Punyanganie S. de Silva

Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease

Introduction Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohns disease (CD) and ulcerative colitis (UC) are limited and conflicting. Methods 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. Results 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). Conclusions 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.

Older age is associated with higher rate of discontinuation of anti‐TNF therapy in patients with inflammatory bowel disease

Background:In increasingly aging populations, awareness of outcomes of older patients treated with biologics is becoming more important. However, few studies to date have investigated the safety and durability of anti-tumor necrosis factor (TNF) therapy in this subgroup. Methods:This was a retrospective single-center study with cases comprising all IBD patients who began anti-TNF treatment at age >60 years. Cases of Crohns disease (CD) and ulcerative colitis (UC) were identified from medical record review. Our controls consisted of patients younger than age 60 years on anti-TNF treatment and patients >60 years on treatment with immunomodulators. Kaplan–Meier survival estimates were used to calculate the probability of remaining on anti-TNF therapy. Results:We identified a total of 54 IBD patients who initiated anti-TNF therapy over the age of 60 years (mean 73, range 61–97 years). Among these, a total of 38 patients (70%) discontinued anti-TNF therapy after a mean of 24.1 months. At 12 months after initiation, 75% of patients older than age 60 years were still on anti-TNF agents compared to 93% among younger users and 82% among older AZA users (P < 0.05). Compared to older AZA users, older anti-TNF users remained more likely to require early therapy cessation (hazard ratio 2.21, 95% confidence interval 1.29–3.78). Conclusions:The IBD population older than age 60 at the time of initiation of anti-TNF therapy is at higher risk for discontinuation of therapy. They may also be particularly vulnerable to infectious complications requiring hospitalization, suggesting the need for careful monitoring during therapy.

An Association Between Dietary Arachidonic Acid, Measured in Adipose Tissue, and Ulcerative Colitis

BACKGROUND & AIMS 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. METHODS 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. RESULTS 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%. CONCLUSIONS 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.

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

Introduction 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. Methods 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. Results 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). Conclusion 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.

Transition of the Patient with IBD from Pediatric toAdult Care—An Assessment of Current Evidence

Abstract:Inflammatory bowel disease is a chronic disease of remitting and relapsing nature that is increasingly diagnosed in childhood or adolescence. The importance of the transition from pediatric to adult health care is increasingly recognized, yet the preparation of patient and family before transfer and early subsequent care in the adult health care environment can be variable and challenging. Pediatric providers need to start early and prepare patients in a stepwise fashion. However, patients may not have mastered all the steps before transfer or may regress to earlier behaviors during stress. Thus, adult providers will need to understand how to maintain and finish the transition process. This is an updated literature review of the transition process in inflammatory bowel disease, which focuses on the practical ways that both pediatric and adult health care providers can optimize care.

Folic acid deficiency optic neuropathy: A case report

IntroductionNutritional optic neuropathies are uncommon and can be associated with gradual visual loss and optic atrophy or sudden vision loss and optic disc swelling.Case presentationA 44-year-old woman presented with a 4-week history of progressive visual loss and was noted to have bilateral retrobulbar optic neuropathy. No other clinical abnormality was noted. Investigations revealed severe folate deficiency with normal vitamin B12 levels. Her alcohol and tobacco consumption was moderate and subsequent correction of folate levels with oral supplementation has led to improvement in her visual acuity.ConclusionThis case highlights an unusual presentation of folic acid deficiency that may present to the general physician.

High Dietary Intake of Specific Fatty Acids Increases Risk of Flares in Patients With Ulcerative Colitis in Remission During Treatment With Aminosalicylates

BACKGROUND & AIMS: Dietary factors may have a significant role in relapse of disease among patients with ulcerative colitis (UC). However, the relationship between diet and UC is inadequately understood. We analyzed data from the diet’s role in exacerbations of mesalamine maintenance study to determine whether dietary factors affect the risk of disease flares in patients with UC. METHODS: We performed a prospective, multicenter, observational study of 412 patients, from 25 sites, with UC in remission during monotherapy with an aminosalicylate. Patients completed a validated food frequency questionnaire at enrollment and were followed for 12 months. We analyzed the relationship between diet and disease remission or flare for groups of macronutrients and micronutrients, and food groups previously associated with an increased risk of flare. RESULTS: Forty‐five patients (11%) had a UC relapse within 1 year of study enrollment. When analyzed in tertiles, increasing intake of multiple fatty acids was associated with increasing odds of relapse. In multivariable logistic regression analysis, only myristic acid (odds ratio, 3.01; 95% confidence interval, 1.17–7.74) maintained this dose–response relationship. Other foods previously implicated in flares of UC, such as processed meat, alcohol, and foods high in sulfur, were not associated with an increased risk of flare. CONCLUSIONS: In a prospective study of more than 400 patients with UC undergoing treatment with aminosalicylates, we associated high dietary intake of specific fatty acids, including myristic acid (commonly found in palm oil, coconut oil, and dairy fats) with an increased risk of flare. These findings can help design interventional studies to evaluate dietary factors in UC.

100 Dietary Oleic Acid Protects Against the Development of Ulcerative Colitis – A UK Prospective Cohort Study Using Data From Food Diaries

Introduction Dietary factors, including fatty acids, may be involved in the aetiology of ulcerative colitis (UC). Oleic acid (C18:1 cis 9), an n-9 monounsaturated fatty acid (n-9 MUFA) is found in high amounts in olive and grapeseed oils and inhibits the formation of pro-inflammatory metabolites which are found in high concentrations in the mucosa of patients with UC. The aim of this study was to investigate, for the first time in a prospective cohort study, the effect of dietary oleic acid on the risk of ulcerative colitis. Methods A total of 25 639 men and women aged 40–74 years, from general practices in Norfolk UK, were recruited into EPIC-Norfolk (European Prospective Investigation Into Cancer). At baseline, participants completed detailed 7-day food diaries. These were interpreted by nutritionists, using DINER a specifically designed computer programme containing information on the nutrient content of 9000 food items. The cohort was monitored for participants who subsequently developed incident ulcerative colitis. Each case was matched for age and sex with four controls. Conditional logistic regression was used to calculate the odds ratios for oleic acid and the risk of ulcerative colitis, adjusted for cigarette smoking and also n-3 and n-6 PUFAs which influence the inflammatory process. Results In the cohort, 22 participants (45% women) developed incident ulcerative colitis after a median follow-up time of 3.9 years (range 1.8–8.3 years). The extent of the inflammation was left-sided, up to the splenic flexure, in 47% of patients. The highest tertile of dietary oleic acid intake was associated with an odds ratio for UC of 0.11 (95% CI 0.01 to 0.87) with a statistically significant protective trend across tertiles (OR 0.33, 95% CI 0.12 to 0.93, p=0.04). The attritutable fraction, the proportion of cases of UC due to the lower intakes of oleic acid, was 46%. Conclusion The dietary intake of oleic acid was negatively associated with the development of UC. If this is a causal association, then increasing the dietary intake of oleic acid may prevent UC. Oleic acid supplementation could be a possible treatment for patients with this illness.

Association of urinary phenolic compounds, inflammatory bowel disease and chronic diarrheal symptoms: Evidence from the National Health and Nutrition Examination Survey

Endocrine disruptors such as phenolic compounds and parabens may be involved in chronic non-infective disease. While products incorporating these compounds are extensively utilized in consumer and personal products, little is known about their effect on bowel health. Inflammatory bowel disease (IBD) - consisting of the diseases ulcerative colitis and Crohns disease - and irritable bowel syndrome are common chronic non-infectious diarrheal diseases. Despite limited knowledge on the etiology of IBD, these diseases have increased prevalence in industrialized countries and cause significant impairment to quality of life. In the present study we examine relationships between urinary environmental phenolic compounds, chronic diarrhea and inflammatory bowel disease. Data was obtained from the 2005-2010 US National Health and Nutrition Examination Survey (NHANES) including demographics, lifestyle factors, self-reported health conditions, inflammatory markers and urinary phenolic chemical concentrations. Only participants with complete environmental phenols & parabens component were included in our analysis. Chronic diarrheal symptoms were determined by using the 2009-2010 NHANES questionnaire which included questions pertaining to bowel health. We utilized chronic bowel leakage symptoms as a surrogate marker for chronic diarrhea. The presence of IBD was also analyzed from 2009 to 2010 NHANES data, as a sub-analysis for arthropathy directly querying the presence or absence of IBD. Among the subset of 5218 American adults aged 20-80 years in the NHANES study period who completed environmental phenols & parabens component, 25.5% reported chronic diarrheal symptoms. Abnormal markers of inflammation were present in 2200 (42.2%) of respondents. For IBD, 19 individuals with arthropathy confirmed a diagnosis of ulcerative colitis, and 1 person confirmed a Crohns diagnosis. After adjustment for demographics, inflammatory and subsample weighing; lower paraben levels were associated with chronic bowel leakage (diarrheal) symptoms. Higher 4-tert-octylphenol levels was significantly associated with ulcerative colitis. Further study of underlying mechanisms should be considered.

Sexual Dysfunction in Men With Inflammatory Bowel Disease: A New IBD-Specific Scale

Background Men with inflammatory bowel disease (IBD) may have increased sexual dysfunction. To measure the prevalence of sexual dysfunction in our male patients, we aimed to develop a new IBD-specific Male Sexual Dysfunction Scale (the IBD-MSDS). Methods We used a cross-sectional survey and enrolled male patients (N = 175) ≥18 years old who attended IBD clinics at 2 Boston hospitals. We collected information on sexual functioning via a 15-item scale. General male sexual functioning was measured using the International Index of Erectile Dysfunction (IIEF); the Patient Health Questionnaire (PHQ-9) measured depressive symptoms. Medical history and sociodemographic information were extracted from medical record review. Exploratory factor analyses (EFA) assessed unidimensionality, factor structure, reliability, and criterion and construct validity of the 15-item scale. We used regression models to identify clinical factors associated with sexual dysfunction. Results EFA suggested retaining 10-items generating a unidimensional scale with strong internal consistency reliability, α = 0.90. Criterion validity assessed using Spearmans coefficient showing that the IBD-MSDS was significantly correlated with all the subscales of the IIEF. The IBD-MSDS was significantly correlated (construct validity) with the PHQ-9 (P < 0.001) and the composite score for active IBD cases (P < 0.05). Male sexual dysfunction in IBD was significantly associated with the presence of an ileoanal pouch anastomosis (P = 0.047), depression (P < 0.001), and increased disease activity (P = 0.021). Conclusions We have developed and validated an IBD-specific scale to assess the psychosexual impact of IBD. This new survey tool may help physicians screen for and identify factors contributing to impaired sexual functioning in their male patients.