Development and Use of Predictive Biomarkers Dr. Richard Simon.
Health Studies Collegium Predictive Biomarkers Master · Health Studies Collegium Predictive...
Transcript of Health Studies Collegium Predictive Biomarkers Master · Health Studies Collegium Predictive...
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.”
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
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.
Health Studies CollegiumPredictive Biomarkers Master
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
Let’s Rethink Health together!
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
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
6
Predictive Biomarker 2
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
Health Studies CollegiumPredictive Biomarkers Master
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.
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.
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.
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%
Health Studies CollegiumPredictive Biomarkers Master
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)
Predictive Biomarker 3
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.
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
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.
Predictive Biomarker 4
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
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
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
Stop Fighting Disease
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
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
14
Tests of Delayed Hypersensitivity
In Vitro• Antibody (IgG, Serology) tests:
o Static, misleading
• Particle size tests:
o Random, misleading
• Cytokine release:
o Interesting technology
Ex Vivo• Lymphocyte response assays:
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
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
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.
Health Studies CollegiumPredictive Biomarkers Master
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.
Health Studies CollegiumPredictive Biomarkers Master
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.
Health Studies CollegiumPredictive Biomarkers Master
19
Stop Fighting Disease
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
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
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.
Candidate Predictive Biomarker 6
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
Health Studies CollegiumPredictive Biomarkers Master
22
Candidate Predictive Biomarker 7
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
Candidate Predictive Biomarker 8
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)
Health Studies CollegiumPredictive Biomarkers Master
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
Let’s Rethink Health together!
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
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
Allergic Rhinitis: A Case Study (cont’d.)
• 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)
Allergic Rhinitis: A Case Study (cont’d.)
• 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
Health Studies CollegiumPredictive Biomarkers Master
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
Health Studies CollegiumPredictive Biomarkers Master
27
Delayed Hypersensitivity: 4 methods
In Vitro• Antibody (IgG, Serology) tests:
o Static, misleading
• Particle size tests:
o Random, misleading
• Cytokine release:
o Interesting technology
Ex Vivo• Lymphocyte response assays:
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