1. R Keith Randolph PhD Technology Strategy Nutrilite Health Institute
Modulation of Genetically Predisposed Inflammation via a Botanical Formulation— A Nutrigenetic Proof of Principle
R Keith Randolph PhD
Technology Strategy
Nutrilite Health Institute

2. Personalized Nutrition
Nutrition tailored to the individual

3. Heart Health Risks Conventional risk factors Sedentary Lifestyle
Elevated LDL cholesterol
Hypertension
Hyperglycemia
Sedentary Lifestyle
Inflammation

5. Differences In IL-1 Genotype Are The Basis For Quantitative Variations In The Robustness Of The Inflammatory Response
Hyper-Responsive
IL-1 Genotype
Time (hours - days)
Inflammation
Environmental
Challenges
Nonhyper-Responsive
IL-1 Genotype

6. Exaggerated Inflammation (Hyper-responsive IL-1 Genotype) Across Years May Increase Risk To Heart Health
Poor
Health
Good
years

7. Total Cholesterol <200
Individuals w Hyper-Responsive IL-1 Genotype Are At Increased Risk For A First Heart Attack
non Hyper-Responsive
Hyper-Responsive
Age 45-64
Total Cholesterol <200
N= 955
11 Years
Relative risk = 4.03
( ); p= 0.003
ARIC; Offenbacher et al, 2004
This was from the ARIC database. The result pertained to individuals with
total cholesterol < 200 (n= 261 cases and 325 controls). The result is not
technically an OR, but rather the relative risk for time to onset of CHD.
The analysis was adjusted for age, race/center, smoking status, diabetes,
hypertension, BMI, LDL and HDL.

8. Nutrigenomic IL-1 Supplement Objective
Hyper-Responsive
IL-1 Genotype
+IL-1 Nutrigenomic Supplement
Inflammation
Environmental
Challenges
Time (hours - days)
Nonhyper-Responsive
IL-1 Genotype

9. Open Innovation & Partnership
75 years experience w
Nutrition research, Dietary supplement development, & manufacture
>15 years experience w
Clinical Genetic research,
gene testing, counseling

10. Nutrigenetic Botanical Formulation Strategy
Inhibition of IL-1 Production X
CRP
Inhibition of down stream inflammation pathway X
inflammation
within developing
atherosclerotic lesion
Liver
IL-1
inflammatory cytokines, e.g., IL-1, stimulate liver production of downstream inflammatory mediators, e.g., CRP, by liver

11. Development Strategy Genotype clinical research volunteers (IL-1)
(2) In vitro screening for IL-1 inhibition
(3) Clinical evaluation of individual candidate botanicals
(4) In vitro screening for downstream inflammation inhibition
(5) Clinical evaluation of prototype formulas for IL-1 and CRP
inhibition in genotyped volunteers

12. Ingredient Screening Summary for Inhibition of IL-1 Production

13. IL-1 Ingredient Screening Clinical Design
wbc IL-1 gene expression,
ex vivo IL-1 production, hsCRP,
day 14
Rose Hips
Artichoke
10 subjects/arm (5 each Genotype)
Nettle Root
Olive

14. IL-1 Ingredient Screening Clinical Results
At Risk Genotype
Non Risk Genotype

15. Top Performing Ingredient Screening Summary for Inhibition of CRP Production

16. Rose Hips Formulation Markers Dose/day Rose Hips Extract
dehydro-ascorbate
1,200
Blackberry Powder
chlorogenic, ferulic acids
165
Blueberry Powder
anthocyanins, caffeic acid, terpenes, quercetin, catechins
330
Grape Vine Extract
all-trans-resveratrol 40

17. Clinical Trial Design week 12 4 8
Blood draws for IL-1 gene expression,
ex vivo IL-1 production, and CRP
week
Placebo
Rose Hips Formulation 12 4
Intervention 8
n= 50 IL-1 genotyped
volunteers/arm,
CRP= 2-10 mg/L

18. Rose Hips Formulation Reduced Inflammatory Mediators vs Placebo

19. Rose Hips Formulation Preferentially Reduced Inflammatory IL-1 At-Risk Genotype Subjects
Non Risk Genotype

20. IL-1 Heart Health Nutrigenomic Supplement Efficacy Substantiation
3 years
3 clinical 5 sites
>2,500 clinical test subjects
John B McKinney Award in nutrition & metabolism

21. Personalized Nutrition— Opportunity & Need
Prevention oriented
Health risks identified prospectively and addressed through preemptive individualized interventions