Caffeine Safety: A Three-Decade Review and the 2013-2014 Landscape

James R. Coughlin, PhD CFSPresident, Coughlin & Associates

Aliso Viejo, Californiajrcoughlin@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 MeetingNew Orleans

June 23, 2014

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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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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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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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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“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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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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Caffeine and Reproductive Effects

• Began with birth defects (missing digits) in rats gavagedwith 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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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 noincreased risk of osteoporosis.

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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 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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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 Literature13

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.

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Recent Studies / Reviews on Energy Drinks?

~…by researchers who do not know the 30+ years of caffeine literature

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Congressional and FDA Concerns

over Caffeine in Energy Drinks

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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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“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 caffeine21

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• 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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Mike Taylor’s Blog on Caffeine

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Other Regulatory Agencies

Concerns

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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 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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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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What Happens Next?

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Thank You!