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CHEERS FOR CHOCOLATE

Science, Vol. 284

April 2, 1999

The list of sin-free foods keeps growing. First red wine, then coffee and tea were pronounced potentially beneficial in moderation. Now, studies presented at last week's American Chemical Society meeting in Anaheim, California, suggest that another guilty pleasure - chocolate - has its salubrious side.

The idea that chocolate may have some health benefit is plausible, says Joe Vinson, a chemist at The University of Scranton in Pennsylvania. That's because it comes from plants, which are prolific producers of polyphenols, antioxidant compounds believed to mop up free radicals that can damage DNA. But what is a bit of a shock, says Vinson, is that chocolate is chock-full of such compounds. He found that a single candy bar's worth of milk chocolate - 40 grams - harbors more than 300 milligrams of polyphenols, equivalent to a day's worth of fruits and vegetables. If that bar is dark chocolate, it holds 2 days' worth. Chemist Harold Schmitz of the M&M Mars candy company took the work a step further, showing that a family of flavonoids, a subclass of chocolate polyphenols, helped neutralize low density lipoproteins or "bad cholesterol" in the test tube.

So should chocoholics stop worrying and indulge? Well, no says, Vinson, because chocolate is still "high in saturated fats and calories." But "a little chocolate may even be good for you."

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CHOCOLATE LOVERS GET GOOD NEWS

Journalist: Barbara Durbin

The Oregonian FOODday

Tuesday, June 15, 1999

Its antioxidant polyphenols, which act a lot like vitamin E, may help your heart, and fight cancer and ulcers.

It sounds like a chocoholic's dream - a delicious fairy tale come true: Chocolate might be good for your heart, help fight cancers and ulcers.

That's if...

If chocolate behaves in people the same way it has in test tubes and lab animals

Scientists don't want to jump to conclusions, even though an overly eager public already has just one question: How much can I eat?

Researchers are exploring compounds found in chocolate, similar to those in coffee, that seem to help your health.

Joe A. Vinson, a professor of chemistry at The University of Scranton in Scranton, PA., has studied polyphenols - a class of compounds present in plant foods, including cocoa beans.

In your body, polyphenols are antioxidants, the good guys that go after free radicals. Free-radical molecules are very toxic and reactive, Vinson says. They can weaken cells, making you more susceptible to cancer and heart disease, for instance.

In the lab, Vinson explains, polyphenols "behave very much like vitamin E" - perhaps the best known antioxidant vitamin. Polyphenols also fight against oxidation of LDL, the so-called bad cholesterol, which can contribute to heart disease.

When you eat a lot of fat, you're creating "a negative oxidative effect," he says. Polyphenols might counter some of that "stress".

In one of Vinson's studies, researchers induced early signs of atherosclerosis (hardening of the arteries) in hamsters by "stressing" them (putting three males in a cage) and controlling their diet.

Hamsters fed even dilute tea as their beverage had lowered lipids - fats in the blood that can contribute to heart disease. (Oh, in case you're having hamsters to dinner, they don't particularly like coffee, compared to water. But, Vinson says, they just love wine and beer)

Vinson notes that studies on human population have shown tea drinking reduced risk of heart disease, although nobody knows exactly how that works.

Vinson also discovered that compared with the 20 most commonly eaten fruits and vegetables, chocolates has much higher levels of polyphenols. But slow down before you pour a bowl of Snickers bars for breakfast. This doesn't mean you should choose chocolate over fruits and vegetables, he warns. He doesn't advocate eating a lot of chocolate because of its high fat and calories.

In comparing polyphenol contents, Vinson notes cocoa powder comes in first, dark chocolate next, then milk chocolate, and, last, hot chocolate mixes, in which chocolate is more dilute.

He found green, black and oolong teas were higher in polyphenols than other beverages.

Coffee was lower than teas and "very comparable" to red vines, (Remember the "French paradox," where by red-wine drinking French have lower rates of heart disease than we do, in spite of diets higher in fat.)

Even so, coffee - even decaffeinated coffee - is higher in polyphenols than fruit juices, which have been touted as good source of antioxidants. In fact, because American drink so much more coffee than tea, coffee (including decaffeinated) is our No. 1 source of polyphenols.

In conjunction with the University of California at Davis, Harold H. Schmitz, a researcher with M&M Mars, Inc. (the candy folks), has found chocolates have a "diverse array" of flavonoids - a category of polyphenols.

Schmitz isn't saying you should run out and stock up on chocolate. But he notes "well-done" studies that show chocolate's fat, high in stearic acid, is not the kind that raises blood cholesterol.

naomi Osakabe, a researcher from Nagoya, Japan, who's also researching the antioxidant effects, says polyphenols in cocoa bean liquor show anti-ulcer properties in lab rats and inhibit tumors on the skin of mice.

Schmitz notes these results so far as "promising". But like the scientist that he is, he says these are very preliminary findings.

"Good science takes time," he says. But, he adds, "If you like chocolate and it fits into a well-balanced diet," and if you have dessert - why not chocolate?"

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CHOCOLATE: NEW FACTS COME TO LIGHT

Today's Chemist at Work (ACS)

Journalist: Mary Ann Ryan

July, 1999

Chocolate lovers of the world, listen up: your day of vindication may be at hand. You have no doubt been indulging your cravings despite everything you know about the junk-food status of those candy bars, death-by-chocolate cakes, and hot fudge sundaes you eat. But now comes news from the ACS National Meeting in Anaheim, and other sources as well, holding out the hope that chocolate might not be all bad.

I am talking about papers presented at the Anaheim meeting entitled, "Chocolate: A Rich Source of Polyphenol Antioxidants in the American Diet," (1) "Capacity of Polyphenolic-Rich Beverages [including cocoa] to Inhibit LDL Oxidation," (2) and "Potential Cardiovascular Health Benefits of Oligomeric Procyanidins [a subclass of polyphenol antioxidants] Present in Chocolate and Cocoa." (3)

These findings intrigued me because a considerable body of published research on fruits and vegetables suggests that the antioxidant compounds found in these foods in abundance provide protection against cancer and cardiovascular disease. Teas and wine have also been identified as excellent sources of antioxidants. And now chocolate, considered sublime for its taste and texture but cursed (from a health standpoint) for the fat and sugar that invariably accompany them, is shown to be high in compounds with antioxidant activity. Could this boost chocolate up a few notches in the health column?

Following up on the Anaheim papers with a literature search on chocolate, I came across some additional information guaranteed to put a smile on the faces of chocoholics. How about "Chocolate Lovers May Live Longer," a December, 1998, Associated Press article reporting on a Harvard University School of Public Health study finding that people who consume candy live, on average, almost a year longer than those who don’t. (4) Or several publications based on research at Pennsylvania State University showing that stearic acid, the main saturated fatty acid in chocolate, does not raise blood cholesterol levels as other saturated fats do. (5) And finally a few reports that cast doubt on some firmly entrenched, negative beliefs about chocolate concerning caffeine content, migraine headaches, allergies, and addictive effects. (See the box, "Misconceptions About Chocolate.")

As I read these various reports, I felt as though I were being transported back in time to Woody Allen’s movie Sleeper from the 1970’s. The main character, Miles Monroe, is the owner of The Happy Carrot Health Food Store in Greenwich Village before he is frozen for 200 years. He wakes up after his long sleep to find that the new health foods are hot fudge, steak, and cream pies.

Although it is unlikely we will be elevating chocolate to health-food status anytime soon, the new findings about chocolate were interesting enough to prompt a further look into what is known about it and how consumption of it might affect health.

[SIDEBAR]:

Chocolate Candy Consumption

Americans eat a lot of chocolate in the form of candy (about 4.6 kg/yr per person, or >10 lbs) but not as much as people in some of the northern European countries. Estimated chocolate intake in Switzerland, the country with the highest consumption, is 9.9 kg/yr (>20 lbs) for each person, double the U.S. amount. (ref.) A typical milk chocolate bar (1.4 oz) has a mass of 40 grams, so U.S. consumption would approximate 114 candy bars a year for every inhabitat, if we simplify things a bit by assuming that all chocolate candy intake is in the form of such bars. Each bar contains approximately 210 calories, 13 grams of fat (7 of which are saturated), 23 g of carbohydrate, and 3 g of protein. (ref)

Some Basics About Chocolate

Chocolate comes from beans harvested from the cocoa tree (Theobroma cacao), native to Central America. The beans are fermented, dried, roasted and pressed to give a chocolate liquor, which consists about a 50:50 mix of cocoa particles and cocoa butter.

If the chocolate liquor is further pressed to extract more of the cocoa butter (all but 10-25% of it), and the remaining paste cooled, ground, and sifted, cocoa powder results. The primary nutrients in cocoa besides the fats and fatty acids from the cocoa butter that remains in it, include various carbohydrates (a portion of which is the dietary fiber cellulose) and protein. Other contents present in smaller quantity are mineral salts (of Mg, P, Na, K, Ca, Fe, Zn, Cu, Mn), theobromine (the principal alkaloid of the cocoa bean), caffeine, polyphenols, and water.

A combination of cocoa and cocoa butter with other ingredients produces the delectable forms of chocolate we find in candy bars and other foods. Nutrition information from the Mayo Clinic ("Ask the Mayo Dietician," www.mayohealth.org) describes the different forms of chocolate as follows:

  • Unsweetened chocolate is a mixture of cocoa powder and refined cocoa butter. It is too bitter to eat and is used mainly in baking.
  • Dark chocolate (bittersweet and semisweet) contains cocoa, cocoa butter and varying amounts of sugar.
  • Milk chocolate has milk as well as cocoa, cocoa butter, and varying amounts of sugar. Flavorings such as vanilla are sometimes added.
  • White chocolate contains no chocolate liquor and no polyphenols, but only cocoa butter, sugar, milk and flavorings.

Most of the ingredients of chocolate have been known for some time. Of greater interest are the new findings that chocolate contains substantial amounts of antioxidants in the form of complex mixtures of phenolic compounds, and that these may have beneficial effects on health. Some background on what is known about dietary antioxidants in general may be helpful before we look at those in chocolates.

Benefits of Dietary Antioxidants

Why should antioxidants be important to health? Cells in the body are constantly exposed to reactive oxygen species (ROS) such as hydrogen peroxide (H202), superoxide anion(O2-), hydroxyl radical (OH-), and hypochlorous acid (HOCl) which are capable of causing cellular damage. Most of the ROS are produced in the course of ordinary biological processes and are prevented from doing harm by the body’s internal antioxidant defense systems; i.e., antioxidant enzymes within the cells. However, the defense system is not perfect, and some ROS escape it. Furthermore, illnesses, aging, or external factors such as air pollution, smoking, or the effects of UV radiation can lead to additional ROS and overwhelm the internal defenses. This is where food sources of antioxidants become important, forming a second line of defense to scavenge free radicals and prevent damage.

Consumption of fruits and vegetables – good sources of antioxidants – have been found to correlate positively with protection against cardiovascular disease, cancer, and cataracts, as well as slowing the effects of aging. In addition to fruits and vegetables, tea and wine are also high in antioxidant compounds. Some researchers believe that it is the antioxidants in wine that are responsible for the "French paradox," the finding that moderate wine consumption correlated with the lower mortality rate from heart disease in certain people in France despite their intake of foods high in saturated fat. Phenolic antioxidants have been shown to inhibit the oxidation of LDL cholesterol, and mounting evidence suggests that it is the oxidized form of LDL that leads to the buildup of fatty plaques in arteries.

Vitamin C, E, and beta-carotene are antioxidants. However, these substances are only part of a much larger mix of antioxidant compounds found in fruits and vegetables. Therefore, much of the recent research has reported "total antioxidant activity" or "total antioxidant capacity" of specific foods or beverages. (See the box on "Foods and Beverages High in Antioxidants" for more information.)

Antioxidants in Chocolate

The excitement over antioxidants in chocolate appears to have been started by a letter published in the medical journal Lancet in 1996. (6) Researcher Andrew Waterhouse and colleagues at the University of California, Davis, Department of Viticulture and Enology, had noticed in analyzing the cocao bean that it was a rich source of phenols. Phenols occur in most plant products, but had been found to be especially abundant in fruit, vegetables, wine, and tea. To determine whether chocolate products are also rich in phenols, the researchers took cocoa powder and baking chocolate from the kitchen and a milk chocolate candy bar from a vending machine to analyze them using a standard test for phenols in wine. They also tested cocoa extract for its antioxidant activity by determining its ability to inhibit oxidation of LDL cholesterol purified from human blood. Among their findings from this preliminary experiment were that of the three forms of chocolate, cocoa had the highest levels of phenols, followed by baking chocolate and milk chocolate; that a standard 1.5 oz milk chocolate bar had approximately the same quantity of phenols as a 5 oz glass of red wine; and that cocoa powder extract was a potent antioxidant for LDL oxidation.

More recent research by Joe Vinson at The University of Scranton, who has been studying total polyphenols in foods and beverages in the American diet, turned his attention to chocolate. His studies have shown that on a weight basis, " … the concentration of polyphenols in milk chocolate is higher than in red wines, black or green teas. It is 20 times higher than in tomatoes, 2 times higher than in garlic and over 3 times higher than in grapes." He also notes that dark chocolate provides over twice the level of polyphenols as milk chocolate per serving. However, white chocolate contains no polyphenol antioxidants.

Harold Schmitz, Group Manager for the Analytical and Applied Sciences Group at M&M/MARS, says that an important next step in studying antioxidants in chocolate and other foods will be to gain an understanding of the biological effects of different fractions of the polyphenolic compounds, rather than just looking at total polyphenols. His group, working in collaboration with researchers at UC Davis, has developed an analytical method based on HPLC/MS for separating and identifying procyanidins, a diverse subgroup of polyphenols. (7) They are finding that not only do procyanidins collectively have antioxidant activity and possible cardiovascular benefits, but that different fractions of procyanidin oligomers (e.g., dimers, trimers, tetramers, etc.) have different antioxidant potentials and, therefore, probably different biological potentials.

This last point raises an important issue. Because little is known about the physiological effects of specific antioxidants in the complex mixtures found in chocolate, fruits, vegetables and other sources, and because these mixtures do not contain exactly the same compounds (there is some overlap, but there are many differences), it is wise to follow the standard advice of dieticians: health is best served by eating a wide variety of foods and a balanced diet. In other words, don’t start substituting chocolate for broccoli thinking you will get the identical antioxidant benefit.

So, how much chocolate can I eat?

Taking into consideration all that has been said above about chocolate, we are still left with the question as to whether it is generally a good food for health. As with many questions in life, this one does not have a simple answer. Chocolate is usually consumed in forms that have a high sugar and fat content, and for this reason ought to be limited in the diet. Yet the antioxidants it contains are likely to be positive for health, although more in vivo research needs to be done to confirm this. I asked Julie Seed, a dietician at the Francis Stern Nutrition Center of Tufts University, how she might assess chocolate’ s place in the diet in light of its high antioxidant content. She said, "We would still need to consider whether it is the preferred source of these compounds, which are also abundant in fruits and vegetables." There is no definitive answer. But at least we have more evidence than we did a few years ago that chocolate is a more complex and interesting food than we may have thought, and that it may have some health benefits.

[SIDEBAR]:

Misconceptions About Chocolate

Chocolate is high in caffeine: The amount of caffeine in a one ounce piece of chocolate (sweet, semisweet, dark, or milk) ranges from 10-20 mg. By comparison, a 6-oz cup of regular coffee brewed contains 105 mg, a cup of tea 35 mg, and 12 oz of cola 35-50 mg. (Source: Mayo Clinic Web site, www.mayohealth.org).

Chocolate causes migraine headaches. A double-blind, placebo-controlled study of chocolate’s ability to induce headaches in 63 women with chronic headache was conducted at the University of Pittsburgh Pain Evaluation and Treatment Institute in 1997. Conclusion: Contrary to the commonly held belief of patients and physicians, chocolate does not appear to play a significant role in triggering headaches in typical migraine, tension-type, or combined headache sufferers." (Source: Cephalalgia 1997 Dec. 17(8):855-62)

Chocolate is a common cause of allergies: A recent study showed that only one out of 500 people who thought they were allergic to chocolate actually tested positive. (ref. needed)

Chocolate is Addictive: Although many people experience cravings for chocolate, there is little evidence from existing studies that these are due to addiction. The Mayo Clinic Health Letter (February, 1995) says, "It’s more likely chocolate cravings occur simply because chocolate tastes so good."

[SIDEBAR]:

Foods and Beverages High in Antioxidants

[To be added]

REFERENCES [to be added]

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LOCALS GOBBLE UP LATEST CHOCOLATE RESEARCH

Journalist: Ann Olander

CITY NEWS – Upland/Claremont

May 28, 1999

Good news for chocolate lovers.

Recent research indicates possible health benefits.

"We can have it occasionally and have no feelings of guilt," said Lorraine Lubanski, registered dietician at Pomona Valley Hospital Medical Center.

Lubanski of Claremont quickly added that she tries to encourage patients to stay within American Heart Association guidelines. Because 1 ounce of chocolate has 150 calories and 10 grams of fat, eating the treat should be compensated for in the diet.

A few patients and family members have asked her about the recently publicized health benefits of eating chocolate, Lubanski said. Studies are still ongoing. But the potential benefits sound exciting to chocoholics.

Consumer Reports in its March issue reported that about half the fat in chocolate is believed to have a neutral effect on cholesterol.

Citing a recent study where male college graduates who ate a moderate amount of chocolate lived about a year longer than those who ate none, the article tentatively hypothesized that the phenols, or antioxidants, in chocolate might help prevent artery clogging.

In a March 29 article in The Los Angeles Times, Rosie Mestel reported more good news about chocolate from the American Chemical Society’s annual spring conference in Anaheim.

"Scientists … report that chocolate is chock-full o’ antioxidant chemicals known as polyphenols and flavenoids, which when fed to rats and mice help protect against such things as heart disease, cancer and ulcers," Mestel wrote.

Joe A. Vinson, Professor of Chemistry, The University of Scranton, Scranton, Pa., one of the chief researchers who presented papers on antioxidants in chocolate at the ACE conference, has done research on antioxidants in many other foods and beverages, such as tea and coffee.

Discovering one piece of the puzzle may spur further research on the other pieces, Vinson said after the conference during a visit to the Inland Valley.

"I very seldom eat chocolate," he said, adding that he eats hard candy, which has fewer calories.

But he enjoyed visiting the popular A-Kline Choclatier in Claremont, where he sampled one of its top-selling chocolate truffles, and declared it "marvelous."

More women buy chocolates than men, said Kim Battersby, manager of the longtime popular store that features hand-dipped chocolates.

"Chocolate’s my favorite thing in the world," said Choclatier employee Courtney McGrady, adding that she eats it every day.

Neither woman thought more people were eating chocolate because of the new research.

"Any new findings I question, said Marsha Craighead, a frequent customer who owns the Bloomers Women’s Clothing shop next door. "I think it takes time to research anything."

Lubanski said people can substitute cocoa for hard chocolate in recipes, to reduce calories as well as fat.

As discussed on the San Francisco Exploratorium’s TV program on chocolate last fall, large-scale, controlled human studies are missing and more research is needed. But the initial research is encouraging.

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NOT-SO-GUILTY PLEASURES

Journalists: Stephen Reucroft and John Swain

Boston Globe

April, 1999

Good news for chocolate lovers – the stuff may actually be good for you. Choclate contains polyphenols, antioxidant compounds that can protect cells from highly reactive chemical fragments called free radicals. Free radicals can come from exposure to radiation, or from a wide range of chemical reactions that go on all the time in the body. Joe Vinson of The University of Scranton, in Pennsylvania, reports that chocolate is so loaded with polyphenols that you can get as much from a 12-ounce bar of milk chocolate as from a day’s supply of fruits and vegetables. If you like dark chocolate, so much the better, as a similarly sized bar will give you a two day supply.

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TAKE TWO CUPS OF COFEEE AND CALL ME TOMORROW

Coffee and chocolate contain antioxidants that may promote health

Journalists: Sophie L. Wilkinson

C&EN Washington

April 12, 1999

From the ACS Meeting:

Wouldn’t it be lovely if coffee and chocolate were good for you? Well, don’t just roll your eyes and turn the page. Evidence presented during a symposium at the American Chemical Society’s national meeting last month in Anaheim, Calif., on the chemistry and health benefits of caffeinated beverages, sponsored by the Division of Agricultural and Food Chemistry, indicates this may be so.

Coffee and chocolate products contain a range of polyphenolic antioxidants known as flavonoids, which may have health benefits such as prevention of heart disease. And there may be far more of them than are commonly accounted for, according to Joe A. Vinson, professor of chemistry at The University of Scranton, in Scranton, PA.

Much of the work on dietary intake of flavonoids relies on Dutch research that has focused on just five flavonoids, Vinson said. But "they are not measuring all the compounds that are there," he protested. "There are 4,000 known ones, and more all the time. And I think all polyphenols are good for you."

Vinson decided to study all of the antioxidants together, excluding vitamin C. In terms of polyphenol content, he found that "coffees are lower than teas and lower than wines, but higher than just about anything else you can think of in beverages (like fruit juices)." But because Americans drink a lot of coffee, it represents their top source of antioxidants from food.

Of course, data on food samples themselves don’t necessarily translate into actual health benefits. To help clarify the situation, Vinson gave coffee to hamsters for a couple of weeks and then examined the concentration of lipids circulating in their blood. Oxidation of lipids is the initial step in atherosclerosis.

Coffee consumption had no effect on the hamsters’ lipid levels, but it did reduce plasma oxidation by about 30%. That indicates that "the antioxidants are preventing lipids that are circulating in the plasma from being oxidized," Vinson said. And coffee drinking tripled the hamsters’ "lag time," the time it takes to oxidize the antioxidants in low-density lipoprotein (LDL) – the "bad" form of cholesterol - in a test tube. Preventing LDL oxidation is believed to interfere with the onset of heart disease.

The impact on lag time represents a "very large change," Vinson said. "If you were to start taking vitamin E suddenly at 800 IUs [international units] per day, your lag time might go up 30%." He cautioned, however, that the hamsters were drinking more coffee on a weight basis than a human could. He will soon have results from long-term hamster studies.

Vinson is also studying chocolate’s possible benefits. "People normally think of chocolate as bad, and it is bad in terms of calories and fat and sugar," he said. However, cocoa butter, the fat in chocolate, contains a lot of stearic acid. And that is "an unusual saturated fatty acid that doesn’t raise cholesterol," said Vinson, who partakes of both chocolate and coffee "in moderation."

He found that polyphenol levels in milk chocolate, dark chocolate, and cocoa powder are extremely high on a weight basis. A 40-g milk chocolate bar contains more than 300 mg of polyphenols; dark chocolate has more than double that; and cocoa powder has about four times that. "It is loaded!" Vinson said.

The amount of polyphenols in a serving of dark chocolate is comparable to that in a cup of black tea and higher than in a glass of red wine, "the things we normally think of as great sources of antioxidants. So chocolate is extremely high in polyphenols compared to other foods. The next question is, ‘Are they absorbed, do they work?’’"

Harold H. Schmitz, group research manager of analytical and applied sciences at M&M/Mars in Hackettstown, N.J., has also been studying flavonoids in chocolate and cocoa. The firm, which he says is the world’s leading chocolate company, is interested in procyanidin flavonoids because they influence flavor.

Schmitz and his colleagues have developed an analytical technique that for the first time can separate into individual fractions the family of procyanidins that can be found in chocolate products and other plant-based foods. Rather than using the typical reserved-phase high-performance liquid chromatography methodology – which yields "one big hump" for all the procyanidins – the Mars team used normal-phase HPLC hooked to a mass spectrometer.

Using the new method, they determined that the procyanidins can occur as monomers or as oligomers, with two, three, or more units linked together. Because food-processing techniques affect the amount and type of these substances found in chocolate products, Schmitz cautioned that his results cannot be generalized to all such foods.

He next set out to determine whether the different procyanidin fractions show different antioxidant activity. In vitro tests showed that they had significant activity, and that an oligomer’s ability to inhibit LDL oxidation rises as it increases in size. Schmitz said these results are "quite exciting, because cocoa and certain chocolates contain greater quantities of these higher oligomers than some other foods." He added that the work suggests that "not all antioxidants are created equal, not all polyphenols or flavonoids in cocoa and certain chocolates are created equal."

Schmitz believes further research is needed to assess his results. One or two in vitro experiments aren’t enough to prove that chocolate can prevent heart disease, he said.

In addition to the potential cardiovascular effects of chocolate and coffee, symposium participants presented data on the effects of caffeine on the brain and on behavior. Andrew P. Smith, a professor of experimental psychology at the University of Bristol in England, combed through 10 years of literature on the impact of caffeine on cognition and mood.

In such studies, test subjects may be brought to a lab for baseline measurements and then given a cup of caffeinated coffee (instant coffee, for example, contains abou 60 mg of caffeine) or decaffeinated coffee (which has less than 1 mg of caffeine). After a half hour, their performance is tested again. They are asked how alert they are feeling, and they may perform a task that requires sustained concentration. They may, for instance, have to press a button every time a particular number appears on a computer screen.

The research confirmed what millions of imbibers believe, that caffeine improves alertness and the ability to concentrate. "This is particularly beneficial when your alertness is reduced – for example, when you are sleep-deprived or when you have a minor illness like the common cold," Smith told C&EN. Because caffeine "has a very slow half-life – between three and five hours – these [beneficial] effects can go on for quite a long while."

Typical daily consumption of caffeine is around 120 to 150 mg for a 60-kg person, or 2 to 2.5 mg per kg, according to Astrid Y. Nehlig, research director at the French National Institute of Health & Medical Research (INSERM) in Strasbourg. At doses up to about 300 mg per day, caffeine induces positive effects on mood, alertness, vigilance, and feelings of well-being. But doses above 400 mg results in negative feelings, including bad mood, aggressitivity, and anxiety.

These behavioral effects can be correlated with caffeine’s impact on glucose metabolism in the brain, Nehlig told C&EN. At a dose of 1 mg per kg, cerebral activity increases only in a few regions of the brain. These include the caudate nucleus, which mediates locomotion, and the raphe nuclei and locus coeruleus, which are involved in the control of mood states and sleep.

As the dose rises to 2.5 mg per kg and then to 5 mg per kg, activity increases in other brain regions affiliated with locomotion, mood, and sleep, and in the amygdala – which controls anxiety levels. Nehlig noted that the caffeine in her tests is administered in a single dose rather than spread out over an entire day, so these concentrations represent quite a high dose.

Nehlig then turned to a question that has persisted for a decade: Can caffeine induce dependence? She examined caffeine’s impact on the shell of the nucleus accumbens, the area in the brain involved in addiction and reward that is activated by amphetamines, cocaine, morphine, and nicotine. Her tests indicate that doses up to 5 mg per kg have no impact on activity in this area.

At 10 mg per kg, activity does increase there, "but this increase occurs in a nonspecific way," Nehlig said. "When you give caffeine at that dose to animals, you have a generalized increase in activity all over the brain, maybe 50 structures out of 60." This contrasts with drugs of abuse, which at low doses selectively activate this nucleus. Nehlig concluded that "it is very unlikely that caffeine can induce dependence by a mechanism that resembles that of the common drugs of abuse."

Nehlig compared caffeine’s effects to those drugs because both act on the neurotransmitter dopamine. She plans to now check into the mechanism of dependence induced by the drugs that influence GABA (¡ -aminobutyric acid) neurotransmission, including alcohol and the benzodiazepenes (such as Valium).

While some people "claim that they are totally unable to stop caffeine," Nehlig said, for most people a cup of coffee is simply a source for feelings of well-being and an upbeat mood.

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