Healthy Chocolate Science Update
First Quarter -- 2009

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The information in this work is for educational purposes only and should not be used to diagnose and treat diseases. All serious health conditions should be treated by a competent health practitioner. Neither the publisher nor the author of this book in any way dispenses medical advice, prescribes remedies, or assumes responsibility for those who choose to treat themselves. The publisher and author have taken great care to ensure the accuracy of the information herein; however, errors may have been included. The publisher and author reserve the right to update or otherwise change the content of this work at any time without prior notice.

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Copyright Steven Warren M.D. and GoodNewsAboutChocolate.com (2009). Redistribution of this work is permitted; however, this work may not be sold, altered, or otherwise changed without the express written consent of the publisher and author.

Cocoa in World History
There is no denying that cocoa has played a major role in the development of both Mesoamerican and European History. Even today, fortunes are won and lost on the price fluctuations of this highly sought-after commodity, as traders bet on the moves of cocoa futures. Cocoa is produced in mass amounts in only a handful of countries around the world, many of which are not always politically or economically stable.

Recent discoveries in Honduras revealed traces of cocoa on cups and plates dating back to 2000 B.C. Between 200 and 900 A.D., the Mayan culture celebrated cocoa as a central part of their agriculture, economy, medicine and religion.

Still used today, the word "cacao" is derived from ancient Olmec and subsequent Mayan languages ("kakaw"), while the term "cacahuatl" also related to the root origin of cacao, is from ancient Aztec.

In 1737, Swedish scientist Carolus Linnaeus named the tree that produces these unsightly, yet highly prized cocoa bean pods "Theobroma cacao" -- literally meaning "cocoa, food of the gods". This name is a nod in reference to the mythical history of the tree among the ancient Mesoamericans.

Cocoa as Medicine
While cocoa was a celebrated and valued part of ancient Mesoamerican society, ancient records have also revealed more than 150 uses of cocoa for medicinal purposes.

The Europeans were first introduced to cocoa by the Spanish conquistadors around 1505 A.D. By the mid-1600s, European healers were "prescribing" cocoa as a medicine to stimulate the health function of the spleen and digestive tract, as well as a cure for all manner of other ailments and diseases. Cocoa was valued as a means to heal colds and cough attacks, enhance mental acuity, fight inflammation and improve overall nutrition.

Some Noted Mentions of Cocoa in History
Thomas Jefferson: "The superiority of chocolate, both for health and nourishment, will soon give it the preference over tea and coffee in America which it has in Spain(1).

William Clark (famed explorer): "I felt my Self [sic] very unwell and derected [sic] a little Chocolate which Mr. McClellan gave us, prepared of which I drunk about a pint and found great relief."

Baron Justus von Liebig (German chemist): "Chocolate is a perfect food, as wholesome as it is delicious, a beneficent restorer of exhausted power. It is the best friend of those engaged in literary pursuits."

Jean Anthelme Brillat-Savarin (lawyer, politician): "It has been shown as proof positive that carefully prepared chocolate is as healthful a food as it is pleasant; that it is nourishing and easily digested... that it is above all helpful to people who must do a great deal of mental work."

Other Historical References
Deanna Pucciarelli and Louis Grivetti from the University of California, Davis, recently published a paper titled, "The Medicinal Use of Chocolate in Early North America." This paper discussed the long history of medicinal chocolate in North America dating back to the 16th century (2). The paper suggested that medicinal chocolate was very prominent in many of the remedies prescribed for an assortment of illnesses, referring to advertisements of the day, including the following: "Always on hand pure cocoa and Homeopathic Chocolate, without any admixture of spices, are to be had, by the single cake or by the box of 25 pounds each."

In 1849, the Scientific American journal published the statement, "During last summer, those individuals who were habitually using chocolate or broma, neither had attacks of cholera or dysenteric affections, while other in the same families, taking their daily potations of tea, coffee, or simple cold water, were suffers."

Dr. Albert Bellow suggested that "Cocoa differs from tea and coffee in that it is rich in nutritious food, and having in it no tannin or other deleterious elements, its theobromine, or characteristic property, being connected with albumen a muscle-making element."

Cocoa products were considered "well-known [as] valuable foods, since they [act] as respiratory excitants."

Advertisements in the late 1900‘s touted cocoa‘s benefits for patients with asthma, bronchial, and lung trouble.

The famous physician Dr. Benjamin Rush wrote, "Chocolate differs considerably from both [tea and coffee], possessing no exhilarating virtue, or only in a small degree, but is more nutritive, and in South America constitutes a considerable part of the food."

Regarding his treatment for yellow fever, Dr. Rush related, "As soon as the pulse is reduced, I indulge them in weak chocolate." He recommended chocolate for gout, yellow fever, and many other diseases at the time.

Cocoa was a common medicine included in the well-known "house call" medical bags carried about by doctors during the 19th century.

One medical book from the time said this about treating whooping cough: "Let the child live on a light diet, little or no meat, cake, pastry, or heavy food, but an abundance of mucilaginous drinks [such as] chocolate."

Cocoa was a mainstay in medical recommendations throughout Europe, North and South America until as recent as the third decade of the 19th century.

A copy of Dr. Pucciarelli and Dr. Grivetti‘s paper can be found at the World Cocoa Foundation website.

Post-Industrial Chocolate: From Good to Bad
With the coming of the Industrial Revolution, chocolate manufacturers found themselves in regional and global competition for consumers.

At the same time that chocolate was being served in liquid form as a medicine for the sick, it was also being produced with added fats and sugars as a cheap candy.

The mid- to late-1800s saw the creation of a tremendous market for chocolate penny candy, as well as for fancy boxed chocolates that have since become synonymous with love and courtship.

By the 1950s, chocolate had completely lost its association with health and healing. Many of today‘s most famous chocolate companies got their start during the Great Depression, known to those in the business as the "hungry thirties" due to the popularity of this cheap diversion from the doldrums of everyday life amid the harsh economic crisis.

Are we experiencing the "hungry 2000s" today? In an article dated April 11, 2009, Time Magazine noted that sales of Swiss chocolate were still going strong, despite the recession.

According to the last paragraph of the article: "the question of why there is no meltdown in the chocolate business may be more a matter of psychology than economics. 'There is well-documented evidence going back to Freud, showing that in times of anxiety and uncertainty, when people need a boost, they turn to chocolate,‘ says [Stephane Garelli, director of the World Competitiveness Center at the Institute of Management Development (IMD) in Lausanne]'. 'That's why when the economy is bad, chocolate is still selling well.'"
(Chocolate Sales: A Sweet Spot in the Economy, Time Magazine, April 11, 2009)

A Renaissance in Chocolate
Only in the past few years has cocoa been re-examined as a health food and nutritious source of antioxidants, anti-inflammatories, vitamins and minerals.

Overall, the demand for cacao remains very high, with an estimated 3.5 million tons (that‘s 7,000,000,000 pounds) consumed during 2008.

Cocoa Science Update
The last 10 years have seen resurgence in interest about the health benefits of cocoa. Numerous studies have been sponsored, increasingly so over the last three years. Every year, more human studies on cocoa uncover yet more mechanisms associated with the action of cocoa.

Studies have focused not only on the antioxidant properties of cocoa, but also on anti-inflammatory properties, mood enhancing properties, and other beneficial properties of cocoa in its dark, bitter form. During 2008 alone, more than 50 studies were conducted related to the health benefits of cocoa, including epidemiological studies and human dietary trials.

Cocoa is King
What is in cocoa that provides all of these benefits?

Cocoa is a complex food. There are over 300 different components found in cocoa, but the processing methods used play a major role in whether cocoa retains its beneficial properties.

The major components of cocoa are cocoa butter (a neutral fat, consisting of oleic, stearic, and palmitic fatty acids), minerals (copper, magnesium, potassium, iron, zinc and calcium), theobromine (and trace amounts of caffeine), and the "mood chemicals" -- PEA, tyramine, tryptophan, and serotonin.

Actually, this is just a small list of the 300 chemicals found in cocoa.

And, very importantly, we mustn‘t overlook the polyphenols contained in cocoa.

Polyphenols are what bring the majority of health benefits from this amazing product. Polyphenols consist of a large class of compounds that provide antioxidant and anti-inflammatory benefits that are often found in fruits and vegetables.

One class of these polyphenols is called flavonoids, which can be further categorized into smaller families (flavanones, flavones, flavonols, flavanols (flavan-3-ols), anthocyanins, and isoflavones).

We can go a step further, and break down the flavanol family into (1) single compounds ("monomeric compounds" epicatechins and catechins) and (2) combined compounds ("oligomeric compounds" procyanidins). These substances are the true backbone of the health properties of cocoa.

Epicatechin is the predominant polyphenol in cocoa, and accounts for the majority of the health benefits we get when we eat properly processed cocoa. Cocoa is one of the most polyphenol-rich foods to be found anywhere on our glorious green planet. But, some or most of the beneficial components can be stripped away and completely wasted, depending on how the cocoa bean is processed. Lose the valuable chemical components, lose the health benefits.

Healthy Chocolate Science Update -- Q1 2009
In this paper, I will examine the influence of manufacturing processes on the availability of flavonols contained in cocoa beans. I will also present the most recent research conducted in 2008 on cocoa and health, and connect the results of the University of Utah study on Xocai with other pertinent studies.

A 2008 study completed by researchers in Spain examined the impact of manufacturing processes on cocoa powder. The researchers found that "Dutching" (or alkalinization) of cocoa powder resulted in a 60% loss of total flavonoid capacity. While Dutching might make cocoa more palatable by removing bitterness, it also robs cocoa of most of the beneficial properties associated with flavonoids.

Even the process of fermenting cocoa beans contributes to the loss of potent flavonoids.

This study also showed that Dutch processing results in a 67% loss of the epicatechins, which is the main powerhouse flavonoid in cocoa.

Need more convincing? The researchers also discovered that Dutching contributes to an 86% loss of the other important flavonol in cocoa -- quercetin. Quercitin is a very potent antioxidant and free-radical scavenger that was not even reported to be found in cocoa before this study came out.

Pound-for-pound, unprocessed cocoa contains as much quercetin as broccoli, apples, or red grapes.

As recently as August 2008, a study reported the discovery of dietary resveratrol in cocoa powder (about half as much as an average California red wine), further bolstering the argument of cocoa as a beneficial food. Resveratrol is a very potent antioxidant, associated with anti-inflammatory, anti-aging, and platelet aggregation inhibiting benefits.

Why is the preservation (or even enhancement) of cocoa polyphenols of such great importance? The answer is two-fold: the obvious biological activity of polyphenols, and the limited absorption of polyphenols in the gut. This means the more potent the cocoa, the more beneficial to the consumer. Epicatechin demonstrates the highest absorption in the blood, which is why it is important to maximize the amount available in the product.

Several studies have examined the absorption of flavanols into the bloodstream ("bioavailability"). These studies found that the gastric environment has little-to-no effect on polyphenols. Epicatechins and catechins are readily absorbed by the upper intestinal gut into the bloodstream. Epicatechin metabolites (glucuronide, sulfate, and methyl) are found in blood plasma very soon after hitting the intestinal gut. The larger molecules of flavanols not absorbed in the small intestine travel to, and are metabolized by, bacteria in the large intestine, producing other beneficial polyphenols. These valuable compounds can be found even up to six or 12 hours after the cocoa product has been ingested.

These studies also discovered epicatechin metabolites and quercetin in the brain bloodstream soon after the ingestion of cocoa.

Another important factor to consider is whether an increase of polyphenols increases antioxidant levels in the blood. Studies have found definite increases in blood ORAC levels associated with cocoa consumption, indicating that the flavonoids are being utilized by the body. The ORAC (oxygen-radical absorbance capacity) test measures the capacity of a compound to absorb or neutralize oxygen-free radicals, which are harmful to the body. An increased presence of antioxidants gives the body another weapon to fight damaging molecules that are created inside the body every day.

An increase of total serum glutathione, also shown in these studies, indicates that the flavonol molecules are actually doing their jobs inside the living body. Glutathione (a protein found inside cells) is essential for the function of immune cells and disease-fighting.

Another interesting and informative test determines whether the metabolites (breakdown products) of the flavonoids are found in the urine. Presence of metabolites in urine indicates that the molecules are being used by the body. One of the easiest molecules to check in urine is isoprostane -- a molecule that damages the body. If antioxidants are absorbed and functioning correctly, there should be a reduced level of isoprostane found in urine. High levels of isoprostane are associated with increased risk for dementia.

The study performed in 2008 by the University of Utah showed statistically significant increases of ORAC levels in blood plasma, increases of glutathione levels in plasma, and decreases in isoprostane levels found in urine. University of Utah researchers found these results using both a standard dose of Xocai Activ™ (one ounce, three times per day), as well as an increased dose (three ounces, three times per day). These findings confirmed other reports of increased serum ORAC levels, increased glutathione levels, and decreased isoprostane levels found in other in-vivo tests (tests performed in the human body) with dark cocoa powder.

Latest Research and Relevance to the University of Utah Study
Next, allow me to present some of the latest studies performed on dark cocoa, relating them to the results of the University of Utah study.

It‘s no secret that cardiovascular diseases are the leading cause of death in the United States and many other countries around the world. Some projections have cardiovascular disease becoming the number one cause of death in every country of the world by 2010.

It‘s also no secret that dietary changes and intake of flavonol-rich foods have been associated with improvements in cardiovascular disease. The flavonoids and other compounds of cocoa have been clearly shown to reduce the risk of cardiovascular disease in humans. Many such studies have shown an improved endothelial (blood vessel) function, platelet function, insulin sensitivity, blood pressure, and decreases in chemicals that cause inflammation in the body.

A study performed last year looked at post-menopausal women, total flavonoids and cardiovascular mortality found that only a few foods were able to demonstrate significant improvements -- apples, pears, strawberries ... and chocolate. None of the other fruits and vegetables studied shows a capacity to improve cardiovascular health.

In past reports, I discussed two large studies that showed the benefits of cocoa in reducing cardiovascular mortality -- a major study in the Netherlands on elderly men, and a study conducted on the Kuna Indian population of the San Blas Islands in Panama. These studies involved long-term observations that indicated improved cardiovascular benefit of cocoa consumption.

A study conducted this year by the University of Illinois found that the consumption of flavonol-enriched cocoa bars resulted in significant reduction in systolic blood pressure (8.2% decrease) and diastolic blood pressure (8.2% decrease) compared to a placebo group. The improvement occurred within a four-week period, and continued throughout the entire study. These findings were very interesting, especially considering the fact that study participants had no pre-existing hypertension.

A group of researchers from the United Kingdom reported in the American Journal of Clinical Nutrition about a meta-analysis of numerous studies completed on cocoa flavanols and blood pressure.

These researchers found forty-three different studies regarding the effect of chronic (over a long period of time) intake of flavonoids on blood pressure, and seven studies regarding the effect of acute intake. Black tea, red wine and grape juice demonstrated no significant effects on blood pressure. Cocoa, however, presented a 5.88mm reduction in systolic blood pressure, and a 3.33mm reduction in diastolic blood pressure -- statistically significant findings.

Cocoa studies conducted this year found that cocoa increases vasorelaxation (dilates the blood vessel walls) in healthy subjects. Effects were also positive for patients with hypertension, coronary heart disease, the elderly, post-transplant heart patients, and patients with high cardiovascular risk.

The University of Utah study found that basically healthy patients experienced a decrease in systolic and diastolic blood pressure by 5mm within two weeks of a program eating unprocessed cocoa. These findings corroborated other studies, and delivered the same success you would find with weight loss, dieting, and even some blood pressure medications.

It is widely accepted among medical professionals that even a small drop in blood pressure translates to a marked reduction in heart attacks, strokes, and other cardiovascular diseases.

A group of researchers from Yale found this year that acute ingestion of both solid dark chocolate and liquid cocoa improved the blood vessel function and lowered blood pressure in overweight adults. Sugar-free or low glycemic products aided in further improvements in blood pressure.

Research has uncovered the fact that the dilation of blood vessels is achieved via an NO-dependent (Nitric Oxide) mechanism. A decrease in NO is associated with increases in arteriosclerosis and cardiovascular risk. After consuming a flavanol-rich beverage, test subjects experienced an increase in NO, generated by NO synthase. Cocoa stimulates this mechanism to create even higher levels of NO in test subjects.

We also see some evidence that cocoa also acts like an angiotensin converting enzyme (ACE) inhibitor, further lowering blood pressure.

Researchers in Switzerland found that within two hours of consumption of flavanol-enriched cocoa, subjects experienced a significant reduction of serum oxidative stress, improved coronary vessel function, and decreased platelet adhesion. Researchers also noted an increase in serum epicatechin levels at the same time.

This year, a group of researchers from the University of California, Davis, found a capacity in flavonoids to protect myocardial (heart) tissues during damaging events. They found that epicatechins confer cardioprotection to the heart muscle during short- and long-term ischemia reperfusion myocardial injury. In lay terms, the epicatechins protected the heart muscles after a heart attack that caused a decrease in blood flow to the heart.

Within the last year, two other studies concluded that dark cocoa only produced a minimum result. However, a review of the studies found that the first used only approximately 300mg of total flavonoids per day, which is far below the therapeutic amount of 600mg to 900mg of total flavonoids. The second study used 900mg of total flavonoids, but only administered twice per day, which the researchers themselves thought may have contributed to decreased results.

Cocoa molecules are short-lived in the blood stream; at least three times per day appears to be the necessary frequency to enjoy continued results.

A second range of studies examined the conditions of insulin resistance related to impaired glucose tolerance, or "prediabetes" which increases the risk of cardiovascular events, diabetes, decreased endothelial NO (level of nitric oxide in the blood vessels) bioavailability, and increased oxidative stress.

Several studies conducted within the last year examined the impact of flavanol-enriched cocoa ingestion on the oral glucose tolerance test (OGTT), endothelium-dependent vasorelaxation, blood pressure, and serum C-reactive protein (CRP is a measure of inflammation) in adults with hypertension and impaired glucose tolerance.

A study by researchers at Tufts University and the University of L‘Aquilla used 1008mg of total flavonoid cocoa product divided into 3 daily doses, compared to a flavonoid-free cocoa product.

These researchers found that flavonols increased the bioavailability of NO and decreased the formation of oxygen- and nitrogen-free radicals. They also found that flavonols and resveratrol inhibit IκB kinase, and downregulate nuclear factor-κB (an oxidation pathway that causes blood vessel damage and increases fat-induced insulin resistance). This study confirmed other research that flavonol-rich cocoa improved the dilation capacity of blood vessels, and reversed the dysfunction of blood vessels in prediabetics and smokers.

These scientists concluded that high-dose flavanol cocoa improved insulin sensitivity, increased B-cell function (cells that produce insulin), decreased blood pressure, and increased the flexibility of the blood vessel walls. They also found an increase in the QUICKI (quantitative insulin sensitivity check index), which correlates to improved insulin sensitivity, as well as improved scores in the oral glucose tolerance test.

In their study, the University of Utah also found a statistically significant increase in QUICKI, as well as improved two-hour glucose tolerance test scores. U of U scientists also found that unprocessed cocoa powder did improve the function of the pancreas, and lowered diabetic risk. Cocoa was found to be as effective in increasing insulin sensitivity as weight loss, exercise, medications and other dietary supplements.

A study performed in 2008 examined the cerebral (brain) blood flow in healthy elderly people after they ingested flavonoid-rich cocoa. As with similar studies, this study demonstrated a significant increase in cerebral blood flow attributed to the cocoa. Blood flow in the middle cerebral artery, one of the main arteries in the brain, was measured for subjects who ingested 900mg of flavanols. They noted that NO is a critical regulator of brain perfusion. Again, cocoa increased NO availability, and active the N pathways. These scientists noted an increase in peak cerebral blood flow during the first two to four hours (they initially noted a decrease secondary to the caffeine contained in their cocoa powder). They concluded that this increase in blood flow would help to decrease dementia, strokes and other vascular cognitive impairments.

Other studies have found that flavonoids improve spatial memory, and decrease brain edema, as well as neuronal death in the hippocampus -- a part of the brainthat controls mood.

Epidemiological studies suggest that consuming products with high-flavonoid content delays the onset of dementia and Alzheimer‘s dementia. Neurodegenerative diseases such as dementia and Parkinson‘s disease are increased by oxidative stress, inflammation, and the accumulation of iron and protein aggregrates, which lead to neuronal (brain cell) death.

The antioxidant activity, anti-inflammatory activity and potent iron-chelating activity of cocoa provides a neuroprotective component. Researchers have found that epicatechin reduces the toxic effects of amyloid-C, a component of the senile plaques in the brain associated with dementia. We have even come across some information showing that cocoa can slow down nigrostriatal dopaminergic cell loss in Parkinson‘s disease. The mechanism seems to be connected to mitogen-activated protein kinase signaling pathways that are involved in brain cell survival, regeneration and cell death.

Unprocessed Cocoa and Inflammation
Another important area of health benefits from unprocessed cocoa is the reduction of inflammation.

In her review article this year, Karen A. Cooper examined the last 10 years of research on cocoa and health. She believes that a simple antioxidant mechanism driving the benefits of cocoa is not likely. Rather, it is the inhibition of inflammatory pathways that lead to the reduced risk of chronic diseases.

A 2008 study performed in Italy examined the connection between inflammation and regular consumption of dark chocolate. Like Cooper, the researchers here concluded that cocoa‘s capacity to decrease inflammation is what provides most of the health benefits to the body. They hypothesized that dark chocolate consumption is inversely related to the level of C-reactive protein (CRP), a marker of inflammation that is considered an independent indicator of coronary heart disease.

Inflammation and nitric oxide (NO) production play a major role in the development of arterosclerotic plaque. The Italian scientists found that flavonoid-enriched cocoa did indeed decrease serum CRP in a large population of Italian patients.

Another group in Baltimore found a reduction in CRP and a decrease in inflammation in women who consumed approximately 700mg of flavonoids per day.

Recently, a group of researchers from the University of California, Davis, teamed with scientists in Italy examined the anti-inflammatory impact of cocoa flavanols. This group discussed how the production of inflammatory chemicals (cytokines) increases the risk of heart disease, such as hardening of the arteries and congestive heart failure. If the inflammatory pathways can be altered, they argued, then there would be a reduction in heart disease.

Nuclear factor-kappaß (NK-κß) is one of the factors that control inflammatory response, cellular proliferation (growth), and cellular adhesion. Studies have shown that epicatechin and catechin molecules reduce NK-κß activation, and consequently reduce inflammation cytokines.

Cocoa also exerts a significant effect on TNFα (tumor growth factor) which increases the body‘s anti-inflammatory ability. Cocoa flavanols also inhibit the formation of other inflammatory chemicals like IL-2 (interleukin).

Overall, cocoa flavanols inhibit a multitude of infl