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1
Stress Markers and Effects of Minor Bioactive Compounds on Heart Health Risk Factors
R. Keith Randolph PhD, Nutrilite Health Institute
Victor A. Tutelyan, Prof, MD, PhD, Russian Institute of NutritionMoscow November 16-17, 2011
2
Objectives
• Overview of selected stress marker outcomes from a recent assessment study conducted in collaboration with the Russian Institute Of Nutrition
• Overview of research focused on the development of a botanical nutraceutical designed to moderate inflammation driven by IL-1 overexpression
3
Traditional Heart Health Risk Factors• Elevated LDL cholesterol• Hypertension• Hyperglycemia• Sedentary Lifestyle• Obesity• Family history
4
Aging Stress Responses—“Wellness” Markers for Heart Health?
Unmitigated AGING stresses are associated with age-related health decline and heart health risks
Inflammation Metabolic stress Oxidative stress DNA Damage Mitochondrial Dysfuntion
5
ION Assessment Study Design
• Study population Patients (40-70 yr old) admitted to the Russian
Institute of Nutrition (Moscow):• 100 individuals with no cardiovascular disease history
(Control group)• 100 individuals with cardiovascular disease history
(CVD group)
• Anthropometric measures, blood chemistries, inflammation & oxidative stress markers
6
Group N (M/F) Age (y) BMI (kg/m2) WHR
Control 100 (27/73)
49.7 ± 6.2 27.5 ± 5.0 0.85 ±
0.12
CVD 100 (29/71)
53.8 ± 7.6*
34.2 ± 9.4*
0.96 ± 0.15*
mean ± SD
* p < 0.05 vs Control
Subject General Characteristics Summary
7
Oxidative & Inflammatory Stress Markers
Group 8-oxo-dG1
(mM/ml)MDA2
(nmol/ml)hsCRP1
(ng/mL)
Control 0.013(0.008 – 0.015) 1.86 ± 0.82 1311.0
(484 – 3,042)
CVD 0.018(0.016 – 0.019)* 2.12 ± 0.81* 3493.0*
(1,685 – 7,087)
• No difference was found between groups in antioxidant activity determined by SOD and GSHPx blood level.
1median (Q25%-Q75%).
2mean ± SD.
*p < 0.05 vs Control
8
Conclusions
• There is clear evidence of metabolic, oxidative and inflammatory stress in overweight Russian adults with and without CVD
• Individuals presenting with CVD exhibit heightened signs of stress
9
Time (hours - days)
Infl
am
mati
on
Differences In IL-1 Genotype Are The Basis For Quantitative Variations In The Robustness Of The Inflammatory Response
EnvironmentalChallenges
Hyper-responsiveIL-1 Genotype
Non-hyper-responsiveIL-1 Genotype
10
Exaggerated Inflammation (Hyper-responsive IL-1 Genotype) Across Years May Increase Risk To Heart Health
Poor
Health
Good
Health
years
11
IL-1 Genotype Are At Increased Risk For A First Heart Attack
1987-89
Age 45-64
Total Cholesterol <200
N= 955Relative risk = 4.03
(1.58-10.24); p= 0.003
non Hyper-Responsive
Hyper-Responsive
11 Years
12
Open Innovation & Partnership
>15 years experience w
Clinical Genetic research,
gene testing, counseling
75 years experience w
Nutrition research, Dietary
supplement development, & manufacture
13
Research Strategy
(1) Genotype clinical research volunteers (IL-1)
(2) In vitro screening for IL-1 inhibition (gene expression & production)
(3) Clinical evaluation of individual lead botanicals
(4) Development of multi-component botanical formulation
(5) Clinical evaluation of prototype formulas for IL-1 and CRP
Inhibition
14
Rose Hips Formulation
MarkerDose
mg/day
Rose Hips Extract
dehydro-ascorbate
1,200
Blackberry Powder
chlorogenic acid 165
Blueberry Powder anthocyanins 330
Grape Vine Extract
all-trans-resveratrol 40
15
Clinical Trial DesignBlood draws for IL-1 gene expression,
ex vivo IL-1 production, and CRP
n= 50 IL-1 genotyped
volunteers/arm,
CRP= 2-10 mg/L
0week
Placebo
Rose Hips Formulation
12
4
Intervention
8
16
Rose Hips Formulation Reduced Inflammatory Mediators vs Placebo
CRP
>10% >20% >30%0
10
20
30
40
50
60
Placebo
RH B GV
*
**P=0.02* P=0.03
**
**
% o
f G
eno
1 S
ub
ject
sw
AV
G C
RP
Lo
wer
ing
@
12
Wee
ks
IL-1 Production
0
25
50
75
100
125
PlaceboRH B GV
*
*P<0.0001
IL-1
Pro
du
cti
on
% o
f B
as
eli
ne
IL-1 Gene Expression
0
50
100
150
200
RH B GV Placebo
*
*P<0.0001
IL-1
Ge
ne
Ex
pre
ss
ion
% o
f B
as
eli
ne
17
Rose Hips Formulation Preferentially Reduced IL-1 in At-Risk Subjects
CRP
>10% >20% >30%0
25
50
75
100
Genotype 1Genotype 0
#P=0.088*P=0.03#
*
% o
f S
ub
ject
sw
AV
G C
RP
Lo
wer
ing
@ 1
2 W
eeks
IL-1 Production
>20% >50% >70%0
25
50
75
100
Genotype 1Genotype 0
% o
f S
ub
ject
sw
AV
G IL
-1 P
rod
uct
ion
Lo
wer
ing
@ 1
2 W
eeks
*
*P=0.05
IL-1 Gene Expression
>20% >50% >70%0
25
50
75
100
Genotype 1
Genotype 0
*P=0.02#P=0.1*
#
% o
f S
ub
ject
sw
AV
G IL
-1 G
E L
ow
erin
g @
12
Wee
ks
At Risk Genotype
Non Risk Genotype
19
IL-1 Nutrigenetic Research Conclusions
• Nutritional interventions that moderate inflammatory stress are feasible.
• Inflammation driven by overexpression of IL-1 can be moderated via nutritional interventions.