In Panama, as in much of the western world, diseases of the circulation are the most common cause of death, and cancer is second. The difference in risk of death due to these two classes of illness, cancer and heart disease, between San Blas and mainland Panama was very large. Our original hypothesis was that this would be the case if flavanol-rich cocoa and its influence on nitric oxide synthesis had implications for disease pathogenesis, as has been suggested 26
. We could explain this extraordinary difference in the risk of death by proposing either a better prognosis or a lower incidence of these illnesses in San Blas. A reduced incidence is the most likely explanation, but both a better prognosis and a reduced incidence could have a similar explanation.
The San Blas is the oldest indigenous district in the Republic of Panama, having a relatively homogeneous population both biologically and ethnically. It exhibits one of the highest levels of poverty and economic and social exclusion in Panama. The district has two hospitals, six health centers, and eleven health posts, which do not guarantee access to all levels of service. About 40,000 inhabitants are spread over forty-nine communities that are widely dispersed along the entire Caribbean Coast of Panama. The profile of health of the Kuna residing in the San Blas revealed substantial premature death due to infections: Infectious and parasitic diseases made a contribution more than 4-fold higher than in the rest of the country. The principle reasons were diarrhea, tuberculosis, AIDS, influenza, and malaria.
One major limitation of our findings involves how the diagnosis on the death certificates was established. Medical diagnosis follows a well-defined sequence in which suspicion is raised from findings obtained from a medical history and physical examination, followed up with specific tests designed to establish the diagnosis. In the case of cancer, for example, examination of tissue obtained at biopsy is required for diagnosis. In the case of heart disease, the diagnosis will be established through some combination of medical history and physical findings supplemented by the results of tests, including x-ray, angiography, ultrasound examination, the electrocardiogram, and occasionally a biopsy. The availability of the laboratory examination probably differs in the San Blas and the mainland, but the difference is relative, not absolute. In the hospital in Ailigandi, for example, an electrocardiogram machine has been available for more than fifteen years, and the physicians who staff the hospital have worked in Panama City and know how to diagnose myocardial infarction. During those fifteen years, there have been no cases of myocardial infarction diagnosed on Ailigandi (personal communication). Differences in the ability to establish a diagnosis may have played a larger role in the frequency of cancer diagnosis than in the frequency with which heart disease was diagnosed, although thousands of Pap smears and biopsies are performed annually in the San Blas. In 4 of 5 years, no cases of cervical cancer were diagnosed.
Age of the communities at risk is important. As both diseases of the circulation and cancer increase in frequency with age, death at an earlier age from infection could have influenced the outcome. In fact, the communities living in San Blas are not younger: The percentage of Kuna who are over the age of 55 years is substantially and statistically higher than in mainland communities. Adjustment for age served to enhance the difference in the frequency with which disease of the circulation or cancer led to death in the San Blas versus the mainland.
Although compatible with the possibility that a diet extraordinarily rich in flavonoids contributed to the low frequency of circulatory disease and cancer, it is obvious that other possibilities exist. These include especially different patterns of diagnosis discussed above. As another alternative to flavanoid intake to account for the difference in disease frequency, the possibility that differences in other risk factors contributed cannot be ignored. Unfortunately, the death certificates contained none of this information beyond age. As the difference was so very large, and the explanation is so important, follow-up population-based studies will be important to examine these risk factors prospectively. Until such data are available, the results of this study should be interpreted with great caution.
Other lifestyle variables may play a role in health outcomes by region. Stress is commonly suspected to be lower on the islands than on the mainland (commonly by people who have actually never visited the islands). We have assessed stress in the Panamanian mainland and islands, and there is a difference favoring the islands, but it is small 30
. Another possible difference is diet. We and others have examined the diet in the San Blas and Kuna living in the Panamanian mainland carefully and although several differences are noted, the most remarkable is cocoa intake 14
. However, we have no information on diet and the frequency of other risk factors in non-Kuna living in the Panamanian mainland. Obtaining this information should have a high priority. There is very probably less exposure to pollutants in the water and in the air in the San Blas compared to the mainland, especially for those inhabitants that live in the city. Tobacco use by Kuna is limited both in the indigenous island site and the mainland.
Other variables may influence age-specific death rates by region. One common practice among the Kuna involves working on the mainland on a job for a salary for many years, followed by retirement to the San Blas indigenous island life where life is less stressful, and less expensive. To the extent that occurred, and if twenty or thirty years of life on the Panamanian mainland do not lead to changes that cannot be reversed by return to the island, differences between the two locations may have been underestimated.
If indeed they do protect, how might the flavonoids provide protection? Our hypothesis was that in the case of vascular disease the responsible pathway could involve stimulation of nitric oxide synthesis and thereby reversal of endothelial dysfunction 23, 24
. Alternative possibilities, also possibly related to nitric oxide, include improvements in insulin sensitivity 25
, improvements in platelet function 15
, inhibition of LDL oxidation 28
, and an increase in plasma HDL cholesterol concentration 29
. The influence of nitric oxide on insulin sensitivity would also provide an explanation for the difference in the frequency of diabetes mellitus 25
in the San Blas and the mainland 1
. In addition, a role in carcinogenesis may be hypothesized through nitric oxide cell-to-cell communication 1
Death certificates provide core information, especially important at the national level 31, 32
. The findings can be misleading. For example, if someone dies with both cancer and diabetes, the cancer is far more likely to be recorded 33
. This problem should not have influenced our findings, as heart attack, stroke, and cancer are likely to have been chosen from among a range of possible diagnoses, and there is no reason why the pattern should differ on the mainland and in the San Blas.
Despite the other possible explanations for the large differences in deaths from cardiovascular disease and cancer with an array of possible confounding factors, it is improbable that these could abolish the cardiovascular and cancer protective effect observed among the San Blas Kuna as compared to the mainland. Although the findings are compatible with effect of the flavanol-rich cocoa on health, clearly a large number of alternative possibilities exist involving diet, physical activity, stress and genetic factors. An observational study of this kind cannot prove causality. Indeed, only a randomized, controlled clinical trial in which all of these factors can be controlled will lead to a definitive conclusion. All of these issues can be addressed, but that will take time and substantial resources.