You may be one of the many Americans who start the day with a caffeine-rich cup o' joe to wake up. But have you ever stopped to wonder how caffeine worksâand whether it does anything but keep your eyelids from getting heavy? Technically speaking, caffeine is a xanthine alkaloid compound that stimulates the central nervous system, temporarily increasing alertness. In fact, caffeine is the most widely consumed legal psychoactive agent (a substance that affects brain functioning) in the nation. But research shows that caffeine, found in numerous botanical sources, may also have a variety of legitimate uses beyond increasing alertness.
Caffeine by any other name
It can be difficult to detect caffeine in common products, because it isn't always listed as such on the label. Caffeine is included in some products under the names guaranine (found in guarana berries, Paullinia cupana) and mateine (found in matÃ©, Ilex paraguariensis). In addition to coffee (Coffea arabica), other botanical sources of caffeine include black, green and white tea (Camilla sinensis), kola nut (Cola acuminata, C. nitida), and chocolate or cocoa (Theobroma cacao). In fact, caffeine is found in the seeds, leaves or fruit of more than 60 plants. Many of these also contain other CNS stimulants. For instance, coffee contains small amounts of theophylline, and tea contains small quantities of both theobromine and theophylline.1
Caffeine from natural or synthetic sources is sometimes added to foods and beverages that do not naturally contain the ingredient. Natural caffeine is derived through the process of making decaffeinated coffee;2 synthetic caffeine is produced in a lab.3,4 In the past, natural caffeine was often extracted using various solvents such as benzene, chloroform, trichloroethylene and dichloromethane. Now, safer and more environmentally friendly methods are available, including water extraction, supercritical carbon dioxide extraction (which is safer than many organic solvents)5 and various nonhazardous organic solvents, such as ethyl acetate.6
Beyond a morning pick-up
Caffeine is most often used to increase mental alertness and stave off fatigue, but it has several other common applications. It is often combined with other stimulants in weight-loss products, mixed with analgesics for treating headaches and taken orally to enhance athletic performance. Other applications include the treatment of asthma and attention deficit hyperactivity disorder in children.
Alertness and memory. According to common dogma, caffeine improves wakefulness, and research backs this. Studies show us that caffeine (4 mg per kilogram of body weight) can increase mental alertness and improve semantic memory, logical reasoning, free recall and recognition memory tasks.7 Taking multiple small doses of caffeine (four times 65 mg over five hours) improves performance on various tasks and can bring about increased alertness.8 In fact, this is one area where the research is quite strong, even in children.9
ADHD. Various effects of caffeine consumption on alertness and performance have been studied in children with ADHD. In one review, caffeine was more effective than no treatment for decreasing a variety of symptoms associated with ADHD, such as impulsivity and aggression. It also improved parents' and teachers' perceptions of children's symptom severity, and was deemed more effective than placebo in decreasing hyperactivity. However, amphetamines were more effective than caffeine for reducing hyperactivity, impulsivity, aggression and teachers' perceptions of children's symptom severity.10
Weight loss. Myriad weight-loss products contain caffeine and often a combination of other CNS stimulants. The theory behind using caffeine for weight loss is simple: It increases both thermogenesis (calorie burning) and lipolysis (fat breakdown) so it should lead to weight loss if used daily. Unfortunately, no studies indicate that caffeine consumption leads to actual weight or fat loss, though some have shown a temporary increase in metabolism when caffeine is combined with ephedra.11,12 In one randomized, double-blind, placebo-controlled study in overweight individuals, 192 mg of caffeine combined with 90 mg of ephedra (n=84) taken daily for six months resulted in slightly more weight loss versus placebo (n=83).13 Other studies indicate that caffeine in combination with other stimulants may show some promise for weight and fat loss, but more research is needed to confirm preliminary results.13,14,15
Headache. Caffeine is included in some over-the-counter pain relievers and headache remedies because it is believed to increase their effectiveness by helping the body absorb the drugs more rapidly. Many studies have examined this idea. In a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study, 1,555 migraine sufferers were divided into three treatment groups. Six hundred sixty-nine subjects were given a combination product containing acetaminophen (250 mg), aspirin (250 mg) and caffeine (65 mg); 666 were given ibuprofen (200 mg); and 220 received placebo. Both treatment groups had significantly better pain relief and improvement in associated symptoms of migraine than those who took the placebo, while the AAC group was superior to IB on six measures of pain and symptoms associated with migraine, including speed of relief from pain.16 In another randomized, controlled clinical trial, 188 subjects with migraines took an OTC medication (containing 500 mg of acetaminophen, 500 mg of aspirin and 130 mg of caffeine) or the prescription drug sumatriptan (50 mg) at the first sign of a migraine attack. The OTC medicine was significantly more effective than sumatriptan according to a variety of measures, including pain intensity difference, pain relief, response, sustained response, relief of associated symptoms, use of rescue medication, disability relief and global assessments of effectiveness.17
Asthma. Caffeine is chemically related to theophylline, which is used to treat asthma. Caffeine itself is a bronchodilator and can reduce respiratory muscle fatigue. Therefore, there has been significant interest surrounding the role of caffeine in treating asthma. A Cochran review of randomized crossover trials examining the use of oral caffeine versus placebo in adults with asthma found six studies involving a total of 55 people that qualified for review. This review found that compared with a placebo, caffeine improves lung functioning for up to two hours post-consumption. In addition, forced expiratory volume improved slightly for up to two hours after caffeine consumption, and mid-expiratory flow rates improved slightly for up to four hours. The review concluded that caffeine modestly improves airway functioning for up to four hours after consumption.18
Blood sugar and diabetes. Consumption of both caffeine and coffee has been associated with various effects on blood glucose and type 2 diabetes mellitus risk, but results have been mixed, especially with regard to coffee (caffeinated or decaffeinated).19,20 In one epidemiological study of 17,413 individuals, coffee, green tea and total caffeine consumption were all associated with a reduced risk of type 2 diabetes. However, a major limitation of this study was that diabetes was self-reported.21 In another study, both caffeinated coffee and caffeine alkaloids were associated with glucose intolerance, with caffeine alkaloids showing a much stronger association.22 Other research relates caffeine consumption to reduced insulin sensitivity (and therefore reduced glucose uptake) in lean and obese people and type 2 diabetics, compared with those who took placebos;23 to acute impaired glucose management in men with type 2 diabetes;24 and to impaired insulin-glucose homeostasis in obese men.25
Caffeine biochemistry and safety
The body completely absorbs caffeine within 45 minutes after ingestion.26 Caffeine is an antagonist of the neuro?transmitter adenosine, binding to its receptor sites and leading to a reduction in adenosine activity. This decrease in adenosine activity increases dopamine, which stimulates the CNS.27 The bodies of people who regularly consume caffeine adapt to the continual presence of the substance by increasing the number of adenosine receptors within the CNS. This increase in total receptor sites decreases the stimulatory effects of caffeine, so more is needed to achieve the same effect. Any reduction in caffeine intake among frequent users will lead to withdrawal symptoms such as headaches, irritability and decreased ability to concentrate. Once adenosine receptors adapt to the decrease, however, the withdrawal symptoms subside.28
The amount of time it takes each person's body to eliminate caffeine varies and depends on several factors including age, liver function, pregnancy status, medication use and enzyme levels. In healthy individuals, half of the total caffeine consumed at a given time is eliminated in approximately three to four hours.29 Caffeine is metabolized in the liver and produces three metabo?lites: paraxanthine, theobromine and theophylline. Paraxanthine boosts lipolysis, increasing levels of glycerol and free fatty acids in the bloodstream. Theobromine dilates blood vessels, enhancing blood flow to the brain; it also increases urine production. Theophylline relaxes smooth muscles of the bronchi and raises heart rate.30
In the United States, caffeine has GRAS status, meaning it is generally recognized as safe by the U.S. Food and Drug Administration.31 Every person's tolerance to caffeine differs, however, and caffeine may be unsafe for some when consumed in high doses, especially over long periods of time. Doses of 250 mg to 300 mg or more per day may result in tachyarrhythmia (rapid, irregular heartbeat) and difficulty sleeping. Ingesting approximately 10 g to 14 g of caffeine (150-200 mg per kilogram of body weight) can cause death.32 (See sidebar for caffeine levels in common beverages.)
Some individuals should monitor their consumption of caffeine or avoid it altogether. Pregnant women should keep their caffeine consumption below 300 mg per day. Caffeine crosses the placenta, and very high doses may lead to spontaneous abortion, low birth weight or premature birth.33,34 Caffeine may also adversely affect those with anxiety disorders,35 cardiac problems,36 glaucoma37 and hypertension.38 In addition, several medicines may interact negatively with caffeine. Caffeine can increase the risk of adverse effects when taken with stimulant drugs such as diethylpropion (Tenuate), epinephrine, phentermine (Ionamin) and pseudoephedrine (Sudafed).32,39 In addition, caffeine can impair metabolism of riluzole (Rilutekâused to treat amyotrophic lateral sclerosis, also known as Lou Gehrig's Disease),40 cause an additive increase in blood pressure when taken with phenylpropanolamine (used in decongestants and weight loss products),41 and exacerbate psychotic symptoms while increasing the potential for toxicity when taken with clozapine.42
The majority of people who consume caffeine do so to increase alertness and mental functioning temporarily. As an ergogenic aid, caffeine may increase performance, memory and alertness, and it may offer some benefits for those with ADHD, asthma or headaches. However, people who take it hoping to enhance weight loss may be disappointed. Worse yet, they may experience some of the negative side effects associated with high levels of caffeine consumption.
Marie Spano, M.S., R.D., is vice president of the International Society of Sports Nutrition and a spokeswoman for the Tea Council of the USA.
1. Newall CA, et al. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
2. Politte J. How'd They Do That? Making Decaf Coffee. American Chemical Society. http://www.cas.org/portal/vhemistry?PID. Accessed June 18, 2007.
3. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, N.J. 1989.
4. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes Publications, Park Ridge, N.J. 1985.
5. Kaiser CS, et al. Pharmaceutical applications of supercritical carbon dioxide. Pharmazie 2001;56(12):907-26.
6. Ramalakshmi K, Raghavan B. Caffeine in coffee: its removal. Why and how? Crit Rev Food Sci Nutr 1999;39(5):441-56.
7. Smith A, et al. Effects of breakfast and caffeine on cognitive performance, mood and cardiovascular functioning. Appetite 1994;22(1):39-55.
8. Brice CF, et al. Effects of caffeine on mood and performance: a study of realistic consumption. Psychopharmacology 2002;164(2):188-92.
9. Bernstein GA, et al. Caffeine effects on learning, performance, and anxiety in normal school-age children. J Am Acad Child Adolesc Psychiatry 1994;33(3):407-15.
10. Leon R. Effects of caffeine on cognitive, psychomotor, and affective performance of children with Attention-Deficit/Hyperactivity Disorder. J Atten Disord 2000;4(1)27-47.
11. Toubro S, et al. The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans. Int J Obes Relat Metab Disord 1993;17:S73-7.
12. Boozer CN, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord 2002;26:593-604.
13. Hackman RM, et al. Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial. In J Obes 2006;30(10):1545-56.
14. Belza A, et al. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects. Int J Obes 2007;31(1):121-30.
15. Greenway FL, et al. Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition. Obes Res 2004;12(7):1152-7.
16. Goldstein J, et al. Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study. Headache 2006;46(3):444-53.
17. Goldstein J, et al. Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine: results from the ASSET trial. Headache 2005;45(8):973-82.
18. Bara AI, Barley EA. Caffeine for asthma. Cochrane Database Syst Rev 2001;(4):CD001112.
19. Greenberg JA, et al. Coffee, diabetes, and weight control. Review. Am J Clin Nutr 2006;84(4):682-93.
20. Adeney KL, et al. Coffee consumption and the risk of gestational diabetes mellitus. Acta Obstet Gynecol Scand 2007;86(2):161-6.
21. Iso H, et al. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006; 144(8):554-62.
22. Battram DS, et al. The glucose intolerance induced by caffeinated coffee ingestion is less pronounced than that due to alkaloid caffeine in men. J Nutr 2006;136(5):1276-80.
23. Lee S, et al. Caffeine ingestion is associated with reductions in glucose uptake independent of obesity and type 2 diabetes before and after exercise training. Diabetes Care 2005;28(3):566-72.
24. Robinson LE, et al. Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes. J Nutr 2004;134(10):2528-33.
25. Petrie HJ et al. Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss. Am J Clin Nutr 2004;80(1):22-8
26. Newton R, et al.Plasma and salivary pharmacokinetics of caffeine in man. Eur J Clin Pharm 1981;21(1): 45-52.
27. Fredholm B, et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 1999;51(1): 83-133.
28. Juliano LM. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology 2004;176(1):1-29.
29. Physician's Drug Handbook; 11th edition. Philadelphia, PA: Lippincott Williams & Wilkins, 2005.
30. Dews PB. Caffeine: Perspectives from Recent Research. Berlin: Springer-Verlag 1984.
31. FDA. Center for Food Safety and Applied Nutrition, Office of Premarket Approval, EAFUS: A food additive database. Available at: vm.cfsan.fda.gov/~dms/eafus.html. Accessed June 18, 2007.
32. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html.
33. Klebanoff MA, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44.
34. Fernandes O, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44.
35. Smith A. Effects of caffeine on human behavior. Food Chem Toxiocol 2002;40:1243-55.
36. Cannon ME, et al. Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products. Med J Aust 2001;174:520-1.
37. Avisar R, et al. Effect of coffee consumption on intraocular pressure. Ann Pharmacother 2002;36:992-5.
38. Nurminen ML, et al. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831?9.
39. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8.
40. Sanderink GJ, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72.
41. Brown NJ, et al. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71.
42. Hagg S, et al. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63.
43. Foster S, Duke JA. Eastern/Central Medicinal Plants. New York, NY: Houghton Mifflin Co., 1990.
44. Robbers JE, et al. Pharmacognosy and Pharmacobiotechnology. Baltimore, MD: Williams & Wilkins, 1996.
45. Esmelindro AA, et al. Influence of agronomic variables on the composition of mate tea leaves (Ilex paraguariensis) extracts obtained from CO2 extraction at 30 degrees C and 175 bar. J Agric Food Chem 2004;52:1990-5.
46. Saldana MD, et al. Extraction of methylxanthines from guarana seeds, mate leaves, and cocoa beans using supercritical carbon dioxide and ethanol. J Agric Food Chem 2002;50:4820-6.
47. McGuffin M, et al, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
48. Mayo Clinic. Caffeine content of common beverages. http://www.mayoclinic.com/health/caffeine/AN01211. Accessed June 21, 2007.
Natural Foods Merchandiser volume XXVIII/number 8/p. 44-45