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This study shows, for the first time to our knowledge, that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans, which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods. This trial was registered at clinicaltrials.gov as NCT01091922.

We have investigated the bacterial-dependent metabolism of (2 )-epicatechin and (þ )-catechin using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal region of the human large intestine. Incubation of (2)-epicatechin or (þ )-catechin (150 mg/l or 1000 mg/l) with faecal bacteria, led to the generation of 5-(3 0 ,4 0 -dihydroxyphenyl)-g-valerolactone, 5-phenyl-g-valerolactone and phenylpropionic acid. However, the formation of these metabolites from (þ )-catechin required its initial conversion to (þ )-epicatechin. The metabolism of both flavanols occurred in the presence of favourable carbon sources, notably sucrose and the prebiotic fructo-oligosaccharides, indicating that bacterial utilisation of flavanols also occurs when preferential energy sources are available. (þ )-Catechin incubation affected the growth of select microflora, resulting in a statistically significant increase in the growth of the Clostridium coccoides -Eubacterium rectale group, Bifidobacterium spp. and Escherichia coli, as well as a significant inhibitory effect on the growth of the C. histolyticum group. In contrast, the effect of (2)-epicatechin was less profound, only significantly increasing the growth of the C. coccoides -Eubacterium rectale group. These potential prebiotic effects for both (þ )-catechin and (2 )-epicatechin were most notable at the lower concentration of 150 mg/l. As both (2)-epicatechin and (þ )-catechin were converted to the same metabolites, the more dramatic change in the growth of distinct microfloral populations produced by (þ )-catechin incubation may be linked to the bacterial conversion of (þ )-catechin to (þ)-epicatechin. Together these data suggest that the consumption of flavanol-rich foods may support gut health through their ability to exert prebiotic actions. Flavanols: Prebiotics: Faecal microflora: Large intestineRepresenting one of the most important lifestyle factors, diet can strongly influence the incidence and onset of CVD (1) , and thus a healthy diet is an essential factor for healthy ageing (2) . A number of dietary intervention studies in human subjects and animals, in particular those using Vitis vinifera (grape), Camellia sinensis (tea) and Theobroma cacao (cocoa) have demonstrated beneficial effects on vascular function (3 -5) . While such foods and beverages differ greatly in chemical composition and macro-and micronutrient content, they have in common that they are amongst the major dietary sources of flavanols. The in vivo effects of flavanols will be dependent on the absorption and metabolism of flavanols in the gastrointestinal tract. Studies have indicated that flavanols are subject to extensive metabolism by phase I and II enzymes to yield O-methylated, sulfated and glucuronidated forms during transfer from the small-intestinal lumen to the portal blood (6) . However, significant amounts of ingested (2 )-epicatechin, (þ)-catechin, and their structurally related oligomeric forms (procyanidins), escape absorption in the small intestine, instead rea...

Background: Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities.Objective: The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects.Design: This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who were randomly assigned to consume daily for 8 wk a drink containing 993 mg [high flavanol (HF)], 520 mg [intermediate flavanol (IF)], or 48 mg [low flavanol (LF)] cocoa flavanols (CFs). Cognitive function was assessed at baseline and after 8 wk by using the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT) A and B, and the Verbal Fluency Test (VFT).Results: The changes in MMSE score in response to the 3 different treatments were not different. In contrast, there was a positive impact of the intervention on specific aspects of cognitive function. Mean changes (±SEs) in the time required to complete the TMT A and B after consumption of the HF (−8.6 ± 0.4 and −16.5 ± 0.8 s, respectively) and IF (−6.7 ± 0.5 and −14.2 ± 0.5 s, respectively) drinks significantly (P < 0.0001) differed from that after consumption of the LF drinks (−0.8 ± 1.6 and −1.1 ± 0.7 s, respectively). Similarly, VFT scores significantly improved among all treatment groups, but the magnitude of improvement in the VFT score was significantly (P < 0.0001) greater in the HF group (7.7 ± 1.1 words/60 s) than in the IF (3.6 ± 1.2 words/60 s) and LF (1.3 ± 0.5 words/60 s) groups. Significantly different improvements in insulin resistance (P < 0.0001), blood pressure (P < 0.0001), and lipid peroxidation (P = 0.001) were also observed for the HF and IF groups in comparison with the LF group. Changes in insulin resistance explained ∼17% of changes in composite z score (partial r2 = 0.1703, P < 0.0001).Conclusions: This dietary intervention study provides evidence that regular CF consumption can reduce some measures of age-related cognitive dysfunction, possibly through an improvement in insulin sensitivity. These data suggest that the habitual intake of flavanols can support healthy cognitive function with age. This trial was registered at www.controlled-trials.com as ISRCTN68970511.

Abstract-Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing Ϸ990 mg (high flavanols), Ϸ520 .02 seconds, respectively). Similarly, verbal fluency test score was significantly (PϽ0.05) better in subjects assigned to high flavanols in comparison with those assigned to low flavanols (27.50Ϯ6.75 versus 22.30Ϯ8.09 words per 60 seconds). Insulin resistance, blood pressure, and lipid peroxidation also decreased among subjects in the high-flavanol and intermediate-flavanol groups. Changes of insulin resistance explained Ϸ40% of composite z score variability through the study period (partial r 2 ϭ0.4013; PϽ0.0001). To the best of our knowledge, this is the first dietary intervention study demonstrating that the regular consumption of cocoa flavanols might be effective in improving cognitive function in elderly subjects with mild cognitive impairment. This effect appears mediated in part by an improvement in insulin sensitivity. 1,2 MCI represents an interesting field of research, because MCI increases the risk of later developing dementia, and, in this phase, an interventional therapy could have the greatest potential to improve cognitive performance and to slow down disease progression.3 A growing body of evidence suggests that specific dietary components may impact brain function through the regulation of neurotransmitter pathways, signal-transduction pathways, and synaptic transmission. 4 Several dietary components, including omega-3 fatty acids, B vitamins, vitamins D and E, and choline, have been identified as having favorable effects on cognitive abilities. 4 More recently, evidence suggests that the consumption of flavonoids, a diverse group of polyphenolic compounds widely present in plant-based foods, may be associated with a decreased risk of incident dementia 5 and with a lower prevalence of cognitive impairment, 6 a better cognitive evolution over a 10-year period, 7 and better dose-dependent performance of several cognitive abilities in elderly subjects. 8 Among the flavonoids, flavanols, a subclass abundant in tea, grapes, red wine, apples, and cocoa products, including chocolate, have been proposed to be highly effective in Received February 11, 2012; first decision March 6, 2012; revision accepted July 11, 2012. Correspondence to Giovambattista Desideri, University of L'Aquila, Department of Life, Health, and Environmental Sciences, Viale S Salvatore, Delta 6 Medicina, 67100 Coppito, L'Aquila, Italy. E-mail giovambattista.desideri@cc.univaq.it © 2012 American Heart Association, Inc. reversing age-related declines in neurocognitive performance by increasing the number of and strength of connections between neurons, reducing neuronal loss attributed to neurodegenerative processes, and throu...