Rev, 2000; 52: 673-751.

Kim Y J, Park H J, Yoon S H, Kim M J, Leem K H, Chung J H, Kim H K. Anticancer Effects of Oligomeric

Proanthocyanidins on Human Colorectal Cancer Cell Line, S

NU-C4 World J Gastroenterol. 2005; 11(30): 4674-4678.

Jaffe R, Mani J. Clinical Evidence in Favor of Specific Polyphenolics. In: Watson RR, Preedy

VR, Zibadi S, Eds. Polyphenols in Human Health and Disease, Academic Press, 2013: 695-705.

Polyphenolic Ascorbate

Synergists

Flavonoids & Flavanols

hsCRP Pro-Repair Antioxidant Nutrients

Jaffe R, Mani J. Clinical Evidence in Favor of Specific Polyphenolics. In: Watson RR, Preedy VR, Zibadi S, Eds.

Polyphenols in Human Health and Disease, Academic Press, 2013, 695-705.

Jaffe R. Cardioprotective Nutrients. In: Watson RR, Preedy VR, Eds. Bioactive Food as Dietary Interventions in

Cardiovascular Disease. Academic Press, 2013. p 103-119.

Purer, uncontaminated,

micellized = better uptakeAscorbates & Live Greens GGOBE

Butyrates

& EPA/DHA6

Only 100% l-ascorbate,

fully reduced & buffered

1

Personal C

Cleanse

BioDetox4

Polyphenolics

Dark fruits;

super foods2

High sulfur

foods5

Balanced

Natural Forms

B methyl

cofactors3

• 3 grams; 1 tsp

• Every 15 min

• 12 grams / hour

• 1.5 grams; ½ tsp

• Every 15 min

• 6 grams / hour

Individual Ascorbate

Based on Oxidative Stress

Healthy Moderate Ills

• 6 grams; 2 tsp

• Every 15 min

• 24 grams / hour

Chronic Ills

Ascorbate Calibration± Probiotics, recycled Glutamine, Mg, Polyphenolics

• Health Studies Collegium, Joy in Living The Alkaline Way, 20th ed. 1990-2015. • Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85-94.

• Level of Evidence III and IV

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%<

4

5-1

0

11-1

5

16

-20

21

-25

26

-30

31

-35

36

-40

41

-45

45

-50

50

-60

61

-70

71

-80

81

-90

91

-10

0

10

1-1

10

11

1-1

20

12

1-1

30

13

1-1

40

14

1-1

50

15

1-1

60

16

1-1

70

17

1-1

80

18

1-1

90

19

1-2

00

>2

00

Ascorbate needs from 4-100+ g/day

Jaffe R. Cardioprotective Nutrients. In: Watson RR, Preedy VR, Editors Bioactive Food

as Dietary Interventions in Cardiovascular Disease. Academic Press, 2013, 103-119.

% S

ub

jects

Ascorbate Calibration Amount (gm)

Individual Ascorbate Need Based on Calibration (gm)

Based on Jaffe Protocol 1987-2017

~5%(185) <4 gm (healthy);

~10% (348) from 5-10 gm (usual)

~80% (2798) from 10-130 gm (walking worried/wounded)

~5% (166) > 130 gm (multiple chronic diseases)


Homocysteine; hsHCY

2-Amino-4-sulfanylbutanoic acid

47

Homocysteine <6 is Predictive Biomarker

Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma Homocysteine

Levels and Mortality in Patients with Coronary Artery Disease. NEJM. 1997; 337(4): 230-236.

http://www.ncbi.nlm.nih.gov/pubmed/16373990


9

Healthy Methylation: B Complex, C

Arch Chem. 2004; 50: 3-32. Arch Intern Med 2003; 163: 1933-1937. NEJM. 2002; 346: 476-483.

Schroecksnadel K, et. al. Hyperhomocysteinemia & Immune Activation. Clin Chem Lab Med 2003;

41(11):1438-1443.

0%

50%

100%

150%

200%

Difference in Senility Risk

Se

nilit

y R

isk

(%

)

Relative Risk of Senility in

Relation to Homocysteine Levels

Difference in Five-Year Mortality Risk

0%

200%

400%

600%

800%

1000%

Relative Risk at

Different Homocysteine Levels

Re

lati

ve

Ris

k (

%)

Methylation cofactors

delivered in lingual dots

hsHomocysteine

50

WHAT IF?

*Essentially Not Detectable.

Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma

homocysteine levels and mortality in patients with coronary artery disease.

New Engl J Med. 1997; 337(4): 230-236.

CV

D

0.6

0.4

ND*

<6 mol/L

Pro

bab

ility o

f Liv

ing

10 Y

ears

>0.9

90%

99%

Cardiovascular Disease (CVD) vs

Probability of Living 10 Years

80%

60%

40%

<9 mol/L <12 mol/L <15 mol/L <18 mol/L

Effect on homocysteine levels: 2 lozenges/day

hsHomocysteine < 6µmol/l is goalOral injection: hydroxocobalamin B12 + folates + B6

Genqing Liang, Jamie Larkin, Russell Jaffe. Healthier homocysteine levels using oral methylation factors AACC/ASIP posters

Jaffe R, Mani J. Clinical Evidence in favor of specific polyphenolics. In: Watson RR, Preedy VR, Zibadi S, Eds. Polyphenols in

Human Health and Disease, Academic Press, 013, 695-705.

p<0.055

6

7

8

9

10

11

12

13

14

0 Month 3 Month

Ho

mo

cyst

ein

e Patient 1

Patient 2

Patient 3

Homocysteine < 6µmol/l is goalAscorbates, Polyphenolics & Probiotics

1. Super multi/mineral w/40 actives; o Keep urine sunshine yellow

2. Vitamin C powder and tabsules 100% buffered, fully reduced l-ascorbate w/ K+, Zn++, Mg++ & Ca++

o Amount based on ‘C Cleanse’

3. Polyphenolics: Quercetin dihydrate + soluble OPC

4. Recycled Glutamine w/PAK

5. Magnesium as glycinate, ascorbate, & citrate w/ Choline Citrate to enhance uptake; o 1st AM urine pH

6. Fermented foods (40 g) and 40-60+ Bn probiotics /day

Alpha & Beta Carotene,

Astaxanthin,

Zeaxanthin,

Cryptoxanthin,

Lutein,

Lycopene

hsHomocysteine < 6µmol/l is goalLifely Colors: Carotenoids & B Complex

Chew B P, Park J S. Carotenoid Action on the Immune Response. J Nutr. 2004 Jan; 134(1): 257S-261S.

D'Adamo C R, Miller R R et al. Higher Serum Concentrations of Dietary Antioxidants are Associated with Lower

Levels of Inflammatory Biomarkers During the Year After Hip Fracture. Clin Nutr. 2012 Oct; 31(5): 659-665

Brady J, Holford P. Homocysteine Revisited the H Factor Solution, BHP, N Bergen, NJ, 2003

Jaffe R, Mani J. Clinical Evidence in favor of specific polyphenolics. In: Watson RR, Preedy VR, Zibadi S, Eds.

Polyphenols in Human Health and Disease, Academic Press, 2013, 695-705.

As part of

comprehensive liver

detox sylimarin,

carnitine fumarate,

CoQ10, carotenoids

micellized softgel

Mixed Natural

Carotenoids:

Targeted Supplementation

Chew B P, Park J S. Carotenoid Action on the Immune Response. J Nutr. 2004 Jan; 134(1): 257S-261S.

D'Adamo C R, Miller R R et al. Higher Serum Concentrations of Dietary Antioxidants are Associated with Lower Levels of Inflammatory Biomarkers During the

Year After Hip Fracture. Clin Nutr. 2012 Oct; 31(5): 659-665

Brady J, Holford P. Homocysteine Revisited the H Factor Solution, BHP, N Bergen, NJ, 2003

Jaffe R, Mani J. Clinical Evidence in favor of specific polyphenolics. In: Watson RR, Preedy VR, Zibadi S, Eds. Polyphenols in Human Health and Disease,

Academic Press, 013, 695-705.

For healthy methylation

• Vitamin B12 (hydroxocobalamin)

• B6

• Mixed natural folates

Lingual dot for optimum uptake

Comprehensive antioxidants

• Pure sylimarin

• CoQ10

• Mixed natural carotenoids

• Mixed natural tocopherols

Micellized in a softgel for

increased uptake

hsHomocysteine < 6µmol/l is goalLifely Colors: Carotenoids & B Complex


10

Garlic, ginger, onions, broccoli sprouts, eggs

GGOBE, Sulforaphane, IP6, minerals

Glutamine recycled by PAK cell energy repair

Homocysteine

BioDetox Super Foods

Jaffe, R. Diabetes as an Immune Dysfunction Syndrome. In: Watson RR, Preedy VR, Eds.

Bioactive Food as Dietary Interventions for Diabetes, Academic Press, 2013, 41-52.


Immune Tolerance

Lymphocyte Response Assays

hsLRA

56

Functional Immunology

• Immune system = amplified response to foreigners

• Inflammation = repair deficit; toxin / immunotoxin load

• Delayed allergies require cell culture ex vivo hsLRA tests

to distinguish helpful from harmful defenses

• Comprehensive detoxification & immune repair:

- Eat, Drink, Think, Do

Personalized lifestyle repair

Proactive primary prevention in practice

Your Immune System

Defends & Repairs

Defense Repair

Immune System: IDRS

• Human immune system:

* Innate: Repair & cancer deletion

* Adaptive: Defense & Repair

• Over burdened immune system…

Hidden (delayed) hypersensitivity/allergy

Compare delayed allergy/hypersensitivity tests

http://youtu.be/cJU7ZaWe5-o

1st line Innate

Immune System (nonspecific, surveillance)

Engulfs, recycles, renews

2nd line Adaptive

Immune System (specific, acquired)

Protects / remembers re-exposure

Helper/Suppressor cells:

Th1/Th2 lymphocytes

Bacteria-killing substances

Skin protects outside

Mucous membranes

protect inside

Innate tissue response…

Scavenger cells recycle

Antibodies

B lymphocytes

Defense WBCs

Immune System: Defends & Repairs

http://youtu.be/cJU7ZaWe5-o


11

Innate Immune System

Skin, Nose, Mouth,

Lungs, GI Tract

Many microbiomes…

repairs & anti-cancer

as able.

Eliminate foreign invaders before they get in

Natural Killer Cell & Virus-cell

Adaptive

Immune

System

Blood, Lymph & tissue systems

Utilizes memory & antibody mechanism: specific.

Attacks invaders that get inside.

Natural

Artificial

Passive (maternal)

Active (infection)

Passive

(antibody transfer)

Active

(immunization)

Adaptive Immune System Antibodies: Specific B Cell Response

• Binds to immobilize

foreign antigen

• Only when too much

work for recycling

innate system to do

• Only when under stress

• More likely when lack

of protective nutrients

Lymphocytes

Delayed immune system life-long memory carriers:o Detect foreign ‘antigens’

o Activate immune system

o Energetically and nutritionally costly… like running molecular marathon

B Cells

T Cells

B Lymphocytes: Free Ag stimulates Ab

• From bone marrow stem cells

• B cells migrate to lymphoid organs

• Recognize antigens from cell receptors

• Basis for antibody-mediated immunity

B Cells

Dividing


12

T Lymphocytes: Th1/Th2 Helpers, CT, NK

4 main subsetso T Helper… response

o T Suppressor…

response

o CT

Cytotoxic/suppressor

o NK (natural killer)

“T” for thymus… no Ab

No allergies… tolerance

Neutralize infections & allergens

Defends then repairs daily wear/tear

50 Bn Dendritic WBCs recycle 50 pathogens/cell

A Healthy Immune System


Start Restorative Healing

Immune system

tolerance

&

delayed

allergies cost

Identify Hidden Immune Burdens

Delayed Allergies: Symptoms

in Hours to Weeks

History/Serology

not helpful

Type II – Reactive Antibody; B-Cell

Type III – Immune Complex; vasculitis

Type IV – T-Cell Mediated

Tests of Delayed Hypersensitivity

Ex Vivo• Lymphocyte response assays:

o hsLRA <3% !

In Vitro• Antibody (IgG, Serology) tests:

o Static, misleading

• Particle size tests:

o Random, misleading

• Cytokine release:

o Interesting technology

LRA tests clinically indicated for All…

• Autoimmune conditions

• Chronic inflammatory conditions

• Chronic degenerative conditions

• Distinguish immune tolerance & intolerance


13

Hidden Immune Burdens

Delayed hypersensitivities/allergies hard to find.

Symptoms occur…

Symptoms often not specific… reactors drain vitality;

unwell; get up and go got up and went

3 Hours to 3 Weeks

After exposure

75% immune system within gut: Peyer’s patchs

Leaky Gut

Microbiome Essentials

• Prebiotic fibers:

40-100 g/day; 80:20::soluble:insoluble

• Probiotic bugs:

40-100 billion CFU/day; live, dairy free medium

• Symbiotics: Recycled Glutamine

1.5-6 g/day taken on rising, before bed &/or exercise

75

Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota. Introducing the concept of prebiotics. J Nutr

1995;125:1401–1412.

Xue H, Sufit AJ, Wischmeyer PE. Glutamine therapy improves outcome of in vitro and in vivo experimental colitis models. JPEN J Parenter

Enteral Nutr. 2011 Mar;35(2):188-197.

Gibson GR, Collins DM, Concept of Balanced Colonic Microbiota, Prebiotics, and Synbiotics". in "Probiotics, other nuritional factors, and

intestinal microflora", Nestle Nutrition Workshop Series, Vol. 42, Lippincott-Raven, Philadelphia, 1999.

GI Transit Time Measurement

Activated Charcoal, 2 caps/50 #

6-12 caps (1.5-3 g)

+ 8 oz water between meals

Goal: 12-18

hours intake to

excretion

Usual: 72-144 hours

Kim ER, Rhee P-L, How to Interpret a Functional or Motility Test, J Neurogastroenterol Motil, 2012; 18(1): 94-99

Jaffe R, Evaluating GI Transit time, Holistic Primary Care, 2010, Winter edition 11(4).

Jaffe R, Evaluating GI Transit time . Holistic Primary Care (Online News for Health and Healing), 2010, Winter edition 11(4).

Average: ≥ 36-96++ hours

• toxin reabsorb

• drain metabolism

• chronic GI or systemic illness

Healthy: 12-18 hours

Short: <10 hours

• malabsorption

• malnutrition

GI Transit Time

77

Activated Charcoal

6-12 caps

(1.5-3 grams charcoal)

+ 8 oz water

between meals

<150 lbs: 6 caps

150 – 200 lbs: 8 caps

200- 250 lbs: 10 caps

>250 lbs: 12 caps

GI Transit Time


14

Tests of Delayed Hypersensitivity








o hsLRA <3%

Particle Size Tests

➢ Particle size tests (automated cytotoxic):

o Device measures blood particles

➢ Detect Any particle 10 micron in size…

not just reactive lymphocytes

o Lots of 10 µ particles in blood…

Rouleaux RBC, platelet clumps, granulocyte debris…

o Low specificity, not predictive

o Not reproducible

Hodsdon, W, Zwickey H. Reproducibility and Reliability of Two Food Allergy Testing Methods,

Natural Medicine Journal, 2010; 2(3): 8.

Lymphocyte Response Assays

(hsLRA <3% variance on results)

hsLRA (ELISA/ACT™ method)

• Directly observe lymphocytes under conditions

similar to body (ex-vivo)

• ALL 3 delayed allergy paths

• Advanced method

few false positives (<1%)

• Intolerances (if any) can then

be detected & digestion strengthened

hsLRA Cell Culture Tests

Non-reactive

lymphocytes

Olympus SC35 Magnification 600x

Reactive

lymphocytes

Hyman M, Mani J, Jaffe R. Diabetes and Insulin Resistance, Food and Nutrients in Primary Care. In: Kohlstadt I, Ed. Advancing Medicine with Food and Nutrients, 2nd Ed., CRC Press, 2012.p 373-390.

hsLRA

Comprehensive

Functional

Ex-Vivo

www.DrRussellJaffe.com

www.HealthStudiesCollegium.org

Hypersensitivity/Allergy Types

Immediate AllergiesType I – Acute, RAST (IgE) Histaminic

Delayed AllergiesType II – Reactive Antibody; B-Cell

Type III – Immune Complex; vasculitis

Type IV – T-Cell Mediated

Delayed/hidden allergies

HARD to identify by

history / serology

http://www.DrRussellJaffe.com


15

Lymphocyte Response Assay

(Amplified Advanced Cell Culture Test)

Ex vivo sample for >500 cell cultures:

• Foods, additives / preservatives

• Environmental chemicals

• Toxic minerals/heavy metals:

• Medications

• Molds

• Danders, hairs, and feathers

• Herbs

Health Assessment Questionnaire (HAQ)

➢ Personalized

recommendations based on

Health Assessment

Questionnaire:

• Supplements

• Activity & environment

recommendations

• Rotation diet option

➢ Joy in Living:

The Alkaline Way

Stop Fighting

Start Healing

Outcome Evidence

Community based FM study

• Substitute for immunoreactive substances

identified by LRA by ELISA/ACT tests

• Correct nutritional deficiencies that reduce defense

and repair abilities

• Initiate detox mechanisms that remove xenotoxins

for individual

• Concentrate on enhancing human healing

response

Multiple Successful Outcome Studies

“A Novel Treatment for Fibromyalgia Improves

Clinical Outcomes in a Community-Based Study”

• 50% less pain

• 70% less depression

• 50% more energy

• 30% less stiffness

Jaffe RM, Deuster PA. A Novel Treatment of Fibromyalgia Improves Clinical Outcomes in a Community-Based Study. Journal of

Musculoskeletal Pain, Vol. 6, No. 2.

Case-Controlled Outcome Study:

? 3 mos. placebo

effect

RELATIVE

OUTCOME

Jaffe RM, Deuster PA. A Novel Treatment of Fibromyalgia Improves Clinical Outcomes in a

Community-Based Study. Journal of Musculoskeletal Pain, Vol. 6, No. 2.

90

Overall Health Scores Change in Study Subjects


16

“Tolerance loss in diabetics:

Link with foreign antigen exposure”

• >1 % in HbA1C levels in bothType 2 & Type 1 diabetes

• 18% reduction of insulin levels in Type 2 diabetes

Jaffe R, Mani J, DeVane J, Mani H. Tolerance loss in diabetics: Association with foreign antigen exposure. Diabetic

Medicine: Journal British Diabetic Association 2006 Aug; 23(8): 924-925.

hsLRA: Successful Diabetes StudiesComparison of immuno-reactants in

Type 1 and Type 2 diabetes

69

46

69

15

27

28

80

92

56

28

0 20 40 60 80 100

Cow dairy

Additives

Env Chem

Toxicminerals

SweetenersType 1 DM

Type 2 DM

Jaffe R, Mani J, DeVane J, Mani H. Tolerance loss in diabetics: Association with foreign antigen exposure. Diabetic Medicine: : A Journal of the British

Diabetic Association 2006 Aug;23(8): 924-5.

Candidate Predictive Biomarker 5

Metabolic Acidosis Risk

Mineral Status &

pH [Ur]

93

1st AM Ur pH

Seifter JL. Integration of acid-base and electrolyte disorders.

N Engl J Med.2015 Jan 22;372(4):391-2. Integration of acid-base and

electrolyte disorders.

Julian Seifter

After six or more hours rest,

the urine fluid equilibrates

with the GU tract lining cells.

Clinically useful assessment

of metabolic acidosis risk and

intracellular mineral (K & Mg)

1st AM Ur pH as Predictive Biomarker

• Status: cell acids & minerals

• Enzyme catalysts pH sensitive

Jaffe R. The Alkaline Way in Digestive Health. In: Watson RR, Preedy VR, Eds. Bioactive Food as Dietary Interventions in Liver and Gastrointestinal Disease. Academic Press, 2013, 1-21.

• Protein efficiency

>90+% or <10%

• Mg++ forgotten

electrolyte

pH: Cells Elective Protection or Survival

Siggaard-Andersen Acid-base Nomogram

Siggaard-Andersen, O. Therapeutic Aspects of Acid-Base Disorders. Modern Trends in Anaesthesia, Ed.

EVANS & GRAY, Butterworths, 1967, Vol. 3, 99p.


17

Urine >6º rest

Excess acid

wears you out

Too Acidic

(<6.5)

Healthy Repair /

Restore Zone

Healthy pH

(6.5-7.5)

Catabolic illness

tears you down

Too Alkaline

(>7.5)

Jaffe R, Mani J. Clinical Evidence in Favor of Specific Polyphenolics. In: Watson RR, Preedy VR & Zibadi S, Eds. Polyphenols in Human Health and Disease,

Academic Press, 2013: 695-705

Predictive Goal Value = pH 6.5 – 7.5

Metabolic Acidosis Risk

Buffering Mineral Need vs Probability of Living 10 Years

Metabolic

Acidosis

Catabolic

Ammonia Loss

Bu

fferi

ng

Cap

acit

y %

[Ce

llu

lar

Min

era

ls]

60

80

90

100

<5 5.5 6.5 7.5 >9

Pro

ba

bility

of L

ivin

g 1

0 Y

ea

rs

40

.99

.75

.60

.90

.95

6 7 8 8.5

pH (Urine >60 Rest)

Alkaline Way

Mg++ /

Choline

Citrate, etc.

Biomarkers Solutions:

Magnesium, Mg++

+

Jaffe R, Uptake of Magnesium with Choline Citrate

Level of evidence: III & IV

• Obesity

• Distress

• Metabolic syndrome

• Chronic pathogen

• Repair deficit =

Inflammation

Evidence of toxic eating: 50+% have

Functional Detoxification Need

All pregnant women (US)

exposed to 43+ xenotoxins

2000 v 1900: Industrial

chemicals >15-fold

( 1500%!)

• Board of Governors of the Federal Reserve System.

Industrial capacity and capacity utilization. G.17 (419).

Washington, DC: Board of Governors of the Federal

Reserve System; 2013. http://www.federalreserve.gov/

• Woodruff TJ, Zota AR, Schwartz JM. Environmental

chemicals in pregnant women in the United States:

NHANES 2003-2004. Environ Health Perspect

2011;119:878–85

Evidence POPs harm

“These findings suggest, that for girls, prenatal

exposure to POPs may play a role for later

development of metabolic diseases by affecting the

level of insulin.”Tang-Péronard JL, Heitmann BL, Jensen TK, Vinggaard AM, Madsbad S, Steuerwald U, Grandjean P, Weihe

P, Nielsen F, Andersen HR.Prenatal exposure to persistent organochlorine pollutants is associated with

high insulin levels in 5-year-old girls. Environ Res. 2015 Jul 29;142:407-413.

“We conclude that cytoskeletal proteins and their processing,

glucose metabolism, and mRNA processing may represent

targets affected by exposure to conditions hostile to

pancreatic beta cells, including exposure to DDT and DDE.”Pavlikova N, Smetana P, Halada P, Kovar J Effect of prolonged exposure to sublethal concentrations of

DDT and DDE on protein expression in human pancreatic beta cells. Environ Res. 2015; 14(142):257-263.

http://www.federalreserve.gov/


18

Healthy Detox Specific & Systemic Relief

103

1º detox

Back up removal

Biological Detoxification:

Physiology 1st, Better Outcomes

• Functional, Integrative BioDetox in practice:

• Cautionary Principle: Use nature’s pharmacy first

• Inform, inspire, & motivate by example & with examples

Integrative Detox Assessments

Other Personal detox measures:

1. d-glucaric acid [Ur]

2. Mercapturic acid [Ur]

3. d-penicillamine provocation

Ur essential & toxic min

.

Stephen B. Edelson. Autism: Xenobiotic Influences. Toxicol Ind Health, September 1998 vol. 14 no. 4, 553-563.

Inhibition of mercapturic acid pathway-mediated disposal of 4-hydroxynonenal causes complete and sustained remission of human

cancer xenografts in nude mice. Indian Journal of Experimental Biology Vol. 49, November 2011, pp. 817-825

Jaffe R, HSC d-penicillamine Protocol, 87-05.

Esteller M. Lancet Oncol, 2003; 4: 365-372

Jaffe R. Int Clin Nut Rev, 1990; 10: 265-266

Integrative Detox Assessments

Other Personal detox measures:

1. d-glucaric acid [Ur]

2. Mercapturic acid [Ur]

3. d-penicillamine provocation

Ur essential & toxic min

.

Stephen B. Edelson. Autism: Xenobiotic Influences. Toxicol Ind Health, September 1998 vol. 14 no. 4, 553-563.

Inhibition of mercapturic acid pathway-mediated disposal of 4-hydroxynonenal causes complete and sustained remission of human

cancer xenografts in nude mice. Indian Journal of Experimental Biology Vol. 49, November 2011, pp. 817-825

Jaffe R, HSC d-penicillamine Protocol, 87-05.

Esteller M. Lancet Oncol, 2003; 4: 365-372

Jaffe R. Int Clin Nut Rev, 1990; 10: 265-266

Compare

Provocation

D-Pen

EDTA

DMPS

DMSA

OSR

Garlic, ginger, onions, broccoli sprouts, eggs

GGOBE, Sulforaphane, IP6, minerals

Glutamine recycled by PAK cell energy repair

BioDetox Super Foods

Jaffe, R. Diabetes as an Immune Dysfunction Syndrome. In: Watson RR, Preedy VR, Eds. Bioactive Food as Dietary Interventions for Diabetes, Academic

Press, 2013, 41-52.


19


Start Restorative Detoxification

Safer toxin removal (3 phases)

Phase I... metabolism Phase II... conjugation Phase III...lipotropic

Pro Repair / Pro Detox Nutrients

Purer, uncontaminated,

micellized = better uptake

Omega 3:

EPA/DHA

6

Only 100% l-ascorbate,

fully reduced & buffered

Personal C Cleanse

1

Whole Greens

BioDetox

4

Polyphenolics

Dark fruits;

super foods

2

GGOBE

High sulfur foods

5

Jaffe R, Mani J. Clinical Evidence in Favor of Specific Polyphenolics. In: Watson RR, Preedy VR, Zibadi

S, Eds. Polyphenols in Human Health and Disease, Academic Press, 2013, 695-705.

Jaffe R. Cardioprotective Nutrients. In: Watson RR, Preedy VR, Eds. Bioactive Food

as Dietary Interventions in Cardiovascular Disease. Academic Press, 2013. p 103-119.

Balanced

Natural Forms

B methyl cofactors

3

White C C, Viernes H, Krejsa C M, Botta D, Kavanagh, T J. Fluorescence-based microtiter plate assay for

glutamate–cysteine ligase activity. Analytical Biochemistry 2003; 318 (2): 175–180.

Sulfur amino acids + lipotropics + minerals

Sulfur-containing amino acids

• Cysteine / Cystine

• Methionine / Homocysteine

Boost immune function

Neutralize cell acid

Methylate; transport

Detoxifies, build glutathione, radioprotective...

Liver / Organ Detox support

• Beat oxidative stress!!

Micellized softgel with Silymarin

+ mixed natural carotenoids

+ tocopherols + CoQ10 + D3

• Protects & repairs liver, spleen, kidney

1. Hajaghmohammadi AA, Ziaee A, Rafiei R, The Efficacy of Silymarin in Decreasing Transaminase Activities in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial, Hepatitis Monthly, 2008; 8(3): 191-195.

2. Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T, Silymarin attenuated the amyloid β plaque burden and improved

behavioral abnormalities in an Alzheimer's disease mouse model. Biosci Biotechnol Biochem. 2010 Nov 23;74(11): 2299-2306.

3. Galhardi F, Mesquita K, Monserrat JM, Darros DM, Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat

brain. Food Chem Toxicol. 2009 Oct;47(10):2655-2660.

EPA/DHA

• Distilled, Nitrogen protected

• Fat soluble toxins gone

• Restores cell membrane flexibility

• Toxic minerals gone

• Magnesium protects EFAs

Personalized detox liver spleen support

30-60 day comprising of

• Sulfur amino acids + lipotropics + minerals

• Omega 3 good fats: EPA and DHA

• Buffered ascorbates

• Prebiotics, Probiotics & Symbiotics


20

Abdollahzad H, Eghtesadi S, Nourmohammadi I, Khadem-Ansari M, Nejad-Gashti H, Esmaillzadeh A. Effect of vitamin C supplementation on

oxidative stress and lipid profiles in hemodialysis patients. Int J Vitam Nutr Res.2009 Sep;79(5-6):281-7.

Ryan MJ, Dudash HJ, Docherty M, Geronilla KB,Baker BA, Haff GG, Cutlip RG Alway SE. Vitamin E and C supplementation reduces oxidative

stress, improves antioxidant enzymes and positive muscle work in chronically loaded muscles of aged rats. Exp Gerontol.2010 Nov;

45(11):882-95.

Englard S, Seifter S. The biochemical functions of ascorbic acid. Annu Rev Nutr. 1986;6:365-406

Jaffe R, Brown S. Acid-Alkaline balance and its Effect on Bone Health. Intl J Integrative Med, 2000; 2 (6): 7-18.

Universal antioxidant

• L-Ascorbate 100% reduced & buffered

• Repairs & renews better

• Universal maternal antioxidant

Ascorbate: Toxic Mineral Excretion

Pump toxins out more safely…

• 3 grams; 1 tsp

• Every 15 min

• 12 grams / hour

• 1.5 grams; ½ tsp

• Every 15 min

• 6 grams / hour

Assess Individual Ascorbate Need

Based on Oxidative Stress

Healthy Moderate Ills

• 6 grams; 2 tsp

• Every 15 min

• 24 grams / hour

Chronic Ills

Ascorbate Calibration± Probiotics, recycled Glutamine, Mg, Polyphenolics

• Health Studies Collegium, Joy in Living The Alkaline Way, 20th ed. 1990-2015.

• Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85-94.

• Level of Evidence III and IV

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%<

4

5-1

0

11-1

5

16

-20

21

-25

26

-30

31

-35

36

-40

41

-45

45

-50

50

-60

61

-70

71

-80

81

-90

91

-10

0

10

1-1

10

11

1-1

20

12

1-1

30

13

1-1

40

14

1-1

50

15

1-1

60

16

1-1

70

17

1-1

80

18

1-1

90

19

1-2

00

>2

00

Ascorbate needs from 4-100+ g/day

Jaffe R. Cardioprotective Nutrients. In: Watson RR, Preedy VR, Editors Bioactive Food

as Dietary Interventions in Cardiovascular Disease. Academic Press, 2013, 103-119.

% S

ub

jects

Ascorbate Calibration Amount (gm)

Individual Ascorbate Need Based on Calibration (gm)

Based on Jaffe Protocol 1987-2017

~5%(185) <4 gm (healthy);

~10% (348) from 5-10 gm (usual)

~80% (2798) from 10-130 gm (walking worried/wounded)

~5% (166) > 130 gm (multiple chronic diseases)

Food Effects on Body Chemistry

Jaffe R. The Alkaline Way in Digestive Health. In: Watson RR, Preedy VR, Eds. Bioactive Food as Dietary Interventions

in Liver and Gastrointestinal Disease. Academic Press, 2013, 1-21.

http://www.health.harvard.edu/mind-and-mood/relaxation-techniques-breath-control-helps-quell-errant-stress-responseGerbarg PL1, Jacob VE, Stevens L, Bosworth BP, Chabouni F, DeFilippis EM, Warren R, Trivellas M, Patel PV, Webb CD, Harbus

MD, Christos PJ, Brown RP,Scherl EJ. The Effect of Breathing, Movement, and Meditation on Psychological and Physical Symptoms

and Inflammatory Biomarkers in Inflammatory Bowel Disease: A Randomized Controlled Trial. Inflamm Bowel Dis. 2015 Sep 30.

Mindfulness Practices

Mind, body and spirit are connected

http://www.ncbi.nlm.nih.gov/pubmed/16373990

http://www.health.harvard.edu/mind-and-mood/relaxation-techniques-breath-control-helps-quell-errant-stress-response


21

Alkalinization brings healthy balance

Jaffe R. The Alkaline Way in Digestive Health. In: Watson RR, Preedy VR, Eds. Bioactive Food as Dietary Interventions in Liver

and Gastrointestinal Disease. Academic Press, 2013, 1-21.

• Alkalinizing foods & water

• Activity & 1st AM Ur pH

• Mg++ w/Choline Citrate

• Abdominal breathing

• Green light & sunlight

• Eat in harmony with your nature & lifestyle

• Eat locally grown, vine ripened, organic or biodynamically

derived, as possible

• Make restorative sleep a priority

• Work muscles & relax in = proportions

In summay

Healthy immune system repairs, detoxifies, energizes and deletes abnormal cells.

Functional cell culture detects delayed hypersensitivities accurately: hsLRA by ELISA/ACT method

Comprehensive detoxification, alkalinization, personalized antioxidant/supportive nutrient intake and lifestyle changes restore immune tolerance, rebuild and renew.


123

Vitamin D

(25 OH-Cholecalciferol)

Vitamin D is Primary Biomarker

• Liver & Kidney hydroxylate

adhesion molecule between cells

• Communicates enough is enough

• Bone, vessel, & brain health

• Anti-cancer surveillance

40+ MM poorly absorb D…

mucosal uptake!

Vitamin D is Primary Biomarker

Mike Holick,

1995 to today

“I recommend to all of

my patients that they

should take 2000-

3000 IU of vitamin D

a day from dietary

sources, sensible

sun exposure and

supplements.”

~ Mike Holick

126

Heaney RP. Vitamin D in Health and Disease. Clin J Am Soc Nephrol. 2008; 3(5): 1535-1541.

Shute, EV. Proposed Study of Vitamin E Therapy. Can Med Assoc J. 1972; 106(10): 1057-1058.

500 IU cholecalciferol/drop

in MCT w/Rosemary Oil

Deficiency

Vitamin D 50-80 ng/ml Goal Value

hsCRP, IL-10 &

Insulin Resistance


22


Essential Fats:

Omega-3 Index

127

Omega -3 Index

High Omega 6/3 ratio

• Increased inflammation

• Immune imbalance

• Th1 Th2 diseases

Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother.2002 Oct;56(8):365-79.

Harris WS and von Schacky C. The Omega-3 Index: A New Risk Factor for Death from CHD? Preventive Medicine 2004;39:212-220.

William Harris, Ph.D.,

1985 to today

Omega 3 Index >8% Goal Value

Your hsOmega-3 Index is within the target range.

You are advised to maintain your current intake of omega-3 fatty acids.

HS-Omega-3 Index® = 16.4%

Reference Range*: 0.5% = 10.6%

2% 4% 6% 8% 10%

Undesirable under 4% Desirable over 8%Intermediate

SAMPLE RESULT


DNA Oxidative Risk:

8-OHdG

130

DNA Oxidative Risk (8-OHdG)

Marker of oxidative stress and antioxidant status in cell nucleus

8-OHdG in ng/mg creatinine

Highest

Risk

HIGHEST

Probability of

10yr Survival

<5 8.5 >25

Predictive Goal Value: 8-OHdG < 5

Lowest

Risk

LOWEST

Probability of

10yr Survival

Parkinson’s

Alzheimer’s

Huntington’s

Rheumatoid Arthritis

Pancreatitis

Bladder &

Prostate Cancer

Inflammatory

Bowel Disease

DNA Oxidative Stress (8-OHdG)


23

Omega-3 Index & 8-Oxoguanine

Ur Oxidative Risk; Antioxidants Needed

Heaney RP. Vitamin D in Health and Disease. Clin J Am Soc Nephrol. 2008; 3(5): 1535-1541.

Shute, EV. Proposed Study of Vitamin E Therapy. Can Med Assoc J. 1972; 106(10): 1057-1058.

? Liver

Detox: Comprehensiv

e Super Multi

(40 actives)

CoQ10

300-1200 mg/d w/

Tocopherols in

Rice Bran Oil

Silymarin,

l-Carnitine

fumarate,

Lycopene,

Carotenoids

EPA/DHA

3-6+ g/d,

nitrogen

distilled

Omega 3 Index &

8-oxoguanine Solutions

134

Personal Ascorbate

Calibration

1

Colorful

Super Fruits

2

Natural Methyl

Cofactors

3

GGOBE Super Foods

4 5

Test Name Test Descriptions Predictive Goal Values

hsHgb A1c

(hsHemoglobin A1c)

Sugar / insulin / energy…

AGE <5%

hsCRP

(hsC-Reactive Protein)

Repair, inflammation

immune status <0.5 mg/L

hsHCY

(hsHomocysteine)

Detox, epigenetic,

methylation… Sulfur < 6 µmol/L

hsLRA

(hsLymphocyte Response

Assay)

Immune memory /

repair tolerance

No delayed

reactions

Essential Predictive Biomarkers

to Determine Functional Age

Predictive Biomarker Tests

to Determine Your Functional Age

Test

Name

Test

Descriptions

Predictive Goal

Values

hsHgb A1c

(hsHemoglobin A1c)

Sugar/insulin/energy… AGE<5%

hsCRP(hsC reactive protein) Repair & inflammation immune status <0.5 mg/L

hsHCY

(hsHomocysteine)

Detox, epigenetic, methylation… Sulfur < 6 µmol/L

hsLRA

(hslymphocyte response assay)Immune memory/immune tolerance No reactions

Ur pH >6º rest

(1st AM Urine pH)

Mineral status &

cell acid/alkaline balance6.5 – 7.5

Vitamin D(25-Hydroxy-cholecalciferol)

Cell communication status50 – 80

ng/mL

Omega-3 Index

(Omega 3/6 EFA ratio)Omega 3:6 ratio; EFAs

>8%

8-OHdG

(8-Oxo-Guanine)Oxidative stress/antioxidant nucleus status

<5 ng/mg

creatinine

Qualified Predictive Biomarkers

Personalized, Evidence-Based, Comparative

hsHgb A1c:

Sugar, insulin… AGEs

hsCRP:

Inflammation, repair

disease

8 oxo-guanine:

Oxidative stress… ALEs

hsHomocysteine:

Methylation, detox…Sulfur

Omega 3:6; EFAs

Omega 3 Index:

Immune Tolerance

hsLRA :

Cell talk & adhesion

Vitamin D:

cell acidosis risk

1st AM urine pH:

Jaffe R, Predictive Biomarkers Provide

Evidence for Comparative Effectiveness

Research, HSC 90_13:01 Advisory on

Predictive Medicine & Health

Promotion.

Gruenewald TL, Seeman TE, Ryff CD,

Karlamangla A, Singer BH.

Combinations of Biomarkers Predictive

of Later Life Mortality. PNAS, 2006;

103 (38): 14158-14163.

Summary

• Stop fighting disease

• Focus on…o CAUSES not consequences

o OPPORTUNITIES for recovery

o PREDICTIVE GOAL VALUES not statistical ranges

o NATURE, NURTURE, & WHOLENESS

o BIODETOX

• Evoke human healing response… better clinical outcomes



24

FASCP, FACN, FACAAI,

FOCIS, FAMLI, FRSMSenior Fellow, Health Studies Collegium

Founder and Chairman,

PERQUE™ Integrative Health,

ELISA/ACT™ Biotechnologies,

RMJH Rx

Russell Jaffe, MD, PhD, [email protected] ; drrusselljaffe.com

Success in Chronic Illness

“I have found the LRA by ELISA/ACT to be the most

reliable and effective solution to solving my patient’s

chronic health conditions.”

Norman Schwartz, MD, Milwaukee, WI

Hashimoto’s Thyroiditis Case Study 2

History: ED, 36 YO woman, P5 G3

• Symptoms: Low energy, +18 kg, “little joy in life”,morning temperature often <98˚F

• Routine Lab tests: o Total T3 and T4: normal

• Additional tests:o Free T3, normal freeT4

o TSH, 2 hour glucose & insulin,

o free cortisol, free DHEA

141

Inflammation = Repair Deficits

Thyroid gland attacked

Increase in

tissue permeability

Loss of thyroid functioning

Autoimmune Thyroiditis

Overloaded Immune System

Hashimoto’s Thyroiditis Case Study 2 (cont’d.)

• Delayed lymphocyte response test + HAQ Interventions:

o Substitute for: Cow dairy, MSG, Arsenic, Sulfite & Chloroform

o Individualized nutrients & Alkalinizing lifestyle program

• Rx: 2 gr desiccated thyroid if AM temp <98ºF, green lights & salt/soda baths

• Outcome: 6 months: o Asymptomatic,

o -10kg wt.,

o D/C thyroid hormones,

o Free cortisol & DHEA, glucose & insulin: ALL NORMAL143

Migraine Success

“I have not had any migraines since I started on the

LRA program after having them for 20 years. It’s

great to be free of them.”~BH, Herndon, VA


25

Chronic Fatigue Success

“I was amazed by my fast recovery from a

4 year struggle w/ chronic fatigue syndrome &

depression once I began the LRA program. I have

returned to work, & my energy level & health are

stronger than before I got sick. I never thought I could

be this healthy”

~AA, Newton, MA

Rashes/Hives

History: 58 YO woman, Dx Rashes & hives

• Symptoms: Rashes, hives, blisters on hand, itching, throat closing and brain fog

• Therapeutic plan: Delayed lymphocyte response test (cow dairy, potato, sulfite/metabisulfite, food colorings & organophosphates)

• Early Outcome: 2 week avoidance, reduction in rashes, blisters gone, significant skin improvements

146

Allergic Rhinitis: A Case Study

History: SA, 58 yo HF

Since childhood: Perpetual cold,

constant sneezing, stuffy/runny nose,

itchy throat

Immediate allergies to dust, pollen & grasses

Dx: 57 yo Chronic Unresponsive Allergic Rhinitis: Rx

antihistamines & decongestants

Allergic Rhinitis: A Case Study (cont’d.)

• Therapeutic interventions:

o Delayed lymphocyte response test : 11 reactions

including cadmium, pyrene, clove, propylene glycol,

candida albicans, saccharine

• Implementation:

o Reduce immune burden by substituting for true

reactive items (Strong for 6 months; Moderate for 3

months)

o Follow Alkalinizing lifestyle program


• Implementation (cont’d):

o Health Assessment Questionnaire (HAQ) for

❖ personal activity,

❖ attitude & mindfulness practices

❖ personalized supplement needs.

o Supplements include buffered l-ascorbate,

polyphenolics quercetin dihydrate & soluble OPC,

multi strain probiotics, magnesium & choline citrate

(to keep Urine pH, after 6º rest, between 6.5-7.5)


• Outcome:

o Post nasal drip dramatically reduced, more restful sleep and no heavy head in the mornings

o Five months later: Different person! No fatigue and seasonal allergies have gone

Systematic substitution, alkalinization & optimized nutritional supplementation allowed SA to repair, rebuild her microbiome & heal her metabolome


26

Ulcerative Colitis

History: 31yoF, 10/13 Dx ulcerative colitis

• OTC “cleanse” 06/13 triggered bloody stools.

• PMH: ‘large polyp’ removed from small intestine as

infant. Mother’s Dx IBS.

• Initial Rx: Lialda™

Ulcerative Colitis (cont’d.)

• Therapeutic interventions:

o LRA tests: 18 reactions… Corn, Black tea, olive, xanthan

gum, orange ginger, pinene and food dyes

• Implementation:

o Substitute immune burden (Strong for 6 mo; Mod for 3 mo)

o Supplements based on HAQ: Multivitamin/multi-mineral,

Essential Omega 3, 6, 9 EFAs, bone building nutrients,

Recycled glutamine w/ PAK, comprehensive probiotic,

blood building complex (w/ ferrous aspartate),

hydroxocobalamin & polyphenolics.

Ulcerative Colitis (cont’d.)

• 1.5 years latero CBC “normal”: HgB: 12.9

❖ CRP: 1.14 & Ferritin: 14 (40-70 optimal)

o on Asacol… reducing slowly, 3/day from 6/day

o Weight back up to 132#

o Amenorrheic but breast tissue coming back

o Acupuncture 1/mo.

o Family healthier: Husband lost weight and kids eating healthier too!

• F/U: Repeat LRA… soon

Fatigue/Sleep

History: 52 yo BM for chiropractic

• Neck pain/stiffness with intermittent B/L

finger tip parasthesia, fatigue, poor

sleep & tender everywhere

• Labs: High Cholesterol, TG & glucose,

Low Vitamin D

Words and Meaning

• Immune Tolerance

• Immune Intolerance

• Antigen

• Allergy

• Atopy

• Delayed hypersensitivity

• Food Intolerance

• Inflammation

Words and Meaning

• Immune Tolerance: Phagocytic recycler cells

• Immune Intolerance: Acquired T & B cells

• Antigen: Antigen Presenting Cells

• Allergy: Hypersensitivity (Acute or Late Phase)

• Atopy: Allergic disposition

• Delayed hypersensitivity: DTH / Hidden

• Food Intolerance: Weak digestion

• Inflammation: Repair Deficit


27

Delayed Hypersensitivity: 4 methods








o hsLRA <3% !

Bhante effect… the first 40 years

I practiced

the abuse of life,

since then,

the use of life….

which do you choose?

Sam Dech Preah Ven Bhante

V B Dharmawara Mahathera Mahatma

Decoded healing system

brought forward by Buddha

but lost >1,000 years ago.

• Green light meditation

• Green dichromatic light

• Forest and plant green

• Sihanook family advisor

• Jarhalal Lal Nehru’s doc

• Dalai Lama’s mentor

Bhante at 109

7 years after full

recovery

from stroke

1887 or 1889 Ukiah, CA 1996

Ven Bhante V B Dharmawara

Mahathera Mahatma Sam Dech Preah

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