This document provides an overview of caffeine safety issues from the perspective of James Coughlin, PhD. Some key points: - Many earlier studies linked caffeine to health issues but most of these links have been disproven. Caffeine is generally recognized as safe in the amounts consumed from coffee, tea, and soda. - Newer concerns have been raised about added caffeine in energy drinks and foods. The FDA has expressed concerns about a lack of understanding around appropriate levels and uses of added caffeine. - Several regulatory agencies like the FDA, EFSA, and Health Canada are examining the scientific evidence on caffeine safety, conducting reviews of the literature, and exploring safe intake levels for both the general public and vulnerable

1. Overview of Caffeine Safety Issues:
What’s All the Fuss About?
James R. Coughlin, PhD CFS
President, Coughlin & Associates
Aliso Viejo, California
jrcoughlin@cox.net
www.linkedin.com/in/jamescoughlin
Panel Discussion - “Caffeine, Energy
Drinks and Ingredients: Are You
Prepared for FDA Action?
Supply Side West Global Expo &
Conference
Las Vegas, October 8, 2014

2. Is the Increased Concern
about Caffeine’s Safety
Justified?
I Don’t Believe It Is!
2

3. Agenda
• Caffeine & Health Issues - My Historical Perspective
• Caffeine Safety Issues in 2013-2014…
• Caffeine-containing Beverages’ Long History of Safe Use
• Energy Drinks & Newer Foods / Beverages
• U.S. Congress & FDA, Health Canada, EFSA
• Cardiovascular Issues – the Key Topic of Debate
3

6. My 30+ Years Perspective on Caffeine / Health
…on Rats, Mice & Humans, and Almost Every Disease
…on “Good” & “Bad” Science
…on “Good” & “Bad” Policy Decisions & Media Coverage
…on Caffeine’s Beneficial Health Effects
… First 20 Years: Much Bad News! Caffeine was linked to
many animal toxicities and human diseases!
6

7. Caffeine’s “Maligning” Started in 1970’s and
Ballooned in 1980’s/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?
• Central Nervous System: anxiety, sleep disturbance,
“addiction”?
7

9. What “Science” Allowed the Myths to Build
and Why Do a Few Still Persist?
… Studies of Acute vs. Chronic Effects:
 Acute effects testing of non-caffeine consuming
subjects (the “caffeine-naïve” subject)
 Partial / full tolerance to caffeine develops in humans
consistently consuming caffeine and coffee daily
… Most of the Myths and Fears are based on:
 Massive doses of caffeine fed to pregnant animals
 Smaller, poorly done and not-well-controlled human
studies with confounding and biases
 Many unwarranted assumptions, erroneous analyses
and factual misrepresentations in the literature.
9

10. But since 2000 or so…
 The “Good News” is that almost all of the
earlier bad news about coffee and caffeine
was WRONG!
 Medical evidence has been building strongly
that coffee and caffeine may actually be
GOOD for us!!!
 Let’s briefly examine the evidence for some
of the myths and facts.
10

11. 11

12. “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 caffeine comes from energy drinks
• Intakes from energy drinks represent less than 2% of
total daily mean caffeine values for all caffeinated
beverage consumers.
Sponsor: International Life Sciences Institute
12

13. 13

14. Caffeine and Reproductive Effects
• Issue first began with birth defects (missing toes) in rats
force-fed by stomach tube with very high-doses of
caffeine (FDA, 1978)
• But no adverse effects were seen in FDA’s follow-up
“sipping” study of the same high doses
• Human studies followed: delayed conception, premature
birth, low birth weight babies, fetal death, spontaneous
abortion (miscarriage), congenital birth defects
• But now there are more than 25 published reviews
supporting caffeine’s safety.
14

17. Caffeine and “Addiction”
17

18. Caffeine and “Addiction”
• Dependence, tolerance and withdrawal headache were cited
in many published studies going back to the late 1980’s (but
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” (the new term for addiction) in the American
Psychiatric Assn’s DSM-5 “bible” (published May 2013)
• However, DSM-5 did recognize caffeine intoxication and
withdrawal disorders
• Addiction over-warnings trivialize dangers of real drugs of
abuse.
18

19. Coffee/Caffeine and Cancer Risk
• Coffee contains trace levels of animal carcinogens
produced by heat in the “Maillard Browning Reaction,”
including acrylamide and furan
• Over 550 human epidemiology studies have been
published since the 1970’s on many human organs
• Most health authorities across the globe now agree that
coffee drinking (and caffeine) is NOT a cancer risk, and
coffee may actually reduce the risk of numerous
cancers
• I have termed this the “Coffee-Cancer Paradox”
19

20. Summary Conclusions on the “Bad” Health Effects
• Long established history of safe global caffeinated coffee
consumption (and decaffeinated as well)
• But more animal, clinical & epidemiologic studies will be
published, and continued media attention is sure to come
• More recent studies and re-examinations of older disease
issues have been quite reassuring
• Consumers can be assured that their health will not be
adversely affected by the enjoyment of coffee and
caffeine as currently consumed.
20

21. 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.
21

22. 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 added
Caffeine
22

23. U.S. Congress and FDA Concerns
over Caffeine and Energy Drinks
23

24. 24

25. Very Recent Studies / Reviews on
Concerns over Energy Drinks…
…done by researchers who do not know
the 30+ years of caffeine literature…on
hypertension, arrhythmias, heart
attacks, strokes, reduced mortality
25

26. “Experts” Letter to FDA Commissioner
26

27. Caffeine has become the
“Poster Child” for GRAS troubles
“Generally Recognized as Safe”
(1958 Food Additives Amendment)
27

28. “Food additives on the rise as FDA scrutiny wanes”
Washington Post, August 17, 2014
• “The explosion of new food additives coupled with an easing of oversight
requirements is allowing manufacturers to avoid the scrutiny of the FDA,
which is responsible for ensuring the safety of chemicals streaming into the
food supply.”
• “We simply do not have the information to vouch for the safety of many of
these chemicals,” said Michael Taylor, the FDA’s Deputy Commissioner for
Food.
• “Within the past six months, top officials at the FDA and in the food industry
have acknowledged that new steps must be taken to better account for the
additives proliferating in the food supply.”
• “This is what happened with caffeine. In 1959, the FDA approved it as GRAS,
allowing soft drink manufacturers to add it to their products. But now food
manufacturers are loading caffeine into energy drinks, maple syrup, jelly beans
and marshmallows.”

29. FDA Statement on Wrigley’s “Alert Energy”
Caffeine Gum Withdrawal (May 2013)
Michael R. Taylor, FDA Deputy Commissioner for Foods & Vet. Medicine:
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.
29

30. 30

31. 31

32. My U.S. Senate Oral Testimony
1. The caffeine content in energy drinks is equivalent to that
of an equal amount of coffee, and less than that of
coffeehouse coffees.
2. The health outcomes of caffeine consumption have been
thoroughly studied for decades, and the best available
scientific & clinical evidence does not support the idea that
caffeine should be prohibited (and certainly not a single
source of caffeine).
3. Coffee, tea and soda are the primary sources of caffeine in
U.S. diets, including diets of children and teens. Current
exposure assessments conducted by the FDA indicate that
caffeine consumption by children and youth is not a safety
concern.
32

33. 33

34. IOM Workshop Objectives Set by FDA
• Evaluate the epidemiological, toxicological, clinical and other relevant
literature to describe important health hazards associated with caffeine
consumption from ALL foods and beverages.
• Delineate vulnerable populations who may be at risk from caffeine
exposure.
• Describe the possible risk of caffeine’s 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.
34

35. Mike Taylor’s Blog on Caffeine
35

36. 36

37. 37

38. Caffeine Interest by Non-U.S.
Regulatory Agencies
38

39. 39

40. European Food Safety Authority (EFSA)
• Zucconi et al., 2013. “Gathering consumption data on specific
consumer groups of energy drinks.” [190 pages]
www.efsa.europa.eu/publications
• EFSA opinion on caffeine’s safety was requested by the EC (Feb
2013); established a Working Group on Caffeine…
• 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
• Several meetings of the Scientific Panel on Dietetic Products,
Nutrition and Allergies (NDA Panel)
• Draft Opinion will issue mid-December, public review &
consultation for 6-7 weeks, adoption by Spring 2015.
40

41. Food Standards Australia New Zealand
(FSANZ)
41

42. Cardiovascular Issues
42

43. “Tolerance to the Humoral and Hemodynamic Effects of Caffeine in
Man” – Vanderbilt University’s David Robertson (1981)
• Previous studies showed acute caffeine given to 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 long term adverse effects of caffeine on BP, heart rate,
plasma renin activity, plasma catecholamines, or urinary
catecholamines.
43

44. 44

45. 45

46. 46

47. 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
47

48. 48

49. 49

50. 50

51. Take Home Messages…
~
Attackers should understand the
Caffeine literature before they accuse it
as the causative agent!
~
Caffeine in coffee, energy drinks & other
foods and beverages is safe for human
consumption!
51

52. Thank You for
Your Attention!
jrcoughlin@cox.net