chocolate, cocoa and cardiovascular...
TRANSCRIPT
Chocolate, Cocoa
and Cardiovascular Disease
Isabella Sudano
Cardiovascular Center Cardiology
University Hospital Zürich
No conflict of interest related to the
topic of this presentation but
Isabella Sudano
Cardiovascular Center Cardiology
University Hospital Zürich
I love Chocolate!
Joshipura, K. J. et. al. Ann Intern Med 2001;134:1106-14
Intake of fruits & vegetables and CAD risk
Nurses' Health Study and the Health Professionals'
Follow-Up Study
N=84’251
S. Yusuf, et al. Lancet 2004
Interheart Study
N=30.000 52 countries
Chocolate
Popular for thousands of yearsIn Honduras, archaeologists
uncovered elaborately designed
bowls dating to 1600 BC, and believe
that the Aztecs used these bowls to
serve liquid chocolate thousands of
years ago.
Cocoa was revered by Mayans, and
was considered a food of the gods.
This is how the cocoa tree got its
scientific name theobroma cacao,
from the Greek words "theo" (god)
and "broma" (drink).
Chocolate consumption and prevalence of coronary
heart disease
Djoussé L et al, Clinical Nutrition 2011
Chocolate consumption and Myocardial infarction and Stroke
Buijsse et al, Eur Heart J 2010
Cocoa intake & 15-year mortality among elderly men
Zupten-Trial, NL
Buijsse, B. et al. Arch Intern Med 2006;166:411-7
-24% -43%
Blueberry data - Prior et al., J. Ag. Food Chem., 46, 2686-2693; Strawberry data - Wang et al., J. Ag. Food Chem., 44, 701-705
Garlic data - Cao et al., J. Ag. Food Chem., 44, 3426-3431; Chocolate data - Adamson et al., J. Ag. Food Chem., 47, 4184-4188
Flavonoid content
50 grams dark chocolate
6 apples
15 glasses of orange juice,
28 glasses of white wine
2 glasses of red wine
Antioxidant capacity
Ability to Neutralize Free Radicals
(ORAC: µmol Trolex equiv/g)
Polyphenols: Chemical Structure
Manach Am J Clin Nutr 2004;79:727-47
Polyphenols Catechin
Epicatechin
Catechins and Epicatechins found in food
Source Flavanol content per mg/kg or mg/L
Chocolate 460-610
Beans 350-550
Apricot 100-250
Cherry 50-220
Peach 50-140
Blackberry 130
Apple 20-120
Green tea 100-800
Black tea 60-500
Red wine 80-300
Cider 40
Manach C et al. Am J Clin Nutr 2004;79:727-47
Plasma antioxidants
from chocolate
FRAP = ferric-reducing antioxidant potential
DC = dark chocolate
MK = milk
MC = milk chocolate
DC
DC + MK
MC
Serafini M; Nature. 2003 Aug 28;424(6952):1013
Ying Wan et al. Am J Clin Nutr 2001
Plasma concentration of
epicatechins after ingestion of
dark chocolate
Chocolate is not
equal to Cocoa
During conventional chocolate
manufacturing the concentrations of
polyphenols markedly decrease
In particular fermentation and
roasting have detrimental impact
Polyphenol concentration depend on
the agricultural origin of raw cocoa
Payne MJ et al, J. Agric. Food Chem. 2010, 58, 10518–10527
Blood Pressure
Reduction
Improved
vascular function
Other:
Anti-Inflammatory
Sweet effects of cocoa
Reduce fasting glucose
and improved
insulin sensitivity
Reduced
platelet reactivity
Cocoa Effect on Blood Pressure
Holenberg, J Cardiovasc Pharm 06
systolic BP
diastolic BP
Ried K, D. et al. BMC Medicine 2010
Ried K, D. et al. BMC Medicine 2010
Blood pressure lowering effects of cocoa
Taubert, D. et al. JAMA 2007;298:49-60
Habitual low dose (6 grams) intake of cocoa reduces blood pressure and increases bioactive nitric oxide over a period of 18 weeks
44 adults aged 56 through 73
years (24 women, 20 men)
with untreated upper-range
prehypertension or stage 1
hypertension without
concomitant risk factors
Between-Group Comparisons of Blood Pressure, bioactive nitric oxide (S-Nitrosoglutathione) and Total 8-Isoprostane Levels after Dark and White Chocolate
Sweet effects of cocoa
Reduce fasting glucose
and improved
insulin sensitivity
Almoosawi S etal, Br J Nutr 2010
The effect of polyphenol-rich dark chocolate on fasting capillary
whole blood glucose, in healthy overweight and obese subjects
Mixed between–within subjects ANOVA revealed a significant
reduction in fasting capillary blood glucose concentrations
(p=0.002), following dark chocolate consumption.
Grassi, D. et al. J. Nutr. 2008;138:1671-1676
Cocoa improves insulin resistance in patients with impaired glucose tolerance
HOMA-IR homeostasis model assessment of
insulin resistance = fasting insulin*glucose/22.5
FRDC: flavanol-rich
dark chocolate
FFWC: flavanol-free
white chocolate
Improved
vascular function
Sweet effects of cocoa
Cardiovascular effects of cocoa: Potential mechanisms
Corti R, Flammer AJ et al. Circulation 2009
Schroeter Hagen et al. (2006) Proc Natl Acad Sci USA 103, 1024-9
Parallel elevation of circulating NO species, plasma flavanols and enhancement of endothelial function
FMD % Increase RXNO (nM) Sum of plasma flavanols (nM)
hFCD = high flavonoid cocoa drink
lFCD = low flavonoid cocoa drink
RXNO = plasma nitroso species
FM
D in
%
Dark Chocolate
Effect of commercially available flavonoid-rich
chocolate on vascular function in young smokers
F. Hermann, Heart 2006;92;119-120
Grassi, D. et al. J. Nutr. 2008;138:1671-1676
Cocoa improves vascular function in
hypertensive patients
Cocoa improves vascular
function in diabetic patients
Balzer J, et al., JACC 2008;51(22):2141-9
flavanol-rich cocoa (321 mg flavanols per dose)
nutrient-matched control (25 mg flavanols per dose)
N = 41 medicated diabetic patients
Heart Transplanted Patients
Flammer AJ, et al, Circulation 2007 Nov 20;116(21):2376-82.
FM
D %
0
2
4
6
8
10 Dark chocolate
Control chocolate
**
*♯
V1 V2 V3 V4
Baseline + 2 hours + 2 weeks + 4 weeks
* p<0.05 as compared to baseline in the group receiving flavonoid-rich chocolate♯ p=0.004 between V4 in the group receiving flavonoid-rich and control chocolate
Flammer AJ, Sudano I et al, Submitted
Heart failure patients
Sweet effects of cocoa
Reduced
platelet reactivity
Aspirin-like effect of cocoa on platelet function
Pearson DA et al, Thromb Res. 2002 May 15;106(4-5):191-7.
Shear stress induced platelet plug formation collagen-ADP
induced closure times
Baseline
After 2 hours
F. Hermann, Heart 2006;92;119-120
...in young smokers
Dark chocolate acutely
reduces platelet adhesion....
0
1
2
3
4
5
6
7
8
Baseline 2 hours
Pla
tele
t A
dh
es
ion
(%
)
Flammer AJ, Sudano I et al, Submitted
...in patients with heart failure
...in heart-transplanted patients
Flammer AJ, et al, Circulation 2007
Other:
Anti-Inflammatory
Lipid profile
Sweet effects of cocoa
Dark chocolate and lipids:
While some studies and a recent metaanalysis (Jia LLX et al, Am
J Clin Nutr 2010) suggest that it may reduce total cholesterol,
LDL-cholesterol and ox-LDL and increase HDL, some other
studies showed no effect of cocoa/dark chocolate on lipids (Katz DL et al, Antioxid Redox Signal. 2011 Apr 7)
Dark chocolate modulates inflammation:
-reduces NF-Kb (Lew KW et al, J Nutr 2006),
- reduces reactive oxygen species (Maytin M et al, Curr Ather Rep
1999, Selmi C et al, J Card Pharmac 2006 and Shapiro H et al, Nutrition 2009)
- reduces plasma leukotrienes (Sies H et al, Am J Clin Nutr 2005)
Gastro-esophageal reflux disease
Chocolate has found to reduce lower esophageal sphincter pressure (Wright LE et al, AmJ Dig Dis 1975, Murphy DW et al, Am J Gastroenterology 1988)
No study about symptoms and elimination of chocolate from the diet
Migräne, Costipation, Acne, Weight gain
No conclusive data or no studies
Chocolate and disease: the dark side of the moon
Antioxidative effects of cocoa have been disputed
Fruits and vegetables contain macro- and micronutrients in
addition to flavanols, which may affect total antioxidative capacity
of plasma
The large increase in plasma total antioxidative capacity
observed after the consumption of flavanol-rich food could be
also due to the increased uric-acid levels resulting from fructose
metabolism
Caution remark
Sies H. J Nutr 2007;137:1493-5; Lotito SB, Frei B. Free Radic Biol Med 2006;41:1727-46.
Conclusions
• Cocoa and Chocolate appear to exert beneficial cardiovascular effects, probably mainly mediated by its polyphenols.
• Beneficial vascular effects are most likely due to an increased bioavailability of nitric oxide.
• This may explain the improvement in endothelial and platelet function as well as the effects on blood pressure, and insulin resistance, thus positively impacting cardiovascular health.
Vegetable & fruits or chocolate?
BOTH!
Take Home Message
Chocolate as a drug?
December 27th, 2005
From Nicholas Bakalar
Dark chocolate, but not white chocolate,
may improve vascular and platelet function
in smokers’ damaged arteries. Suisse
researchers recruited 25 smokers, and
divided them into two groups. One group
ate about two ounces of dark chocolate
containing 74 percent cocoa, the other
consumed two ounces of white chocolate,
which contains no cocoa.
Thank you for your attention
Proof of concept: Vascular response afteroral ingestion of Epicatechin
Schroeter, Hagen et al. (2006) Proc. Natl. Acad. Sci. USA 103, 1024-9
p=0.03
p<0.001 p=0.069
p=0.096
TRAP=total reducing antioxidative capacity;
FRAP=ferric reducing antioxidative capacity
Cocoa and antioxidative properties
Flammer AJ, et al, Circulation 2007 Nov 20;116(21):2376-82.
Pulse wave amplitude responses to cocoa and L-NAME
Fisher et al. J Hypertens 2003: 2281-6L-NAME = NG-nitro-l-arginine methyl ester
Baseline demonstrates normal variability in digital pulse wave amplitude
After 4 days of ingestion of flavanol-rich cocoa there is an increase more than 12 h after the last dose of cocoa (P = 0.01)
Exposure to an additional 230 ml dose of cocoa led to a further increase 90 min later (P = 0.01)
After ingestion of cocoa on day 5 the nitric oxide synthesis inhibitor, l-NAME, had a dramatic effect in reversing dilation (P = 0.004)
Pulse wave measured at the finger by volume-sensitive validated calibrated plethysmograph