Caffeine Safety: Issues Raised over the Past Year

James R. Coughlin, PhD CFSPresident, Coughlin & Associates

Aliso Viejo, Californiajrcoughlin@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, ColoradoJuly 7, 2014

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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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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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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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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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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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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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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So with all this more recent goodnews, 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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“Experts” Letter to FDA Commissioner

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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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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 caffeine17

IOM Workshop Objectives• Evaluate the epidemiological, toxicological, clinical and other relevant

literature to describe important health hazards associated with caffeineconsumption.

• 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 preexistingconditions.

• 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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Mike Taylor’s Blog on Caffeine

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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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Cardiovascular Issues

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“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 chroniccaffeine 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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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 diseases28

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 diseases29

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Take Home Message

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Attackers should know their

Caffeine literature before they step

up on their Soapbox to attack it as

the causative agent!

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Thank You!~

Questions?