The World of Caffeine

by Weinberg, Bennett Alan, Bealer, Bonnie K.

  However, the observation that caffeine produces increases of 10 to 20 percent in the number of brain adenosine receptors has prompted speculation that this increase may be the mechanism underlying withdrawal symptoms. The notion here is that the body is not completely fooled by the invasion of caffeine as an adenosine impostor and creates new receptor sites as compensation. When caffeine intake is reduced or eliminated, these extra sites combine with the original sites to uptake a greater amount of adenosine than is normal, with the result that adenosine’s effects, including sleepiness and depression, are multiplied. Thus, this explanation would help account for many of the withdrawal symptoms produced by the abrupt reduction or cessation of caffeine use.

  Unfortunately, there remain some inconsistencies that lead scientists to believe that this explanation is at best incomplete, for it cannot adequately serve to explain the development of tolerance. Tolerance to caffeine can increase to the point where it cannot be overcome by any dose, that is, where it becomes insurmountable, failing to duplicate its former effects in the user regardless of how high a dose is ingested, and there is no easy way to understand how the adenosine blockade theory could be consistent with insurmountable tolerances. In addition, as we have observed in our discussion of cocaine, there is no clear precedent of a competitive antagonist, such as caffeine, losing its potency after chronic administration. And, in fact, caffeine seems to retain its full potency as an adenosine antagonist, even in cases where an insurmountable tolerance to caffeine’s stimulant effects has clearly been achieved. Finally, there seems to be no theoretical basis for expecting that an increase in the number of receptor sites should produce tolerance to the antagonist.

  To put it simply, if caffeine’s mechanism of action is explicable in terms of a competitive blockade of adenosine, we might expect withdrawal symptoms upon cessation of use, but we would still lack any explanation for the development of tolerance. Problems like these make it clear how far science still has to go if it is to reveal the secrets of caffeine. Exactly what it does and exactly how it does what it does are still largely unknown. Fortunately, it is possible to assess the effects of caffeine on human health by means of studies that are independent of a detailed knowledge of its underlying mechanisms.

  Where the Caffeine Is

  Few of us in Western countries today chew the leaves, bark, fruit, or nuts of caffeine-containing plants. We get our caffeine and other methylxanthines from drinks, foods, and pills. In the United States, about 70 percent of our caffeine is found in coffee beans, about 14 percent is found in tea leaves, more than 12 percent is in the form of the crystal caffeine, nearly 3 percent is found in cacao beans, and the remaining fraction from all other sources, including cola nut, maté, and guarana. Chocolate owes some of its stimulating power to the methylxanthine theobromine, and tea contains a small amount of theophylline. The caffeine in cola drinks is not derived from cola nuts, but is a superadded extract from coffee or tea. Caffeine is found in some over-thecounter medications, such as alertness aids and aspirin compounds, and in prescription medications, such as narcotic painkillers, as an adjuvant to their analgesic power.

  In Appendix B are a number of charts listing various dietary and medicinal sources, with the amount of caffeine, theobromine, or theophylline found in each.

  What Is a Cup?

  A figure that is passed around, from one research paper or newspaper article to the next, is that a cup of coffee contains an average of 100 mg of caffeine. This sounds simple and straightforward and suggests that it is fairly easy to determine how much caffeine we are taking in when we have a cup of coffee. Unfortunately, when we scrutinize this figure, many uncertainties arise.

  One problem is, exactly how much liquid is in a “cup of coffee”? A big mug or large paper cup, filled to the brim, may be 10 ounces or even 12 ounces or more. If not filled to the brim, a small cup may hold as little as 4 ounces. Amounts often quoted for cups are 5 ounces or 6 ounces, and the cup itself as a standard liquid measure is 8 ounces. So when we speak of a cup, we may be speaking of 4, 5, 6, 8, 10, 12 ounces or more. Another problem is, how much caffeine is in the coffee, ounce for ounce? This number will vary widely with such variables as method of preparation, type of coffee bean, method of roasting, and amount of coffee used.

  The result of multiplying these two uncertainties produces a remarkably wide range for what might constitute the “correct” value for the amount of caffeine in a “cup” of coffee. A small cup of weak instant coffee might have as little as 50 mg. A large cup of infused coffee steeped for a long time with a lot of robusta beans might have 350 mg. Admittedly these are extreme values, but we believe that doses in the range of 100 to 250 mg are common. According to the Food and Drug Administration, a 5-ounce cup of coffee contains 40 to 180 mg of caffeine. Similar problems beset an evaluation of how much caffeine is found in a cup of tea.

  Studies profiling the caffeine content of coffee and tea as actually served to restaurant customers or consumed at home are rare. One 1988 Canadian study, published in Food and Chemical Toxicology,12 surveyed almost seventy “preparation sites,” and found considerable differences from place to place and even between one day and the next at the same place. A review of the caffeine content of coffee brewed in almost sixty homes showed levels ranging from about 20 mg to nearly 150 mg per cup, more than a sevenfold variation. Coffee tested in eleven restaurants exhibited similar differences. Further, “decaf” served at restaurants sometimes had substantial amounts of caffeine. Finally, there were large variations in the caffeine content among the seventeen brands of instant coffee, even when prepared under controlled laboratory conditions.

  The tests of tea showed a comparable variation in caffeine potency, although, of course, the average levels for tea were lower than those for coffee. According to the Republic of Tea Home Page, the following three factors determine how much caffeine is present in a cup of tea:

  The longer the leaves have been fermented, the greater their caffeine content. Green tea, which is unfermented, has the least caffeine; oolong, which is partially fermented, has about 50 percent more; and black tea, which is fully fermented, has three times as much.

  The longer tea is brewed, the more caffeine is present in the final drink. A cup of black tea infused for three minutes has 20 to 40 mg, while black tea infused for four minutes has 40 to 100 mg.13

  Finally, the caffeine in leaf powder, such as is found in tea bags, is more readily dissolved in water, and, all other factors being equal, it will have almost twice the caffeine as higher-quality full-leaf tea.14

  It is almost impossible to guess or determine how much caffeine is in the coffee we order at restaurants. Few field studies of caffeine content have been made. The following results are adapted from one such study, commissioned by New York City’s WABC-TV Eyewitness News in December 1994, from Associated Analytical Laboratories. Note that a “medium” serving can be more than 13 ounces, and that the caffeine content per serving varies, even among these four samples of coffee, by nearly 100 percent.

  Caffeine Content of Coffeehouse Coffees

  Brand, Size Net Serving Size Total mg mg/6oz

  Dunkin’ Donuts, regular 12.6 oz 275 147.6

  Cooper’s, medium 9.9 oz 146 99.6

  West Side Deli, medium 13.5 oz 295 103.8

  Dalton’s Coffee, regular 8.9 oz 148 99.7

  Similar discrepancies have been observed among the decaffeinated coffees served at leading chains across the country. In 1995, Self magazine submitted nine samples of decaffeinated coffee for analysis to Southern Testing & Research Laboratories in North Carolina. Most decaffeinated coffees had less than 10 mg per 6-ounce cup, but Starbucks had more than twice that much. As you review this chart, which also includes data from other similar studies, remember that most cups actually served contain at least 8 ounces of fluid. Results demonstrating such wide variability help to explain how even one cup of coffee sometimes seems to send you up like rocket, while other times a few cups won’t even start you
r engines.

  Caffeine Content in “Decaf”

  Brand Mg/6-oz serving

  Starbucks decaffeinated 25

  Dunkin’ Donuts decaffeinated 10

  Au Bon Pain decaffeinated 7

  Starbucks decaffeinated espresso 6

  McDonald’s decaffeinated 5

  7-Eleven decaffeinated 4

  Tetley decaffeinated tea 4

  Cooper’s decaffeinated 4

  Dalton’s decaffeinated 2

  Sanka 1.5

  Myths and misconceptions about caffeine content abound. The amount of caffeine that ends up in your cup of coffee is in part a function of the amount of caffeine contained in the beans you start with. In Appendix B is a list of the caffeine content of various beans as a percentage of total weight.15 In general, the cheaper robusta beans contain almost double the caffeine found in the more expensive arabica beans. Although the two have an otherwise similar compositional profile of such components as minerals, proteins, and carbohydrates, arabica beans also contain significantly more lipids. Tea’s variations in caffeine content depend primarily on the age of the leaves and on how the tea leaves have been cured. The caffeine content by percentage of weight of sen-cha, or green tea, is 2.8 percent; of ma-cha, or green powdered tea, is 4.6 percent; and of ban-cha, or coarse tea, is 2 percent.16 Note that ma-cha, the tea most commonly used in the Japanese tea ceremony, which is green tea made from the smallest leaves of the just budding plant, has the highest concentrations of caffeine by weight of any tea, or of any plant source, for that matter. No caffeine is found in brews from herb and mint teas, as would be expected, since the plants from which they are made do not contain caffeine.

  Maté also is an important source of caffeine, but it is even more difficult to estimate how much caffeine is in a cup of maté than it is to do so for a cup of coffee or tea. In addition to Ilex paraguariensis, as many as sixty varieties of plants are used in making the drink. To make matters even more confusing, the caffeine content of maté leaves varies widely according to their age at the time of harvesting. Young maté leaves have at least 2 percent caffeine of their dry weight, while adult leaves, those more than a year old, have about 1.5 percent, and old leaves, those more than two years old, have only about .7 percent.

  Guarana is a major source of caffeine for millions of South Americans and is also widely sold in Europe and the United States in herbal elixirs and powders in health food stores. Typical of these products is “Magic Power,” sold in two forms and which has the following ingredients (assuming 5 percent caffeine by weight in seeds as stated in their literature):

  15 ml alcohol with 5 g guarana seeds, 250 mg caffeine per bottle

  Guarana capsules with 500 mg seeds, 25 mg caffeine per capsule

  In Brazil, where guarana carbonated drinks are widely available, some consumers claim the effects are somewhat different from coffee’s, because guarana doesn’t produce jitters. This difference may be their imagination, or it may, as we have seen in other cases of natural drugs, be the result of the chemical complexity of guarana or the fact that it contains other active alkaloids in addition to caffeine.

  The amount of caffeine found in chocolate and other cacao products is relatively small. A 1.58-ounce milk chocolate Hershey bar has 12 mg, and an average 6-ounce cup of chocolate prepared from a mix has 5 mg. Appendix B lists the caffeine content of other chocolate products.17

  So how much caffeine is in a cup of coffee? Most cups of coffee of about 6 ounces probably contain between 60 and 180 mg of caffeine, which means that 100 mg, the value usually adduced, is as good as any. This is the value repeated throughout this book, and it is meant to be understood in the context of all the reservations and qualifications expressed in this section. The actual content in your cup can range from 40 mg to 400 mg.

  Soft Drinks

  Soft drinks are a major dietary source of caffeine. The amount in each varies widely. Jolt Cola, at or near the top of any list, has 70 mg in a 12-ounce can, CocaCola has 46 mg, and Canada Dry Diet Cola has 1 mg. Coca-Cola has 7.2 mg more caffeine in a 12-ounce serving than its nearest rival in market share, Pepsi, according to the FDA. The agency says the differences don’t appear to have any health consequences. Even though caffeine is on the FDA’s GRAS list, the list of food additives “generally recognized as safe,” the agency has expressed reservations about excessive caffeine consumption by children and any consumption by pregnant women. But FDA spokesman Jim Greene said in reference to most of the soft drinks ranked, “the effect of the milligram differences among these products is basically nil in the long run.”

  Interestingly, 7-Up, one of the best-selling soft drinks in the United States, has made the absence of caffeine the basis for a recent advertising campaign.

  Over-the-Counter and Prescription Medications

  Caffeine is used as one ingredient in a variety of over-the-counter and prescription compounds. The FDA’s National Center for Drugs and Biologics lists more than one thousand over-the-counter brands with caffeine as an ingredient. These fall into four categories: analgesics, cold remedies, appetite suppressants, and diuretics. Several of the most popular brands are listed in the appendix. In addition, caffeine is the only active ingredient in a number of so-called alertness aids, such as Vivarin, which contains 200 mg per pill, and NoDoz, which contains 100 mg per pill.

  Where the Theobromine and Theophylline Are

  Each of the methylxanthines considered here—caffeine, theobromine, and theophylline—acts as a physical and mental stimulant, but each has a somewhat different profile of somatic effects. For example, theobromine is a more potent diuretic than either caffeine or theophylline, while theophylline is more suitable for use as a bronchodilator. Cacao is the major source of theobromine, although it contains small amounts of caffeine as well, and its total methylxanthine content will vary with the variety of the plant and the fermentation process. Tea contains a small amount of theophylline in addition to its predominant methylxanthine, caffeine. Maté leaves are a small source of these methylxanthines, though the amounts are so small that some investigators have failed to detect them. The dried leaf has been reported to contain 0.3 percent theobromine and .004 percent theophylline by weight.18 In addition to caffeine, theobromine, and theophylline, there are other, so-called minor, purine alkaloids, which are found in extremely tiny amounts in coffee.

  Methylxanthine Content of Cacao Products

  Chocolate Product Percent Methylxanthine by Weight

  Sweet chocolate .36% to .63% theobromine

  .017% to .125% caffeine

  Cocoa butter 1.9% theobromine

  .21%caffeine

  Chocolate liquor or baking chocolate 1.2% theobromine

  .21% caffeine

  Milk chocolate .15% theobromine

  .02% caffeine

  Methylxanthine Content of Various Botanicals

  Product Caffeine % Theophylline % Theobromine %

  Coffee 1.34 trace trace

  Tea 3.23 .03 .17

  Cacao .20 trace 1.50

  Maté, cola nut, 2.0 — .10

  gnarana

  Extracting Caffeine: Industrial Processes and Mr. Wizard’s Laboratory

  The United States imports great quantities of caffeine for medical purposes and for spiking soft drinks, most of which is extracted from poor-quality coffee beans or waste tea leaves or collected as a by-product of the decaffeination of coffee and tea. Two techniques are used to produce decaffeinated coffee: bean decaffeination and extract decaffeination. Both are performed on the raw beans to minimize spoilage or loss of aroma.

  Bean decaffeination is used when the bean moisture level is less than 40 percent. This process involves static or rotating drums with a water-saturated solvent, such as dichloromethane or supercritical carbon dioxide, selective for caffeine.

  Extract decaffeination is used when the bean moisture content is more than 60 percent. In this process, raw coffee beans are usually soaked in nearly boiling water for a few minutes to a few hours,
and the resulting liquid is decaffeinated either by liquidliquid extraction with any of the solvents used in the first method or by selective absorprion of caffeine on acid-treated active carbon. Alternative adsorption processes which do not rely on solvents to recover the caffeine from the extract are called “water decaffeination.”19

  Extracting caffeine crystals from tea or coffee is a standard first-year organic chemistry experiment. Many people, far removed from academic laboratories, have wondered if there was some easy way to do the same. An amateur chemist provided an approximation of a home extraction process, although with the availability of Vivarin at every corner pharmacy and supermarket, its hard to understand why anyone would risk trying it, something that we, in any case, strongly recommend against:

  Mix 180 proof ethanol with very finely ground coffee and mash together. Filter off the solvent. Evaporate the paste and, when dry, dissolve in boiling vodka, until the volume is reduced by about 80 percent. Allow the liquid to sit and cool for two days. If you have done everything right, when you return you should find white caffeine crystals precipitating from the solution.20

  Pure caffeine is extremely toxic, and must be handled with hooded ventilation systems, masks, and gloves. Largely for this reason, chemical supply companies are not permitted to sell it to individual purchasers.

  Jar containing pure pharmaceutical-grade caffeine, featuring a chilling warning label, which reads in part: “WARNING! MAY BE HARMFUL IF INHALED OR SWALLOWED. HAS CAUSED MUTAGENIC AND REPRODUCTIVE EFFECTS IN LABORATORY ANIMALS. INHALATION CAUSES RAPID HEART RATE, EXCITEMENT, DIZZINESS, PAIN, COLLAPSE, HYPOTENSION, FEVER, SHORTNESS OF BREATH. MAY CAUSE HEADACHE, INSOMNIA, NAUSEA, VOMITING, STOMACH PAIN, COLLAPSE AND CONVULSIONS. MAY CAUSE DIGESTIVE DISTURBANCES, CONSTIPATION, CARDIAC DISORDERS, AND DEPRESSION. MAY CAUSE EPIGASTRIC PAIN, CARDIAC AND RESPIRATORY DISORDERS, AND DEPRESSED MENTAL STATES. EYE CONTACT MAY CAUSE IRRITATION, REDNESS, AND CONJUNCTIVITIS. INGESTION MAY PRODUCE GASTROINTESTINAL IRRITATION, VOMITING, AND CONVULSIONS. FATALITIES HAVE BEEN KNOWN TO OCCUR. Target Organs Affected: Eyes, Skin, Central Nervous System, Repiratory and Gastrointestinal Tract.” (Photograph by Paul Barrow, Biomedical Communications, University of Pennsylvania Medical Center, © 1999 Bennett Alan Weinberg and Bonnie K.Bealer.)