The roots of Hollenberg's fascination with cocoa go back to the early 1990s when he was looking for genes that might protect humans against high blood pressure. "A logical possibility is that, if there are 'bad genes' that predispose people to high blood pressure, there might be 'good genes' that protect against it," he says.

To test that idea, Hollenberg needed to find an isolated, interbreeding group of people among whom high blood pressure is uncommon and does not rise with age. Then he could sample their blood and study how their genes differ from those without such protection.

Such a population was known to live on a group of islands off the Caribbean coast of Panama, where they have been relatively isolated for more than 500 years. As it turned out, however, the plan didn't work. The blood pressures of several hundred Kuna Indians who had moved to Panama City and its suburbs were checked. Diet, stress, and other factors had taken away their resistance to hypertension. So it wasn't in their genes.

Were they eating too much salt? Hollenberg investigated that, and found that Kuna living on both the islands and the mainland consume as much if not more salt than people in the United States.

With funds from the Baxter Foundation, Hollenberg then conducted a study of what the islanders eat and drink. "The most outstanding finding was the fact that most them consume cocoa as their major drink and do so every day," he reports, "Many Kuna, in that hot and humid climate, probably drink more than five cups per day."

Tests by Mars reveal Kuna cocoa to be much richer in flavanols than any available in stores in the United States or Western Europe. That's because of handling after harvest and processing to improve taste and appearance.

The flavanol family also has caught the world's attention as an ingredient of red wine and some teas, and flavanols are considered to be at least partially responsible for these beverages' reputation for lowering the risk of heart disease and even extending life span.

In another big surprise, lab tests reveal that Kuna cocoa stimulates the body to produce something called nitric oxide, a notorious compound present in cigarette smoke and automobile exhausts. However, NO, as it is also called, has a good side. "It turns out to be part of an internal regulatory system that operates in the heart, blood vessels, brain, penis, liver, pancreas, lungs, eyes, and likely every other organ in the body," says Thomas Michel, a professor of medicine at Harvard Medical School who was one of the first to recognize the wonders of NO. "It is a versatile gas that could lead to new treatments for high blood pressure, blocked arteries, congestive heart failure, stroke, dementia, and impotence." (See April 2, 1993, Gazette)

To sum it up, nitric oxide relaxes blood vessels to allow an increased flow of blood and oxygen to the heart, brain, and other organs of the body. Hollenberg thinks that flavanols somehow activate a gene or genes that make NO.

Strokes and so-called vascular dementia involve restricted flow of blood to the brain, so Hollenberg and others naturally regard flavanol-rich cocoa as a possible treatment for those ills. Stroke is one of the world's major killers, and dementias, including Alzheimer's disease, afflict 10 percent of people over the age of 65.

One study, conducted with more than 1,300 elderly people in France, found that flavanoids, a larger category that includes flavanols, decreased the risk of dementia. In Holland, researchers followed 1,730 people aged 55 and older for six years. Their results suggest that a decreased flow of blood to the brain precedes and possibly contributes to the onset of dementia.

In the United States, investigators have linked blood flow problems to certain brain areas of older people who rapidly progressed to Alzheimer's. This raises the interesting possibility of turning back or slowing down both the rise in blood pressure and the loss of cognition with age.

Hollenberg did experiments in which healthy people more than 50 years old drank flavanol-rich cocoa. Blood flow increased in these elders just the way it did when he did the same type of test on healthy young people.

"Among the elderly, cognitive decline is a growing public health issue with enormous medical and financial costs. The prospect of a targeted treatment to reverse the decline in cerebral blood flow that accompanies dementias is extremely promising," Hollenberg told a Feb. 18 meeting of the American Association for the Advancement of Science during a session titled "The Neurobiology of Chocolate: A Mind-Altering Experience."

He also described "exciting possibilities" for new types of flavanol drugs for treating type 2 diabetes and preeclampsia, a serious condition that affects about 7 percent of pregnant women in developed countries and more than twice that number in some African nations. In Kuna women, "the problem is very uncommon," Hollenberg notes.