1. Coffee, Caffeine and Cardiovascular Disease
Ahmed El-Sohemy
Canada Research Chair in Nutrigenomics
Department of Nutritional Sciences
University of Toronto

2. Diet Genes Nutrigenomics: Using genomic information and techniques in
molecular genetics & genomics to address
issues important to nutrition and health.
Diet
Genes
Food preferences

3. Why bother with genetics/genomics?
 Challenges for Nutritional Epidemiology
Measurement error
Confounding (residual)
Recall Bias (case-control)

4. Is Coffee associated with CVD?
 Risk
No Effect
 Risk

5. Is Coffee associated with CVD?
Coffee or associated lifestyle?
Are coffee abstainers at  risk?
Does risk depend on age?
Which component of coffee?
There are a number of important issues that often need to be addressed regarding the epidemiology of coffee and heart disease, which might explain some of the inconsistencies in studies
In some populations, coffee is assoicated with unhealthy lifstyle factors such as smoking and inactivity, factors of which may be associated with the disease. Therefor its possible that previous associations might have been due to residual confounding
It has been proposed that the higher risk of heart disease among the group with the lowest intake might be due to individuals with underlying diseases who are limiting their coffee intake 12,14.
Some studies report that young individuals may be more sensitive to the effects of coffeeor alteratively, cofee becomes a less significant health factor. Therefor studies made up of predominately younger subjects would more likely report an associatiion compared to studies consisting of older subjects.

6. Bioactives in coffee aliphatic acids magnesium potassium caffeine
melanoidins
This is especially difficult given the numerous compounds found in a single cup of coffee, which may have benefical or adverse effects on the heart.
Of all these compounds however, caffeine has been one which has been strongly implicated in the development of hdx .
diterpenoids
polyphenols

7. Caffeine (1,3,7-trimethylxanthine)
Caffeine has been consumed in some form for thousands of years and is currenlty the most widely consumed stimulant in the world with an estimated 80 to 90% of adults reporting regular consumption of caffeine-containing beverages and foods.
Sources of caffeine.
Intakes vary by courntry and individual

12. Caffeine
Metabolism
SNPs
Caffeine
Target
SNPs
Coffee
CVD

13. Caffeine
Metabolism
SNPs
Caffeine
Target
SNPs
Coffee
CVD

14. Caffeine Paraxanthine 1,7-dimethyluric acid
CYP1A2
Paraxanthine
1-methylxanthine
1-methyluric acid
5-acetylamino-6-formylamino-3-methyluracil
1,7-dimethyluric acid
Para- 1,7 dimethylxanthine

15. Genetic Variation in CYP1A2 -163 AC
fast
slow

16. Costa Rica Study 2013 cases (myocardial infarction)
2013 population-based controls
- matched (age, sex, area of residence)
Data collection:
- food frequency questionnaire
- health and lifestyle questionnaire
- fasting blood sample (DNA)

17. CYP1A2 Genotype Distribution
Controls %
Cases
A/A
A/C
C/C 46 43 10 45 44 11
rapid
slow

19. Coffee Intake and Risk of Myocardial Infarction*
* P<0.05
Cornelis et al., JAMA 295: , 2006

20. Coffee Intake and Risk of Myocardial Infarction* *
A/A A/C + C/C
* P<0.05
Cornelis et al., JAMA 295: , 2006

21. Coffee Intake and Risk of Myocardial Infarction
Subjects <50 Years of Age * * * *
A/A A/C + C/C
* P<0.05
Cornelis et al., JAMA 295: , 2006

24. Personalized Dietary Advicevs
Public Health Recommendations

25. Recommended Maximum Caffeine Intake
(Health Canada)

29. Genetic modifiers of exposure Genetic modifiers of biological effect
CYP1A2 FMO
CYP2A6 NAT2
CYP2E1
UGT
SULT
CYP1A2 CYP3A4
CYP2D6 CYP1A1 UGT SULT
CYP2C9 CYP2E1
GST
ADR ADORA
HTT GRK
HTR COMT
CETP PLTP
LDLR ACAT
SREBP GST
ACE TNF
NFkB VCAM1
PKC PPARG
PDE CREB
GLUT PKA
GLP1R GLUT
FAS1 ACE
NOX G6PT1
Caffeine
Diterpenes
CHD
Risk
Flavonoids
Figure 2 Potential genetic modifiers of exposure and biological effect
Polyphenols
Curr. Opin. Lipidol, 18: 13-19, 2007

30. Health Outcome Coffee Genes Genotype A Increase Genotype B No effect
Genotype C
Genotype B
Increase
Decrease
No effect

31. Caffeine Consumption Habits Study
Healthy Men and Women aged years (n=940)
Food Frequency Questionnaire
Caffeine consumption
Caffeine Consumption Habits Questionnaire
- Acute effects of caffeine
- Caffeine withdrawal symptoms
- Limiting or avoiding caffeine

32. DRD2 C957T Genotype and “Elevated Mood” Among Men and Women** *
* P<0.05
** P<0.005

33. DRD2 C957T Genotype and Caffeine Intake Among Men and Women*
This is the old one when there were a total of ~640 subjects HOWEVER, this analysis excluded mood disorder
* P<0.05

35. ACKNOWLEDGMENTS
Hannia Campos
Edmond Kabagambe
Tom Wolever
CCD Investigators
Paul Corey
David Jenkins
Hyeon-Joo Lee
Lindsay Stewart
Daiva Nielsen
Alejandra Navarro-Allende
Susana Huang
Sarah Herd
Darren Brenner
Bibiana Garcia-Bailo
Marilyn Cornelis
Leah Cahill
Karen Eny
Bénédicte Fontaine-Bisson
Ilana Platt
Stephen Ozsungur
Clare Toguri
Advanced Foods and Materials Network Centres of Excellence
Natural Sciences and Engineering Research Council
Canadian Institutes of Health Research
Canada Research Chairs