1. Caffeine Safety: Issues Raised over
the Past Year
James R. Coughlin, PhD CFS
President, Coughlin & Associates
Aliso Viejo, California
jrcoughlin@cox.net
www.linkedin.com/in/jamescoughlin
Symposium - “Caffeine: Critical Science Issues and
Public Health Consequences“
40th Annual Summer Meeting of
The Toxicology Forum
Aspen, Colorado
July 7, 2014

2. Agenda
• My Historical Perspective on Caffeine & Health Issues
• Caffeine Issues in 2013-2014 -
• Energy Drinks & Other Foods / Beverages
• Congressional, FDA, Health Canada, EFSA Focus
• Cardiovascular Issues
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4. My 30+ Year Perspective on Caffeine / Health
…on Rats, Mice & Humans and Almost Every Disease
…on “Good” & “Bad” Science, Policy & Media Coverage
…on Caffeine’s Beneficial Health Effects
… First 20 Years: Much Bad News! Caffeine was linked to
many animal toxicities and human diseases!
… Last 15 or so Years…Very Big Turn Around: “Good News”
is that almost all of the Bad News about caffeine was
WRONG!
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5. Caffeine’s “Maligning” Started in Late 1970’s and
Ballooned in the 1980’s and Early 1990’s
• Coffee and heart attacks…was it the caffeine?
• Caffeine and birth defects in rats (U.S. FDA, 1978);
hundreds of subsequent studies on reproductive &
developmental effects in humans
• Caffeine and urinary calcium loss; osteoporosis risk?
• CNS: anxiety, sleep disturbance, “addiction”
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8. ILSI – “Beverage Caffeine Intakes in the U.S.”
• 96% of beverage caffeine consumed from coffee, soft
drinks and tea; Coffee remains the largest contributor
• Energy drinks & shots and chocolate beverages
contribute little to caffeine intakes
• Teenagers (13–17 years) or young adults (18–24
years): 9-10% of their caffeinated beverage intake
was energy drinks
• Intakes from energy drinks represent less than 2% of
total daily mean caffeine values for all caffeinated
beverage consumers.
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10. Caffeine and Reproductive Effects
• Issue first began with birth defects (missing digits) in
rats gavaged with very high-doses (FDA, 1978), but no
adverse effects seen in FDA follow-up “sipping” study
• Human studies followed: delayed conception; premature
birth; low birth weight babies; fetal death; spontaneous
abortion (miscarriage), congenital defects
• But now there are more than 25 published reviews
supporting caffeine’s safety:
• Peck, Leviton, Cowan (Food Chem. Toxicol. 2010)
• Brent, Christian, Diener (Birth Defects Res. 2011)
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11. Caffeine and “Addiction”
• Dependence, tolerance and withdrawal headache were
cited in many published studies going back to the late
1980’s (mostly among psychiatric patients consuming
up to 20 cups/day)
• Current view is very reassuring:
• Caffeine use was not classified as a “substance use
disorder” (new term for addiction) in APA’s DSM-5
psychiatric “bible” (published May 2013)
• However, DSM-5 did recognize caffeine withdrawal
• Addiction over-warnings trivialize dangers of real drugs
of abuse.
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12. Caffeine’s Beneficial Physiological Effects
• Mild central nervous system (CNS) stimulant
• Improves cognitive performance and mental processing; increases
wakefulness; improves work performance and enhances mood
• Increases capacity for physical work & exercise; improves
muscular performance and endurance sports
• Relaxes smooth muscle, especially bronchial (opens airways), and
increases blood flow in heart and kidneys
• Produces a slightly higher metabolic rate (some evidence of an
ergogenic “fat burning” effect)
• Risk reductions for Parkinson’s & Alzheimer’s diseases,
depression & suicide.
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13. So with all this more recent good
news, why are we still worrying about
Caffeine?
~
New safety concerns have been raised
for Energy Drinks and new food
products containing caffeine
~
…by researchers who do not know the
caffeine literature supporting its safety
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14. “Experts” Letter to FDA Commissioner
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15. Added Caffeine in Gum - FDA Statement on
Wrigley’s Announcement (May 8, 2013)
Michael R. Taylor, FDA Deputy Commissioner for Foods and Veterinary
Medicine, provided this response to Wrigley's announcement regarding
withdrawal of Alert Energy Caffeine Gum:
On May 8, 2013, Wrigley (a subsidiary of Mars) announced its decision to pause
production, sales, and marketing of Alert Energy Caffeine Gum. This announcement
was made following a series of discussions with the FDA in which the agency
expressed concerns about caffeine appearing in a range of new foods and beverages.
The FDA applauds Wrigley’s decision and its recognition that we need to improve
understanding and, as needed, strengthen the regulatory framework governing the
appropriate levels and uses of caffeine in foods and beverages. The company’s action
demonstrates real leadership and commitment to the public health.
We hope others in the food industry will exercise similar restraint. We look forward to
working with industry, the scientific and medical community, and all interested parties
to address the issues posed by added caffeine in foods and beverages.
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17. Institute Of Medicine (IOM) - FDA Requested Workshop on
“Potential Health Hazards of Caffeine In Food and Dietary
Supplements”
21 Questions Posed in “Backgrounder” Document (6/28/2013)
• Exposure
• Absorption, distribution, metabolism, and excretion (ADME)
• Cardiovascular effects
• Neurological and behavioral effects
• Tolerance and withdrawal
• Population risk characteristics
• Scientific data on caffeine
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18. IOM Workshop Objectives
• Evaluate the epidemiological, toxicological, clinical and other relevant
literature to describe important health hazards associated with caffeine
consumption.
• Delineate vulnerable populations who may be at risk from caffeine
exposure.
• Describe the risk of cardiovascular and other health effects, including
additive effects with other ingredients and effects related to preexisting
conditions.
• Explore safe caffeine exposure levels for general and vulnerable
populations.
• Identify data gaps on caffeine stimulant effects, including but not limited
to cardiovascular, central nervous system, or other health outcomes.
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20. Mike Taylor’s Blog on Caffeine
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22. European Food Safety Authority
• EFSA. 2009. Scientific Opinion of the Panel on Food Additives and
Nutrient Sources added to Food, on a request from the Commission on
the use of taurine and D-glucurono-γ-lactone as constituents of the so-
called “energy” drinks. EFSA Journal 935, 1-31.
• Zucconi et al., 2013. “Gathering consumption data on specific consumer
groups of energy drinks.” [190 pp.] www.efsa.europa.eu/publications
• EFSA opinion on caffeine’s safety requested by the EC (Feb 2013):
• Maximum levels of caffeine intake from all sources
• Risk of interaction of caffeine with alcohol and other ingredients of
“Energy Drinks”
• Focus: general population, adults performing physical activities of
various intensities, pregnant & lactating women, children &
adolescents
• EFSA’s Working Group on Caffeine: Draft Opinion will issue in
September, public consultation for 6-8 weeks, adoption by end of
year.
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23. Cardiovascular Issues
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24. “Tolerance to the Humoral and Hemodynamic Effects of
Caffeine in Man” – Vanderbilt’s David Robertson (1981)
• Previous studies showed acute caffeine in caffeine-naïve subjects
increased BP, heart rate, plasma epinephrine & norepinephrine,
plasma renin activity and urinary catecholamines
• Robertson did a double-blind study of the effects of chronic
caffeine administration on these same variables
• Demonstrated that near complete tolerance for both the humoral
and hemodynamic variables developed over the first 1-4 days of
caffeine intake
• Showed no longterm adverse effects of caffeine on BP, heart rate,
plasma renin activity, plasma catecholamines, or urinary
catecholamines.
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28. Cardiovascular Disease (CHD), Stroke and Overall
Mortality of Coffee / Caffeine Consumption
* All studies – either no increased risk or reduced risk *
• Andersen 2006 – Iowa Women’s Health Study, coffee
• Lopez-Garcia 2006, 2006, 2008, 2011 – Harvard cohort studies, coffee & caffeine
• Greenberg 2008 – Framingham cohort, caffeinated coffee
• Zhang 2009, 2009 – Harvard Nurses & Health Professionals cohort, men &
women, coffee
• Wu 2009 – Meta-analysis of 21 cohort studies, coffee
• de Koning Gans 2010 – Coffee / tea & CHD / mortality / stroke
• Larsson 2011 – Meta-analysis, coffee / stroke
• Mesas 2011 – Meta-analysis, hypertensives, coffee RCTs & cohort studies
• Freedman 2012 – NIH-AARP cohort, coffee, total & cause-specific mortality
• Floegel 2012 – EPIC / Europe cohort study, coffee / chronic diseases
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29. Cardiovascular Disease (CHD), Stroke and Overall
Mortality of Coffee / Caffeine Consumption
* All studies – either no increased risk or reduced risk *
• Andersen 2006 – Iowa Women’s Health Study, coffee
• Lopez-Garcia 2006, 2008, 2011 – Harvard cohort studies, coffee & caffeine
• Greenberg 2008 – Framingham cohort, caffeinated coffee
• Zhang 2009, 2009 – Harvard Nurses & Health Professionals cohort, men &
women, coffee
• Wu 2009 – Meta-analysis of 21 cohort studies, coffee
• de Koning Gans 2010 – Coffee / tea & CHD / mortality / stroke
• Larsson 2011 – Meta-analysis, coffee / stroke
• Mesas 2011 – Meta-analysis, hypertensives, coffee RCTs & cohort studies
• Freedman 2012 – NIH-AARP cohort, coffee, total & cause-specific mortality
• Floegel 2012 – EPIC / Europe cohort study, coffee / chronic diseases
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32. Take Home Message
~
Attackers should know their
Caffeine literature before they step
up on their Soapbox to attack it as
the causative agent!
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33. Thank You!
~
Questions?