Article

Dietary arachidonic and oleic acid intake in ulcerative colitis etiology: A prospective cohort study using 7-day food diaries

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Abstract

Dietary fatty acids may be involved in the etiology of ulcerative colitis (UC). Arachidonic acid (AA), an n-6 polyunsaturated fatty acid, is a precursor of the proinflammatory cytokines prostaglandin E2 and leukotriene B4, and its metabolism is competitively inhibited by oleic acid (OA). This study aimed to prospectively investigate whether AA is positively and OA is negatively associated with incident UC development, using data from 7-day food diaries. A total of 25 639 men and women, aged between 40 and 79 years, from Norfolk, UK, were recruited into the prospective European Prospective Investigation into Cancer (EPIC)-Norfolk cohort between 1993 and 1997. At baseline, participants completed 7-day food diaries, checked by nutritionists using a database containing 11 000 foods and 55 000 portion sizes. The cohort was monitored until June 2004 to identify participants who developed UC. Each patient was matched for age and sex with four controls, and conditional logistic regression was used to calculate adjusted odds ratios for AA and OA intakes, and UC association. Of the participants, 26 (58% men) developed incident UC (53% left sided) after a median follow-up time of 3.8 years (0.5-8.3 years). The highest AA tertile was positively associated with an odds ratio of 6.09 [95% confidence interval (CI) 1.05-35.23], with a trend across tertiles [odds ratio (OR) 2.43, 95% CI 1.06-5.61, P=0.04]. The highest tertile of OA intake was inversely associated with a 0.03 OR for UC (95% CI 0.002-0.56) and an inverse trend (OR 0.30, 95% CI 0.10-0.90, P=0.03). Dietary AA was positively and OA was inversely associated with UC development, with large effect sizes in a dose-dependent manner. This supports roles for measuring these nutrients in future etiological studies and modifying intake in future interventional studies in patients with established disease.

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... In the recent years, prospective studies on diet have emerged. Findings from the European Investigation into Cancer and Nutrition (EPIC) Study and the Nurses' Health Study (NHS) are particularly noteworthy because of their large well-characterized cohorts [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. These studies have investigated the involvement of dietary factors such as dietary patterns, vitamin D, dietary fibre, zinc, dairy products, n-3 and n-6 polyunsaturated fatty acids (PUFA), and protein, particularly animal protein, in IBD development [14,[16][17][18][19][20][21][22][23][24][25][26][27][28][29]. ...
... Findings from the European Investigation into Cancer and Nutrition (EPIC) Study and the Nurses' Health Study (NHS) are particularly noteworthy because of their large well-characterized cohorts [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. These studies have investigated the involvement of dietary factors such as dietary patterns, vitamin D, dietary fibre, zinc, dairy products, n-3 and n-6 polyunsaturated fatty acids (PUFA), and protein, particularly animal protein, in IBD development [14,[16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The increases in IBD seen in developing countries as they adopt a Western lifestyle [5], and the high incidence among immigrants coming from low to high incidence areas, strongly suggest the involvement of other environmental factors such as lifestyle factors in disease aetiology [31]. ...
Preprint
We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.
... A recent report from the European Prospective Investigation in Cancer (EPIC) study, did not identify a correlation between body mass index (a measure of obesity) and IBD morbidity (113), therefore proposing that a hypercaloric diet per se is not enough to trigger the development of IBD. Epidemiological studies indicate an increased risk of IBD is associated with a higher consumption of red and/or processed meat, dietary fat [especially n-6 polyunsaturated fatty acids (PUFAs)] and low levels of vitamin D (VitD) (4,114,115). In addition, an association between disease activity and intake of total fat [trans, saturated, and monounsaturated fatty acids (MUFAs)] and a high n-6/n-3 PUFA ratio has been identified in patients with CD (116). ...
... The specific role of MUFAs in IBD and asthma remains inconclusive. For example, a prospective study by de Silva and colleagues showed that a dietary oleic acid was inversely associated with UC development (114), while palmitoleic and oleic acid treatment of polarized intestinal epithelial cells impaired epithelial barrier function (159). MUFA and oleic acid intake indicated an increased risk of wheeze and non-atopic asthma, respectively (160). ...
Article
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Recent findings point toward diet having a major impact on human health. Diets can either affect the gut microbiota resulting in alterations in the host’s physiological responses or by directly targeting the host response. The microbial community in the mammalian gut is a complex and dynamic system crucial for the development and maturation of both systemic and mucosal immune responses. Therefore, the complex interaction between available nutrients, the microbiota, and the immune system are central regulators in maintaining homeostasis and fighting against invading pathogens at mucosal sites. Westernized diet, defined as high dietary intake of saturated fats and sucrose and low intake of fiber, represent a growing health risk contributing to the increased occurrence of metabolic diseases, e.g., diabetes and obesity in countries adapting a westernized lifestyle. Inflammatory bowel diseases (IBD) and asthma are chronic mucosal inflammatory conditions of unknown etiology with increasing prevalence worldwide. These conditions have a multifactorial etiology including genetic factors, environmental factors, and dysregulated immune responses. Their increased prevalence cannot solely be attributed to genetic considerations implying that other factors such as diet can be a major contributor. Recent reports indicate that the gut microbiota and modifications thereof, due to a consumption of a diet high in saturated fats and low in fibers, can trigger factors regulating the development and/or progression of both conditions. While asthma is a disease of the airways, increasing evidence indicates a link between the gut and airways in disease development. Herein, we provide a comprehensive review on the impact of westernized diet and associated nutrients on immune cell responses and the microbiota and how these can influence the pathology of IBD and asthma.
... The impact of dietary fats on the development of Crohn's disease has also been demonstrated in numerous studies; for example, as shown by Amre et al. in 2007, consumption of n-3 PUFAs and more favorable n-3 PUFA to n-6 PUFA ratios were associated with a lower risk of CD in the pediatric population [51]. The protective effect of n-3 PUFAs, in particular DHA, has also been demonstrated in the adult population in prospective observational trials by John et al. [52] and de Silva et al. [53]. Fish oil supplementation was also demonstrated to have a beneficial effect on the risk of UC. ...
Article
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Inflammatory bowel disease has become a global health problem at the turn of the 21st century. The pathogenesis of this disorder has not been fully explained. In addition to non-modifiable genetic factors, a number of modifiable factors such as diet or gut microbiota have been identified. In this paper, the authors focus on the role of nutrition in the prevention of inflammatory bowel disease as well as on the available options to induce disease remission by means of dietary interventions such as exclusive and partial enteral nutrition in Crohn’s disease, the efficacy of which is reported to be comparable to that of steroid therapy. Diet is also important in patients with inflammatory bowel disease in the remission stage, during which some patients report irritable bowel disease-like symptoms. In these patients, the effectiveness of diets restricting the intake of oligo-, di-, monosaccharides, and polyols is reported.
... Few reports also demonstrated a slight increased risk of IBD development by excess consumption of animal protein. The same group also reported that a high fat diet, especially rich in cholesterol and animal fats may increase the rate of incidence of IBD [18]. These findings were corroborated by Ananthakrishnan and coworkers, who confirmed the effect of trans fatty acid consumption on UC development [19]. ...
... Interestingly, in the same cohort, dietary oleic acid (e.g., found in olive oil) was inversely associated with UC development (dose-responsive, lower odds ratios with oleic acid intake equal to 21.13-40.93 g/day) [226]. In the study of Morvaridi et al., the consumption of extra virgin olive oil (20 days, 50 mL) significantly decreased inflammatory markers (CRP and erythrocyte sedimentation rate) and improved gastrointestinal symptoms (including bloating, fecal urgency and incomplete defecation) in patients with UC [227]. ...
Article
Full-text available
Despite the increasing knowledge with regard to IBD (inflammatory bowel disease), including ulcerative colitis (UC) and Crohn’s disease (CD), the etiology of these conditions is still not fully understood. Apart from immunological, environmental and nutritional factors, which have already been well documented, it is worthwhile to look at the possible impact of genetic factors, as well as the composition of the microbiota in patients suffering from IBD. New technologies in biochemistry allow to obtain information that can add to the current state of knowledge in IBD etiology.
... There were no significant differences (P>0.05) in the GC-MS chromatogram of fresh and stored tiger nut oil. People who consumed the most oleic acid were 89 percent less likely to develop ulcerative colitis than those who consumed the least oleic acid (De Silva, 2014). A diet high in oleic acid may reduce the inflammation seen in obesity and non-insulin dependent obesity. ...
Conference Paper
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Innovativenes is critical to the success of any business venture. The current study examined the innovative practices adopted by some informal businesses across three sectors in the Nigerian economy: manufacturing, agriculture and services. Primary data were obtained from business owners and managers in the informal business sector in Nigeria. Simple random sampling technique was used to select 778 respondents in three (3) out of six (6) geopolitical zones in Nigeria. Data collection were done with the aid of Google form. The overall aim of the survey was to provide information on the innovation activities of enterprises in the informal business sector. The retrieved data were analyzed using frequency counts and percentage distribution. Findings revealed that majority (76.5%) of the respondents attested that their customers were satisfied with current products, and were willing to pay for and interested in new products. This was closely followed by respondents (66.5%) who introduced environment-friendly products or services. About 60.8% of the respondents changed/upgraded technology (tools & equipment), looked for and used new sources for supply of raw materials and tools that were cheaper and/or better than old sources of supply. The study indicated that frequent changes in policies and government as well as civil unrest and crises are some of the factors hindering innovation activities in informal businesses. Cost of acquiring modern technologies and funding was ranked highest among economic factors that hindered innovation.
... In a prospective cohort of 25,639 people recruited from the EPIC study (European Prospective Investigation into Diet and Cancer), it was shown (after 7-11 years of followup), that oleic acid use represents a protective factor for UC incidence, as the highest tertile of oleic acid intake was inversely associated with UC incidence (OR 0.03, 95% CI 0.002-0.56) [79]. Thus, the study exhibited additional benefits of olive oil in the primary prevention of UC. ...
Article
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With the rising global burden of inflammatory bowel disease (IBD) and the rising costs of novel biological drugs, there is an increasing need for dietary approaches and functional foods that could modulate the course of IBD. The Mediterranean diet has proven to be efficacious in managing chronic inflammatory diseases, and recent studies have also shown its benefits in the setting of IBD. Since olive oil and its compounds have been shown to provide a considerable anti-inflammatory effect, in this review, we aim to discuss the latest evidence concerning the impact of olive oil and its bioactive compounds on IBD. Numerous preclinical studies have exhibited solid evidence on the mechanisms by which polyphenol-rich extra-virgin olive oil (EVOO) or specific polyphenols like hydroxytyrosol (HT) provide their anti-inflammatory, antioxidative, antitumour, and microbiota-modulation effects. Accordingly, several human studies that explored the effects of olive oil on patients with IBD further confirmed the evidence brought forward by preclinical studies. Nevertheless, there is a need for larger-scale, multicentric, randomized control trials that would finally elucidate olive oil’s level of efficacy in modulating the course of IBD.
... Tjonneland et al. observed a correlation between higher intake of linoleic acid, an n-6 PUFA, and an increased risk of UC, suggesting a possible role for dietary linoleic acid in the etiology of the disease [103]. On the other hand, oleic acid, which is the predominant ingredient of olive oil, was found to be inversely associated with UC development [104]. In agreement with this finding, a large prospective study showed an inverse association between greater longterm intake of long-chain n-3 PUFAs and risk of UC, confirming the protective effect of n-3 PUFA intake [105]. ...
Article
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly affecting the colon and the rectum. Its main characters are represented by relapsing and remitting mucosal inflammation, starting in the rectum and typically extending continuously proximally through part or the entire colon. UC pathogenesis depends on multiple factors, such as genetic predisposition, defects in the epithelial barrier, dysregulated immune responses, and environmental causes. The most frequent symptoms are abdominal pain, weight loss, mucus discharge, bloody diarrhoea, incontinence, nocturnal defecations, fever, and anemia. Existing therapies for UC include 5-aminosalicylic acid (5-ASA) and its derivatives, steroids, immunosuppressants and biological drugs. However, limited efficacy and unwanted adverse effects hardly limit these strategies of treatment. In the last decades, research studies have been driven towards complementary and alternative medicines for the treatment of UC. Various nutraceuticals have exhibited promising results in modulating intestinal inflammation meanwhile improving symptoms. These compounds possess a wide spectrum of positive health effects evidenced by in vitro studies, characterized by their involvement in antioxidant defenses, cell proliferation, and gene expression. The present review analyzes the available data about the different types of nutraceuticals and their potential effectiveness as adjuvant therapy of IBD, with particular emphasis to UC.
... Other studies on plant oils have revealed that when mother rats during gestation and lactation were fed a diet high in safflower oil (around 72% C18:2n-6) compared to those fed diets high in canola oil (C18:3n-3) or high in oleic safflower oil (C18:1n-9), off-springs had more severe colitis (68). When using data from 7-day food diaries, it was also concluded that dietary oleic acid was inversely associated (while C20:4n-6 was positively correlated) with UC development (69). Dietary fatty acids, and the characteristics of the vegetable oils (e.g., the level of refinement), influence the intestinal microbiota, e.g., an altered n-6 to n-3 ratio have been shown to promote the presence of, e.g., Enterobacteria and Clostridia spp. ...
Article
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Inflammatory bowel disease is a chronic and recurring inflammatory condition of the gastrointestinal tract encompassing ulcerative colitis and Crohn's disease. Although the pathogenesis of inflammatory bowel disease remains to be fully elucidated, environmental factors such as diet are believed to play a pivotal role in the onset and management of inflammatory bowel disease. Diet is thought to play an essential role in intestinal inflammation due to its regulatory effects on the microbiota, gut immune system, and epithelial barrier function. Although the evidence remains insufficient to draw firm conclusions on the role of specific dietary components in gastrointestinal diseases, studies have suggested that a Western diet with high intakes of total fats, omega-6 fatty acids, and meat have been associated with intestinal inflammation and relapse of inflammatory bowel disease. In contrast to a Western diet, plant-based diets often result in a reduced intake of total fats and meats and an increased intake of plant fibers which may contribute to reduced intestinal inflammation. This review critically examines the influence of plant-based dietary components on the clinical disease course of inflammatory bowel disease. Furthermore, this review discusses the benefits and possible limitations of plant-derived dietary components in the treatment of inflammatory bowel disease while addressing the principal type of disease and the anatomic site of inflammation within the gastrointestinal tract. Finally, this review points out important directions for future research on the role of diet in inflammatory bowel disease. A better understanding of the role of diet and intestinal inflammation may pave the way for novel dietary interventions and specific foods- or food supplements, which can support the treatment of inflammatory bowel disease.
... Some studies have linked IBS with low-grade inflammation and the infiltration of proinflammatory cytokines and tumor necrosis factor alpha (TNF-alpha) in the colonic mucosa, which may lead to exacerbated IBS symptoms [33]. Of interest is that PUFA has been linked with IBS on an epidemiological level in the EPIC-Norfolk cohort, where they highlighted a protective effect from PUFA intake, specifically oleic acid (a precursor of linoleic acid) [34]. In the present study, we showed an increase in linoleic acid and alphalinoleic acid after the diet intervention. ...
Article
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A 4-week dietary intervention with a starch- and sucrose-restricted diet (SSRD) was conducted in patients with irritable bowel syndrome (IBS) to examine the metabolic profile in relation to nutrient intake and gastrointestinal symptoms. IBS patients were randomized to SSRD intervention (n = 69) or control continuing with their ordinary food habits (n = 22). Food intake was registered and the questionnaires IBS-symptoms severity scale (IBS-SSS) and visual analog scale for IBS (VAS-IBS) were completed. Metabolomics untargeted analysis was performed by gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS) in positive and negative ionization modes. SSRD led to marked changes in circulating metabolite concentrations at the group level, most prominent for reduced starch intake and increased polyunsaturated fat, with small changes in the control group. On an individual level, the correlations were weak. The marked reduction in gastrointestinal symptoms did not correlate with the metabolic changes. SSRD was observed by clear metabolic effects mainly related to linoleic acid metabolism, fatty acid biosynthesis, and beta-oxidation.
... 9 An increasing risk for ulcerative colitis (UC) development was seen from protein sourced from red meat. 10 Despite animal studies suggesting that fat alone or when combined with sugar contribute to ileal inflammation, decreased mucus layer thickness, increased intestinal permeability, induction of NOD2 and TLR5 gene transcription, increased TNFα secretion and markers of dysbiosis, [11][12][13] longitudinal cohort studies did not show associations between CD and total or specific fats, with the exception of one study showing docosahexaenoic acid being protective of CD. 14 Trans unsaturated fatty acids and certain omega-6 polyunsaturated fatty acids (PUFA) increased risk but the monounsaturated omega-9 fatty acid oleic acid decreased risk of UC. 15 16 Total fibre and fibre from fruit were associated with a lower risk of CD onset in the NHS, reducing risk of CD by 40%, 17 but this was inconsistent with the EPIC study, showing that fibre from cereals, but not from fruit or vegetables, reduced risk of CD. 18 There were no associations of fibre in predicting risk of UC. ...
Article
Diet is a key modifier of risk of inflammatory bowel disease development and potentially a treatment option in patients with established disease. International organisations in gastroenterology and inflammatory bowel disease have published guidelines for the role of diet in disease onset and its management. Here, we discuss the major overarching themes arising from these guidelines and appraise recent literature on the role of diet for inflammatory bowel disease prevention, treatment of active disease and maintenance of remission, considering these themes. Except for exclusive enteral nutrition in active Crohn’s disease, we currently possess very little evidence to make any further dietary recommendations for the management of inflammatory bowel disease. There is also currently uncertainty on the extrapolation of epidemiological dietary signals on risk of disease development and preclinical experiments in animal models to management, once disease is established. Until high-quality evidence from clinical research becomes available, the only specific recommendations for inflammatory bowel disease we might safely give are those of healthy eating which apply for the general population for overall health and well-being.
... Infact, perhaps, we were the first to report that oleic acid can protect adrenaline induced myocardial injury through antioxidant mechanisms [20]. Additionally, the role of oleic acid in the amelioration of different oxidative stress induced disorders were also reported [43,44]. Sub-cutaneous administration of adrenaline bitartrate at pharmacological dose causes gastric lesions as evidenced by our tissue morphological studies. ...
Article
The role of oleic acid as a protective antioxidant has recently been recognized. The present study is aimed to explore whether oleic acid can afford protection to rat gastric tissue when challenged with adrenaline. Sixty adult healthy male albino rats were divided into 10 groups comprising of 6 animals each. First group constituted the control. Rats of the second group were injected sub-cutaneously with adrenaline bitartrate at the dose of 0.3mg/ kg body weight, every day for a period of 17 days. Rats of the third, to the sixth groups were orally fed with different doses of oleic acid (2.5, 5, 10, 20 mg/kg body weight/day) respectively. The rats of seventh to tenth groups were orally fed with doses of oleic acid as mentioned above and subsequently injected with adrenaline bitartrate at 0.3mg/kg body weight sub-cutaneously. After the treatment period, the animals were euthanized through cervical dislocation following light ether anaesthesia and gastric tissues were collected for morphological and biochemical studies. Subcutaneously administered pharmacological dose of adrenaline bitartrate caused oxidative stress inducing gastric lesion in male albino rats as evident from the altered levels of biomarkers of oxidative stress, activities of antioxidant and mitochondrial enzymes related to energy metabolism with changes in tissue morphology. Pre-treatment of rats with oleic acid dose-dependently protected against these gastric injuries induced by adrenaline indicating the potentiality of oleic acid in protecting against adrenaline induced gastric injury in male albino rats where antioxidant mechanisms appear to play a pivotal role in mediating such protection.
... 76 Dietary arachidonic acid and oleic acid intake have been positively and inversely associated with UC development, respectively. 77 No associations have been found between alcohol use and incidental diagnosis of IBD. 78 ...
Article
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Acknowledgments We would like to acknowledge academic medical illustrator Jill Gregory, CMI, FAMI, for help with figure design. We would like to thank Professor Paula Borralho, MD, PhD for providing a histology picture for Figure 1. We would like to thank Catarina Gomes, MD for providing a capsule endoscopy for Figure 1. We would like to thank Joseph Murray and Mark Riddle [from the PREDICTS Study] for their careful review and critical revisions of the manuscript. Abstract Inflammatory bowel disease [IBD] is a complex chronic disorder with no clear aetiology and no known cure. Despite recent advances in overall disease management and improved therapeutics, patients with IBD still experience a substantial burden. Furthermore, as the incidence continues to increase in developing areas of the world, it is expected that the burden of IBD to society will increase and exert tremendous pressure on healthcare systems worldwide. Therefore, new strategies to prevent the global increase of IBD are urgently required. Data are being progressively acquired on the period preceding disease diagnosis, which support the concept that IBD has a preclinical period that may reveal the triggers of disease and may be amenable to early intervention. Having a better knowledge of this preclinical period will increase the potential not only for improved understanding of disease pathogenesis and improved therapeutics, but also for disease prediction and prevention.
... (5.07%), these were also different from that of the seeds essential oils analyzed in this study. Oleic acid which is one of the principal component of the essential oils have been known to be an important dietary compound because it plays beneficial roles in human health; it improves heart conditions by lowering cholesterol and reducing inflammation [22], it also increases burning of fat which helps with weight loss [23], protects cells from free radical damage, prevent type 2 diabetes, prevents ulcerative colitis [24], generates brain myelin [25], involves in proper brain function [26,27] and restores proper metabolism in failing hearts [28]. ...
Article
This study determines the secondary metabolites of the essential oils of ripe and unripe seeds of Azadirachta indica and then evaluated their antioxidant and antimicrobial potentials. Ripe and unripe seeds were subjected to hydrodistillation using a Clevenger-type apparatus and analyzed using gas chromatography and gas chromatography-mass spectrometry (GC-MS). Antioxidant and antibacterial activities of the volatile oils were also investigated using 2,2- diphenyl-1-picrylhydrazyl (DPPH) and agar well diffusion methods, respectively. The GC-MS analysis showed that the essential oils of ripe and unripe seeds contained fourteen (14) and twenty-three (23) therapeutically active compounds, respectively. Compounds present in high quantity in the essential oil of ripe seeds were: 5-hydroxymethyltetrahydro-2- furanol (35.5%) and 2,5-dimethyl-1,5-heptadiene-3,4-diol (11.8%), palmitic acid (5.0%) and methyl-9-octadecenoate (5.0%), while 2-methyl-2-pentanethiol (31.9%), cis-oleic acid (21.0%), 4-methyl-5-nonanone (10.5%), toluene (6.0%) and o-xylene (6.0%) were the principal compounds in the essential oil of the unripe seeds. Essential oils of both ripe and unripe seeds showed high inhibition against Staphylococcus aureus. The essential oil of the unripe seeds showed moderate to high inhibition against Pseudomonas aeruginosa. Free radical scavenging of the two essential oils gave IC50 values of 2.00 and 2.50 for ripe and unripe seeds essential oil, respectively. Essential oil of unripe seeds has higher antimicrobial strength than that of the ripe seed. Essential oils of the seeds of A. indica could serve as a good source of pharmaceuticals and industrially useful compounds.
... Consistent with this hypothesis, the "western diet" was associated with an increased risk of IBDs [56]. Accordingly, in prospective studies, dietary n-6 fatty acids were positively correlated with UC risk, while dietary n-3 fatty acids showed a negative association [57][58][59][60]. ...
Article
Inflammatory bowel diseases (IBDs), such as Crohn's disease and ulcerative colitis, are lifelong diseases that remain challenging to treat. IBDs are characterized by alterations in intestinal barrier function and dysregulation of the innate and adaptive immunity. An increasing number of lipids are found to be important regulators of inflammation and immunity as well as gut physiology. Therefore, the study of lipid mediators in IBDs is expected to improve our understanding of disease pathogenesis and lead to novel therapeutic opportunities. Here, through selected examples – such as fatty acids, specialized proresolving mediators, lysophospholipids, endocannabinoids, and oxysterols – we discuss how lipid signaling is involved in IBD physiopathology and how modulating lipid signaling pathways could affect IBDs.
... However, the potential beneficial effects of OA and its capacity to reduce the risk for high-grade inflammatory conditions, such as UC and CD, are still a contradictory subject. Observational studies, based on food diaries or frequency questionnaires, found different results, with some of them encountering no relation between the intake of OA and the risk of IBDs (Ananthakrishnan et al., 2014;Barnes et al., 2017), while others, a beneficial (de Silva, Luben, Shrestha, Khaw, & Hart, 2014) or even a harmful association (Rashvand, Somi, Rashidkhani, & Hekmatdoost, 2015). Also, no relation was found when associated the content of OA in the serum of UC or CD patients with the disease severity or the concentration of pro-inflammatory cytokines (Scoville et al., 2019;Wiese et al., 2016). ...
Article
Inflammatory bowel diseases (IBDs), mainly Crohn’s disease and ulcerative colitis, are high-prevalent chronic gastrointestinal disorders that may cause an important reduction in life quality. Such diseases are characterized by their immune-mediated inflammatory, oxidative and dysbiotic events, which can lead to important symptoms in patients, such as abdominal pain, bloody diarrhea and body weight loss. In the last years, alternative natural options have been postulated for the prevention or treatment of IBDs, since common drug therapy may not be well accepted due to recurrent adverse effects and/or partial efficacy. Among those new natural products, agro-industrial byproducts, such as the peel and seed of foods, are emerging as cheap and pro-ecological options, as they are rich in bioactive compounds, such as polyphenols, but also in non-phenolic compounds, like unsaturated fatty acids, dietary fibers and prebiotics, carotenoids, bioactive peptides, and vitamins. In that sense, Latin America is rich in little explored native fruits and vegetables, from which great amounts of byproducts can be produced. Studies have shown that the byproducts from Latin American vegetables, such as passion-fruit (Passiflora edulis), pineapple (Ananas comosus) and pumpkin (Cucurbita spp.), for example, could represent interesting tools against IBDs, judging by the results of in vitro and animal studies. Therefore, the aim of this review is to discuss the potential role of non-phenolic compounds from native Latin American food byproducts in the prevention or treatment of IBDs, by highlighting their anti-inflammatory, anti-oxidative and/or anti-dysbiotic effects.
... Oleic acid, an omega 9 monounsaturated fatty acid was identified in the methanol extract of B. pilosa in this study and previous study [46]. It has been shown to protect against the development of ulcerative colitis in a UK prospective cohort study [47,48]. Also, treatment with oleic acid increased the survival rate, decreased neutrophil accumulation and lowered plasma TNF-α, prostaglandin E 2 and leukotriene B 4 levels in the peritoneal cavity after LPSinduced endotoxic shock in rodents [49]. ...
Article
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Background Bidens pilosa (BP) possessed anti-inflammatory, antioxidant, and immunomodulatory activities. Its beneficial effects on intestinal inflammation and oxidative stress in 2,4,6 trinitrobenzene sulfonic acid (TNBS) induced colitis in Wistar rats was evaluated. Methods Thirty female Wistar rats weighing 180–200 g were distributed into six groups (n = 5): non-colitic, untreated colitic and colitic rats treated graded doses of methanol extract of BP (50–400 mg/kg). Colitis was induced in rats by intracolonic instillation of 0.2 mL of 40 mg/mL TNBS. BP was administered two days pre-colitis induction and treatments continued until seven days post-colitis induction. A day after the last treatment, rats were euthanized, colon removed aseptically and response to treatment assessed. Phytochemical composition of BP was determined using the GC-MS. Results BP significantly reduced macroscopic colonic damage score, weight/length ratio, colonic lipid peroxidation level, leukocytes infiltration, and TNF- α level in comparison to untreated colitic rats (p ≤ 0.008). Similarly, treatment with 200 and 400 mg/kg BP prevented depletion of colonic glutathione level than other treatment groups (p ≤ 0.0002). Histological findings revealed that treatment with 400 mg/kg BP significantly preserved the mucosal epithelial layer. It also prevented ulceration and sloughing of the mucosal layers and reduced infiltration of inflammatory cells compared to other treatment groups. Among the 16 compounds identified were oleic acid (6.2%) and n- hexadecanoic acid (2.0%) with antioxidant anti-inflammatory activities. Conclusions The beneficial effects of BP in rat colitis might be related to the reduction of leucocytes infiltration, inhibition of oxidative stress and pro-inflammatory cytokines.
... AA, a polyunsaturated fatty acid involved in the metabolism of multiple organs and systems in the body, is catalytically degraded by its rate-limiting enzyme COX-2 to produce a series of metabolites in the event of inflammation or an emergency. These metabolites play an important role in regulating the immune system of the body [32]. At the same time, related studies also show that the pathogenesis of ulcerative colitis is mainly affected by tryptophan metabolites, which also emphasizes the potential relevance between tryptophan metabolism and intestinal microbial regulation [33,34]. ...
Article
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Background: The network pharmacology method was used to predict the active components of Banxia Xiexin decoction, its targets and the key signalling pathways that are activated in the treatment of depression and ulcerative colitis to explore the common mechanism. Methods: The active components and targets of Banxia Xiexin decoction were obtained by searching the ETCM,TCMSP and TCMIP database. The disease targets of depression and ulcerative colitis were obtained by combining the following the DisGeNET, OMIM,Drugbank,CTD and PharmGKB disease databases. The drug and disease target genes were obtained from the intersection of the herbal medicine targets and the disease targets and were imported into the STRING platform for the analysis of PPI network. The network modules were constructed using Cytoscape software. An analysis of the functional annotations of GO terms and KEGG signalling pathways was performed for each network module. Then, the tissue distribution, sub-cellular distribution and protein attributes of the key targets in the pathway were analysed by the BioGPS, Genecards and DisGeNET databases. Results: The mechanism of Banxia Xiexin Decoction in the treatment of depression and ulcerative colitis is related to drug reaction, steroid metabolism, lipid metabolism, inflammatory response, oxidative stress response, cell response to lipopolysaccharide, insulin secretion regulation, estradiol response and other biological functions, mainly through the regulation of 5-hydroxytryptamine synaptic, arachidonic acid metabolism, HIF-1 signaling pathway and NF-kappa B signaling pathway can achieve the effect of same treatment for different diseases. Conclusions: The mechanism of Banxia Xiexin Decoction in treating different diseases involves direct or indirect correlation of multiple signal pathways, mainly involved in drug metabolism and lipid metabolism, but also through comprehensive intervention of the body's nervous system, immune system, digestive system and other systems. The effective components of Banxia Xiexin Decoction are mainly act on eight key target proteins (such as ALB, IL6, VEGFA, TNF, PTGS2, MAPK1, STAT3, EGFR) to carry out multi-target effect mechanism, biological mechanism of treating different diseases with the same treatment, and related mechanism of overall treatment, which provide theoretical reference for further research on the material basis and mechanism of Banxiaxiexin decoction on antidepressant and prevention and treatment of ulcerative colitis.
... %. Apart from being hypotensive, oleic acid also lowers the chance of developing ulcerative colitis [11]. It is known that obesity causes insulin resistance and type II diabetes. ...
Article
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Objective: Wild indigenous fruits are believed to be extremely nutritious, contributing a great deal to the general health of the tribal and rural population. To validate this claim, systematic studies are required to estimate their nutritional composition. The objective of the study was to analyze the fatty acid composition of Syzygium zeylanicum (L.) DC. var. zeylanicum.Methods: The fatty acid composition of S. zeylanicum var. zeylanicum fruits were analysed by GC-MS/MS.Results: The major fatty acids were cis-oleic acid (43.47±0.62 %) and linoleic acid (31.14±0.35%). Total monounsaturated fatty acids in the sample was 44.21%. Omega-6, omega-7 and omega-9 fatty acids were detected. The polyunsaturated fatty acids in thefruits were linoleic acid (31.14±0.35 %) and arachidonic acid (0.15±0.22 %), whereas 24.51 % of the total fatty acids were saturated. The ratio of unsaturated to saturated fatty acids was approximately 3:1. The order of abundance of fatty acids, in some of the healthiest oils, viz. olive, canola, peanut oils is, Oleic acid>Linoleic acid>Palmitic acid>Stearic acid and the same order was observed in the present study.Conclusion: Fruits of S. zeylanicum var. zeylanicum too shows a healthy balance between unsaturated and saturated fats.Â
... According to the number of double bonds, LCFAs could be again subdivided into saturated (no double bond), monounsaturated (one double bond), or polyunsaturated fatty acids (more than two double bonds). Accumulating studies demonstrate that oleic acid of monounsaturated fatty acids (MUFAs) imbues a beneficial effect on intestinal inflammation in IBD [13,14]. However, the roles of PUFAs on intestinal inflammation tend to be perplexing. ...
Article
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Inflammatory bowel disease (IBD) is a complicated disease involving multiple pathogenic factors. The complex relationships between long-chain fatty acids (LCFAs) and the morbidity of IBD drive numerous studies to unravel the underlying mechanisms. A better understanding of the role of LCFAs in IBD will substitute or boost the current IBD therapies, thereby obtaining mucosal healing. In this review, we focused on the roles of LCFAs on the important links of inflammatory regulation in IBD, including in the pathogen recognition phase and in the inflammatory resolving phase, and the effects of LCFAs on immune cells in IBD.
... Oleic acid has been found to be essential for the brain [47] with several health benefits; it is used as an additional constituent in the preparation of cosmetics [48]. It is capable of thwarting ulcerative colitis [49], defending cells from free radical damage [50], reducing blood stress [51], and enhancing fat burning [52]. Palmitic acid, a saturated long-chain fatty acid comprising sixteen carbon atoms, was also found abundantly in both methanol and ethyl acetate extracts of our plant of study (32.87 and 13.57%). ...
Article
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Plants are reservoir for potentially useful bioactive compounds, and owing to the rising occurrences of drug resistance to malaria parasites, there is a need to discover and develop new phytochemicals in plant that can be used as antimalarial agents. In this study, we gave a detailed description of the phytochemicals present in both ethyl acetate and methanolic extracts of Callistemon citrinus ( C. citrinus ) using Gas Chromatography-Mass Spectrometry (GC-MS) analysis; both extracts were also evaluated for their in vitro antimalarial, antitrypanosomal, and cytotoxicity activities against Trypanosoma brucei brucei ( T. b brucei ) parasites, Plasmodium falciparum ( P. falciparum ) malaria parasites 3D7 strain, and human cervix adenocarcinoma cells (HeLa cells); in addition, the antimicrobial and antioxidant efficacies were determined using standard methods. Both extracts were characterized by a high amount of fatty acids (52.88 and 62.48%). The ethyl acetate extract exhibited a greater activity with minimum inhibitory concentration (MIC) values ranging from 0.025 to 0.10 mg/mL while the methanol extract ranged from 0.025 to 0.15 mg/mL. Both extracts were bactericidal to Escherichia coli ATCC 35150 ( E. coli ) and Pseudomonas aeruginosa ACC ( P. aeruginosa ). Qualitative and quantitative phytochemical screenings conducted for both extracts revealed the presence of alkaloids, glycosides, saponins, steroids, and triterpenoids, fat and oils, flavonoids, phenols, and tannins in varying amounts. Both crude extracts exhibited antitrypanosomal potentials with an IC 50 of 6.6/9.7 μ g/mL and antiplasmodial activities with an IC 50 of 8.4/13.0 μ g/mL. Conclusion from this study indicates that apart from the folkloric uses of this plant in traditional settings, the extracts possess a broad spectrum of antimicrobial, antitrypanosomal, and antimalarial activities and some pharmaceutically essential bioactive components with remarkable antioxidant capacities that may be used in the synthesis of novel drugs for the management of different varieties of ailments.
... Oleic acid and ascorbic acid were the major constituent of the tested sample of M. oleifera seed methanolic extract compared to the other constituents. This protecting activity of M. oleifera against CCl 4 toxicity is consistent with previous investigations revealed that the crude extract of M. oleifera is a good scavenger for nitric oxide radicals and has a potential source of natural antioxidant [16,26,27]. In addition, oleic acid reduces blood pressure by increasing fat burning and protects cells from free radical damage [28]. ...
Article
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Carbon tetrachloride (CCl4) causes severe injury to the body particularly the liver and the kidney. The aim of the present study was testing the probable hepatonephro protective effect of Moringa oleifera seed methanolic extract against CCl4 toxicity in male rat. 24 male rats were divided into 4 groups (n=6); the first group (G1) was the negative control group, rats of the other three groups were injected with CCl4 twice a week. Rats of the second group (G2) were kept without treatment as positive CCl4 group, the third group (G3) received a daily dose of M. oleifera methanolic extract and the fourth group (G4) received a silymarin dose as a positive treated group. The HPLC analysis of M. oleifera seed methanolic extract revealed that it is rich in ascorbic and oleic acids. Rats of the CCl4 positive control group showed an increase in kidney and liver injury markers, interleukin-6, bilirubin and lipid peroxidation, and a decrease in antioxidants activity and total protein. In addition, liver and kidney tissues showed drastic histopathological changes. Treating the CCl4 hepatonephrotoxicity in G3 and G4 with either M. oleifera seed methanolic extract or silymarin, respectively significantly alleviated all altered biochemical and histological changes approaching the normal values. M. oleifera methanolic extract revealed more protection to liver and kidney in G3 than silymarin in G4. This protecting activity of M. oleifera seed methanolic extract against CCl4 hepatonephrotoxicity may be ascribed to its high content of phenols and flavonoids, in addition to ascorbic acid and oleic acid.
... The most prevailing compounds are 4.7% hexadecanoic acid methy ester, 2.65% 9, 12octadecadienoic acid, 9-octadecenoic acid methyl ester 7.65% and 7.75% n-hexadecanoic acid (palmitic acid). Also, oleic acid was found to be 15.05% and People consuming the highest amounts of oleic acid were 89% less likely to have ulcerative colitis than those consuming the least amount of oleic acid [28] and a diet high in oleic acid may reduce the inflammation seen in obesity and non-insulin dependant obesity [29] . Linoleic acid was found to be 3.19% and linoleic acid has been shown to prevent the development of atherosclerosis, reduce body fat while improving lean body mass, and modulate immune and/or inflammatory responses [30] . ...
Article
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Tiger nut oil, although not entirely new, still largely remains unexploited in major parts of the world and underutilized even in regions where it is cultivated, especially in Nigeria. Therefore, the aim of this study is to investigate the physiocochemical characteristics and nutritional benefits of tigernut oil. From 4 kg ground powder soxhlet extracted using n-hexane there was oil yield of 32.95%. The pale yellow oil had a specific gravity refractive index of 1.452, relative density 0.919 g/cm 3 , acid value 2.21 mg/KOH/g, saponification value 143.05 mg/KOH/g, iodine value 80.37g/100g and ester value 62.68. Fat soluble vitamin content analysis revealed vitamin A (72.93UI), vitamin D (49.17UI), vitamin E (55.44UI) and vitamin K (15.3mcg) and Ca, Mg, K, Na, P, Mn, I, Ni, and Zn were found in varying proportions all of which was found to fall within the daily recommended intake limit. GC/MS revealed that it contains noticeable levels of oleic acid (15.05%), tetrasiloxane (9.245%), β-sitosterol (8.860%), n-hexadecanoic acid (7.753%) and 9-octadeceadienoic acid (7.649%). Thus, tigernut is oil rich tuber, could find application as an industrial raw material and could be used for cooking.
... There are conflicting reports regarding the therapeutic potential of MUFAs in IBD. A large prospective cohort study has demonstrated that dietary oleic acid intake is inversely associated with UC development (142). In contrast, other studies have shown that a high intake of MUFAs increases the risk for the development of UC and CD. ...
Article
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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD remains incompletely understood, accumulating evidence suggests that various environmental factors, including dietary nutrients, contribute to its pathogenesis. Dietary nutrients are known to have an impact on host physiology and diseases. The interactions between dietary nutrients and intestinal immunity are complex. Dietary nutrients directly regulate the immuno-modulatory function of gut-resident immune cells. Likewise, dietary nutrients shape the composition of the gut microbiota. Therefore, a well-balanced diet is crucial for good health. In contrast, the relationships among dietary nutrients, host immunity and/or the gut microbiota may be perturbed in the context of IBD. Genetic predispositions and gut dysbiosis may affect the utilization of dietary nutrients. Moreover, the metabolism of nutrients in host cells and the gut microbiota may be altered by intestinal inflammation, thereby increasing or decreasing the demand for certain nutrients necessary for the maintenance of immune and microbial homeostasis. Herein, we review the current knowledge of the role dietary nutrients play in the development and the treatment of IBD, focusing on the interplay among dietary nutrients, the gut microbiota and host immune cells. We also discuss alterations in the nutritional metabolism of the gut microbiota and host cells in IBD that can influence the outcome of nutritional intervention. A better understanding of the diet-host-microbiota interactions may lead to new therapeutic approaches for the treatment of IBD.
... was reported based on the EPIC study. 54 More notably, PUFAs can be categorized into anti- inflammatory n-3 PUFAs (α-linolenic acid [ALA], docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) and pro-inflammatory n-6 ...
Article
The current review aimed to elucidate the role of diet in every stage of inflammatory bowel disease, from aspects of prevention, treatment and rehabilitation. Western diet, characterized by overconsumption of refined sugar, saturated fat and low consumption of dietary fiber, may partly be blamed for its pathogenesis. Some immune‐modulated nutrients (fibers, monounsaturated fatty acids, n‐3 polyunsaturated fatty acids and vitamin D) exert their potential beneficial effects on gut microbiota and immune function, resulting in clinical remission and/or preventing relapse. However, data is limited to conclude optimal micronutrient levels and therapeutic implications. Further, diet itself is complex; it is reasonable to evaluate diet as a whole rather than a single type of food. Some specific dietary patterns are generated for the management of inflammatory bowel diseases with controversial results. Only exclusive enteral nutrition has been widely recommended for pediatric patients with non‐stricture active Crohn’s disease. Self‐monitor, avoidance of certain types of foods, limited access to alcohol and smoking, supplementation of minerals and vitamins if deficiency is confirmed, and adherence to the diet enriched in vegetables and fruits and low in animal food and un‐digested fiber during flares are the most common dietary recommendation. Further clinical trials with a high evidence rank are warranted.
... The inhibitory effects of olive oil total phenolic fraction on some key inflammatory mechanisms such as NF-kB activation, iNOS induction and IL-8 and IL-6 production, provide strong evidence that it is able to prevent or delay the progression of intestinal inflammation. Considering that also oleic acid, which represents the highly concentrated monounsaturated fatty acid in olive oil, has been proven to reduce colonic inflammation [65], extra virgin olive oil consumption may be considered a useful tool in the prevention and management of IBD. ...
Article
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Dietary habits may strongly influence intestinal homeostasis. Oxysterols, the oxidized products of cholesterol present in cholesterol-containing foodstuffs, have been shown to exert pro-oxidant and pro-inflammatory effects, altering intestinal epithelial layer and thus contributing to the pathogenesis of human inflammatory bowel diseases and colon cancer. Extra virgin olive oil polyphenols possess antioxidant and anti-inflammatory properties, and concentrate in the intestinal lumen, where may help in preventing intestinal diseases. In the present study we evaluated the ability of an extra virgin olive oil phenolic extract to counteract the pro-oxidant and pro-inflammatory action of a representative mixture of dietary oxysterols in the human colon adenocarcinoma cell line (Caco-2) undergoing full differentiation into enterocyte-like cells. Oxysterols treatment significantly altered differentiated Caco-2 cells redox status, leading to oxidant species production and a decrease of GSH levels, after 1 h exposure, followed by an increase of cytokines production, IL-6 and IL-8, after 24 h. Oxysterol cell treatment also induced after 48 h an increase of NO release, due to the induction of iNOS. Pretreatment with the phenolic extract counteracted oxysterols effects, at least in part by modulating one of the main pathways activated in the cellular response to the action of oxysterols, the MAPK-NF-kB pathway. We demonstrated the ability of the phenolic extract to directly modulate p38 and JNK1/2 phosphorylation and activation of NF-kB, following its inhibitor IkB phosphorylation. The phenolic extract also inhibited iNOS induction, keeping NO concentration at the control level. Our results suggest a protective effect at intestinal level of extra virgin olive oil polyphenols, able to prevent or limit redox unbalance and the onset and progression of chronic intestinal inflammation.
... [14][15][16][17][18][19][20] Similarly, environmental factors have been investigated in large cohorts with prospectively collected lifestyle data, such as the European Investigation into Cancer and Nutrition Study as well as the Nurses' Health Study. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] In light of the notable impact that environment factors play in disease development, which is further supported by the increasing incidence of these disease, 6 11 it stands to reason that modifying environment factors such as lifestyle may influence treatment response. Accordingly, quite a few patients ask their healthcare professionals for lifestyle recommendations that can influence the effectiveness of treatment, and in particular the outcomes achieved with TNFi. ...
Article
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Introduction Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes. Methods and analysis This prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn’s disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14–16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics. Ethics and dissemination The principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. Trial registration number NCT03173144 ; Pre-results.
... Oleic acid is a mono-saturated omega-9-fatty acid with many health's benefits and is safe in present practices for use and concentrations in cosmetics [17]. Oleic acid prevents ulcerative colitis [25], protects cell from free radical damage [26], reduces blood pressure [27] and increases fat burning [28]. ...
Article
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The fixed oil from M. Oleifera seed oil was analyzed by a combination of GC and GCMS. Twenty four (24) constituents amounting to 96.81% of the total oil were identified. The major constituents were Oleic acid (22.51%), Palmitic acid (10.64%), 9-octadecenol (12.76%) and phenylbut-3-yne (5.79%). The fixed oil of M. Oleifera seed is rich in fatty acids (44.93%) followed by hydrocarbons (32.95%), others are aldehyde (12.76%) esters (3.55%) and oxygenated hydrocarbon (2.62%). The oil was found to contain moderate level of unsaturated fatty acids, mainly Oleic acid (22.51%) and Erucic acid (1.98%). The dominant saturated acids were Palmitic (10.64%), Stearic acid (6.07%), Arachidic acid (2.21%) and Docosanoic (Behenic acid) (1.03%). The physio-chemical analyses and proximate composition of the n-hexane extract of M. Oleifera seed oil were also determined using standard analytical methods. Results showed that the specific gravity and refractive index were 0.9050 & 1.456. The recorded acid value, iodine value, Saponification number, free fatty acids and peroxide values were in the order 6.73mgKOHg-1 , 68.65g100g-1 , 180.92mgKOHg-1 , 4.21mgKOHg-1 , 2.60 meqKg-1. The percentage yield of the oil was 38.0% and the color of the oil was cream yellow. The following fatty acids were identified from the GCMS analysis. Myristic acid, Oleic acid, Palmitic acid, Stearic acid, Erucic acid, Arachidic acid and Docosanoic acid (Behenic acid). The result of the proximate composition showed that the seed contain 10.50% moisture, 39.57% crude protein, 5.00% ash, 5.00% crude fiber, 32.50% fat and 7.44% carbohydrate. The seed oil of M. Oleifera showed good physio-chemical properties and could be utilized successfully as a source of edible oil for human consumption and for industrial applications.
... Кроме того, арахидоновая кислота входит в со- став фосфолипидов клеточных мембран (например, клеток печени, мозга, мышечных волокон) [137]. На основании результатов одного из проспективных когортных исследований была выдвинута гипотеза о том, что поступающая с пищей арахидоновая кислота может способствовать развитию язвен- ного колита (в дозозависимой манере), в то время как олеиновая кислота (ω-9-МНЖК), конкурентно ингибирующая метаболизм арахидоновой кислоты, напротив, препятствует этому [138]. ...
Article
Background: The effect of gut microbiota dysbiosis on human metabolome and the potential of microbial and endogenous metabolites as biomarkers of chronic intestinal inflammation (CII) are not clear. Methods: Forty ulcerative colitis (UC) patients, 43 celiac disease (CD) patients and 42 healthy volunteers (HV) were enrolled. The qRT-PCR was used for fecal microbiota assessment. Serum metabolomic assays were conducted using the GC-MS. UC patients were randomised into A1 and A2 groups and CD patients were randomised into B1 and B2 groups. A1 and B1 groups received oral calcium butyrate plus inulin for 28 days as supplement to oral mesalazine in UC or gluten-free diet (GFD) in CD. A2 and B2 groups received standard treatment or GFD. Results: Butyrate-producing bacteria (BPB) were depleted in UC compared with HV. CD patients had lower Bifidobacterium spp. counts than HV or UC. Taxonomic dysbiosis in both UC and CD was characterised by a higher Bacteroides fragilis/Faecalibacterium prausnitzii ratio compared with HV. Significant changes in gut microbiota in both UC and CD were accompanied by changes in serum microbial metabolites levels. In UC serum lactic acid, 2-hydroxybutyric acid (2-HBA), 3-hydroxyisobutyric acid (3-HIBA), 2-hydroxyisovaleric acid (2-HIVA), 3-hydroxycinnamic acid, succinic acid (SA), benzoic acid (BA) and 4-hydroxyphenylacetic acid (4-HPAA) levels were significantly increased compared with HV. Serum levels of caproic acid, linoleic acid (LA) and eicosadienoic acid (EDA) in UC were significantly lower than in HV. Serum of CD patients showed significant increases in stearic acid (StA), 2-HIVA, SA, fumaric acid and BA compared with HV. De novo lipogenesis index (DNL) (C16:0/C18:2n-6) was significantly elevated in UC compared with both HV and CD. The ELOVL6 elongase activity index (C18:0/C16:0) and the StA/lA ratio (C18:0/C18:2n-6) in UC were significantly increased compared with HV. AA/EDA ratio (C20:4n-6/C20:2n-6) was increased in both UC and CD. Oral butyrate plus inulin significantly enhanced fecal BPB, reduced elevated B. fragilis/F. prausnitzii ratio, lowered serum pro-inflammatory SA and 2-HIVA and restored the initially lowered LA and EDA. 85% of UC patients in A1 (butyrate) group demonstrated significant improvement in rectal bleeding and stool frequency by day 14, compared with 55% in A2 group. Conclusions: The changes in serum metabolome, reflecting metabolic pathways disturbances (glycolysis, TCA cycle, fatty acid metabolism, ketone body metabolism, phenylalanine, tyrosine and tryptophan metabolism, microbial metabolism) are observed in both UC and CD. Some of metabolites and a new metabolomic index (AA/EDA ratio) may be considered as candidate biomarkers of CII. Oral butyrate plus inulin has a prebiotic (butyrogenic) effect, restoring BPB.
... Linoleic (C18:2 n-6, LA) and arachidonic acids (C20:4 n-6, AA) are the two most common n-6 PUFAs in typical Western diets. LA is virtually found in every food we eat and is the predominant PUFAs in meats, dairy products, vegetables, vegetable oils, cereals, fruits, nuts, legumes, seeds and breads; AA usually comes from red meat, sunflower and corn oils [6]. Evidence shows that, through cyclooxygenase (COX)mediated peroxidation, AA and its metabolites (PGs-2, 2-series prostaglandins) could be tightly implicated in inflammatory disorders and consequently in cancer development, by stimulating cell proliferation and survival, tumor cell invasiveness and production of proangiogenic agents [7][8][9][10]. ...
Article
Background: Scientific evidence has been accumulated about the effects of polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3 PUFAs might improve the efficiency of anticancer drugs has recently been considered. The role of n-6 PUFAs, in contrast, needs to be better assessed. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. This review aims to report the most updated evidence on the role of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing on the potential mechanisms by which PUFAs exert their effects. Methods: We undertook a structured search in PubMed on February 17th 2017 for peer-reviewed research articles published from 2013. The search syntax used was: PUFA or PUFAs and cancer. Results: Contradictory results were found, most likely due to the genetic background, the different dietary sources used, the interaction among different nutrients, and the tumor subtypes. However, the more recent findings strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the other hand, n-6 PUFAs are often associated with an increased risk of cancer, even if recently their beneficial effects have also been highlighted. Conclusion: N-3 PUFAs may represent a potential therapeutic agent contributing to treat at least some type of human cancers. However, studies with larger sample sizes and longer follow-up times are still needed. To increase the knowledge about how food and nutrition can improve human health it is advisable to deliver an open access nutritional database.
... Numerous epidemiological studies highlighted the role of dietary intake of monounsaturated fatty acids (MUFA) or PUFA in ulcerative colitis (UC) development. Higher intake of LA is associated with an increased risk of UC [11], while docosahexaenoic acid (DHA) (n-3 PUFA) [12] or oleic acid (n-9 MUFA) [13,14] consumption is beneficial. Ananthakrishnan et al. found that greater fish intake was associated with lower risk of CD [15]. ...
Article
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Background: Inflammatory bowel diseases (IBD) occurred in genetically predisposed people exposed to environmental triggers. Diet has long been suspected to contribute to the development of IBD and epidemiological studies highlight the lower IBD risk in people with a well-balanced diet. Supplementation with n-3 polyunsaturated fatty acids (PUFA) protects against intestinal inflammation in rodent models while clinical trials showed no benefits. We hypothesized that intervention timing is crucial and dietary fatty acid pattern may influence intestinal environment to modify inflammation genesis. The aim of this study was to evaluate the dietary effect of PUFA composition on intestinal inflammation. Methods: Animals received diet varying in their PUFA composition for four weeks before TNBS-induced colitis. Four n-3/n-6/n-9 ratios were tested: 1:4:16 for control diet, 1:1:4 for n-3 diet, 1:16:16 for n-6 diet and 1:4:24 for n-9 diet respectively. Colon Inflammatory markers (inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α(TNFα), interleukin-6 (IL-6)) and gut barrier function parameters were assessed. Inflammatory pathways PCR arrays were determined. Results: Colitic groups had a lower body weight compared to control rats (P<0.01) and an increased colon weight length ratio (P<0.01). N-3 diet significantly decreased colon iNOS, COX-2 expression, IL-6 production and LTB4 production (p<0.05, p<0.001, p<0.05, p<0.05 respectively) but tended to decrease colon TNF-α production (P=0.0617) compared to control diet. Tight junction proteins (claudin-1, occludin) expressions and MUC2 and TFF3 mRNA levels were not different among groups. N-9 diet also decreased colon IL-6 production (P<0.05). Conclusions: Dietary n-3 PUFA influence colitis development by attenuating inflammatory markers. Further research is required to better define dietary advice with a scientific rationale.
... Oleic acid is a monounsaturated x-9 fatty acid widely distributed in nature (De Silva et al. 2014). Oleic acid is a bactericidal agent against important pathogenic microorganisms including methicillin-resistant Staphylococcus aureus and Helicobacter pylori (Farrington et al. 1992). ...
Article
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Persian shallot, Allium hirtifolium Boiss. (AH), is an Iranian native medicinal plant belongs to Alliaceae family. Here, we investigated in vitro antibacterial activity of hydro-alcoholic extract derived from bulbs of AH. We also employed in silico molecular docking to decipher mechanisms of its antibacterial effects. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) against E. coli ATCC 25922 were determined. Molecular docking was performed for major phytochemicals of AH against ribosome recycling factor (RRF). E. coli ATCC 25922 was gentamicin-resistant while AH showed MIC (42±18 μg/ml) and MBC (106±36 μg/ml) against E. coli. In silico results reported all phytochemicals of AH shown acceptable negative binding affinity (kcal/mol) with RRF. In essence, the binding affinities of alliogenin (-11.6), gitogenin (-11.6), kaempferol (-10.2), linoleic acid (-8.4), oleic acid (-8.0), palmitic acid (-7.4), palmitoleic acid (-8.4), quercetin (-10.8), and shallomin (-13.4) with RRF were comparable to that of gentamicin (-12.6). In sum, hydro-alcoholic extract of bulbs of AH could be considered as a commercial phytobiotics if in-depth antibacterial assays employed in future studies. More interestingly, shallomin showed more promising binding affinity with RRF and can be considered as lead molecule for future drug discovery.
... Tjonneland et al [59] observed a correlation between higher intake of linoleic acid, a n-6 PUFA, and an increased risk of UC, suggesting a possible role for dietary linoleic acid in the etiology of the disease. On the other hand, oleic acid, which is the predominant ingredient of olive oil, was found to be inversely associated with UC development [60] . In agreement with this finding, a prospective large study showed an inverse association between greater long-term intake of long-chain n-3 PUFAs and risk of UC, confirming the protective effect of n-3 PUFA intake, while no specific fatty acids appeared to be associated with the risk of CD [61] . ...
Article
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Conventional therapies for inflammatory bowel diseases (IBD) involve combinations of pharmacologic agents such as aminosalicylates, azathioprine, and corticosteroids. Recently, the therapeutic scenario has been heavily increased by the introduction of agents including monoclonal antibodies targeted to specific proinflammatory cytokines, to adhesion molecules, and the induction of anti-inflammatory cytokines and T-cell activation. However, the use of these drugs is accompanied by a certain number of side effects, with some of them being quite severe, rising concerns about the safety profile. Furthermore, the cost of these emerging therapeutic strategies is significant , considering the increasing incidence and the chronic trend of IBD. Nutraceuticals is a broad term used to describe any product derived from food sources claiming extra health benefits beyond the intrinsic nutritional value found in foods. The beneficial effects of nutraceutical compounds in human health have been emerging in the last decades. Although few clinical trials have been performed in IBD patients, nutraceuticals, such as herbal products or vitamins, are generally accepted as safer alternative/supplementation to conventional therapy. In vitro and IBD-animal models studies have shown their involvement in several biological processes, including antioxidant defenses, cell proliferation, gene expression, which could account for a role in the maintenance of the mucosal barrier integrity, the control of the inflammatory pathways and the modulation of the immune response. These data suggest a wide spectrum of positive effects exerted by nutraceuticals, with a high potential for a therapeutic use in humans. In the present review, the beneficial effects of the most investigated nutraceutical compounds in the setting of human IBD are discussed.
Article
The American Heart Association suggests that consuming ω-6 fatty acids (5–10% of total energy) can prevent cardiovascular disease by improving lipoprotein profiles. However, some studies warn of deleterious effects of these due to eicosanoid biosynthesis. We explored the five years for clinical evidence of ω-6 fatty acids on several diseases including inflammation, cancer, cardiovascular disease, and metabolic syndrome. Predefined criteria identified a total of 21 articles in 5 databases. Some studies indicated that dietary arachidonic acid was not related to increase of pro-inflammatory cytokines. In cohort studies, ω-6 fatty acids prevented the onset of digestive and lung cancer. ω-6 Fatty acids improved blood lipoprotein profiles. Moreover, consuming ω-6 fatty acids delayed diabetes mellitus and chronic renal disease and had positive effects on muscle recovery and glaucoma. In conclusion, ω-6 fatty acids have beneficial effects on cancers, blood lipoprotein profiles, diabetes, renal disease, muscle function, and glaucoma without inflammation response.
Article
Historically, dietitians played a minor part in the management of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Patients were commonly referred for consequences of uncontrolled disease, such as malnutrition and bowel obstruction risk. Today, dietitians are fundamental members of the multidisciplinary IBD team, from educating on the role of diet at diagnosis and throughout the lifespan of a patient with IBD to guiding primary induction therapy. This aspect is reflected in published guidelines for IBD management, which previously placed diet as only a minor factor, but now have diet-specific publications. This Review describes a four-step approach in a dietitian's assessment and management of diet in patients with IBD: (1) identifying and correcting nutritional gaps and dietary imbalances; (2) considering diet to treat active disease with the use of exclusive enteral nutrition (EEN) or emerging diets that could replace EEN; (3) using therapeutic diets to control existing complications of IBD, such as reduced fibre to prevent bowel obstruction in stricturing disease or a fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet to manage co-existing functional gut symptoms; and (4) considering the role of diet in preventing IBD development in high-risk populations.
Article
In recent years, the role of diet in the pathogenesis of inflammatory bowel disease (IBD) has gained great interest within the scientific community. Eating habits from industrialised countries (the so-called western diet or WD) have been associated with a higher incidence of IBD in observational studies, although the dietary factors responsible for the development of the disease are still to be elucidated. Some components of the diet with proinflammatory potential may cause changes in immunity and intestinal microbiota, leading to the inflammatory reaction that causes IBD-related lesions. The quality of available evidence is low, due to methodological issues, such as the lack of intervention studies, small sample size and heterogeneity of studies. For this reason, scientific societies have offered their recommendations using clinical practice guidelines and consensus documents, in order to establish a common criterion in the nutritional treatment of patients with IBD. The objective of this review was to summarise the data published regarding diet in IBD and review the recommendations given by scientific societies.
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Food-borne illnesses are a major health concern worldwide. While 1 in 6 individuals are infected in the United States yearly, there is little research into which dietary factors can alter the risk of infection. Despite evidence suggesting a correlation between obesity and enteric infection, the few reported studies focus on the role of dietary factors and the impact on host tissues and susceptibility. The direct impact of dietary constituents on the virulence of a pathogen has largely been ignored. One component of the Western diet that has been correlated with increasing inflammatory diseases is increased consumption of omega-6 polyunsaturated fatty acids such as arachidonic acid. Here, we show that arachidonic acid directly alters the pathogenicity of the food-borne pathogen Yersinia enterocolitica . Using in vitro cellular adherence assays, proteomic peptide mass fingerprint profiles and in vivo mouse models, we show that arachidonic acid can alter the pathogenesis of Y. enterocolitica by increasing proliferation and intracellular invasion. These findings have major implications in more than food safety, potentially revealing how current dietary habits may increase the virulence of food-borne pathogens.
Article
Aim Previous research has shown that individuals with inflammatory bowel disease avoid specific food items, such as fibre rich foods, in order to manage symptoms. Dietary fibre and the traditional Mediterranean diet are both associated with reduced mucosal and systemic inflammation, gut barrier integrity, and microbiota diversity. There is limited data on the diet composition of individuals with inflammatory bowel disease. The aim of this study was to evaluate how it compares to the traditional Mediterranean diet and national dietary guidelines. Methods Outpatients with inflammatory bowel disease were recruited to the study between February and August 2019. Demographic and medical information was obtained for consenting participants. All participants completed a dietary assessment of usual intake (24-h diet recall and 17-point ready reckoner) from which a Mediterranean diet adherence score was calculated. Dietary intake of core food groups was compared to the recommended number of serves outlined in the Australian Guide to Healthy Eating. Results 100 participants were recruited. The mean Mediterranean diet adherence score was 5.1 ± 1.3 (maximum 14 points), 4% of participants scored ≥9 (commonly agreed criteria for Mediterranean diet adherence). Participants also consumed considerably less grains and vegetables than national dietary guidelines recommendations. Conclusions The diet of outpatients with inflammatory bowel disease did not align with Mediterranean diet characteristics. Participants consumed significantly less grains and vegetables than national guidelines, suggesting a low fibre intake. These findings suggest that dietary interventions focusing on improving the diet of individuals with inflammatory bowel disease to align with Mediterranean diet characteristics are warranted.
Article
Background The processing of dietary lipids in the intestinal lumen involves metabolic processes of the host and also of the microbial organisms that reside in the gut. Whereas, in the edible oil, there are also other minor content of components, such as fat-soluble micronutrients. The dietary oils and fats, as well as these accompanied components have different effects on the gut microbiota structure, which is also closely associated with gut inflammation, and the host health. Scope and approach This review of the literature highlights the effects of dietary oils and fats, as well as the minor content of accompanied components on the gut microbiota, and the gut inflammation, with special respect to illustrating the roles of high fat diet (HFD), fatty acid composition, the n6/n3 poly-unsaturated fatty acid (PUFA) ratio, the conjugated linoleic acids (CLAs), the fatty acid chain length and triacylglycerol (TAG) structure, the fat-soluble micronutrients, and some other minor content of components, such as trans-fatty acids (TFAs). The interactions between the dietary oils and fats and gut microbiota are also briefly discussed. Key findings and conclusions The diversity in dietary oils and fats composition affects the gut microbiota structure, and the unhealthy dietary lipid pattern, such as HFD or diet rich in saturated fats may lead to the gut microbiota dysbiosis not only by decreasing their richness and diversity, but also by changing the Firmicutes to Bacteroidetes ratio, further raising the intestinal pro-inflammatory cytokines levels and permeability of the intestine mucosa. The balanced dietary oils and fats intake is recommended to achieve the appropriate fatty acid consumption ratio, especially for the n6/n3 PUFA ratio, thereafter, maintaining both of the gut microbiota homeostasis and host health. The accompanied minor content of fat-soluble bioactive components also showed positive roles for the overall gut health. However, more clinic evidence should be provided in future studies.
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Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic and multifactorial diseases that affect the intestinal tract, both characterized by recurrent inflammation of the intestinal mucosa, resulting in abdominal pain, diarrhea, vomiting and, rectal bleeding. Inflammatory bowel diseases (IBD) regroup these two disorders. The exact pathological mechanism of IBD remains ambiguous and poorly known. In genetically predisposed patients, defects in intestinal mucosal barrier are due to an uncontrolled inflammatory response to normal flora. In addition to the genetic predisposition, these defects could be triggered by environmental factors or by a specific lifestyle which is widely accepted as etiological hypothesis. The involvement of the CD40/CD40L platelet complex in the development of IBD has been overwhelmingly demonstrated. CD40L is climacteric in cell signalling in innate and adaptive immunity, the CD40L expression on the platelet cell surface gives them an immunological competence. The IL-1, a major inflammation mediator could be involved in different ways in the development of IBD. Here, we provide a comprehensive review regarding the role of platelet CD40/CD40L in the pathophysiological effect of IL-1 in the development of Crohn’s disease (CD). This review could potentially help future approaches aiming to target these two pathways for therapeutic purposes and elucidate the immunological mechanisms driving gut inflammation.
Article
Context: Increased free fatty acids (FFAs) levels, typical in obesity condition, can contribute to systemic lipotoxicity and inflammation adversely influencing Inflammatory Bowel Disease development and progression. Anthocyanins possess health promoting properties mainly associated to the induction of Nrf2-regulated cytoprotective proteins. Objective: Using a novel experimental model, we evaluated the in vitro intracellular mechanisms involved in FFAs modulation of intestinal epithelial lipotoxicity and the protective effects of cyanidin-3-O-glucoside (C3G) in Caco-2 cells. Results: Caco-2 exposed to palmitic acid (PA) in the serosal (basolateral) side showed a combined state of epithelial inflammation, inducing NF-κB pathway and downstream cytokines, that was reverted by C3G apical pre-treatment. In addition, PA altered intracellular redox status and induced reactive oxygen species that were reduced by C3G via the redox-sensitive Nrf2 signalling. Discussion and conclusion: Results suggest that anti-inflammatory properties of anthocyanins, mediated by Nrf2, could represent an interesting tool for intestinal inflammatory disorders.
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Background: The relationship between dietary pattern and the risk of chronic obstructive pulmonary disease (COPD) has been described; however, the exclusive role of dietary factors remains controversial. Hence, we conducted this systematic meta-analysis to clarify the role of some nutrients and antioxidant vitamins in the risk of COPD. Materials and methods: PubMed, Embase, and Scopus databases were searched for studies evaluating the associations between COPD outcome measures, symptoms, and mortality, and intake of fruits and vegetables, fiber, fish, n-3 or n-6 fatty acids, and antioxidant vitamins in adults. The random-effect model meta-analyses were used to pool the results. Results: Ten cohort, six case-control, and 20 cross-sectional studies were identified. The pooled relative risks (RRs) of the COPD and confidence intervals (CIs) for the highest intake group compared with the lowest intake group were 0.74 (95% CI: 0.65-0.85) for fruit, 0.65 (95% CI: 0.55-0.78) for dietary fiber, 0.71 (95% CI: 0.58-0.85) for fish, and 0.89 (95% CI: 0.76-0.99) for vitamin C. No association was observed between the risk of COPD and the intake of vegetables, n-3 fatty acids, vitamin E, and β-carotene; however, it was associated with n-6 fatty acids 1.06 (95% CI: 0.87-1.30). Conclusion: The results suggested that a higher intake of fruits, probably dietary fiber, and fish reduce the risk of COPD.
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Vernonia amygdalina is a medicinal plant widely used in traditional medicine in Africa and Asia for the treatment of ailments such as diabetes, inflammation, microbial infections and it has hypoglycaemic properties. The chemical constituents of the methanolic extract of Vernonia amygdalina root, stem bark and leaf were investigated using Gas chromatography-mass spectrometry (GC-MS). The GC-MS analysis of the Vernonia amygdalina root, stem bark and leaf extract revealed the existence of the GC-MS chromatogram of twenty six peaks present. Fifteen chemical compounds were identified in the root of V amygdalina, six were found in the stem bark. while five were identified in the leaf of the plant by GC-MS analysis. The result of the analysis showed that Vernonia amygdalina contains important pharmacologically important bioactive compounds. The presence of these bioactive compounds justifies the uses of the plant for various traditional medicines.
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Genistein is a major isoflavone with antioxidant and anti-inflammatory activity with the hydrophobic feature. To increase the bioavailability, we decided to adjunct genistein with the dietary oils. The present study aims to compare the effectiveness of genistein supplementation with water solution or with oils and find the best possible dietary oil for fortification. Total of 135 male Sprague – Dawley rats were randomly assigned to nine groups including one control group and eight acetic acid-induced colitis groups. Rats in the intervention groups were treated with 5ml/ Kg body weight of oral pure and genistein fortified forms of extra virgin olive oil (EVOO), canola oil (CaO), and rice bran oil (RBO) and Genistein group (G) received 100mg / Kg body weight of genistein in aqueous solution orally. The colitis and control groups did not receive any treatment. The levels of colonic MDA (Malondialdehyde), MPO (Myeloperoxidase) activity, and IL-1β (Interleukin-1β) were evaluated and the stereological analysis of colonic tissues was performed. All of the dietary oils (EVOO, CaO and RBO) were effective on ameliorating oxidative and inflammatory status (p < 0.05), however, EVOO (with or without genistein) prescription induced slightly better results, especially on inflammatory profile. Additionally, delivering genistein via oil vehicle versus genistein in aqueous solution was more efficient in reducing MDA formation, MPO activity and IL-1β concentration. quantitative analysis of colonic tissue was consonant with biochemical analysis. Our findings suggest that oral administration of EVOO, canola oil and rice bran oil can attenuate the elevated IL-1β levels and oxidative damage in induced colitis. Moreover, genistein fortified oils, especially EVOO have more beneficial effects in decreasing these markers in comparison with the pure oils or genistein (aqueous solution).
Chapter
The health of the digestive system is important in order for it to perform its physiological functions appropriately. The physiological parameters of the digestive system depend on the types of food ingested and the presence of bioactive compounds therein. Ingested foodborne bioactive compounds, or phytochemicals, can play an important role in the mediation of the pathophysiology of the digestive system. Pathological conditions are mostly treated with different drugs, and almost all the drugs have undesirable effects. Therefore, adverse effects and toxicity of drugs led scientists to consider alternatives, functional foods, safer bioactive compounds, or nutraceutical-based approaches for the management of gastrointestinal (GI) conditions. In the last few decades, many nutraceuticals with antioxidative, anti-inflammatory, fatty acid, probiotic, and prebiotic properties have been discovered that ameliorate the signs of GI disease. More preclinical and clinical studies will lead us into a new era of nutraceuticals for the management of gut health and conditions in animals.
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Introduction Chronic inflammatory diseases (CIDs) (Crohn’s disease, ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis and multiple sclerosis) are diseases of the immune system that have some shared genetic and environmental predisposing factors, but still few studies have investigated the effects of lifestyle on disease risk of several CIDs. The primary aim of this prospective cohort study is to investigate the impact of fibre, red meat and processed meat on risk of late-onset CID, with the perspective that results of this study can contribute in supporting future diet recommendations for effective personalised prevention. Methods and analysis The study will use data from 57 053 persons from the prospective Danish cohort study ‘Diet, Cancer and Health’ together with National Health Registry data. The follow-up period is from December 1993 to December 2018. Questionnaire data on diet and lifestyle were collected at entry to the Diet, Cancer and Health study. The outcome CID is defined as having a diagnosis of one of the CIDs registered in the National Patient Registry or, for multiple sclerosis, in the Danish Multiple Sclerosis Registry during follow-up and being treated with a drug used for the specific disease. The major outcome of the analyses will be to detect variability in risk of late onset of any CID and, if power allows, disease risk of late onset of each CID diagnosis between persons with different fibre and red meat, and processed meat intake. The outcome will be adjusted for age, sex, body mass index, physical activity, energy, alcohol, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity. Ethics and dissemination The study is approved by the Danish Data Protection Agency (2012-58-0018). The core study is an open register-based cohort study. The study does not need approval from the Ethics committee or Institutional Review Board by Danish law. Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. Trial registration number NCT03456206; Post-results.
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Aims Our earlier studies revealed the cardio-protective effects of oleic acid, a monounsaturated fatty acid, against adrenaline induced myocardial injury. Moreover, it has been found to possess antioxidant properties. Thus, in the present study we have investigated the protective role of oleic acid on adrenaline induced mitochondrial dysfunction in vitro in rat heart mitochondria. Main methods Isolated rat cardiac mitochondria was incubated in vitro with adrenaline-bitartrate alone and with graded doses of oleic acid. Biomarkers of oxidative stress, mitochondrial Krebs cycle enzymes and respiratory chain enzymes along with mitochondrial morphology, membrane potential as well as intactness were analyzed. Isothermal titration calorimetric studies with pure adrenaline and oleic acid was also carried out. Key findings Incubation with adrenaline, in vitro, showed elevated levels of lipid peroxidation and protein carbonylation of mitochondrial membrane, a reduced level of glutathione content along with an altered profile of mitochondrial enzymes, morphology, membrane potential as well as intactness. All these changes were found to be ameliorated when cardiac mitochondria were co-incubated with adrenaline and oleic acid, in vitro. Significance Our earlier studies demonstrated the antioxidant properties of oleic acid. This study suggests that oleic acid binds adrenaline with high affinity gradual saturation of the binding sites of adrenaline. This prevents the generation of ROS and finally providing consequent protection of the cardiac mitochondria and ameliorating adrenaline induced mitochondrial dysfunction. Hence, oleic acid may be considered as a potent future cardio-protective antioxidant.
Thesis
La maladie d’Alzheimer (MA) est un problème majeur de santé publique. Elle se traduit par des atteintes de la mémoire reposant sur des dysfonctionnements synaptiques induits par les oligomères de peptide ß-amyloïde (Aß). Ceux-ci activent la phospholipase A2 cytosolique (cPLA2) qui libère l’acide arachidonique (ARA) des phospholipides (PL) membranaires neuronaux. L’acyl-CoA synthétase 4 (ACSL4) peut limiter cette libération en favorisant la réincorporation d’ARA dans les PL. Dans l’alimentation occidentale, il constitue une part croissante des apports lipidiques. Contrairement à l’acide docosahexaénoïque (DHA), l’influence de l’ARA dans la MA a été peu étudiée. C’est pourquoi nous avons étudié la mobilisation de l’ARA et son effet sur la sensibilité au peptide Aß. Nous avons montré dans un premier temps qu’un apport alimentaire en ARA affecte la mémoire à court terme et sensibilise les capacités d’apprentissage au peptide Aß. Ces altérations sont associées à des diminutions d’expression des récepteurs AMPA et de l’ACSL4, une prolifération astrocytaire et une incorporation accrue en ARA dans les espèces de PL phosphatidylsérine et phosphatidyléthanolamine (PE). D’autre part, la différenciation des cellules HT22 nous a permis de montrer que l’ACSL4 intervient dans l’incorporation de l’ARA et dans l’équilibre ARA/DHA, notamment dans les espèces PE. Cela indique qu’un excès en ARA dans l’alimentation peut constituer un facteur d’aggravation de la MA et que les enzymes assurant sa mobilisation, comme la cPLA2 et l’ACSL4, peuvent moduler ce risque. La caractérisation de leurs niveaux d’expression pourrait permettre de définir des groupes d’individus à risque vis-à-vis de la MA
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Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.
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Data concerning the anti-inflammatory effect of dietary n-3 polyunsaturated fatty acids (PUFAs) in patients with ulcerative colitis (UC) are inconsistent. Salmon fillet contains n-3 PUFAs and bioactive peptides that may improve its effects compared to fish oil alone. We assessed the efficacy of a salmon-rich diet in patients with mild ulcerative colitis. An 8-week intervention pilot study was designed to assess the effects of 600 grams Atlantic salmon consumption weekly in 12 UC patients. Simple clinical colitis activity index (SCCAI), a dietary questionnaire, sigmoidoscopy, selected serum inflammatory markers, fecal calprotectin, and plasma and rectal biopsy fatty acid profiles were assessed before and after intervention. The levels of C20:4n-6 arachidonic acid in biopsies after dietary intervention were correlated with histology and endoscopy scores. The concentrations of n-3 PUFAs, C20:5n-3 eicosapentaenoic acid, C22:6n-3 docosahexaenoic acid, and the n-3/n-6 ratio increased in plasma and rectal biopsies. The anti-inflammatory fatty acid index (AIFAI) increased both in biopsies and plasma accompanied with a significantly reduced SCCAI. Based on evidence of SCCAI and AIFAI and a tendency of decreased levels of CRP and homocysteine, intake of Atlantic salmon may have beneficial effects on disease activity in patients with mild ulcerative colitis.
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Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. High protein intake is associated with an increased risk of incident IBD in French middle-aged women.
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Diet and nutritional status are among the most important modifiable determinants of human health. The nutritional value of food is influenced in part by a person's gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology, and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial, and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized and reproduced much of the bacterial diversity of the donor's microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat, high-sugar "Western" diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle "clinical trials" that test the effects of environmental and genetic factors on the gut microbiota and host physiology. Nearly full-length 16S rRNA gene sequences are deposited in GenBank under the accession numbers GQ491120 to GQ493997.
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Soya isoflavones: genistein and daidzein are increasingly consumed in Western countries. Their beneficial effects are discussed considering nutrition and health in Asia. The present study aimed to check whether chronic ingestions, ethnic origin and dietary context can influence soya phyto-oestrogen bioavailability. Two prospective trials were carried out to blindly assess the pharmacokinetics after acute and chronic intake of soya-based cheese (45.97 (sd1.57) mg isoflavones) taken once a day for 10 d. Twelve healthy young Asians immersed for 2 months in France were randomised in a cross-over design to compare the influence of a Western v. Asian dietary context. The second trial partly nested in the first one, compared Asians under the Western diet to twelve healthy young male Caucasians under the same diet. All volunteers were non-equol producers. After an acute intake of soya in Western diet, Asians exhibited higher maximum concentration measured in plasma (Cmax) and area under the plasma concentration-time curve (AUC) for genistein and daidzein than Caucasians (P = 0.005, 0.006, 0.032 and 0.008, respectively). In Caucasians under Western diet, AUC and Cmax values significantly increased after chronic intake. This was not the case for daidzein in Asians whatever the dietary context. For the first time, it is evidenced that on acute intake of soya cheese, Asians absorb soya phyto-oestrogens better than Caucasians, regardless of whether the background diet is Western or Asian. On chronic ingestions, AUC and Cmax values were increased for daidzein and genistein in Caucasians but not in Asians. There are ethnic differences in isoflavone pharmacokinetic and bioavailability. This may influence health outcomes.
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In spite of growing evidence indicating the benefits of probiotics, the effects of different dietary oils on intestinal microflora and probiotics have not been elucidated. This study aimed to examine the effects of different dietary oils on intestinal microflora in an experimental model of colitis. Eight-week mice were fed isocaloric diets varying only in fat composition for 4 weeks. The oils used were fish oil, canola oil, safflower oil, and chow diet containing beef tallow. Colitis was induced by intracolonic administration of acetic acid on day 21. The inflammation and fecal microflora and serum lipid profiles were evaluated 1 week after induction. Inflammation was highest in the chow diet group followed by safflower, canola, and fish oil fed groups, respectively. The number of fecal bacteroideceae was greater, whereas the number of fecal bifidobacteria was lower in mice fed beef tallow than the other ones. In addition, fish oil reduced the plasma level of triacylglycerole significantly. Polyunsaturated fatty acids (PUFAs) can affect intestinal microflora increasing the number of probiotics. PUFAs might be recommended in addition to probiotics for the prevention and/or maintenance treatment of colitis.
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In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown. To investigate the specificities of these antibodies mucosal immunoglobulins were isolated from washings taken at endoscopy from 21 control patients with irritable bowel syndrome, 10 control patients with intestinal inflammation due to infection or ischaemia, and 51 patients with IBD: 24 Crohn's disease (CD, 15 active, nine quiescent), 27 ulcerative colitis (UC, 20 active, seven inactive). Total mucosal IgG was much higher (p < 0.001) in active UC (median 512 micrograms/ml) and active CD (256 micrograms/ml) than in irritable bowel syndrome controls (1.43 micrograms/ml), but not significantly different from controls with non-IBD intestinal inflammation (224 micrograms/ml). Mucosal IgG bound to proteins of a range of non-pathogenic commensal faecal bacteria in active CD; this was higher than in UC (p < 0.01); and both were significantly greater than controls with non-IBD intestinal inflammation (CD p < 0.001, UC p < 0.01) or IBS (p < 0.001 CD and UC). This mucosal IgG binding was shown on western blots and by enzyme linked immunosorbent assay (ELISA) to be principally directed against the bacterial cytoplasmic rather than the membrane proteins. Total mucosal IgA concentrations did not differ between IBD and controls, but the IgA titres against faecal bacteria were lower in UC than controls (p < 0.01). These experiments show that there is an exaggerated mucosal immune response particularly in active CD but also in UC directed against cytoplasmic proteins of bacteria within the intestinal lumen; this implies that in relapse of IBD there is a breakdown of tolerance to the normal commensal flora of the gut.
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It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe. For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition. Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age. The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.
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The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them. To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls. Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods. A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD. An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.
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Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.
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The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3-7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1-12.9)), protein (OR 3.00 (95% CI 1.25-7.19)), and alcohol (OR 2.71 (95% CI 1.1-6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19-6.4)) or sulphate (OR 2.6 (95% CI 1.08-6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.
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Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a role in the regulation of intestinal inflammation and is activated by both natural (polyunsaturated fatty acid; PUFAs) and synthetic (troglitazone) ligands. The fatty acid content of defined formula diets may play a role in mediating the antiinflammatory effect, but the mechanism is unclear. We evaluated to what extent the effect of PUFAs on intestinal inflammation is mediated via PPARgamma. The human enterocyte-like cell line Caco-2 and human dendritic cells were stimulated by interleukin (IL) 1beta and lipoprotein polysaccharide, respectively, in the presence of PPARgamma agonists (troglitazone or PUFAs) or antagonist (GW9662). Five PUFAs were tested: alpha-linolenic acid (ALA), conjugated linoleic acid (CLA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA). Cytokine production was measured by enzyme-linked immunosorbent assay and PPARgamma, I-kappaB, and inducible nitric oxide synthase (iNOS) expression by Western blot. In Caco-2 cells, IL-6 secretion was significantly decreased by troglitazone, DHA, EPA, and GLA. IL-8 production was significantly decreased by troglitazone, ALA, DHA, EPA, and GLA. PPARgamma expression was significantly increased by troglitazone, DHA, and EPA. iNOS expression was significantly decreased by troglitazone, DHA, and EPA. Troglitazone and PUFAs at 0.1 mumol/L tended to increase the expression of I-kappaB. Addition of GW9662 reversed the effect of troglitazone and PUFAs at 0.1 mumol/L on IL-8 production and decreased the expression of PPARgamma. EPA and DHA also modulated the dendritic cell response to lipoprotein polysaccharide. The tested PUFAs exerted an antiinflammatory effect in vitro in both models. This effect of PUFAs in Caco-2 cells is similar to that of troglitazone on intestinal inflammation mediated by PPARgamma, and the potency of the antiinflammatory effect is linked to the number of double bonds.
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Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohn's disease (CD) and ulcerative colitis (UC) are limited and conflicting. We conducted a prospective study of women enrolled in the Nurses' Health Study cohorts. Diet was prospectively ascertained every 4 years using a validated semi-quantitative food frequency questionnaire. Self-reported CD and UC were confirmed through medical record review. We examined the effect of energy-adjusted cumulative average total fat intake and specific types of fat and fatty acids on the risk of CD and UC using Cox proportional hazards models adjusting for potential confounders. Among 170 805 women, we confirmed 269 incident cases of CD (incidence 8/100 000 person-years) and 338 incident cases of UC (incidence 10/100 000 person-years) over 26 years and 3 317 338 person-years of follow-up. Cumulative energy-adjusted intake of total fat, saturated fats, unsaturated fats, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were not associated with risk of CD or UC. However, greater intake of long-chain n-3 PUFAs was associated with a trend towards lower risk of UC (HR 0.72, 95% CI 0.51 to 1.01). In contrast, high long-term intake of trans-unsaturated fatty acids was associated with a trend towards an increased incidence of UC (HR 1.34, 95% CI 0.94 to 1.92). A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC.
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Background: N-3 polyunsaturated fatty acids (PUFA) are considered important pharmaconutrients for modulating mucosal immunity and therapeutic responses in patients with inflammatory bowel disease (IBD). We investigated the influence of diet therapy involving the use of an "n-3 PUFA food exchange table" (n-3DP) on the fatty acid composition of the erythrocyte membranes of IBD patients and its remission-maintaining effects. Methods: We analyzed the fatty acid composition of the erythrocyte membrane before and after n-3DP intervention in 20 initial-onset IBD patients who had not undergone any dietary intervention. We then analyzed it again and evaluated disease activity after 12-18 months intervention in 230 IBD patients (168 ulcerative colitis, 62 Crohn's disease; follow-up group) in whom n-3DP was introduced after remission had been achieved. The follow-up group was divided into remission and relapse groups. Results: In the 20 initial-onset patients, the mean n-3/n-6 ratio significantly increased after intervention (0.41 ± 0.16 versus 0.70 ± 0.20; P < 0.001). In the follow-up group the ratio in the remission group (n = 145) was significantly higher than that in the relapse group (n = 85) (0.65 ± 0.28 versus 0.53 ± 0.18; P < 0.001). The ratio significantly decreased in those who suffered a relapse after the beginning of treatment (P < 0.01). Conclusions: N-3DP significantly increased the erythrocyte membrane n-3/n-6 ratio in IBD patients, and this ratio was significantly higher in the remission group, suggesting that n-3DP alters the fatty acid composition of the cell membrane and influences clinical activity in IBD patients.
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To evaluate the role of dietary factors in the etiology of inflammatory bowel disease (IBD), we conducted a multicenter hospital-based case-control study in a Japanese population. Cases were IBD patients aged 15 to 34 years [ulcerative colitis (UC) 111 patients; Crohn's disease (CD) 128 patients] within 3 years after diagnosis in 13 hospitals. One control subject was recruited for each case who was matched for sex, age, and hospital. A semiquantitative food frequency questionnaire was used to estimate preillness intakes of food groups and nutrients. All the available control subjects (n = 219) were pooled, and unconditional logistic models were applied to calculate odds ratios (ORs). In the food groups, a higher consumption of sweets was positively associated with UC risk [OR for the highest versus lowest quartile, 2.86; 95% confidence interval (CI), 1.24 to 6.57], whereas the consumption of sugars and sweeteners (OR, 2.12; 95% CI, 1.08 to 4.17), sweets (OR, 2.83; 95% CI, 1.38 to 5.83), fats and oils (OR, 2.64; 95% CI, 1.29 to 5.39), and fish and shellfish (OR, 2.41; 95% CI, 1.18-4.89) were positively associated with CD risk. In respect to nutrients, the intake of vitamin C (OR, 0.45; 95% CI, 0.21 to 0.99) was negatively related to UC risk, while the intake of total fat (OR, 2.86; 95% CI, 1.39 to 5.90), monounsaturated fatty acids (OR, 2.49; 95% CI, 1.23 to 5.03) and polyunsaturated fatty acids (OR, 2.31; 95% CI, 1.12 to 4.79), vitamin E (OR, 3.23; 95% CI, 1.45 to 7.17), and n-3 (OR, 3.24; 95% CI, 1.52 to 6.88) and n-6 fatty acids (OR, 2.57; 95% CI, 1.24 to 5.32) was positively associated with CD risk. Although this study suffers from the shortcoming of recall bias, which is inherent in most retrospective studies (prospective studies are warranted to confirm the associations between diet and IBD risk), the present findings suggest the importance of dietary factors for IBD prevention.
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Aspirin has detrimental effects on the gastrointestinal tract mucosa and may play a role in the aetiology of inflammatory bowel disease. To investigate if the regular use of aspirin is associated with the development of Crohn's disease (CD) and ulcerative colitis (UC) using, for the first time, a prospective cohort study design. A total of 135,780 men and women in Europe, aged 30-74years, were recruited into the European Prospective Investigation into Cancer and Nutrition study. Participants completed questionnaires at baseline detailing their regular aspirin use and were then followed up to identify those who developed either incident CD or UC. Each case was matched with four controls and odds ratios (OR) were calculated, adjusting for cigarette smoking. Potential interactions between aspirin and smoking were assessed. A total of 35 participants developed CD and a further 84 were diagnosed with UC. Regular aspirin intake was positively associated with the risk of developing CD (OR=6.14, 95% CI=1.76-21.35). In those who took aspirin and smoked there was no detectable increased risk of CD (OR=0.30, 95% CI=0.03-3.08). No association was found between regular aspirin use and UC (OR=1.29, 95% CI=0.67-2.46). A strong positive association between regular aspirin use and CD, but not UC, was observed. The data suggest that regular aspirin use should be measured in epidemiological work on CD. If such findings are consistent in other work then aspirin may affect the development of CD in a middle-aged to elderly population.
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The development of gallstones is influenced by obesity and alcohol. This study aimed to precisely quantify these risks and investigate whether the aetiological mechanism may involve serum lipids, for the first time using a European prospective cohort study. The European Prospective Investigation into Cancer-Norfolk, recruited 25 639 men and women, aged 40 to 74 years, between 1993 and 1997. At enrolment weight, height and alcohol intake were recorded and nonfasting blood samples taken to measure serum triglycerides, cholesterol, high-density lipoproteins and low-density lipoproteins. The cohort was monitored for 14 years for symptomatic gallstones. Cox regression estimated sex-specific hazard ratios (HRs) for symptomatic gallstones adjusted for covariates. Symptomatic gallstones developed in 296 people (67.9% women). For each additional unit of BMI, the HR in men was 1.08 [95% confidence interval (CI)=1.02-1.14]; in women the HR was 1.08 (95% CI=1.06-1.11). Every unit of alcohol consumed per week decreased risk in men by 3% (HR=0.97, 95% CI=0.95-0.99) with no effect in women. Serum triglycerides increased risk in men (highest vs. lowest quarter HR=2.02, 95% CI=1.03-3.98) and women (HR=2.43, 95% CI=1.52-3.90). Increased high-density lipoprotein was associated with a decreased risk in men (highest vs. lowest quarter HR=0.22, 95% CI=0.09-0.52) and women (HR=0.55, 95% CI=0.36-0.85). No effects were found for serum cholesterol and low-density lipoprotein. Obesity and alcohol influence gallstone formation, possibly in part through their effects on serum lipids. Reducing obesity may prevent gallstones in the population, as 38% of incident cases of gallstones were associated with a BMI of more than 25.
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Dietary arachidonic acid, an n-6 polyunsaturated fatty acid (n-6 PUFA), might be involved in the etiology of ulcerative colitis (UC). We performed a prospective cohort study to determine whether high levels of arachidonic acid in adipose tissue samples (which reflects dietary intake) are associated with UC. We analyzed data collected from 57,053 men and women in the EPIC-Denmark Prospective Cohort Study from 1993 to 1997. Adipose tissue biopsy samples were collected from gluteal regions at the beginning of the study, the cohort was monitored over subsequent years, and participants who developed UC were identified. A subcohort of 2510 randomly selected participants were used as controls. Concentrations of arachidonic acid were measured in adipose tissue samples. In the analysis, arachidonic acid levels were divided into quartiles; relative risks (RR) were calculated and adjusted for smoking, use of aspirin and nonsteroidal anti-inflammatory drugs, and levels of n-3 PUFAs. A total of 34 subjects (56% men) developed incident UC at a median age of 58.8 years (range, 50.0-69.0 years). Those in the highest quartile for arachidonic acid concentrations in adipose tissue had an RR for UC of 4.16 (95% confidence interval [CI]: 1.56-11.04); a trend per 0.1% increase in arachidonic acid of 1.77 in RR was observed (95% CI: 1.38-2.27). The fraction attributed the highest levels of arachidonic acid was 40.3%. Individuals with the highest relative concentrations of arachidonic acid in adipose tissue have a significantly greater risk of developing UC. Dietary modifications might therefore prevent UC or reduce disease symptoms.
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The aetiology of ulcerative colitis (UC) is largely unknown, although it is plausible that dietary n-3 polyunsaturated fatty acids (PUFAs) may be protective. Metabolites derived from n-3 PUFAs are less proinflammatory than those from n-6 PUFAs. Earlier, no prospective cohort studies have investigated this hypothesis, using dietary information collected from food diaries. The aim of this study was to investigate the total dietary intake of n-3 PUFAs and the specific n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the risk of developing incident UC. Twenty-five thousand six hundred and thirty-nine participants, living in Norfolk UK, aged 45-74 years (median age at recruitment of 59.2 years), completed 7-day food diaries. These were interpreted using a computer programme, which converted food items into nutrients, including n-3 PUFAs. The cohort was monitored for participants who developed UC. Each case was matched with four controls and an analysis performed using conditional logistic regression. In the cohort, 22 incident cases of UC were identified after a median follow-up time of 4.2 years (range 1.8-8.3 years). A statistically significant protective odds ratio (OR) for the trend across tertiles was found for DHA [OR = 0.43, 95% confidence interval (CI)=0.22-0.86, P = 0.02] and borderline statistically significant differences for trends for total total n-3 PUFAs (OR = 0.56, 95% CI=0.28-1.13, P = 0.10) and EPA (OR = 0.53, 95% CI=0.27-1.03, P = 0.06) after adjusting for age, sex, total energy intake, smoking, and other fatty acids. Total dietary n-3 PUFAs, EPA, and DHA, particularly DHA were associated with protection from UC in a cohort aged over 45 years. If the association is causal, then increasing the population's intake of n-3 PUFAs from oily fish may help prevent UC.
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Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and are increased in the mucosa of patients with ulcerative colitis. The aim of this investigation was to conduct the first prospective cohort study investigating if a high dietary intake of linoleic acid increases the risk of developing incident ulcerative colitis. Dietary data from food frequency questionnaires were available for 203 193 men and women aged 30-74 years, resident in the UK, Sweden, Denmark, Germany or Italy and participating in a prospective cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). These participants were followed up for the diagnosis of ulcerative colitis. Each case was matched with four controls and the risk of disease calculated by quartile of intake of linoleic acid adjusted for gender, age, smoking, total energy intake and centre. A total of 126 participants developed ulcerative colitis (47% women) after a median follow-up of 4.0 years (range, 1.7-11.3 years). The highest quartile of intake of linoleic acid was associated with an increased risk of ulcerative colitis (odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.23 to 5.07, p = 0.01) with a significant trend across quartiles (OR = 1.32 per quartile increase, 95% CI = 1.04 to 1.66, p = 0.02 for trend). The data support a role for dietary linoleic acid in the aetiology of ulcerative colitis. An estimated 30% of cases could be attributed to having dietary intakes higher than the lowest quartile of linoleic acid intake.
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Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that regulates intestinal inflammation. PPAR gamma is highly expressed in the colon and can be activated by various dietary ligands. A number of fatty acids such as polyunsaturated fatty acids or eicosanoids are considered as endogenous PPAR gamma activators. Nevertheless, other nutrients such as glutamine, spicy food or flavonoids are also able to activate PPAR gamma. As PPAR gamma plays a key role in bacterial induced inflammation, anti-inflammatory properties of probiotics may be mediated through PPAR gamma. The aims of the present review are to discuss of the potential roles of dietary compounds in modulating intestinal inflammation through PPAR gamma.
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Prostaglandin E2 (PGE2) level in rectal mucosa excised from 17 patients suffering from ulcerative colitis was 2-fold higher than that found in rectal mucosa of 17 normal subjects: 2.0 +/- 0.4 and 0.9 +/- 0.2 ng per mg of wet tissue, respectively. Accumulation of PGE 2 in 24-hr cultures of rectal mucosa specimens obtained from patients with ulcerative colitis was 112% higher than that observed in cultures from control subjects. Addition of sulfasalazine, sulfapyridine, and 5-aminosalicylic, acid to the culture medium of ulcerative colitis mucosa resulted in inhibition of PGE2 production by 34, 32, and 62%, respectively, compared to rectal specimens cultured in drug-free medium. These results suggest that PGE may mediate the inflammatory response in ulcerative colitis and that some of the therapeutic effect of sulfasalazine and its constituents are related to the inhibition of PGE synthesis.
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A relationship between not smoking and ulcerative colitis has been examined in all English reports. This paper evaluates the ulcerative colitis/nonsmoking and the Crohn's disease/smoking association by meta-analysis and against causality criterion for chronic diseases. A review of the literature, meta-analysis of selected studies, and assessment of causality criterion all suggest that not smoking and ulcerative colitis and smoking and Crohn's disease are consistent with a causal relationship. It is not inconceivable that tobacco may contain some substance beneficial to ulcerative colitis patients. Identification of the specific product in tobacco producing a beneficial effect would be a prudent next step in the study of this association. In spite of the findings of this review and analysis, the author finds no justification for health care providers to change the Surgeon General's recommendations on smoking or tobacco use for ulcerative colitis patients specifically.
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The long chain fatty acid composition of phospholipids in colonic mucosa was determined by high performance liquid chromatography in nine patients with active ulcerative colitis and eight healthy controls. The arachidonic acid composition was 12.5 +/- 1.4 mol % (mean +/- 2 SEM) in the inflamed colonic mucosa from the patients with active ulcerative colitis and 6.8 +/- 1.2 mol % in the intact mucosa from healthy controls (p less than 0.001). In the inflamed colonic mucosa, oleic acid and palmitoleic acid were concomitantly decreased (p less than 0.001 and p less than 0.02, respectively), while docosahexaenoic acid was increased (p less than 0.05). Histopathological examination showed that there was a three fold increase in the cell density of inflammatory infiltrate in the lamina propria of the inflamed colonic mucosa (p less than 0.001). The cell density of inflammatory infiltrate correlated with the arachidonic acid composition of phospholipids in colonic mucosa (r = 0.89, p less than 0.005). These findings indicate that inflammation alters the long chain fatty acid composition of phospholipids in colonic mucosa. The observed increase in the arachidonic acid composition of phospholipids in inflamed colonic mucosa may contribute to the enhanced arachidonic acid metabolism in patients with active ulcerative colitis.
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Leukotriene B4, an arachidonic acid metabolite, is a potent chemotactic agent, and is thought to be an important mediator of inflammation. To investigate the role of this compound as a mediator of inflammation in inflammatory bowel disease, arachidonic acid was incubated with ionophore and colonic mucosa from patients with inflammatory bowel disease and from normal subjects. Mucosa from patients with inflammatory bowel disease converted 2.17% of exogenous arachidonate to leukotriene B4; mucosa from normal subjects converted 0.37%. The production of leukotriene was blocked by sulfasalazine. To determine if inflammatory bowel mucosa contained endogenous leukotriene B4, lipid extracts were analyzed by high pressure liquid chromatography. Mucosa from patients with inflammatory bowel disease contained 254 ng of leukotriene B4 per gram and mucosa from normal subjects contained less than 5 ng of leukotriene B4 per gram. The presence of significant amounts of leukotriene B4 in colonic mucosa in patients with inflammatory bowel disease, combined with the known biologic effects of leukotriene B4, suggests that it may be an important mediator of inflammation in inflammatory bowel disease.
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Delivery of 5-aminosalicylic acid to the colon by sulphasalazine, other azo-bonded compounds and controlled-release preparations is introduced in the context of metabolism by epithelial cells and therapeutic efficacy in ulcerative colitis. Potential modes of action are then reviewed, including actions on luminal bacteria, epithelial cell surface receptors, cellular events (such as nitric oxide release or butyrate oxidation), electrolyte transport and epithelial permeability. Evidence for an influence of salicylates on circulating and lamina propria inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic peptides and inflammatory mediators, such as eicosanoids, platelet-activating factor, cytokines or reactive oxygen metabolites. The precise mechanism will remain uncertain as long as the aetiology of ulcerative colitis is unknown, but a pluripotential mode of action of salicylates is an advantage when influencing the network of events that constitute chronic inflammation.
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Metabolites of arachidonic acid have been implicated in the pathophysiology of ulcerative colitis-they can stimulate intestinal secretion, increase mucosal blood flow, and influence smooth muscle activity. The influence on the mucosal transport function of culture medium in which colonic mucosal biopsy specimens had been incubated was investigated using rat stripped distal colonic mucosa in vitro as the assay system. Colonic tissue from patients with colitis and from control subjects was cultured. Medium from inflamed tissue contained more prostaglandin E2 (PGE2) and leukotriene D4 (LTD4) and evoked a greater electrical (secretory) response in rat colonic mucosa than control tissue medium. In inflamed tissue, cyclo-oxygenase inhibition (indomethacin) attenuated PGE2 but increased LTD4 production; conversely lipoxygenase inhibition (ICI 207968) inhibited LTD4 production but enhanced PGE2 output. Each inhibitor alone enhanced the electrical response in the rat colon. Inhibition of both enzymes (indomethacin plus ICI 207968) caused a fall in both PGE2 (82%) and LTD4 (89%) production and in the electrical response (57%). Inflamed tissue treated with a phospholipase A2 inhibitor (mepacrine) produced less PGE2, LTD4, and electrical responses when compared with inflamed tissue, either untreated (91%, 92%, and 79% respectively) or treated with cyclo-oxygenase and lipoxygenase inhibition. Incubation with bradykinin stimulated eicosanoid release and electrical response, while a bradykinin antagonist caused a modest inhibition. Analysis of these observations suggests that a combination of arachidonic acid derivatives accounts for about half the secretory response. Other products of phospholipase A2 activity are probably responsible for much of the remainder, leaving up to 20% the result of types of mediator not determined in this study.
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Dietary factors have been considered as a possible risk factor for ulcerative colitis (UC). However, available data are inconsistent. The aim of the present study was to evaluate the etiological role of dietary factors in the development of UC. Recently diagnosed (<6 Months) UC patients (n = 43) and age- and gender-matched population controls (n = 43) were studied in a case-control design. The crosscheck dietary history method was used to assess dietary intake of 5 yr before the study. Adipose tissue fatty acid composition was used as a biomarker of long-term fat intake. Conditional logistic regression-derived odds ratios (OR), and 95% confidence intervals (CI) were used for statistical analysis. Dietary intake ORs were adjusted for energy intake. High intakes of monounsaturated fat (OR: 33.9 [95% CI 2.6-443.1]), polyunsaturated fat (OR: 5.1 [95% CI 1.0-26.7]), and vitamin B6 (OR: 6.9 [95% CI 1.6-30.7]) were associated with an increased risk to develop UC. No other significant associations were found with UC risk. High intakes of mono- and polyunsaturated fat and vitamin B6 may enhance the risk of developing UC. Whether this observation is a true risk factor in the development of UC or rather a reflection of a certain dietary lifestyle needs to be investigated.
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