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Could compounds in chocolate yield new pharmaceutical approaches to major disorders?
Strange but true, few who love its taste associate it with good health, but recent reports that a confectionery company was seriously examining the pharmaceutical potential of chocolate achieved widespread international media coverage.1
In fact, the health-related properties of chocolate have long been debated and it appears that certain people in the industry believe compounds in chocolate could yield new pharmaceutical approaches to major disorders. In an industry that is seeking new sources of innovative products, this could be one of the most unusual avenues to be explored in a long time.
Chocolate has a loyal following in most countries (Figure 1), but it has taken a strange route through history to arrive in its modern form. Although its health benefits have been poorly characterized scientifically, there must be little doubt that chocolate's persistence in society through the ages owes much to the general feeling of well-being that it brings to those who consume it.
Figure 1 Regional cocoa consumption.
The exact origins of chocolate are mysterious, but most historians agree that it was first consumed in Central America. In 2002, residues in a ceramic vessel, found at a Mayan site in north-eastern Guatemala, were found to contain theobromine — considered to be a chemical marker for cacao. When these findings were placed in the context of linguistic assessments of the ancient regional cultures it led to the theory that chocolate use could date back to as early as 500 BCE.2
The Aztec and Mayan civilizations were experts at cultivating the cacao tree and using its seeds to produce a chocolate-like substance, which they drank unsweetened. There are numerous hieroglyphs that depict the central role of chocolate in Mayan society, being used by rulers and the priestly classes. The Aztecs took on the beverage, referring to it as xocalatl meaning warm or bitter liquid. Cocoa beans were also used as a currency and exacted as tribute from people ruled by Aztecs.2–4
When the Spanish arrived in the New World they observed the drinking of xocalatl with interest and curiosity. The Aztec Emperor Moctezuma is reported to have consumed several goblets of the drink, believing it to be an aphrodisiac.2–4 Aztecs also believed that by drinking chocolate they would gain some of the wisdom of Quetzalcoatl, their God of learning and of the wind.
Following the Spanish conquest of Mexico, chocolate found its way to Europe with other discoveries from the new colony. Yet it remained a guarded secret within the Spanish empire and it did not find its way to other European countries until over a century later. In the 1570s, chocolate was being used by the Spanish in a sweetened form, and gained popularity as a medicine and aphrodisiac. As a result of rising demand, shipments began to arrive from Mexico. Starting in the 1650s, chocolate began to appear across Europe as a beverage for the elite classes. Over the following century, demand grew and this pushed down the price of cocoa beans, thereby bringing chocolate into the reach of wider society. Cocoa production also began to spread with plantations in the West Indies, the Far East and Africa.2–4
Interestingly, a number of the original chocolate manufacturers were apothecaries (early chemists), who wished to take advantage of the reported medicinal properties of cocoa. Apothecaries became a major force in chocolate manufacture, as they possessed the necessary skills and equipment to blend the cocoa ingredients for consumers. In fact, both Fry's of Bristol and Terry's of York, two well-known names in British chocolate history, were founded by apothecaries.3
The increased popularity of chocolate led to a series of innovative developments. A major step forward was in its transformation from a beverage to a solid form that retained its taste and so could be eaten. As others experimented with further enriching the taste and developing pastes that could be moulded into bars, businessmen began to mass-produce chocolate using the latest technology of the industrial revolution. Some industrialists, particularly those in Switzerland, who went on to found Nestlé and Lindt, became interested in modifying chocolate's consistency and through the addition of milk created the version of chocolate that is well-known today.2–4
Chocolate's origins hint at medicinal properties, but proving these in a conclusive manner to a modern scientific audience has proved elusive. Nevertheless, this has not dimmed the enthusiasm of those pursuing research in this field. A notable amount of chocolate-based research focusing on a range of medical conditions has appeared in peer-reviewed scientific journals over the last year. Most of this research has centred on chocolate-derived antioxidant flavonols, but additional chocolate compounds and their properties are also being explored.
In general, reports that chocolate-derived flavanols can reduce the risk of dementia, diabetes, heart attacks and strokes have been based on small studies, with few details on how this approach could be extended into mainstream medicine.5,6 Critics have pointed out that research in this area is limited and that the nature of the source of flavanols has driven the publicity rather than any positive clinical results. Furthermore, it is important to note that chocolate is not the only source of these compounds.
Just as the film Charlie and the Chocolate Factory appeared in cinemas, a study involving chocolate appeared in Hypertension, the Journal of the American Heart Association. The study was conducted by research groups at University of L'Aquila (Italy) and at Jean Mayer USDA Human Nutrition Research Center on Aging (Tufts University [Boston, MA, USA]). According to the researchers, dark chocolate decreased blood pressure in a number of hypertensive volunteers.7,8 Furthermore, it had beneficial effects for these volunteers in terms of lowering cholesterol levels and improving sugar metabolism. In contrast, white chocolate did not produce these favourable effects.7,8
The researchers linked the beneficial effects to flavanols, which are found in high amounts in dark chocolate, but not in white chocolate. However, the authors of the study did stress that the dark chocolate used in the study differed from commercially-available milk chocolate products, which are low in flavanols. Although the results of these types of cardiovascular studies are interesting, the researchers involved have often distanced themselves from the ensuing media publicity in case their work is misinterpreted as an open endorsement for people to eat chocolate to lower their blood pressure! As is often pointed out, research into the cardiovascular effects of flavanols from cocoa remains at an early stage. Furthermore, many people already have a diet that is too high in fat and so a large intake of chocolate will not improve their health outcome.
Another widely-covered chocolate-related study appeared in April 2005 in the Journal of Molecular Cancer Therapeutics.9,10 Researchers at Georgetown University (Washington DC, USA) reported that pentameric procyanidin, which naturally occurs in cocoa had potential anticancer properties. The work was performed in vitro on breast cancer cell lines, where it was found that pentameric procyanidin inactivated various proteins that had a role in regulating the cell cycle.9,10 In contrast, normal human mammary epithelial cells in primary culture were resistant to the effects of this cocoa-derived compound on their ability to proliferate. The novel aspect of the study was the manner in which pentameric procyanidin exerted its effects, as it appeared to jointly deactivate several regulatory proteins. Nevertheless, the study was performed in vitro and so much further work is required before the relevance to human cancer can be ascertained.
A more unusual study was published online in FASEB Journal (Federation of American Societies for Experimental Biology [Bethesda, MD,USA]) by a team at Imperial College (London, UK) and focused on the cough-suppressant properties of chocolate.11 Theobromine found in chocolate was found to be nearly a third more effective in stopping persistent coughs when compared with codeine, one of the most well-known cough medicines.11 The initial findings were considered of interest as persistent coughing often affects patients with lung disease. Nevertheless, much remains to be done before chocolate can be developed cough remedy (Figure 2).
Figure 2 Theobromine levels in chocolate.
The main driver of the current medical interest in chocolate appears to be Mars Inc., which held a conference in Switzerland where researchers discussed how pharmaceutical products could be derived from cocoa sources.1 Up until now, chocolate research has been a predominantly academic exercise and so the interest of a major company in medical applications could transform the perceptions of this field of study.
Using chocolate as a medical product itself remains unlikely because of the variation in flavanol levels with respect to cocoa content. It is also important to note that each stage in the processing of cocoa alters its chemistry.12 A study conducted by the scientific research agency of the US Department of Agriculture ranked flavanols and antioxidant capacity in a range of commercially available chocolate products. Natural cocoa powder was ranked highest in terms of antioxidant capacity followed by unsweetened baking chocolate. Milk chocolates were ranked lowest in terms of antioxidant capacity.13
Furthermore, most of the research promoting flavanols continues to be sponsored by food companies and observers have suggested that transforming chocolate into a health-related product is not a new concept, but has resulted in little progress over the years. During 1995, Japan held an International Symposium on Chocolate and Cocoa Nutrition, which led to a series of popular television broadcasts called "the surprising effects of cocoa." This stimulated considerable medical research into the potential health benefits of chocolate, as well as huge sales of cocoa products.14
Mars Inc. remains publicly upbeat about its latest developments and believes it possesses intellectual property of interest to pharmaceutical companies. It claims to be discussing licensing deals and joint venture agreements based on developing products from cocoa-derived compounds. As the second-largest chocolate manufacturer in the US and one of the world's largest food-processing companies, and with a reported value of over $30 billion, its move towards the pharmaceutical sector cannot be ignored.
However, whether it gives rise to extra sales of chocolate (Figure 3) and gives the media more to think about than amusing headlines remains to be seen. For the moment, though, pharmaceutical researchers can stick to eating chocolate.
Figure 3 Total confectionary sales of major chocolate manufacturers.
Dr Faiz Kermani is European marketing manager business development at Chiltern International Ltd, UK.
1. Mars Talks Up Cocoa's Medicinal Potential www.washingtonpost.com
2. Ancient Chocolate Found in Maya "Teapot" http://news.nationalgeographic.com
4. The Culture of the Cocoa Bean http://inventors.about.com
5. Chocolate May be Healthy for Your Heart www.cnn.com
6. A Small Portion of Dark Chocolate a Day Keeps Heart Attacks and Strokes Away www.medicalnewstoday.com
7. This week in the medical journals www.cnn.com
8. D. Grassi et al., Hypertension 46, 398 (2005).
10. Researchers Find That Chocolate Compound Stops Cancer Cell Cycle in Lab Experiments http://gumc.georgetown.edu
11. Chocolate Could be Cough Medicine http://news.bbc.co.uk
12. Questions and Answers — Chemistry of Cocoa and Chocolate www.icco.org
13. Study Reveals Differing Amounts of Naturally Occurring Flavanols in Chocolate and Cocoa Powder www.prnewswire.com
14. Health Benefits of Cocoa and Generic Promotion of Benefits in Japan www.icco.org