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Flavonoids and Cardiovascular Health – What Flavonoids and Cardiovascular Health – What Progress Has Been Made Towards Public Health Progress Has Been Made Towards Public Health
Recommendations for Flavonoids?Recommendations for Flavonoids?
Carl L. KeenCarl L. KeenDepartment of NutritionDepartment of Nutrition
University of California, DavisUniversity of California, [email protected]@ucdavis.edu
ICPH 2013ICPH 2013
Buenos Aires, ArgentinaBuenos Aires, ArgentinaOctober 19October 19thth, 2013, 2013
Disclosures for: Carl L. KeenDisclosures for: Carl L. KeenAFFILIATION/FINANCIAL INTERESTS
CORPORATE ORGANIZATION
Grants/Research Support: Research Support From Mars Incorporated; California Walnut Board & California Strawberry Board
Scientific Advisory Board/Consultant:
Mars/Waltham Scientific Advisory Boards
McCormick Spice Advisory Board
Speakers Bureau: None
Stock Shareholder: None
Other Financial or Material Support/Honorarium:
None
Why address this issue?
Accepted Fact:Accepted Fact: Diets rich in plant foods are associated with Diets rich in plant foods are associated with
an overall positive health status and a decreased risk for an overall positive health status and a decreased risk for certain diseases (e.g. vascular disease, certain cancers) certain diseases (e.g. vascular disease, certain cancers)
Fruits, vegetables and CHDFruits, vegetables and CHD
“ “ There are very few studies to date examining There are very few studies to date examining provision of, or advice to increase the provision of, or advice to increase the consumption of, fruits and vegetables in the consumption of, fruits and vegetables in the absence of additional dietary advice or other absence of additional dietary advice or other lifestyle interventions for the primary prevention of lifestyle interventions for the primary prevention of CVD. The limited evidence suggests advice to CVD. The limited evidence suggests advice to increase fruit and vegetables as a single has increase fruit and vegetables as a single has favorable effects on CVD risk factors but more favorable effects on CVD risk factors but more trials are needed to confirm this.”trials are needed to confirm this.” Hartley et al., The Cochrane Collaboration, 2013.Hartley et al., The Cochrane Collaboration, 2013. (similar points made in Dauchet et al. Nat Rev Cardiol. 2009)(similar points made in Dauchet et al. Nat Rev Cardiol. 2009)
The inverse association seen between the The inverse association seen between the consumption of plant food-rich diets and the risk consumption of plant food-rich diets and the risk for CVD is due to multiple nutritional variables:for CVD is due to multiple nutritional variables:
favourable sodium/potassium profile favourable sodium/potassium profile low in saturated fatlow in saturated fat
high essential nutrient contenthigh essential nutrient contenthigh fibre content high fibre content
high in select “non-essential” phytochemicalshigh in select “non-essential” phytochemicals
Flavonoid Intake and Risk of CHD Mortality Flavonoid Intake and Risk of CHD Mortality – Seven Countries Study– Seven Countries Study
Hertog et al. Arch Intern Med 1995; 155: 381-6
Limited Analysis:Limited Analysis:
Two Classes:Two Classes:
•Flavonol Flavonol quercetinquercetin kaempferolkaempferol myricetinmyricetin
•FlavoneFlavone luteolinluteolin apigeninapigenin
Flavanols & Vascular HealthFlavanols & Vascular Health
Speculation:Speculation:The inverse association often reported between The inverse association often reported between the consumption of plant food-rich diets and the the consumption of plant food-rich diets and the
risk for CVD is due to numerous factors risk for CVD is due to numerous factors including flavonoid-induced changes in: oxidant including flavonoid-induced changes in: oxidant
production and defence; the immune system; production and defence; the immune system; platelet reactivity, vascular reactivity, tissue platelet reactivity, vascular reactivity, tissue
repair and blood pressure. repair and blood pressure.
Biomarkers are needed for the Biomarkers are needed for the assessing an individuals assessing an individuals
status for the phytochemical(s) status for the phytochemical(s) in question, as well as for in question, as well as for following the acute, and following the acute, and chronic impact of these chronic impact of these
phytochemicals on select phytochemicals on select health parameters health parameters
Recommendation 3:Recommendation 3:The FDA should use the same degree of scientific rigor for The FDA should use the same degree of scientific rigor for evaluation of biomarkers across regulatory areas, whether evaluation of biomarkers across regulatory areas, whether they are proposed for use in the arenas of drugs, medical they are proposed for use in the arenas of drugs, medical devices, biologics, or foods and dietary supplements.devices, biologics, or foods and dietary supplements.
Recommendation 4:Recommendation 4:The FDA should take into account a nutrient’s or food’s source as The FDA should take into account a nutrient’s or food’s source as well as any modifying effects of the food or supplement that well as any modifying effects of the food or supplement that serves as the delivery vehicle and the dietary patterns associated serves as the delivery vehicle and the dietary patterns associated with consumption of the nutrient or food when reviewing health with consumption of the nutrient or food when reviewing health related label claims and the safety of food and supplements.related label claims and the safety of food and supplements.
Recommendation 5b:Recommendation 5b:Congress should grant the FDA authority to request studies and Congress should grant the FDA authority to request studies and sufficient authority to act on the results of studies on consumer sufficient authority to act on the results of studies on consumer understanding of claims on foods and supplements.understanding of claims on foods and supplements.
Evaluation of Biomarkers 2010-Evaluation of Biomarkers 2010-The Biomarker Evaluation Process RecommendationsThe Biomarker Evaluation Process Recommendations
Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease; IOM, 2010Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease; IOM, 2010
Evaluation of Biomarkers 2010-Evaluation of Biomarkers 2010-Case StudiesCase Studies
Evaluation of Biomarkers and Surrogate Endpoints in Chronic Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease; IOM, 2010Disease; IOM, 2010
Consumption of Flavanol-containing Beverage ProductsConsumption of Flavanol-containing Beverage Products
- Uptake of Flavanols into the Circulation-- Uptake of Flavanols into the Circulation-
00
100100
200200
300300
Resp
on
se (
nA
)R
esp
on
se (
nA
)
Catechin
EpicatechinEpicatechin0 hours0 hours1 hours1 hours2 hours2 hours6 hours6 hours
00
100100
200200
300300
Resp
on
se (
nA
)R
esp
on
se (
nA
)
Catechin
EpicatechinEpicatechin0 hours0 hours1 hours1 hours2 hours2 hours6 hours6 hours
0 hours0 hours1 hours1 hours2 hours2 hours6 hours6 hours
time [h]
-1 0 1 2 3 4 5 6 7
Cir
cula
tin
g F
lava
no
ls/M
etab
olit
es [
nM
]
0
250
500
1000
1500
2000
2500
3000
epicatechin catechin 4'MEC EC-7Gluc 4'MEC-Gluc Sum
Blood Plasma Flavanols/Metabolites after eating a Blood Plasma Flavanols/Metabolites after eating a high-flavanol cocoa producthigh-flavanol cocoa product
Schroeter et al. PNAS 103:1024-29,2006Schroeter et al. PNAS 103:1024-29,2006
Flavanol Metabolites Mixture ProfileFlavanol Metabolites Mixture Profile % of Total% of Total
(−)-epicatechin (−)-epicatechin
(+)-catechin(+)-catechin
Procyanidin Dimer B2Procyanidin Dimer B2
O-methyl-epicatechinO-methyl-epicatechin
Epicatechin-glucuronideEpicatechin-glucuronide
O-methyl-epicatechin-glucuronideO-methyl-epicatechin-glucuronide
3.73.7
1515
0.70.7
7.57.5
9.49.4
63.763.7
[mol/L]
0.01 0.1 1 10 100 1000 10000
Tro
lox
equi
vale
nt [
mol
/L]
0.0
5.0e+4
1.0e+5
1.5e+5
2.0e+5
2.5e+5Flavanol Metabolites
Range ofDietary Relevance
Human Plasma [ORAC]
*
*
It is unlikely that the antioxidant properties of the flavanols It is unlikely that the antioxidant properties of the flavanols being studied trigger the observed reduction in platelet being studied trigger the observed reduction in platelet reactivityreactivity
Acceptable Biomarkers – Antioxidant activity?
Pearson et al. Pearson et al. Thromb ResThromb Res 2002; 106: 191-7 2002; 106: 191-7Pearson et al. Pearson et al. Thromb ResThromb Res 2002; 106: 191-7 2002; 106: 191-7
Aspirin + CocoaAspirin + Cocoa
00 22 66
** **
Clo
sure
Tim
e (s
)C
losu
re T
ime
(s)
AspirinAspirin
00 22 66
****
0
5050
100100
150150
200200
CocoaCocoa
00 22 66
** Epi-collagenEpi-collagen
ADP-collagenADP-collagen
Epi-collagenEpi-collagen
Clo
sure
Tim
e (s
)C
losu
re T
ime
(s)
AspirinAspirin
00 22 6600
2020
4040
6060
8080
100100
120120
140140
100100
120120
140140
CocoaCocoa
00 22 6600
2020
4040
6060
8080
**
100100
120120
140140
Aspirin + CocoaAspirin + Cocoa
00 22 6600
2020
4040
6060
8080
****
Time (hr)Time (hr)
Like Aspirin, CF (897 mg total flavonoids) can influence blood Like Aspirin, CF (897 mg total flavonoids) can influence blood clotting (PFA-100) times in healthy adultsclotting (PFA-100) times in healthy adults
ReferenceReference TypeType DoseDose DurationDuration SubjectsSubjects nn Platelet TestPlatelet Test
Pace-Asciak ‘96Pace-Asciak ‘96Red wineRed wineWhite wineWhite winePurple grape juicePurple grape juice
375 ml/day375 ml/day375 ml/day375 ml/day500 ml/day500 ml/day
4 wks4 wks Healthy adultsHealthy adults 2424
AggregationAggregation ---- Aggregation Aggregation
AggregationAggregation
Duffy ‘01Duffy ‘01 Black TeaBlack Tea 900 ml/day900 ml/day 4 wks4 wks CAD patientsCAD patients 4949 ---- Aggregation Aggregation
Freedman ‘01Freedman ‘01 Purple grape juicePurple grape juice 7 ml/kg/day7 ml/kg/day 2 wks2 wks Healthy adultsHealthy adults 2020 AggregationAggregation
Rein ‘00Rein ‘00 Cocoa beverageCocoa beverage 300 ml300 ml 1 dose1 dose Healthy adultsHealthy adults 1010 Platelet ReactivityPlatelet Reactivity
Heptinstall ‘06Heptinstall ‘06 Cocoa Beverage Cocoa Beverage 600-900 mg600-900 mg 1 dose1 dose Healthy adultsHealthy adults 1212 Collagen stimulated Collagen stimulated
Platelet AggregationPlatelet Aggregation
Flammmer ‘07Flammmer ‘07 ChocolateChocolate 40 g40 g 1 dose1 dose Heart Heart transplanttransplant
Platelet adhesionPlatelet adhesion
Hamed ‘08Hamed ‘08 ChocolateChocolate 100 g / day100 g / day 1 week1 week Healthy adultsHealthy adults 2828 Platelet ReactivityPlatelet Reactivity
Erlund ’08Erlund ’08 ““Berries”Berries” 100 g100 g 8 wks8 wks Health AdultsHealth Adults 7272 Platelet ReactivityPlatelet Reactivity
Ostertag ’10 Ostertag ’10 Cocoa/ChocolateCocoa/Chocolate ““Moderate Moderate amount”amount” AcuteAcute Meta AnalysisMeta Analysis
10 10
StudiesStudies Platelet ReactivityPlatelet Reactivity
Carnevale ’12Carnevale ’12 ChocolateChocolate 40 g40 g 1 dose1 doseHealthy AdultsHealthy Adults
SmokersSmokers4040 Isoprostanes, NOX2Isoprostanes, NOX2
Ostertag ‘13 Ostertag ‘13 ChocolateChocolate
300 mg300 mg AcuteAcute Healthy AdultsHealthy Adults 4242 Platelet ReactivityPlatelet Reactivity
Effects of Flavanols and Flavanol-Rich Food Effects of Flavanols and Flavanol-Rich Food Consumption on Platelet FunctionConsumption on Platelet Function
Water-soluble tomato concentrate (WSTC I and II) and platelet Water-soluble tomato concentrate (WSTC I and II) and platelet aggregation. aggregation.
Scientific substantiation of a health claim related to water-soluble Scientific substantiation of a health claim related to water-soluble tomato concentrate (WSTC I and II) and platelet aggregation tomato concentrate (WSTC I and II) and platelet aggregation pursuant to Article 13(5) of Regulation (EC) No 1924/2006.pursuant to Article 13(5) of Regulation (EC) No 1924/2006.The EFSA Journal (2009) 1101, 1-15.The EFSA Journal (2009) 1101, 1-15.
Acceptable Biomarkers - Platelet Function ?Acceptable Biomarkers - Platelet Function ?
Scientific opinion on the modification of the authorization of a Scientific opinion on the modification of the authorization of a health claim related to water-soluble tomato concentrate and helps health claim related to water-soluble tomato concentrate and helps to maintain a healthy blood flow and benefits circulation pursuant to maintain a healthy blood flow and benefits circulation pursuant to Article 13(5) of Regulation (EC) No 1924/2006 following a to Article 13(5) of Regulation (EC) No 1924/2006 following a request in accordance with Article 19 of the Regulation (EC) No request in accordance with Article 19 of the Regulation (EC) No 1924/2006.1924/2006.The EFSA Journal (2010) 8(7), 1689.The EFSA Journal (2010) 8(7), 1689.
Vascular Endpoints - FMD/PATVascular Endpoints - FMD/PAT
IschemiaIschemia(arterial occlusion)(arterial occlusion)
HyperemiaHyperemia(transient increase in(transient increase in
organ blood flow)organ blood flow)
Shear StressShear Stress(arterial occlusion)(arterial occlusion)
NO-ProductionNO-Production(endothelial cells)(endothelial cells)
Arterial DilationArterial Dilation(relaxation of smooth(relaxation of smooth
muscle)muscle)
FMD – Nitric Oxide – Flavanol/MetabolitesFMD – Nitric Oxide – Flavanol/Metabolites
0 1 2 3 4 5 6
0
2
4
6
8
10
12
0 1 2 3 4 5 6
-2
-1
0
1
2
3
4
0 1 2 3 4 5 6
0
500
1,000
1,500
2,000
2,500
3,000
3,500
*#
*#
*#
aF
low
-me
dia
ted
dila
tion
(%
)
Time after cocoa drink (h)
hFCD lFCD
*#
#
*#
*#
b
***
Incr
ea
se R
XN
O (
nM
)
*#
*#
*#*#
*#
c
**
*
Su
m o
f p
lasm
a f
lava
no
ls (
nM
)
Cocoa-mediated increasesin FMD are inhibited by L-NMMA
infusion and NOS inhibition
Schroeter et al. PNAS 2006Schroeter et al. PNAS 2006
0 1 2 3 4
0
1
2
3
4
* **#
**#
Time after Ingestion (h)
PA
T in
de
x
Water 1 mg/kg Epicatechin
d
0 1 2 3 4
0
2
4
6
8
10
*#*#
Time after Ingestion (h)
Flo
w-m
edia
ted d
ilatio
n (
%)
Water 1 mg/kg Epicatechin
b
Epicatechin - FMD Epicatechin - FMD
Schroeter et al. PNAS 103:1024-29,2006Schroeter et al. PNAS 103:1024-29,2006
ReferenceReference TypeType DoseDose DurationDuration SubjectsSubjects nn Vascular ResponseVascular Response
Heiss 2005Heiss 2005 CocoaCocoa 88 -370 mg88 -370 mg 1-day1-day SmokersSmokers 1111 ↑↑FMD, RXNOFMD, RXNO
Schroeter 2006Schroeter 2006 CocoaCocoa 917 mg 917 mg 1-day1-day Healthy AdultsHealthy Adults 1616 ↑↑FMD, RHI, RXNOFMD, RHI, RXNO
Heiss 2007Heiss 2007 CocoaCocoa 918 mg 918 mg 1-week1-week SmokersSmokers 11 11 ↑↑FMDFMD
Balzer 2008Balzer 2008 CocoaCocoa 963 mg 963 mg 30-days30-days DiabeticsDiabetics 4141 ↑↑FMDFMD
Heiss 2010Heiss 2010 CocoaCocoa 375 mg375 mg 30-days30-days CAD patientsCAD patients 1616 ↑↑FMD, CAC, NitriteFMD, CAC, Nitrite
Monohan 2011Monohan 2011 CocoaCocoa 69 – 1095 mg69 – 1095 mg 1-day1-day Older HealthyOlder Healthy
AdultsAdults
2323 ↑↑FMDFMD
Loffredo 2012Loffredo 2012 ChocolateChocolate 40 g40 g 1-day1-day SmokersSmokers
Healthy AdultsHealthy Adults
4040 ↑↑FMDFMD, ↓NOX2, ↓NOX2
Nogueira 2012Nogueira 2012 ChocolateChocolate 50 g50 g 4 wks4 wks HypertensiveHypertensive 2020 ↑↑RHIRHI
Mellor 2013Mellor 2013 ChocolateChocolate 13.5 g13.5 g 1-day1-day DiabeticsDiabetics 1010 ↑↑RHIRHI
Effects of Flavanols and Flavanol-Rich Food Effects of Flavanols and Flavanol-Rich Food Consumption on Vascular FunctionConsumption on Vascular Function
How Does FMD/PAT Compare to Blood How Does FMD/PAT Compare to Blood Pressure as An Accepted Marker?Pressure as An Accepted Marker?
• Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events and restenosis in patients undergoing coronary stent implantation: a prospective study.
Akcakoyun M, et. al. Coron Artery Dis, 2008; 19:337-343
• Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease.
Kitta Y, et. al., J Am Coll Cardiol 2009;53:323-30
Rubinshtein, R et al. Eur Heart J 31:1142-8, 2010Rubinshtein, R et al. Eur Heart J 31:1142-8, 2010
Scientific Opinion on the substantiation of a health related to cocoa Scientific Opinion on the substantiation of a health related to cocoa flavanols and maintenance of normal endothelium-dependent flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to article 13(5) of regulation (EC) No vasodilation pursuant to article 13(5) of regulation (EC) No 1924/2006.1924/2006.The EFSA Journal (2012) 10(7), 2809.The EFSA Journal (2012) 10(7), 2809.
Acceptable Biomarkers - FMD?Acceptable Biomarkers - FMD?
Scientific opinion on the substantiation of a health claim related to Scientific opinion on the substantiation of a health claim related to vitamin K2 and contribution to the normal function of the heart and vitamin K2 and contribution to the normal function of the heart and blood vessels (ID 125, further assessment) pursuant to Article 13(1) blood vessels (ID 125, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006.of Regulation (EC) No 1924/2006.The EFSA Journal (2012) 10(6), 2714.The EFSA Journal (2012) 10(6), 2714.
ReferenceReference TypeType DoseDose DurationDuration SubjectsSubjects nn Blood PressureBlood Pressure
Grassi 2005Grassi 2005 ChocolateChocolate ~ 500 mg~ 500 mg 2 wks2 wks Healthy adultsHealthy adults 1515 ↓↓ SystolicSystolic
Taubert 2007Taubert 2007 ChocolateChocolate 30 mg /day30 mg /day 18 wks18 wks Pre Pre Stage 1 Stage 1 hypertensivehypertensive
4444 ↓ ↓ Systolic, DiastolicSystolic, Diastolic
Davison 2008Davison 2008 CocoaCocoa 902 mg902 mg 12 wks12 wks Overweight/Overweight/
ObeseObese
4949 ↓ ↓ Diastolic, MAPDiastolic, MAP
Balzer 2008Balzer 2008 CocoaCocoa 960 mg960 mg 30 dys30 dys MedicatedMedicated
DiabeticsDiabetics
4141 No ChangeNo Change
Manuiyappa 08Manuiyappa 08 CocoaCocoa ~ 900 mg~ 900 mg 2 wk2 wk HypertensiveHypertensive 2020 No ChangeNo Change
Shiina 2009Shiina 2009 ChocolateChocolate 550 mg550 mg 2 wks2 wks Healthy AdultsHealthy Adults 3939 No ChangeNo Change
Davison 2010Davison 2010 CocoaCocoa 33, 372, 712, 33, 372, 712, 1052 mg /day1052 mg /day
6 wks6 wks HypertensiveHypertensive 5252 ↓↓ 24 hr ambulatory 24 hr ambulatory
SBP, DBP, MAP at SBP, DBP, MAP at
high flavanol intake high flavanol intake
Desideri 2012Desideri 2012 CocoaCocoa 45, 520, 990 45, 520, 990 mg /daymg /day
8 wks8 wks Cognitively Cognitively ImpairedImpaired
9090 ↓ ↓ Systolic, Diastolic (520 and Systolic, Diastolic (520 and 990 mg)990 mg)
Sarria 2013Sarria 2013 CocoaCocoa 416 mg416 mg 4 wks4 wks Healthy AdultsHealthy Adults 4444 No ChangeNo Change
Effects of Flavanols and Flavanol-Rich Food Effects of Flavanols and Flavanol-Rich Food Consumption on Blood PressureConsumption on Blood Pressure
Aatola et al, Circulation 122:2521-8, 2010Aatola et al, Circulation 122:2521-8, 2010
Fruit and Vegetable Intake in Childhood is Inversely Associated Fruit and Vegetable Intake in Childhood is Inversely Associated with Pulse Wave Velocity in Adulthoodwith Pulse Wave Velocity in Adulthood
↑ ↑ PWV = ↑ Arterial StiffnessPWV = ↑ Arterial Stiffness
Vegetable consumption in childhood inversely associated withVegetable consumption in childhood inversely associated withAdulthood PWV (p = 0.02)Adulthood PWV (p = 0.02)
Persistently high consumption of both fruits and vegetables from childhoodPersistently high consumption of both fruits and vegetables from childhoodTo adulthood was also associated with a lower PWV.To adulthood was also associated with a lower PWV.
Evolus® and reduce arterial stiffness. Scientific substantiation of Evolus® and reduce arterial stiffness. Scientific substantiation of a health to a health to Lacotbacillus helveticus Lacotbacillus helveticus fermented Evolus® low-fat fermented Evolus® low-fat milk products and reduction of arterial stiffness pursuant to milk products and reduction of arterial stiffness pursuant to Article 14 of the Regulation (EC) No 1924/2006.Article 14 of the Regulation (EC) No 1924/2006.The EFSA Journal (2009) 1101, 1-15.The EFSA Journal (2009) 1101, 1-15.
Acceptable Biomarkers - Arterial Stiffness?Acceptable Biomarkers - Arterial Stiffness?
Statement on the safety of the “conjugated linoleic acid (CLA)-rich Statement on the safety of the “conjugated linoleic acid (CLA)-rich oils” Clarinol® and Tonalin® TG 80 as Novel Food ingredients.oils” Clarinol® and Tonalin® TG 80 as Novel Food ingredients.The EFSA Journal (2012) 10(5), 2700.The EFSA Journal (2012) 10(5), 2700.
CAD patients (n=519) withHighest
Medium
Lowestnumbers of EPCs.
New Biomarkers - circulating EPC levels? New Biomarkers - circulating EPC levels?
Werner et al., NEJM, 2005
Hill, JM et al. NEJM 348:593-600, 2003Hill, JM et al. NEJM 348:593-600, 2003
Circulating Endothelial Progenitor Cells, Circulating Endothelial Progenitor Cells, Vascular Function, and Cardiovascular RiskVascular Function, and Cardiovascular Risk
Heiss et al., JACC, 2010
FMDCACBP
NOxRea
do
uts +
+++
1 30
Control9 mg of flavanols
twice a day
Treatment375 mg of flavanols
twice a day
Time (days)Time (days)
• n=16• medicated CAD patients
Day 1 Day 30Day 1
30 1
Control9 mg of flavanols
twice a day
Treatment375 mg of flavanols
twice a day
Wash-out
Day 30
FMD ++++
++++
++++
CF effects in medicated CAD PatientsCF effects in medicated CAD Patients
0.0
0.5
1.0
1.5
FI
*#a
CD
34+/K
DR
+ (
%M
NC
)
*
C
pre post pre post0.0
0.5
1.0 *#
*#
b
CD
133
+/K
DR
+ (
%M
NC
)
pre post pre post0
1020
120
130
140
FI
*#
a
Sys
tolic
BP
(m
mH
g)
C
0
5
10
*
*#
b
FM
D (
%)
CF Has Vascular Effects in CAD PatientsCF Has Vascular Effects in CAD Patients
Heiss et al., JACC, 2010Heiss et al., JACC, 2010
Blackenberg, S et al. Circulation 121:2388-97, 2010Blackenberg, S et al. Circulation 121:2388-97, 2010
Contribution of 30 Biomarkers to 10-Year Cardiovascular Risk Contribution of 30 Biomarkers to 10-Year Cardiovascular Risk Estimation in 2 Population Cohorts: The MONICA, Risk, Genetics, Estimation in 2 Population Cohorts: The MONICA, Risk, Genetics,
Archiving, and Monograph (MORGAM) Biomarker ProjectArchiving, and Monograph (MORGAM) Biomarker Project
Conclusions/Summary:Conclusions/Summary:
The results obtained from numerous The results obtained from numerous intervention trials support the concept that the intervention trials support the concept that the consumption of flavanol-rich foods can result consumption of flavanol-rich foods can result in acute (1 – 30 days) improvements in in acute (1 – 30 days) improvements in vascular health parameters that are vascular health parameters that are suggestive of a decreased risk for select suggestive of a decreased risk for select chronic diseases. chronic diseases.
Conclusions/Summary:Conclusions/Summary:
With respect to dietary recommendations for With respect to dietary recommendations for “flavonoids”, the emphasis should be on “flavonoids”, the emphasis should be on defined members of the class, rather than the defined members of the class, rather than the entire classentire class
Conclusions/Summary:Conclusions/Summary:
When considering the development of When considering the development of biomarkers for following the effects of a food biomarkers for following the effects of a food or a non-essential nutrient on the risk for or a non-essential nutrient on the risk for select diseases, there may be value in aiming select diseases, there may be value in aiming for a model that takes into consideration the for a model that takes into consideration the effects of the food/nutrient on multiple risk effects of the food/nutrient on multiple risk factors for the disease of interest.factors for the disease of interest.