Does Flavanol Intake Influence Mortality from Nitric Oxide-Dependent Processes? Ischemic Heart Disease, Stroke, Diabetes Mellitus, and Cancer in Panama

Abstract

Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer -all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.

Antihypertensive and cardioprotective effects of theLagenaria sicerariafruit inNG-nitro-L-arginine methyl ester (L-NAME) induced hypertensive rats

“…The effects of plant flavonoids on mammalian cells have been of substantial recent interest with attention focused on the implications of these agents for cardiovascular disease and for cancer. Some epidemiological studies designed to examine a possible protective effect of flavonoids in cardiovascular disease have reported inverse associations (Bayard et al, 2007). Krauze and Cisowiski (1994) reported the separation of complex of flavone C-glycosides of LS.…”

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

“…Interest in cocoa flavanols in particular was triggered by the finding that Kuna Indians living off the coast of Panama had a significantly lower incidence of vascular-related diseases compared to those living in Panama city (Bayard et al 2007;Hollenberg et al 1997), with dietary habits, and specifically the high intake of home-prepared cocoa found to be the most likely candidate for this disparity (Fisher & Hollenberg 2005). As with other forms of flavanols numerous studies have provided evidence that cocoa flavanols can enhance endothelial function in healthy individuals (Monahan et al 2011), smokers (Heiss et al 2005), diabetics (Balzer et al 2008), hypertensive patients (Grassi et al 2005), patients with coronary artery disease (Heiss et al 2010) and heart transplant recipients (Flammer et al 2007).…”

Cocoa, Blood Pressure, and Vascular Function

“…Interestingly, this was not related to genetic factors, since the same population, migrated from the San Blas islands to Panama City for economic reasons, showed to have BP levels similar to other urban dwelling people (31). In addition, when compared to other American citizens, a marked reduction in cardiovascular mortality was noticed (33). To explain this difference, many environmental factors were investigated, such as differences in lifestyle or tobacco use, but ruled out as contributories.…”

“…A subsequent study evaluated the minimum dose required for BP lowering. A population of 52 subjects with untreated mild arterial hypertension was randomized to receive cocoa beverage containing different doses of flavanols (33,372,712, or 1,052 mg per day, respectively). After 6 weeks, only the highest flavanol dose (1,052 mg per day) demonstrated a significant reduction in 24-h SBP (5.3 ± 5.1 mmHg; p = 0.001), DBP (3 ± 3.2 mmHg; p = 0.002), and mean arterial BP (3.8 ± 3.2 mmHg; p = 0.0004) (53).…”