1. Health Benefits of Coffee Consumption Vanderbilt Coffee Conference October 26, 2007

2. Coffee is healthful (…rather than harmful) Physicians in the U.S. have long advised their patients that coffee consumption is potentially detrimental to health Attitudes are changing due to emerging epidemiologic and mechanistic research which shows health benefits of coffee compatible with good health health promoting behaviorCoffee consumption is now best viewed as compatible with good health and perhaps even as a health promoting behavior

3. Latest epidemiologic studies consistently show coffee consumption reduces rates of common diseases Depression/anxiety Heart disease Type 2 Diabetes associated with obesity Parkinson’s and Alzheimer’s diseases Cancer Alcohol/drug addiction

4. Coffee is not only caffeine & is altered in roasting and metabolism Compound Green beans Roasting Metabolism __________________________________________________ __ Total CGA8%5%0% 5-CAQA5%2%0% 2% CAQ0%2%0% CA0%1%1% 4% DHCA0%0%4% Caffeine2%2%2% __________________________________________________ __ CGA = chlorogenic acidsCAQ = caffeoylquinides 5-CAQA = caffeoylquinic acidQA = quinic acids CA = caffeic acidDHCA = dihydrocaffeic acid

5. mechanisms Study of coffee constituents may help us better understand the mechanisms for health benefits of coffee consumption Depression/anxiety (suicide)* * Atherosclerosis (cardiovascular deaths)* * Degenerative brain disorders (Parkinson’s and Alzheimer’s diseases)* * Cancer* Alcohol/drug addiction, type 2 diabetes, and obesity* * (cirrhosis)* *Antioxidant activity *Opioidergic modulation *Adenosine agonism

6. damage DNA, lipids, proteinsHighly reactive oxygen species formed in the body can damage DNA, lipids, proteins ROS implicated in cancer, heart disease, diabetes, neurodegenerative disorders, and aging, etc. neutralize ROSCan natural constituents of coffee neutralize ROS and their adverse consequences? improve endothelial functionDoes coffee improve endothelial function and thereby have protective effects against atherosclerosis and other related diseases? Do antioxidant actions account for some of the health benefits of coffee?Do antioxidant actions account for some of the health benefits of coffee? Antioxidant activity of coffee

7. : Dihydrocaffeic acid (DHCA) inhibits breakdown of endothelial cell vitamin E J. Huang et al. / Journal of Nutritional Biochemistry 15 (2004) 722 –729

8. DHCA repairs endothelial dysfunction by its antioxidant effects

9. Inhibits release of several neurotransmitters Increases regional blood perfusion Stabilizes membrane potentials and decreases heart and brain tissue excitability Prevents cellular damage during various tissue insults (e.g., oxidant stress, excitotoxicity) Caffeine is a potent adenosine antagonist Do CGAs in coffee modify the effects of caffeine on the adenosine system?Do CGAs in coffee modify the effects of caffeine on the adenosine system? Adenosine effects of coffee

10. Effect of DIFEQ and vehicle on horizontal locomotor activity in C57BL6/J mice dePaulis et al, European Journal of Pharmacology 442 (2002) 215– 223

11. Chlorogenic acid opposes the effects of caffeine on adenosine Adenosine A 2A -receptor Transporter A 1 -receptor Caffeine CGA -

12. Endogenous opioids modulate ‘pleasure’, pain, mood, and ‘drive’ centers in the brain as do opiate drugs, e.g. morphine Opioid antagonists can prevent relapse in alcoholism and other addictions CGA quinides inhibit mu-opioid receptors Can quinides in coffee be used to treat alcoholism or other addictions?Can quinides in coffee be used to treat alcoholism or other addictions? Opioid activity of coffee

13. Coffee extract antagonizes morphine-induced analgesia de Paulis et al, Psychopharmacology (2004) 176: 146–153

14. Chlorogenic acid blocks mu-opioid receptor Endogenous opioid Mu-opioid receptors CGA

15. Effect of Vivitrex ® (Long-Acting Injectable Naltrexone) in Maintenance of Abstinence 0 10 20 30 40 50 60 70 80 90 100 Percent Abstinent p < 0.025 Placebo (n = 28) Vivitrex (n = 28) 12354678109111213151416171820192122232524262728302931 Weeks JC Garbutt et al, JAMA 2005;293:1617-1625

16. U.S. Obesity Surgeries per Year (1995-2005) Reflect Cost of Diabetes 15% of all healthcare costs in U.S. 150 M diabetes cases worldwide Prevalence expanding (50% per decade) due to over-eating Predicted prevalence of 300 M by 2050

17. Association between coffee consumption and type 2 diabetes in individual cohort studies and meta-analysis of all cohort studies RM van Dam and FB Hu, JAMA. 2005;294:97-104

18. Quinides of roasted coffee enhance insulin action in concious rat Shearer et al, J. Nutr. 133: 3536–3539, 2003

19. ‘Behavioral’ Addictions: Drives Gone ‘Awry’ Nutrition ------------ Obesity Reproduction ------ Sex Exploration --------- Gambling ‘…as far as the brain is concerned, a reward’s a reward, regardless of whether it comes from a chemical or an experience.’ Constance Holden, Science (2001)

20. Coffee Consumption and Duration of Sobriety in AA Participants (n=235) Reich et al (in preparation)

21. Length Sobriety r=0.16 p=0.013 Coffee use (cups/day) is significantly correlated with duration of sobriety r=0.16 p=0.013 Reich et al (in preparation)

22. Brain Reinforcement Pathways

23. Collaborators Vanderbilt UniversityVanderbilt University –Tomas de Paulis, Ph.D. –Mary Dietrich, Ph.D. –Reid Finlayson, M.D. –Edward F. Fischer, Ph.D. –Ruggero Galici, Ph.D –Junjun Huang, M.D. –James May, M.D. –Michael P. McDonald, Ph.D. –Michael S. Reich, B.S. –David H. Wasserman, Ph.D. National Institute on Alcohol Abuse and AlcoholismNational Institute on Alcohol Abuse and Alcoholism –David M. Lovinger, Ph.D. Universidade Federal do Rio de Janeiro, BrazilUniversidade Federal do Rio de Janeiro, Brazil –Adriana Farah, Ph.D. –Darcy Roberto Lima, M.D., Ph.D. –Luiz C. Trugo, Ph.D. University of Calgary, Alberta, CanadaUniversity of Calgary, Alberta, Canada –Jane Shearer, Ph.D. University of Guelph, Ontario, CanadaUniversity of Guelph, Ontario, Canada –Terry E. Graham, Ph.D.

24. Brazil Colombia Guatemala Japan Mexico USA (NCA, Kraft Foods, Nestle, Sara Lee, Starbucks) Acknowledgements