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Title: Polyphenol curcuminoids and prevention of endotoxaemia and low-grade inflammation
Author: Meutia, Nuraiza
ISNI:       0000 0004 7223 7015
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2018
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Non-communicable disease (NCD) represent a modern global health challenge, with decreased life expectancy and quality of life, and a greater increase in health costs. Overweight and obesity are recognized as key risk factors for NCD, and the major link between these states is low-grade inflammation (LGI). Adipose tissues are now established as major contributors of pro-inflammatory molecules. One driver for low-grade inflammation is endotoxaemia (characterised by an increase in circulating endotoxin, or lipopolysaccharide (LPS)). Endotoxin is released in the gut lumen as part of the cell wall of Gram-negative bacteria, and endotoxaemia has been associated with high-fat high-calorie intake, one of the factors contributing to obesity. Thus high-fat high-calorie intake, endotoxaemia, LGI, obesity and NCD may all be linked and dietary approaches, such as functional foods with anti-inflammatory properties, may modulate this interaction. Curcuminoids (polyphenols found in the turmeric root) have anti-inflammatory and anti-bacterial effects and are potential dietary agents for preventing LGI and NCD. Little is known about the potential preventive action of curcuminoids on LGI. Therefore, this thesis aims to investigate the potential for curcuminoids to reduce endotoxaemia and LGI in apparently healthy overweight and obese people. A systematic review of the evidence for the anti-inflammatory effect of curcuminoids in healthy people and people at risk of NCD was performed. Nine papers describing five intervention studies published in this context have been assessed. Promising effects were seen in reducing CRP level (mean difference -0.71 mg/dl; 95% CI: -1.31 to -0.12; p < 0.05) and increasing adiponectin level (mean difference 5.12 ng/ml; 95% CI: 3.78 to 6.45; p < 0.01). However, there was insufficient data to make a clear conclusion that curcuminoids reduce LGI in those groups, thereby justifying the need for further work on the topic. In the second study, the phenolics and curcuminoids content in fresh turmeric root, turmeric powder, and four types of supplements were characterised to choose the supplement for a human intervention. Amongst all turmeric extracts assessed, the supplement BCM-95® (Dolcas-Biotech, Landing, NJ, USA) had the highest total phenolics (7.11 vs 1.94 mg GAE/g in average) and curcumin content (191.75 vs 13.7 mg/g in average). Therefore, BCM-95® was used in the later studies. The fate and effect of curcuminoids in the human gut were investigated further using established in vitro models for digestion and fermentation. Phenolic compounds were released after gastric and intestinal digestion. The presence of oil during digestion increased the release of phenolics from turmeric extracts. The presence of curcuminoids in a 24 h fermentation by faecal bacteria in vitro did not affect the production of short-chain fatty acids from Raftiline, which was used as the substrate for fermentation. The third study investigated the effect of curcuminoids on the intestinal permeability and endotoxin translocation using Caco-2 cell monolayers intestinal model. Administration of 115 nM of curcuminoids (in BCM-95®) for 3 day (3 h each day) unexpectedly resulted in increased monolayer permeability (by 30%) and endotoxin translocation (by 6-fold). The final study was a double-blind, placebo-controlled, crossover trial of curcuminoids supplementation (BCM-95®) for 21 days in healthy overweight and obese adults (n =14). Due to ongoing work in other parts of this project, the treatment code was not broken at the time of submission. In conclusion, there is very little published data on curcuminoids and LGI, however the Caco-2 cell monolayers study in this thesis suggest that turmeric may impair gut permeability under the experimental conditions tested. The effect may be dependent on the type of curcuminoids, the dose, and the associated oils. From the digestion study, it would appear that it is better to consume supplements associated with oil in order to optimize the release of phenolics. Although we cannot determine which of the two treatments in the human study was the active compound, the study was feasible, no side effects were reported and there was a difference between treatments. The relevance of this will be known when the code is broken.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General)