Caffeine From the Beginning of Time to Now

1. CaffeineFrom the Beginning of Time to Now Frankie Roman MD JD FOCUS Fall Las Vegas October 3, 2013

2. CAFFEINEFrom the beginning of Time to Now Frankie Roman,MD JD Focus Conference May 13,2010

3. History of Coffee • Discovery of caffeine rich leaves of Ilex Yuayusa in the tomb of a Shaman from highland Bolivia dating from around 500 A.D. • The oldest existing text documenting caffeine in medicine is written in The Canon of Medicine of the Islamic physician, Avicenna (980-1037)

4. History of Coffee • The first commercial cultivation of coffee occurred in the fourteenth century in Arabia. • Coffee spread to Europe in the seventeenth century and then to South America and finally North America. • After oil, coffee is the second most valuable commodity in the world.

5. Superstitions and Rituals • Tea leaf reading by Chinese fortune tellers • Turkish fortune tellers used the finished cup of coffee containing both liquid and grounds by turning it onto the saucer until cool, then cup turned back up and any coffee grounds remaining in cup are “read”.

6. Caffeine • coffee – 100 to 150 mg of caffeine • Instant coffee – 85 to 100 mg • Tea – 60 to 75 mg • Cola – 40 to 75 mg • Cocoa – 50 mg • OTC cold preparations – 15 to 60 mg/tab • OTC stimulants – 100 to 200 mg

7. Caffeine • Half-life 3 to 7 hours • Effects may last as long as 8 to 14 hours • 500 mg of caffeine has same alerting effects as amphetamine 5 mg • Promote wakefulness by blocking adenosine receptors in brain • Intoxication – restlessness, nervousness, flushed face,GI disturbances and insomnia

8. Caffeine • Effects are prolonged in children,pregnant women, elderly and hypothyroidism • May trigger panic attacks • Abrupt withdrawal – irritability,dysphoria,fatigue,headache,EDS and flulike symptoms 18-24 hours after last dose.

9. Gastrointestinal • Both caffeine containing and caffeine-free coffee stimulates gastric acid secretion. • Both caffeine containing and caffeine-free coffee stimulate gastrin release.

10. Basal Metabolic Rate • Caffeine increases resting metabolic rate in lean as well as obese individuals for up to 24 hours after ingestion. • Caffeine ALONE is not effective in promoting weight loss in overweight individuals in several controlled studies.

11. Smuggling • In the 1600s a Muslim pilgrim named Baba Budan smuggled seven seeds out by taping them to his stomach and cultivating them in southern India. • The Dutch smuggled one coffee tree to Holland • The French smuggled one coffee tree to Martinique in 1723 – believed that much of the world’s current supply probably derives.

12. Bunn • Chewed • Brewed the leaves and berries with boiled water as a weak tea • Grounded the beans and mixed them with animal fat for a quick energy snack • Made wine out of the fermented pulp • Made sweet beverage out of husks of coffee cherry – kisher • Finally someone roasted the beans, grounded them and made infusion – coffee!

13. Coffee Producers • Brazil is world’s largest producer of coffee with 33.6 million bags per year • Columbia – 11.8 million bags • Vietnam – 10.75 million bags Note: 1 bag is equivalent to 132 pounds

14. Consumption • Over 100 million Americans consume an average of 3.1 cups per day • Starbucks - about 20,000 stores in the USA - over 4000 stores overseas - price of Venti Mocha Moscow $ 8.98 New York City $ 4.71

15. Instant coffee • Instant coffee market – 21 billion dollars worldwide • Pervasive throughout Europe • About 80 % of coffee sales in the U.K.

16. Problems with interpretation of data • Cup size • Caffeine content of the different coffees used • Possibility that many people who drink coffee frequently may drink weaker coffee (café americano) • Use of paper filters in brewing coffee • Cigarette smoking • Individual variability in metabolism of compounds found in coffee.

17. 1 Starbucks Grande Coffee(Caffeine 330 mg) is equal to: • 5.5 shots of espresso (caffeine 60 mg) • 1.7 Wired Waffles (caffeine 200 mg) • 5.5 Midol tablets (caffeine 60 mg) • 253.8 Oreos (caffeine 1.3 mg) • 4.1 Red Bulls (caffeine 80 mg) • 9.4 Coca Colas (caffeine 35 mg) • 6.1 Mountain Dews (caffeine 54 mg) • 1.6 5-Hour Energy (caffeine 208 mg) • 55 Kit Kat bars (caffeine 6 mg) • 330 Hershey’s Kisses (caffeine 1 mg)

18. Energy Beverages • Red Bull introduced in Austria in 1987 and 10 years later in the USA • Hundreds of different brands in the market place • Caffeine content ranges from 50 mg to an alarming 505 mg per can or bottle • USA is world’s largest consumer with estimate of 290 million gallons in 2007

19. Energy Drinks • U.S. residents consumed estimated 2.3 billion energy drinks in 2005 and 6 billion in 2010. • 6% of young men in USA report consuming a daily energy drink • In a recent survey of U.S. overseas troops., 45% reported daily use. • Sales of energy drinks in the USA increased 16% in single year to almost 9 billion dollars in 2011.

20. Caffeine - Legal • In 1911, under the authority granted by the FDA, U.S. agents seized 40 kegs and 20 barrels of Coca-Cola syrup in Chattanooga, Tennessee. The caffeine level was considered to be a significant public health hazard ( both cocaine and alcohol had been removed from recipe). • In 2012, the FDA investigating the caffeine containing energy drinks due to safety concerns. Linked to unexpected deaths in healthy persons.

21. Energy Beverage Consumption has been shown to be positively associated with: • Marijuana use • Sexual risk taking • Fighting • Failure to use seat belts • Taking risks on a dare • Smoking • Alcohol abuse • Illicit Drug use

22. Energy Drinks Mixed with Alcohol • May offset the sedating effects of alcohol • Reduced sensation of intoxication impairs judgment relative to risky behaviors • Reduced sensation of intoxication induces more alcohol consumption which further impairs judgment and neurocognitive function.

23. Energy Drinks Mixed with Alcoholexperimental studies • Caffeine reverses alcohol related impairment on tests of reaction time, psychomotor speed and simulated driving performance at moderate but NOT HIGH levels. • Does NOT decrease error rates • Antagonizes the effects of alcohol on response execution but NOT on inhibitory control (increase risk taking behaviors)

24. Caffeine Poisoning The Swedish Experience • Out of 5000 forensic autopsies ,1% had caffeine levels exceeding 10 ug/ml • 1 cup of brewed coffee results in blood caffeine level of 1-2 ug/ml • 20 cases had caffeine levels higher than 80 ug/ml ( lethal dose) • Arrhythmias were most common cause of caffeine related death ( average age 41) • Ingestion over a brief time of 3 to 10 grams of caffeine might be lethal. • Restriction of caffeine tablet sales from 250 to 30 pills per customer appears to have decrease rate of fatal caffeine overdoses.

25. Energy Drinks Mixed with AlcoholPublic Health Response • In 2008, 13 State attorney generals negotiated settlements by which 2 national breweries agreed to remove caffeine and all other stimulants from their products. • In 2010, FDA sent warning letters to 7 producers of premixed caffeinated alcoholic beverages, halting production and sale. • In 2012, several states prohibited the sale of Four Loco ( premixed, caffeinated, high alcohol content beverage) after significant number of students were treated for excessive consumption.

26. Diabetes Protection • Meta-analysis of 18 studies conducted between 1966 and 2009 with information on 457,922 patients by Dr Rachel Huxley of the George Institute for International Health, Australia revealed: 1.Drinking 3-4 cups of coffee per day associated with 25% lower risk of Type 2 diabetes than drinking 2 cups or less 2.Each additional cup of coffee consumed was associated with a 7% reduction in the excess risk of diabetes.

27. Diabetes Protection 3.Results were independent of effects involving gender, geographic region, dx vs self-reporting. 4. Three to four cups of DECAF coffee per day had about a third lower risk of diabetes than those who didn’t drink decaf. 5. Three to 4 cups of tea per day had about a 20% lower risk of diabetes.

28. Diabetes Protection • Protective effects of tea and coffee may not be solely related to caffeine • Possible role of other chemicals including magnesium, lignans,and chlorogenic acids • Catechins in tea may decrease glucose production in GI leading to lower levels of glucose and insulin • Green tea may prevent damage to pancreatic beta cells.

29. Coffee Break • Invention of the Pan American Coffee Bureau in 1952. • “Give yourself a coffee break – and get what coffee gives to you”. • 80 % of firms polled in 1952 introduced coffee breaks in their work days.

30. Parkinson’s Disease • Inverse association between coffee intake and PD risk in men in several large prospective cohort studies. • Men who regularly consumed at least 1 cup of coffee daily had 50% less risk of developing PD over next 10 years than nondrinkers. • Consumption of tea and other caffeinated beverages was also inversely associated with PD.

31. Parkinson’s Disease • Inverse relationship of caffeine and risk of PD not found in women (Nurses Health Study) • May be due to the modifying effect of estrogen replacement therapy. • Coffee consumption was inversely associated with PD risk in woman who had never used post menopausal estrogen. • Significant increase in PD risk in post menopausal estrogen users who drank at least 6 cups of coffee daily.

32. Suicide Risk • 10 year study of 128,000 pts participating in a California health plan the relative risk of suicide decreased by 13% for every cup of coffee consumed daily. • Reason for this inverse association unknown. • NOT ENOUGH DATA to support recommendations for coffee consumption in clinically depressed patients.

33. Cardiovascular Disease • Acute consumption of coffee raises BP in normotensive and hypertensive individuals • Two-three cups of coffee (200-250 mgs of caffeine) has been found to increase systolic BP by 3-14 mm of mercury and diastolic BP by 4-13 mm of mercury in normotensive individuals • Pressure effect of caffeine may be more pronounced in hypertensive individuals

34. Cardiovascular Disease • Cardiac arrhythmias – coffee or caffeine intake equivalent to 5-6 cups daily was NOT found to increase the frequency or severity of arrhythmias in healthy individuals, coronary heart disease pts or people with pre-existing ventricular ectopy. • Few studies regarding cerebral vascular accident have NOT found a significant association between coffee consumption and risk of stroke.

35. Cardiovascular Disease • Consumption of BOILED coffee dose dependently increased serum total and LDL cholesterol • FILTERED coffee resulted in minimal change in serum cholesterol • Cholesterol raising factors in unfiltered coffee have been identified as cafestol and kahweol.

36. Cardiovascular Disease • Elevated plasma total homocystine concentration associated with increase risk for coronary heart disease, stroke, and peripheral vascular disease. • Plasma total homocystine has been positively associated with coffee consumption in a dose dependent manner. • Abstention from coffee for at least 6 weeks resulted in 11% decrease in fasting homocystine concentration (average of 4 cups of filtered coffee per day consumers)

37. Coronary Heart Disease • High coffee intake associated with significant increase risk of coronary heart disease or myocardial infarction. • Older study found that acute coronary syndrome was three times higher in people who drank 600 ml of coffee per day than nondrinkers. • Prospective cohort studies have not found significant association between coffee consumption and risk of coronary artery disease. • Possible explanation – decrease consumption of BOILED coffee with corresponding increase in consumption of FILTERED coffee.

38. Coffee Stop Campaign • Encourage drivers to stop every two hours for coffee as a safety measure. • “Make that one for the road coffee” • Created a furor in the south – mistaken as encouraging drunk driving • Changed to “Stay Alert, Stay Alive….Make it coffee when you drive”. • Note: National Sleep Foundation has campaign Drive Alert, Arrive Alive.

39. Special Risk Groups Breast feeding infants and young children • Caffeine is detectable in breast milk within 15 minutes of consumption and peaks one hour later • American Academy of Pediatrics – caffeine is a maternal medication usually compatible with breast feeding • High maternal caffeine intake associated with irritability and poor sleeping patterns in infants • No adverse effects reported at maternal intake of 2-3 cups of coffee daily.

40. Young Children and Coffee • Meta analysis of nine short term clinical trials of caffeine in children including 4 in normal children and 5 in children with ADHD found: NO significant effects on cognition and behavior.

41. Coffee worker’s lung • Hypersensitivity pneumonitis • Antigen – coffee bean dust • Source of antigen – coffee beans

42. Coffee houses • Wealthy people had a coffee room in their homes • Coffee houses – kaveh kanes sprang up by the end of the fifteenth century • Troublemaking social brew – “ranging from gambling to involvement in irregular and criminally unorthodox sexual situations”.

43. History of Coffee • Caffeine consumption goes back at least 1000 years • One of first reported consumption were by members of the Galla tribe in Ethiopia. • Legend has it that an Ethiopian goat herder discovered coffee’s stimulating effects when he noticed the friskiness of the goats after munching on the red berries of a local shrub.

44. Caffeinated Coffee Consumption Conclusion 2013 • NO evidence that it increases the risk for any form of malignancy • NO conclusive evidence that it increases the risk of fibrocystic breast disease • Can cause mild to moderate sleep disturbances • Can cause GI distress but not the result of caffeine as similar symptoms can be seen with decaffeinated

45. Caffeinated Coffee Consumption Conclusion 2013 • Does not result in worsening of diabetic control • Does not increase risk for diabetic complications • May actually decrease risk for developing Type 2 diabetes • Caution is warranted in the use of energy drinks due to recent reports of abuse and deaths in the 21 and under population.