The document provides a historical perspective on caffeine and health issues over the past 30+ years. It summarizes that in the 1970s-1990s, many studies linked caffeine to negative health outcomes in animals and humans. However, in the last 15 years, most of these findings have been disproven by larger and higher quality studies showing little or no adverse health effects of caffeine. Recent concerns have focused on caffeine in energy drinks and other new products. Several regulatory agencies are reviewing the science on caffeine safety. The document outlines many of the recent reviews, studies, and regulatory activities around caffeine.

1. Caffeine Safety: A Three-Decade
Review and the 2013-2014 Landscape
James R. Coughlin, PhD CFS
President, Coughlin & Associates
Aliso Viejo, California
jrcoughlin@cox.net
www.linkedin.com/in/jamescoughlin
Symposium - “The Buzz on Caffeine:
New Developments in Safety and Regulation of
Foods and Dietary Supplements“
IFT Annual Meeting
New Orleans
June 23, 2014

2. Outline
• My Historical Perspective on Caffeine & Health Issues
• Caffeine in 2013-2014 -
• Energy Drinks & Other Foods / Beverages
• Congressional, FDA, Health Canada, EFSA Focus
• Where do we go from here?
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3. My 30+ Year Perspective on Caffeine / Health
…on Rats, Mice & Humans
…on Almost Every Disease
…on “Good” & “Bad” Science and Policy
…on “Good” & “Bad” Media Coverage
…on Caffeine’s Beneficial Health Effects
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4. Caffeine/Health Conclusions:
1978 - 2014
… First 20 Years:
A lot of Bad News! Caffeine was linked to many animal
toxicities and human diseases!
… Last 15 or so years…Very Big Turn Around:
The “Good News” is that almost all of the Bad News
about caffeine was WRONG!
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5. Caffeine’s “Maligning” Started in the 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);
subsequest studies on reproductive & developmental effects
in humans
• Caffeine and urinary calcium loss; osteoporosis risk?
• Caffeine anxiety, sleep disturbance, “addiction”
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7. “Tolerance to the Humoral and Hemodynamic Effects
of Caffeine in Man” – David Robertson et al. (1981)
• Acute caffeine in subjects who do not normally ingest caffeine
shown to increase blood pressure, heart rate, plasma epinephrine
& norepinephrine, plasma renin activity and urinary
catecholamines
• Robertson used a double-blind design to study the effects of
chronic caffeine administration on these same variables
• Near complete tolerance, in terms of both humoral and
hemodynamic variables, developed over the first 1-4 days of
caffeine
• No longterm adverse effects of caffeine on blood pressure, heart
rate, plasma renin activity, plasma catecholamines, or urinary
catecholamines could be demonstrated.
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9. Cardiovascular Disease (CHD), Stroke and Overall
Mortality of Coffee Consumption
• Andersen 2006 – Iowa Women’s Health Study, coffee
• Lopez-Garcia 2006, 2006, 2008, 2011 – Harvard cohort studies, coffee
• 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 of coffee RCTs and cohort studies
• Pelchovitz & Goldberger 2011 – Review of caffeine & arrhythmias
• Freedman 2012 – NIH-AARP cohort, coffee, total & cause-specific mortality
• Floegel 2012 – EPIC/Europe cohort study, coffee/chronic diseases
• Cheng 2014 – 6-cohort meta-analysis, caffeine reduced atrial fibrillation
• Je & Giovannucci 2014 – 20-cohort meta-analysis, coffee reduced mortality
• Ding 2014 – 36-cohort meta-analysis, coffee reduced CHD
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10. Caffeine and Reproductive Effects
• Began with birth defects (missing digits) in rats gavaged
with very high-doses (FDA, 1978), but no adverse effects
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 Osteoporosis
• Excess calcium & bone loss in post-menopausal
women causes millions of bone fractures (mostly hip)
• Early 1980’s acute, 24-hour human studies on non-
caffeine consuming subjects were originally
misinterpreted; saw slight calcium losses in urine
• Many longer-term, human clinical studies have
shown little excess calcium loss or bone loss and no
increased risk of osteoporosis.
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12. 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 is not classified as a “substance use
disorder” (new term for addiction) in APA’s DSM-5
psychiatric “bible” (published May 2013)
• DSM-5 did recognize caffeine withdrawal
• Addiction over-warnings trivialize dangers of real drugs of
abuse.
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13. What Science Allowed the Bad Myths to Happen…
and Why have Some New Myths Popped Up?
… Acute vs. Chronic effects:
 Partial / full tolerance to caffeine develops in humans
consistently consuming caffeine and coffee daily
… Most of the Myths and Fears are based on:
 Acute effects’ testing of non-coffee consuming subjects
 Massive doses of caffeine fed to animals for a lifetime
 Smaller, poorly conducted human studies
…Failure to Know the Vast Literature
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14. 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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15. 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.
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16. Recent Studies / Reviews on
Energy Drinks?
~
…by researchers who do not know
the 30+ years of caffeine literature
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17. Congressional and FDA Concerns
over Caffeine in Energy Drinks
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18. “Experts” Letter to FDA Commissioner
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19. 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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21. “Backgrounder” for the Institute Of Medicine (IOM) FDA-
Requested Workshop on “Potential Health Hazards of Caffeine
In Food and Dietary Supplements” (6/28/2013) – 21 Questions
• 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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24. • Goal - To bring together and summarize relevant research
on the use and biology of Energy Drinks and to highlight the
most critical research gaps.
• Sponsored by NIH Office of Dietary Supplements and
several other NIH Institutes.
• Talks focused on patterns of use, sensitive subpopulations,
safety and health effects of Energy Drinks and their
ingredients.
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25. Mike Taylor’s Blog on Caffeine
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26. Other Regulatory Agencies
Concerns
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28. 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 European
Commission (Feb 2013):
• Delays any authorization of certain health claims from art. 13.1
• Maximum levels of caffeine intake from all sources
• Risk of interaction of caffeine with alcohol and other ingredients of
“Energy drinks”
• Population groups: population in general, adults performing
physical activities of various intensities, pregnant women, lactating
women, children and adolescents
• EFSA’s Working Group on Caffeine opinion may issue in the next
few months.
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30. ILSI – “Beverage Caffeine Intakes in the U.S.”
• 96% of beverage caffeine consumed is from coffee, soft drinks and
tea
• Coffee remains the largest contributor to beverage caffeine intakes
• Energy drinks, energy shots and chocolate beverages contribute
little to caffeine intakes
• Only 4.3% of all caffeinated beverage consumers were consumers
of energy drinks
• In teenagers (13–17 years) or young adults (18–24 years), 9-10% of
caffeinated beverage consumers were consuming 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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31. What Happens
Next?
~
Thank You!