Vanderbilt Coffee Conference
October 26, 2007
Health Benefits of
Coffee Consumption
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 health and perhaps
even as a health 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%
0%
CA
0%
1%
1%
DHCA
0%
0%
4%
Caffeine
2%
2%
2%
__________________________________________________
__
CGA = chlorogenic acids
CAQ = caffeoylquinides
5-CAQA = caffeoylquinic acid
QA = quinic acids
CA = caffeic acid
DHCA = dihydrocaffeic acid
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
Antioxidant activity
of coffee
• Highly reactive oxygen species formed in the body
can damage DNA, lipids, proteins
• ROS implicated in cancer, heart disease, diabetes,
neurodegenerative disorders, and aging, etc.
• Can natural constituents of coffee neutralize ROS
and their adverse consequences?
• Does 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?
:
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
DHCA:
dihydrocaffeic acid
Endothelial Cell
Arginine
DHCA
Arg
(+)
eNOS
Smooth
Muscle Cell
GTP
DHCA (+)
GC
Blood
Citr
NO•
ONOODHCA
DHCA
O2• H2O2
cGMP
Adenosine effects
of coffee
• 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?
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
A1-receptor
Adenosine
Transporter
CGA
A2A-receptor
Caffeine
Opioid activity of
coffee
• 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?
Hotplate latency (sec)
Coffee extract antagonizes
morphine-induced
analgesia
25
20
15
10
5
0
Coffee
Morphine 1.0
Coffee +
Morphine 1.0
de Paulis et al, Psychopharmacology (2004) 176: 146–153
Chlorogenic acid
blocks mu-opioid
receptor
Endogenous
opioid
CGA
Mu-opioid
receptors
®
Vivitrex
Percent Abstinent
Effect of
(Long-Acting
Injectable Naltrexone) in
Maintenance of Abstinence
100
90
80
70
60
50
40
30
20
10
0
p < 0.025
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
Weeks
Placebo (n = 28)
Vivitrex (n = 28)
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
reward’s a reward, regardless of whether it
comes from a chemical or an experience.’
Constance Holden, Science (2001)
Coffee Consumption and
Duration of Sobriety in AA
Participants (n=235)
50.0%
45.0%
40.0%
35.0%
30.0%
25.0%
20.0%
15.0%
10.0%
5.0%
0.0%
None
1-2
C ups/Day
3-4
C ups/Day
>4
C ups/Day
<= 15 <= 45 <= 75 <=
<=
<= > 5.5
Days Days Days 1.5 Y r 2.5 Y r 5.5 Y r Y r
Reich et al (in preparation)
Coffee use (cups/day) is
significantly correlated
with duration of sobriety
r=0.16
p=0.013
r=0.16
p=0.013
Reich et al (in preparation)
Length Sobriety
Brain Reinforcement Pathways
Collaborators
• Vanderbilt 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 Alcoholism
– David M. Lovinger, Ph.D.
• Universidade 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,
Canada
– Jane Shearer, Ph.D.
• University of Guelph, Ontario,
Canada
– Terry E. Graham, Ph.D.
Acknowledgements
• Brazil
• Colombia
• Guatemala
• Japan
• Mexico
• USA (NCA, Kraft Foods, Nestle, Sara
Lee, Starbucks)