Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study

BACKGROUND: The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota. OBJECTIVE: We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study. DESIGN: Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured. RESULTS: Compared with the consumption of the LCF drink, the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial (P < 0.01) and lactobacilli (P < 0.001) populations but significantly decreased clostridia counts (P < 0.001). These microbial changes were paralleled by significant reductions in plasma triacylglycerol (P < 0.05) and C-reactive protein (P < 0.05) concentrations. Furthermore, changes in C-reactive protein concentrations were linked to changes in lactobacilli counts (P < 0.05, R(2) = -0.33 for the model). These in vivo changes were closely paralleled by cocoa flavanol-induced bacterial changes in mixed-batch culture experiments. CONCLUSION: 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.

The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans

Dietary nitrate is metabolized to nitrite by bacterial flora on the posterior surface of the tongue leading to increased salivary nitrite concentrations. In the acidic environment of the stomach, nitrite forms nitrous acid, a potent nitrating/nitrosating agent. The aim of this study was to examine the pharmacokinetics of dietary nitrate in relation to the formation of salivary, plasma, and urinary nitrite and nitrate in healthy subjects. A secondary aim was to determine whether dietary nitrate increases the formation of protein-bound 3-nitrotyrosine in plasma, and if dietary nitrate improves platelet function. The pharmacokinetic profile of urinary nitrate excretion indicates total clearance of consumed nitrate in a 24 h period. While urinary, salivary, and plasma nitrate concentrations increased between 4- and 7-fold, a significant increase in nitrite was only detected in saliva (7-fold). High dietary nitrate consumption does not cause a significant acute change in plasma concentrations of 3-nitrotyrosine or in platelet function.

Acute ingestion of a meal rich in n-3 polyunsaturated fatty acids results in rapid gastric emptying in humans

Background: n-3 Polyunsaturated fatty acids (PUFAs) have proven benefits for both the development of atherosclerosis and inflammatory conditions. The effects on atherosclerosis may be partly mediated by the observed reduction in fasting and postprandial triacylglycerol concentrations after both acute and chronic n-3 PUFA ingestion. Objective: The aim of this study was to assess gastric emptying and gastrointestinal hormone release after the consumption of mixed meals rich in n-3 PUFAs or other classes of fatty acids. Design: Ten healthy women (aged 50–62 y) completed 4 separate study visits in a single-blind, randomized design. On each occasion, subjects consumed 40 g oil rich in either saturated fatty acids, monounsaturated fatty acids, n-6 PUFAs, or n-3 PUFAs as part of a mixed meal. [1-13C]Octanoic acid (100 mg) was added to each oil. Gastric emptying was assessed by a labeled octanoic acid breath test, and concentrations of gastrointestinal hormones and plasma lipids were measured. Results: Recovery of 13C in breath was enhanced after n-3 PUFA ingestion (P < 0.005). The cholecystokinin response after the n-3 PUFA meal was significantly delayed (P < 0.001), and the glucagon-like peptide 1 response was significantly reduced (P < 0.05). Conclusion: The inclusion of n-3 PUFAs in a meal alters the gastric emptying rate, potentially as the result of changes in the pattern of cholecystokinin and glucagon-like peptide 1 release.

Nutritional status and clinical outcome in elderly female surgical orthopaedic patients

The possible relationship between nutritional status and clinical outcome following orthopaedic hip surgery was investigated. The nutritional status of 60 elderly female patients admitted for elective total hip replacement (THR) and emergency fractured neck of femur surgery (FNF) was measured over time. Specific measures of clinical outcome, including well-being and functional status, were monitored during hospital stay and at 4, 8 and 26 weeks following discharge. Patients were allocated to a high nutritional risk group where any three of the following were less than the 5th percentile value: serum albumin, haemoglobin, triceps skinfold thickness, mid-upper arm muscle circumference and body weight. Using this definition, malnutrition was present in 4% of THR patients and 41% of FNF patients. It was found that the high risk patients had significantly longer convalescence periods, (median stay27.5 days compared with 0 days, P < 0.0009), and a greater proportion were dependent upon walking frames at 6 months (46% compared with 11%, P < 0.01). Fifty percent of the high risk patients had been living independently prior to admission, in contrast only 29% had returned to their homes at 6 months after discharge. The results indicate an apparent link between clinical outcome and nutritional status based upon the allocation procedure employed, which has the potential for ensuring cost-effective nutritional intervention.

A novel antiserum specific to apolipoprotein B-48: application in the investigation of postprandial lipidaemia in humans

1. Apolipoprotein B-48, the transport protein for chylomicrons, is identical with apolipoprotein B-100 for the first 48% of its sequence. No antiserum has yet been reported that can recognize apolipoprotein B-48, but not apolipoprotein B-100. 2. In the present study an antiserum was raised to the C-terminal sequence of apolipoprotein B-48, using specific chemical reactions to ensure that the charged carboxyl group of the C-terminal isoleucine residue was free. In a Western blot the antiserum was shown to bind to a protein band having the characteristics of apolipoprotein B-48, but not to apolipoprotein B-100. 3. In the early evening 11 subjects were given a test meal which contained 40 g of mixed oil and retinyl palmitate. Blood samples were collected over 9 h. Chylomicron-enriched fractions were prepared and analysed for triacylglycerol, retinyl palmitate and apolipoprotein B-48, the latter after separation using SDS/PAGE and visualization by chemiluminescence on a Western blot. Both triacylglycerol and apolipoprotein B-48 showed an early peak at 1 h, which was not seen with retinyl palmitate. All three substances gave a broader peak between 5 and 6 h postprandially. Retinyl palmitate concentrations declined rapidly during the late (6-9 h) postprandial period, but apolipoprotein B-48 concentrations remained elevated. 4. This study has shown that an antiserum has been produced which is specific for apolipoprotein B-48. This has enabled measurement of postprandial concentrations of the protein that revealed features of chylomicron metabolism which have not been reported previously.

A controlled trial of sip-feed supplements in elderly orthopaedic patients

The potential nutritional and clinical benefits of sip-feed supplements were investigated by means of a controlled trial in elderly female patients admitted for orthopaedic surgery. A nutritional risk assessment procedure (Nutritional Risk Questionnaire, NRQ) was used to identify patients who might benefit from supplementation. Patients identified as high risk who did not receive supplements showed significant losses in triceps skinfold thickness (TSF) and mid-upper arm muscle circumference (MUAMC) measurements during hospitalization. Such changes were not observed in high-risk supplemented patients, but significant losses of MUAMC were also recorded in a group of patients who failed to comply with the supplement. No differences in biochemical parameters, muscle function, or clinical outcome were observed between supplemented and unsupplemented and non-compliant patients. The problems of poor compliance to sip-feed supplements and failure to observe clinical benefit in supplemented patients are discussed.

Effects of inulin on lipid parameters in humans

Convincing lipid-lowering effects of the fructooligosaccharide inulin have been demonstrated in animals, yet attempts to reproduce similar effects in humans have generated conflicting results. This may be because of the much lower doses used in humans as a result of the adverse gastrointestinal symptoms exhibited by most subjects consuming daily doses in excess of 30 g. Two studies that fed either oligofructose (20 g/d) or inulin (14 g/d) observed no effect on fasting total, LDL or HDL cholesterol, or serum triglycerides. Two other studies that fed inulin either in a breakfast cereal (9 g/d) or as a powdered addition to beverages and meals (10 g/d) reported similar reductions in fasting triglycerides (227 and 219%, respectively). In one of these studies, total and LDL cholesterol concentrations were also modestly reduced (5 and 7%, respectively). Because animal studies have identified inhibition of hepatic fatty acid synthesis as the major site of action for the triglyceride-lowering effects of inulin, and because this pathway is relatively inactive in humans unless a high carbohydrate diet is fed, future attempts to demonstrate lipid-lowering effects of inulin should consider the nature of the background diet as a determinant of response.

Structurally-related (−)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards

Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. While recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn is largely a consequence of the lack of availability of authentic standards that would allow for the directed development and validation of expedient analytical methodologies. In the present study, we developed a method for the analysis of structurally-related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally-related (−)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (−)-epicatechin-3′-β-D-glucuronide, (−)-epicatechin-3′-sulfate, and a 3′-O-methyl(−)-epicatechin-5/7-sulfate are the predominant SREM in humans, and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the previously reported discrepancies regarding flavanol metabolism, consisting to a significant extent of inter-laboratory differences in sample preparation (enzymatic treatment and sample conditioning for HPLC analysis) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic.

Upgrading humans via implants - why not?

In his forum paper, Prof. Kevin Warwick considers four different examples of how the use of implant technology is opening up the possibility of upgrading human abilities, particularly in terms of mental cognition. The main thrust is an overview of Prof. Warwick's own research, which led to him receiving a neural implant linking his nervous system bi-directionally with the internet. With this implant in place, neural signals were transmitted to various technological devices to directly control them, in some cases via the internet, and feedback to the brain was obtained from such stimuli as the fingertips of a robot hand, ultrasonic (extra-) sensory input and neural signals directly from another human's nervous system. A view is taken as to the prospects for the future, both in the short-term as a therapeutic device and in the long-term as a form of enhancement, including the realistic potential, in the near future, for thought communication – thereby opening up tremendous commercial potential. The therapy/enhancement dichotomy is considered here, as well as military and medical issues. Clearly though, an individual whose brain is part human/part machine can have abilities that far surpass those who remain with a human brain alone. Will such an individual exhibit different moral and ethical values to those of a human? If so, what effects might this have on society?

Using HIT to deliver integrated care for the frail elderly in the UK: current barriers and future challenges

In this paper we briefly describe the results of a 3 year project examining the use of Health Information Technologies (e.g., electronic patient record systems) to deliver integrated care. In particular, we focus on one group of patient (the frail elderly) and efforts to design an e-health supported healthcare pathway (the frail elderly pathway – FEP). The aim of FEP is to bring together clinicians and staff from health and social care and allow them to share patient information. Our findings show that progress in delivering a fully-supported and working FEP has been slow, not least because of the difficulties experienced by healthcare staff in using current IT systems. In addition, there are many strategic and technical issues which remain unresolved (e.g., systems interoperability).

Effect of prebiotics on the human gut microbiota of elderly persons

The colonic microbiota undergoes certain age related changes that may affect health. For example, above the age of 55–65 y, populations of bifidobacteria are known to decrease markedly. Bifidobacteria are known inhibitors of pathogenic microbes and a decrease in their activities may increase susceptibility to infections. There is therefore interest in trying to reverse their decline in aged persons. As the gut microbiota responds to dietary intervention, both probiotics and prebiotics have been tested in this regard. Probiotics are live microbes in the diet, whereas prebiotics are fermentable ingredients that specifically target components of the indigenous microbiota seen to be beneficial. We have published a recent paper demonstrating that prebiotic galactooligosaccharides can exert power effects upon bifidobacteria in the gut flora of elderly persons (both in vivo and in vitro). This addendum summarizes research that led up to this study and discusses the possible impact of prebiotics in impacting upon the gut health of aged persons.