Health Benefits of Health Benefits of Coffee Coffee ConsumptionConsumption

Vanderbilt Coffee Vanderbilt Coffee Conference Conference

October 26, 2007October 26, 2007

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

• Coffee consumption is now best viewed as compatible with good healthcompatible with good health and perhaps even as a health promoting behaviorhealth promoting behavior

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

Coffee is not only caffeine & is altered in roasting and metabolism

Compound Green beans Roasting Metabolism____________________________________________________Total CGA 8% 5% 0% 5-CAQA 5% 2% 0% CAQ 0% 2%2% 0% CA 0% 1% 1% DHCA 0% 0% 4%4%Caffeine 2% 2% 2%____________________________________________________CGA = chlorogenic acids CAQ = caffeoylquinides5-CAQA = caffeoylquinic acid QA = quinic acidsCA = caffeic acid DHCA = dihydrocaffeic acid

Study of coffee constituents may help us

better understand the mechanismsmechanisms 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 activityAntioxidant activity*Opioidergic modulationOpioidergic modulation*Adenosine agonismAdenosine agonism

• Highly reactive oxygen species formed in the body can damage DNA, lipids, proteinsdamage DNA, lipids, proteins

• ROS implicated in cancer, heart disease, diabetes, neurodegenerative disorders, and aging, etc.

• Can natural constituents of coffee neutralize neutralize ROS ROS and their adverse consequences?

• Does coffee improve endothelial functionimprove endothelial function and thereby have protective effects against atherosclerosis and other related diseases?

• Do antioxidant actions account for some of the Do antioxidant actions account for some of the health benefits of coffee?health benefits of coffee?

Antioxidant activity of coffee

:Dihydrocaffeic acid (DHCA) inhibits breakdown of endothelial cell vitamin E

J. Huang et al. / Journal of Nutritional Biochemistry 15 (2004) 722 –729

DHCA repairs endothelial dysfunction by its antioxidant effects

eNOS

Arginine

Citr

Arg

NO•

O2• -

ONOO-

DHCA

DHCA

(+)

H2O2

GC

(+)GTP

cGMP

Endothelial CellEndothelial CellSmoothSmooth

Muscle CellMuscle Cell

Blood

DHCA

DHCA

DHCA: dihydrocaffeic acid

• 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 Do CGAs in coffee modify the effects of

caffeine on the adenosine system?caffeine on the adenosine system?

Adenosine effects of coffee

Effect of DIFEQ and vehicle on horizontal locomotor activity in C57BL6/J mice

dePaulis et al, European Journal of Pharmacology 442 (2002) 215– 223

Chlorogenic acid opposes the effects of caffeine on adenosine

Adenosine A2A-receptor

Transporter

A1-receptor

CaffeineCaffeineCGACGA

--

• 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 Can quinides in coffee be used to treat

alcoholism or other addictions?alcoholism or other addictions?

Opioid activity of coffee

Coffee extract antagonizes morphine-induced analgesia

0

5

10

15

20

25

Coffee Morphine 1.0 Coffee +

Morphine 1.0

Ho

tpla

te l

ate

nc

y (

se

c)

de Paulis et al, Psychopharmacology (2004) 176: 146–153

Chlorogenic acid blocks mu-opioid receptor

Endogenousopioid

Mu-opioidreceptors

CGACGA

Effect of Vivitrex® (Long-Acting Injectable Naltrexone) in

Maintenance of Abstinence

0102030405060708090

100

Per

cen

t A

bst

inen

t

p < 0.025

Placebo (n = 28) Vivitrex (n = 28)

1 2 3 54 6 7 8 109 11 12 13 1514 16 17 18 2019 21 22 23 2524 26 27 28 3029 31

Weeks

JC Garbutt et al, JAMA 2005;293:1617-1625

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

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

Quinides of roasted coffee enhance insulin action in concious rat

Shearer et al, J. Nutr. 133: 3536–3539, 2003

‘Behavioral’ Addictions: Drives Gone ‘Awry’

• Nutrition ------------ Obesity• Reproduction ------ Sex • Exploration --------- Gambling

‘…‘…as far as the brain is concerned, a as far as the brain is concerned, a reward’s a reward, regardless of reward’s a reward, regardless of

whether it comes from a chemical or whether it comes from a chemical or an experience.’an experience.’ Constance Holden, Science (2001)Constance Holden, Science (2001)

Coffee Consumption and Duration of Sobriety in AA Participants (n=235)

0.0%5.0%

10.0%

15.0%20.0%25.0%

30.0%35.0%

40.0%45.0%

50.0%

<= 15Days

<= 45Days

<= 75Days

<=1.5 Y r

<=2.5 Y r

<=5.5 Y r

> 5.5Y r

None

1-2C ups/Day3-4C ups/Day> 4C ups/Day

Reich et al (in preparation)

Length Sobriety

r=0.16p=0.013

Coffee use (cups/day) is significantly correlated with duration of sobriety

r=0.16p=0.013

Reich et al (in preparation)

Brain Reinforcement Brain Reinforcement PathwaysPathways

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 National Institute on Alcohol Abuse and Alcohol Abuse and AlcoholismAlcoholism– David M. Lovinger, Ph.D.

• Universidade Federal do Universidade Federal do Rio de Janeiro, BrazilRio de Janeiro, Brazil– Adriana Farah, Ph.D. – Darcy Roberto Lima, M.D.,

Ph.D. – Luiz C. Trugo, Ph.D.

• University of Calgary, University of Calgary, Alberta, CanadaAlberta, Canada– Jane Shearer, Ph.D.

• University of Guelph, University of Guelph, Ontario, CanadaOntario, Canada– Terry E. Graham, Ph.D.

•Brazil •Colombia•Guatemala•Japan•Mexico•USA (NCA, Kraft Foods, Nestle,

Sara Lee, Starbucks)

Acknowledgements