brain candy

Mmmm, chocolate. Who among us can resist its siren call? Some find it more irresistible than others, it's true, but one would be hard pressed to find someone who didn't enjoy chocolate in some form or another. And that's been true for millennia, apparently, according to this handy historical recap of the consumption of cocoa -- the stuff that makes chocolate, chocolate -- for both pleasurable and medicinal purposes.

For example, the Mayans drank cocoa 2600 years ago (the earliest record of cacao use), but our modern word, "chocolate," derives from "xocolatl"), a combination of "xocolli" ("bitter") and "atl" ("water") in the Nahuatl language of the Aztecs. The stuff itself derives from the cacao tree, specifically, the beans contained within large pods. Those beans are harvested, allowed to ferment for several days, then dried quickly to ensure mold doesn't have a chance to grow. The beans are then roasted and ground up. The liquor portion of what results is what's used to make cocoa butter (which in turn becomes, say, a Hershey bar or Godiva truffle), while the residue is cocoa powder. (For a nifty guide to tempering chocolate, go here.)

Around 1590, a Florentine named Bernardino de Sahagun reported that drinking a small amount of cocoa resulted in a general feeling of well being. Even today, chocolate is viewed by many as a mood enhancer, an aphrodisiac, an indulgence or a reward. Others report increased alertness and performance due to a sudden energy boost. (Whether that's from the cocoa or just a sugar rush is debatable.) In some, it seems to have an adverse effect, namely nervousness and restlessness. And for bona fide chocoholics,  it's related to appetite, specifically, desire and cravings. But we're talking about individual, subjective impressions in all such cases. What does the actual science say?

Yes, science has something to say on the matter -- quite a bit by now. The 2000 AAAS meeting in Washington, DC, featured a session on the health effects of chocolate -- specifically the benefits to the cardiovascular system to be gained from certain compounds -- which in turn spurred even more research in this particular area. Now, seven years later, at yet another AAAS meeting (this time in San Francisco), scientists have further enhanced their understanding of what kinds of effects chocolate does and does not have on human beings. The neurobiology of chocolate merited an entire session all its own, and needless to say, Jen-Luc Piquant and I were happy to rise a bit earlier than usual in order to learn a bit more about this fascinating (and sinfully delicious) subject.

Chocolate's reputation for indulgent decadence is related to the high percentage of sugar and fat contained in even a single gourmet truffle. (Mmmm... truffles!) High levels of sugar and fat, it is generally agreed, aren't all that good for you. But when it comes to health benefits, it's all about the compounds in cocoa that are subsequently broken down in the body after being consumed, according to Hagen Schroeter, a researcher formerly with the University of California, Davis, who is now working with Mars, Inc. The company funds quite a bit of research into the health effects of cocoa,  providing researchers with its own high-flavanol cocoa product, Cocoapro (TM). So one might say they have a vested interest.

There's quite a few chemical components to cocoa. First, there's the so-called methylxanthines: caffeine and theobromine. Then there's biogenic amines like tyramine and tryptamine, as well as the by-now-well-known cocoa flavanols (which I always confuse with flavonoids; flavanols are a subclass of flavonoids, but that's as far as my understanding goes), most notably epicatechin. There's also dopamine-related compounds like salsolinol, and certain endocannabinoids like anandamide. All of these are being studied in one way or another for their potential effects on human health, whether it be measurable, direct psychophysiological effects, or acquired behavioral and psychological effects (which tend to be a bit more subjective).

Some of the claimed health effects are slight, nearly non-existent in some cases, and it should come as no surprise that dosage matters, as does rate of absorption, metabolism, and other factors. "The mere presence of a substance does not guarantee psychoactivity," says Schroeter, pointing out that many suspected effects on mood and behavior have yet to be scientifically demonstrated. For instance, consider anandamine, which gets its name from the Sanskrit word for "inner bliss" (ananda). There is some evidence showing that it and other endocannabinoids (like N-arachionoylethanololame) may modulate our pleasure response to food and our sense of eating chocolate as a reward, but only if one consumes between 10 and 15 kilograms of chocolate in a single sitting. The most hardcore chocoholics I know would balk at that prospect, I think -- or make themselves sick to their stomachs, long before the "reward" effect kicked in.

Okay, so what about salsolinol, which might be responsible for chocolate cravings and outright addiction? It's found not just in cocoa powder and chocolate, but also port wine and beer, and in bananas, which have a much higher concentration of the compound that all the others combined. Salsolinol can be found in the dopamine-rich areas of the brain and in the spinal fluid, but Schroeter reports that much higher concentrations than found even in bananas would be needed to result in truly, measurable addictive behavior. Ditto for the biogenic amines. Almost all foods contain them in low concentrations, with higher levels found in fermented foods like wine and cheese, as well as fish and nuts. Scientists are still studying the extent of their absorption and distribution throughout the central nervous system, but a 2003 study found no effects from dietary biogenic amines.

That brings us to caffeine, a substance that does increase cognitive and psycho-motor performance at doses found in food and drink, most notably coffee, tea, and cocoa/chocolate -- which might explain why these are the most popular "ingestants" (to use Schroeter's term) in the world. Falling into the same category as caffeine is theobromine. Finally, we have those flavanols, found in tea, wine and cocoas, which have been shown to have positive benefits on cardiovascular healthy by increasing micro-circulation of the blood.

Henrietta van Praag of the The Salk Institute reported some intriguing results from her latest study on the effects of the cocoa flavanol, epicatechin, on learning and memory. Also found in blueberries, green tea and pomegranate, epicatechin does appear to improve cardiovascular function and increase blood flow to the brain, so van Praag was curious as to whether it could also enhance learning. She performed spatial memory experiments with mice. In one experiment, the mice were fed doses of epicatechin combined with regular exercise, then let loose to find their way through a water maze to test their spatial memory. She found their learning was indeed improved compared to the control group. In a second experiment, the mice were fed epicatechin without regular exercise. Again, she found that the mice learned faster and remembered the task longer than the control group.

So Van Praag concluded that a low to medium dose of epicatechin improves learning and memory. But in science, every answer invariably raises a bunch of new questions. For instance, how does epicatechin achieve this effect? What is the cellular/molecular mechanism at work? The hippocampus is the region of the brain associated with learning and memory, and the working hypothesis is that epicatechin increases blood flow in that area. It may also alter the morphology of nerve cells in a subtle yet significant way, namely by increasing the density of the neuronal "spines" of nerve cells.

There's also strong evidence that regularly drinking cocoa may alleviate -- if not cancel out altogether -- the development of age-related hypertension (high blood pressure), and other associated cardiovascular difficulties. Norman Hollenberg of Harvard Medical School specialized in studies on aging and blood brain flow response. His most interesting findings came from a study of the Kuna Indian population in Panama, specifically, the island-dwelling populace rather than those who had been assimilated into the mainland. The isolated Kuna did not exhibit the typical rising blood pressure as they aged; those who had migrated to the mainland, however, did suffer from age-related hypertension. Hollenberg found that the islanders drank incredible amounts of cocoa, more than 20 cups per week, compared to two or three cups for mainland-dwellers. It was the only unique environmental factor that could account for the largely nonexistent occurrence of hypertension among the islanders.

The key may lie in nitric oxide, an ancient hormone that scientists believe facilitates cell-to-cell communication in living organisms. You know, like the slime mold, an organism made up of single cells that must communicate with each other. Hollenberg was intrigued by prior studies indicating that flavanol-rich cocoa -- the bitter-tasting, unprocessed cocoa, I should note, not the excessively sweetened Swiss Miss variety with mini-marshmallows, which has been stripped of much of its natural flavanols -- can influence blood flow to the brain through the nitric oxide pathway, and conducted his own study on healthy subjects over 50.

He found a striking blood flow response that built up over several weeks of regular consumption of large doses of unprocessed cocoa.  His hope is that cocoa might one day be used to prevent or at least slow vascular-related dementia in the elderly -- a subject of deep personal interest to Hollenberg, since both his aged parents suffered from dementia prior to their deaths. Notably, the island-dwelling Kuna not only live longer than the mainland populace -- 94 years compared to 88 years, on average -- but there are almost no cases of age-related dementia. Nor do they suffer from many of the leading causes of death among the elderly in urban populations: cancer, stroke, and diabetes, for example.

Studies with mice and indigenous people are all very well and good, but can the effect on the human brain be measured directly? Ian MacDonald of the University of Nottingham Medical School figured it was worth a try. He has conducted functional magnetic resonance imaging (fMRI) studies to determine if there were any measurable effects from a cocoa-flavanol rich beverage -- namely, whether there would be increased activation in certain regions of the brain while performing a complex cognitive task. FMRI is useful in such cases because it's designed to detect increased blood flow; those areas show up as patches of light in the resulting image. In the brain, this is indicative of increased activity, telling scientists which regions are triggered to perform specific cognitive tasks.

MacDonald's study tested 16 young women, who were asked to perform a complex task switching exercise inside an fMRI machine (essentially a whole-body MRI machine).  They were asked to distinguish between vowels and consonants, and between odd and even numbers, pressing a button with either their right or left hands to record their answers. Just to make things a bit harder, the task was color-coded. If the letter-digit pairs were in red, the subjects responded to the letter; if the letter-digit pair was in blue, they responded to the number.

The women got to practice a bit first, until they could perform the switching tasks with less than 5% error rate. This set a handy baseline for the experiment. They consumed one Mars Cocoapro drink per day for five days and then were tested again. After a two-week interval, they were tested yet again, also after five consecutive days consuming a Cocoapro beverage. The final drink was consumed in both cases about 1-1/2 hours before the test.

Task switching cognitive studies invariably result in an increased delay in the subjects' reaction times (known as the "switch cost"). Could cocoa help reduce the switch cost? Apparently not. MacDonald found that the flavanol-rich cocoa beverage had not effect on either the speed or accuracy with which the young women performed the cognitive tasks, which he thinks might be due in part to the fact that they were young and healthy and arguably already performing at peak capability. However, MacDonald did find an "enhanced response" in the fMRI images that indicated an increase in blood flow in specific areas of the brain during the task, an effect that lasts between two and three hours. He believes this is a strong indication that consuming Cocoapro can increase blood flow and enhance brain function for people who are cognitively impaired, whether by sleep deprivation, fatigue, or advancing age. And cocoa flavanols potentially hold promise as a treatment for dementia and strokes, and for maintaining overall cardiovascular health.

To sum up:

• The "reward" effect from eating chocolate is largely psychological, because it require consuming huge amounts of the stuff in a single sitting to have a significant chemical effect.
• Ditto for the possibility of chocolate being chemically addictive; the chocoholic phenomenon appears to be largely behavioral/psychological in nature.
• Like any food or beverage containing caffeine (and in the case of cocoa, theobromine as well), chocolate does temporarily increase cognitive or psycho-motor performance.
• The jury is still out, however, on whether consuming a flavanol-rich cocoa drink improves learning, memory or one's ability to perform complex cognitive tasks.
• The single best reason for consuming a flavanol-rich cocoa drink like Cocoapro, despite the bitterness, is that it can have a significant positive effect on cardiovascular health, reducing one's risk of high blood pressure, stroke and diabetes -- particularly for aging individuals.

And there you have it: chocolate's current standing in the "healthy vs. unhealthy" debate. As R.J. Huxtable wrote in a 1996 article in Nature, chocolate, it seems is "more than a food but less than a drug." I can't wait for the research to shift to the study of how chocolate works in combination with peanut butter. The Reese's folks should be all over that.

Comments

[TBB]

Blake Stacey beat you to the punch on the Mars, Inc. bit: http://skepchick.org/blog/?p=413#comment-5207

After the news that coffee might serve as a good antioxidant, chocolate may help cognitive abilities, and port wine (which is also what our communion consisted of), this is interesting information to mull over. My blood pressure's just fine, too. Maybe if I keep up with my bad habits I'll live to 150. ;-)

I'm not sure about peanut butter having any particular effect *because* of being mixed with chocolate, but I am wondering about the effects of peanut butter alone; Reese's may have just found a winning addictive combination (at least for me).

Great post...in fact, irresistable.

**Off topic: Speaking of Mr. Stacey and useful links, check this out on Neil Gaiman's blog:
http://www.neilgaiman.com/journal/2007/02/small-ponder-on-mysteries.html

The nfctd part - it's just the coolest, hauntingly beautiful thing I've played with online recently. I went through it several times and it was slightly different each time depending on how I clicked. I think you might like it, Jennifer.

[A quantum diaries survivor]

Hi Jennifer,

Maurizio Scarpa, the pediatrician of my kids, considers chocolate more or less at the same level of arsenic. And he is not a moron - he did quite advanced studies, and also spent a few years in a US clinic. I have never investigated how much his position is shared by his peer, though.

I for sure did not disallow chocolate in my house, but due to the influence of dr. Scarpa, I am relieved to see that neither Filippo nor Ilaria are mad about it.

Don't take me wrong, I love chocolate! It is not compatible with my constant dieting state, but I allow myself to disobey from time to time.

Cheers,
T.

[Dr. Free-Ride]

I can't wait for the research to shift to the study of how chocolate works in combination with peanut butter.

Presumably the animal model to start with on these studies is the rhesus monkey?

[Blake Stacey]

A critical problem with Western religions, to my knowledge unaddressed even by Prof. Dawkins, is the lack of chocolate in their rituals.

It looks like the only difference between a flavanol and a flavonoid is that the former has a hydroxyl group (an oxygen hooked to a hydrogen) attached to that middle hexagon, next to the carbonyl group (the C=O part).

[JScarry]

It's not too surprising that chocolate isn't a part of Western religion since most of the religious rituals were set in place in the Middle Ages-before chocolate was introduced to the West. I'd be more interested to know if coffee is part of Muslim rituals since they have origins at around the same time.

[Monado]

Well, green tea is famously part of Japanese rituals of contemplation. And it's powdered green tea at that, for faster absorbtion.

[Blake Stacey]

You expect me to believe that the Promised Land could be anywhere which chocolate is not? Ahem! Milk and honey just ain't enough, and less'n there be some cacao trees in Canaan which the Good Book never got 'round to mentionin', maybe it cain't be such a Good Book after all.

Well. It's worth thinking about, anyway.

[David Harmon]

I find it interesting that the response to chocolate varies so much between individuals. I've known a fair number of people for whom chocolate really qualified as a "drug of addiction". But while I'm definitely a sugar fiend (munching gummy-worms as I write), I never "got into" chocolate to anything like that degree.

[sharon]

Yay, chocolate!

[darnell]

I recently read an article about you and your latest conquest featured in the Seattle Times. After reading your bio, columnist reviews and your blog, I can't help but wonder, as an intelligent and savy yet somewhat sarcastic writer, do you ever get people who naysay? (ie: negative feedback, or, do all of the scientific facts that you hightlight give you a credibility that people would rather not challenge, more times than not?) As a fellow blogger, I'm wondering how to take the criticism for my honest thoughts without taking it personal. Do you think that there is something to be said, really, about adding in specific facts???

[Nigel]

The milk chocolate sold in England is not very good for you as they use milk solids high in saturated fat. That's the number one problem, not sugar (which you can easily burn up) and cocoa (which is probably a benefit in some ways, as you suggest).

I can't stand plain chocolate, but I don't particularly want to health problems, so when I found out the high saturated fat content of milk chocolate (Cadbury Dairy Milk, for instance) a few years ago, I tried to cut it out. It's been difficult (bad withdrawl effects), but I've survived.

What a shame they don't use skimmed milk solids to make milk chocolate.

You can buy chocolate with artificial sweetener instead of sugar, but that's no use (I need energy, I just don't want saturated fat).

[azi]

since when , is nitrix oxide a hormone?

[darnell]

I have to say, I love your blog. So much, that I've linked your blog to my blog for the Seattle PI.

I First came acrossed your work in an article in the Times. Very creative spin on things. Rock out with your cocktail out! lol....

[Clemens Ferien]

Very interesting article and I never have seen a better explanation what chocolate do and how it works. Before I loved to eat chocolate but now I love it more and can eat it with a good conscience.