Some useful links

There is plenty of basic information on dietary therapy throughout the Internet. If you are interested in the latest medical findings you should consult the global database PUBMED of the medical publications. Below are examples of IBS-related studies:

PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study in patients with atrial fibrillation: Rationale, design and methods.

Changes in gut microbial metagenomic pathways associated with clinical outcomes after the elimination of malabsorbed sugars in an IBS cohort.

Specific diets to manage sugar malabsorption are reported to reduce clinical symptoms of irritable bowel syndrome (IBS). However, the effects of diets for malabsorbed sugars on gut microbiota signatures have not been studied, and associations with clinical outcomes in IBS have not been characterized. 22 IBS patients positively tested for either lactose-, fructose-, sorbitol- or combined malabsorptions were subjected to 2-weeks sugar elimination and subsequent 4-weeks re-introduction. 7 IBS patients tested negative for sugar malabsorption were used as controls. Nutrition and clinical symptoms were recorded throughout the study. Fecal samples were serially collected for 16S rRNA amplicon and shotgun-metagenome sequencing.Dietary intervention supervised by nutrition counseling reduced IBS symptoms during the elimination and tolerance phases. Varying clinical response rates were observed between subjects, and used to dichotomize our cohort into visual analogue scale (VAS) responders and non-responders. Alpha -and beta-diversity analyzes revealed only minor differences regarding 16S rRNA-based fecal microbiota compositions between responder and non-responder patients during baseline or tolerance phase. In shotgun-metagenome analyzes, however, we analyzed microbial metabolic pathways and found significant differences in pathways encoding starch degradation and complex amino acid biosynthesis at baseline between IBS controls and malabsorbers, and notably, between diet responder and non-responders. Faecalibacterium prausnitzii, Ruminococcus spp . and Bifidobacterium longum largely informed these metabolic pathways.Our study demonstrates that diet interventions for specific, malabsorbed carbohydrates reshaped the metagenomic composition of the gut microbiota, with a small community of bacterial taxa contributing to these changes rather than a single species.

KEYWORDS: Carbohydrate malabsorption, diet, irritable bowel syndrome, microbiome

All that a physician should know about FODMAPs.

A diet low in poorly absorbed, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is now considered as an effective strategy for symptoms control in patients with irritable bowel syndrome (IBS). The low FODMAP diet is administered in three phases, namely restriction of all dietary FODMAPs followed by rechallenge and then reintroduction of specific FODMAPs according to the tolerance of patients. A dietician should be involved in patients in whom a low FODMAP diet is planned. While restricting high FODMAPs, it is pertinent that patients are advised a well-balanced diet and suitable alternatives with low FODMAP contents in each food groups are prescribed. Strict adherence to a low FODMAP diet has been shown to improve symptoms, stool output, quality of life, and the overall well-being of patients with IBS. For those who do not respond to this dietary approach, a normal diet may be initiated and other treatment strategies (dietary or nondietary) should be considered. Interestingly, the low FODMAP diet has also been tried in other functional disorders, nonceliac gluten sensitivity, and even inflammatory bowel disease. Since the concept of FODMAP is relatively new, there is only limited data on the content of FODMAP in the Indian food items and there is a need to address this question. There is also a need for well-designed and adequately powered studies to explore the efficacy of low FODMAP diet in patients with IBS. In the present review article, we have compiled all the relevant information about FODMAPs with an objective to provide comprehensive information on FODMAPs to a physician.

KEYWORDS: Adherence, Balanced diet, FODMAP diet, Irritable bowel syndrome

Measuring Diet Intake and Gastrointestinal Symptoms in Irritable Bowel Syndrome: Validation of the Food and Symptom Times Diary.

Patients with irritable bowel syndrome (IBS) identify food as a trigger for the onset or worsening of gastrointestinal symptoms. Despite this, there is no published validated contemporaneous food and symptom diary to investigate the association between diet and IBS symptoms. The objective of this prospective observational study was to assess the construct validity of a novel food diary and symptom questionnaire, the Food and Symptom Times (FAST) diary, and the predictive validity of the food diary component with relation to fiber and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols consumption and subsequent gastrointestinal symptoms. Fifty-one participants with IBS completed the FAST diary and several legacy instruments. The relationship between the FAST gastroenterological symptoms and legacy instruments was examined using Spearman correlation coefficients. Further statistical analysis investigated the relationship between diet and postprandial gastrointestinal symptoms. Consistent with a priori predictions, the FAST symptoms showed moderate correlations with the most similar Patient-Reported Outcome Measurement Information System gastrointestinal scales and the most similar Gastrointestinal Symptom Rating Scale questions, with the exception of the weakly correlated subscale constipation for both instruments. The IBS-Quality of Life instrument showed moderate correlations with the FAST symptom abdominal swelling/distension. The consumption of a high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols meal was associated with participants with IBS-D experiencing abdominal bloating and participants with IBS-C not experiencing abdominal swelling. The consumption of fiber was correlated with abdominal fullness and bloating in participants with IBS-C. The FAST diary validly measures gastrointestinal symptoms as they occur in people with IBS and correlates these symptoms with specific aspects of diet.

Whole-exome sequencing identifies a homozygous pathogenic variant in TAT in a girl with palmoplantar keratoderma.

Palmoplantar keratoderma (PPK) is a defect in cornification that is characterized by progressive hyperkeratosis of palms and soles. Many phenotypes are linked with PPK, making exome-based diagnosis increasingly efficient. In this report, we identified tyrosinemia type II on whole-exome sequencing in a 7-year-old Syrian refugee that presented with PPK. Dietary therapy helped improve her overall symptoms.

KEYWORDS: PPK, Palmoplantar keratoderma

Irritable bowel syndrome and gut microbiota.

To provide an overview of recent studies exploring the gut microbiota in pathogenesis and treatment of irritable bowel syndrome (IBS). Primary bacterial gut disturbances have been linked to the development and severity of IBS. Dysbiosis, or alteration in the normal intestinal flora, modulates intestinal permeability, inflammation, gut motility and likely quality of life. These biomechanical changes are associated with enteric and central nervous system processing as well. When compared to healthy controls, IBS patients display poor quality of life measures and are at increased risk of depression and anxiety. The severity of psychological and gastrointestinal symptoms in IBS has been linked with a distinct intestinal microbiota signature. Efforts to modulate intestinal dysbiosis in IBS have shown little improvement in large systematic reviews. The low FODMAP diet reduces bacteria, such as Bifidobacterum and Actinobacteria. Although rifaximin improves symptoms, it may only stimulate a transient effect on the gut microbiota. Fecal microbiota transplant does not provide prolonged symptom relief in IBS. This review elucidates recent advances in IBS and the gut microbiota. Microbiota changes are one underlying factor in perpetuating global IBS symptoms. The opportunity to exploit this disturbance through treatment modalities requires further investigation.

Ketogenic Dietary Therapy Controversies for Its Second Century.

As the ketogenic diet approaches 100 years of continuous use, we reflect on its successes and consider new avenues of research for the next century. One controversial question is regarding whether ketogenic dietary therapies could be successful first-line treatments for epilepsy. Second, is it possible to mimic the mechanisms of action of ketogenic dietary therapy with a drug (eg, a tablet formulation)? A third controversy worthy of future study involves its expanded usage in adults with refractory epilepsy and its role in treating women of childbearing age. Finally, as flexible, alternative diets have recently become widely available, is it feasible and safe to have families and patients start ketogenic dietary therapy successfully on their own with limited medical supervision?

KEYWORDS: diet, epilepsy, fasting, ketogenic, ketosis

Improving type 2 diabetes mellitus glycaemic control through lifestyle modification implementing diet intervention: a systematic review and meta-analysis.

Type 2 diabetes mellitus represents a significant health problem. Many studies have reported that intensive nutritional intervention by itself or in addition to medications is the best method to improve glycaemic control in type 2 diabetes mellitus. However, in clinical practice, dietary education is not implemented as an integral part in the management of type 2 diabetes mellitus. The purpose of this systematic review and meta-analysis is to analyse the scientific evidence concerning the role of nutritional intervention in the glycaemic control of type 2 diabetes mellitus. We searched Pubmed, Scopus, Cochrane Library and Web of Science databases from inception till May 2019 for randomised controlled trials (RCTs) that include dietary interventions in the management of patients with type 2 diabetes mellitus. A total of 28 studies were included. Our results demonstrated that lifestyle interventions significantly lowered glycosylated haemoglobin levels compared to the usual care for patients with type 2 diabetes mellitus, overall weighted mean difference, WMD = - 0.51. Strategies combining individualized and group-based activities were the most effective, WMD = - 0.95. Most of stratified analyses did not totally resolve heterogeneity, but improvement in HbA 1c levels has been consistently observed. The available evidence from RCTs shows that lifestyle intervention is more effective than the standard care regarding the glycaemic control of type 2 diabetic patients, particularly when there is a weight loss. It is time to translate this evidence to the primary health care practice. The protocol of the present systematic review was registered in PROSPERO, registration number CRD42018090469.

KEYWORDS: Diet, Glycaemic control, Lifestyle intervention, Meta-analysis, Systematic review, Type 2 diabetes mellitus

Potassium citrate supplementation with ketogenic dietary therapy for drug-resistant epilepsy.

Development and validation of circulating CA125 prediction models in postmenopausal women.

Cancer Antigen 125 is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. We developed and validated linear and dichotomous circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, European Prospective Investigation into Cancer and Nutrition, the Nurses' Health Studies, and the New England Case Control Study. The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset and external validation datasets. The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

KEYWORDS: CA125, Early detection, Ovarian cancer, Postmenopausal, Prediction model

Masked bolus gluten challenge low in FODMAPs implicates nausea and vomiting as key symptoms associated with immune activation in treated coeliac disease.

In patients with coeliac disease, FODMAPs in gluten-containing foods, and participant anticipation of a harmful ('nocebo') effect, may contribute to acute symptoms after gluten challenge. To establish acute gluten-specific symptoms linked to immune activation in coeliac disease METHODS: We included 36 coeliac disease patients on a gluten-free diet receiving placebo in the RESET CeD trial. Double-blind, bolus vital wheat gluten and sham challenges low in FODMAPs were consumed 2 weeks apart. Assessments included daily Coeliac Disease Patient Reported Outcome (CeD PRO) symptom scores, adverse events and serum interleukin-2. Median CeD PRO score for nausea increased most. Apart from tiredness and headache, changes in other symptoms were small or absent. Only nausea increased significantly in occurrence with gluten. Without nausea, only tiredness and flatulence were common after gluten. Nausea and vomiting were the only adverse events more common with gluten than sham. Interleukin-2 was always below the level of quantitation at baseline, and after sham. Interleukin-2 was elevated after gluten in 97% of patients, and correlated with severity of nausea and occurrence of vomiting. Nausea and vomiting are relatively specific indicators of acute gluten ingestion, and correlate with immune activation. IBS-like symptoms without nausea are unlikely to indicate recent gluten exposure.

Effect of Structural Individual Low-FODMAP Dietary Advice vs. Brief Advice on a Commonly Recommended Diet on IBS Symptoms and Intestinal Gas Production.

A low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet has been recommended for irritable bowel syndrome (IBS) patients. This study compared the efficacy of two types of dietary advice: brief advice on a commonly recommended diet (BRD), and structural individual low-FODMAP dietary advice (SILFD). Patients with moderate-to-severe IBS were randomized to BRD or SILFD groups. Gastrointestinal symptoms, 7-day food diaries, and post-prandial breath samples were evaluated. The SILFD included identifying high-FODMAP items from the diary, replacing high-FODMAP items with low-FODMAP ones by choosing from the provided menu. The BRD included reducing traditionally recognized foods that cause bloating/abdominal pain and avoidance of large meals. Responders were defined as those experiencing a ≥30% decrease in the average of daily worst abdominal pain/discomfort after 4 weeks. Sixty-two patients, BRD or SILFD, completed the studies. Eighteen patients in SILFD vs. 9 in the BRD group fulfilled responder criteria. Global IBS symptom severity significantly improved and the number of high-FODMAP items consumed was significantly decreased after SILFD compared to BRD. Post-prandial hydrogen breath production after SILFD was significantly lower than was seen after BRD. SILFD was more effective than BRD. This advice method significantly reduced FODMAP intake, improved IBS symptoms, and lowered intestinal H 2 production.

KEYWORDS: dietary advice, food, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), irritable bowel syndrome, intestinal gas

Treatment of eosinophilic esophagitis with diets: an update.

Eosinophilic esophagitis (EoE) is a chronic inflammatory esophageal disease triggered and maintained predominantly by food antigens. It represents a unique form of non-IgE mediated food allergy, largely dependent upon delayed, cell-mediated hypersensitivity. First-line therapies for EoE consist on drugs with anti-inflammatory effect (mainly including topic steroids and proton pump inhibitors) and dietary therapy. An elimination diet that avoids the consumption of food triggers currently remains the only therapy targeting the cause of EoE. Currently, available food allergy tests are suboptimal to predict food triggers for EoE, especially in adult patients. Elemental diets consisting in exclusively feeding patients with amino acid-based formulas and empiric 6-food elimination diets have consistently shown the best efficacy rates. However, their high level of restriction and the need for multiple endoscopies have hampered their implementation in clinical practice. In contrast, studies on 6-food elimination diets have been instrumental to decipher the most common food triggers in patients with EoE, being milk, wheat/gluten, and egg involved in most of patients from the United States, Spain, and Australia. Hence less restrictive empiric schemes, such as a 4-food elimination diet (dairy, wheat/gluten cereals, egg, and legumes) or a 2-food elimination diet (dairy and milk/gluten) were lately developed with good efficacy rates. A step-up strategy may enhance patient uptake and promptly identify most responders to empiric diets with few food triggers This review updates the most relevant advances on dietary therapy for pediatric and adult patients with EoE.

Adherence to the 2018 WCRF/AICR cancer prevention guidelines and chronic lymphocytic leukemia in the MCC-Spain study.

Preventable risk factors for chronic lymphocytic leukemia (CLL) remain largely unknown. The aim of this study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and CLL, in the MCC-Spain case-control study. A total of 318 CLL cases and 1293 population-based controls were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on the 2018 recommendations for cancer prevention (on body fatness, physical activity, and diet) was constructed. We used logistic regression analysis adjusting for potential confounders. Individuals in the highest tertile of the WCRF/AICR score had an odds ratio for CLL of 1.25 compared with individuals with low adherence. Each point increment in the score was associated with an OR for CLL of 1.06. Analyses by severity of disease did not show significant heterogeneity of effects. Overall, our results do not support an association between the WCRF/AICR score and CLL, yet we might have been limited by statistical power and study design to detect modest associations. Further research, ideally with a prospective design, long follow-up, and including additional lymphoma subtypes, is warranted to confirm the impact of composite healthy lifestyle behaviors on lymphoma risk.

KEYWORDS: Case-control study, Chronic lymphocytic leukemia, Nutrition-based guidelines, WCRF/AICR 2018 recommendations

Intestinal Microbiota-Associated Metabolites: Crucial Factors in the Effectiveness of Herbal Medicines and Diet Therapies.

Although the efficacy of herbal medicines (HMs) and traditional Chinese medicines (TCMs) in human diseases has long been recognized, their development has been hindered in part by a lack of a comprehensive understanding of their mechanisms of action. Indeed, most of the compounds extracted from HMs can be metabolized into specific molecules by host microbiota and affect pharmacokinetics and toxicity. Moreover, HMs modulate the constitution of host intestinal microbiota to maintain a healthy gut ecology. Dietary interventions also show great efficacy in treating some refractory diseases, and the commensal microbiota potentially has significant implications for the high inter-individual differences observed in such responses. Herein, we mainly discuss the contribution of the intestinal microbiota to high inter-individual differences in response to HMs and TCMs, and especially the already known metabolites of the HMs produced by the intestinal microbiota. The contribution of commensal microbiota to the inter-individual differences in response to dietary therapy is also briefly discussed. This review highlights the significance of intestinal microbiota-associated metabolites to the efficiency of HMs and dietary interventions. Our review may help further identify the mechanisms leading to the inter-individual differences in the effectiveness of HM and dietary intervention from the perspective of their interactions with the intestinal microbiota.

KEYWORDS: drug interventions, gut microbiota, herbal medicines, inter-individual differences, metabolites, traditional Chinese medicines

Dietary Supplementation With the Ketogenic Diet Metabolite Beta-Hydroxybutyrate Ameliorates Post-TBI Aggression in Young-Adult Male Drosophila .

Traumatic brain injury (TBI), caused by repeated concussive head trauma can induce chronic traumatic encephalopathy (CTE), a neurodegenerative disease featuring behavioral symptoms ranging from cognitive deficits to elevated aggression. In a Drosophila model, we used a high-impact trauma device to induce TBI-like symptoms and to study post-TBI behavioral outcomes. Following TBI, aggression in banged male flies was significantly elevated as compared with that in unbanged flies. These increases in aggressive behavior were not the result of basal motility changes, as measured by a negative geotaxis assay. In addition, the increase in post-TBI aggression appeared to be specific to concussive trauma: neither cold exposure nor electric shock-two alternate types of trauma-significantly elevated aggressive behavior in male-male pairs. Various forms of dietary therapy, especially the high-fat, low-carbohydrate ketogenic diet (KD), have recently been explored for a wide variety of neuropathies. We thus hypothesized that putatively neuroprotective dietary interventions might be able to suppress post-traumatic elevations in aggressive behavior in animals subjected to head-trauma-inducing strikes, or "bangs". We supplemented a normal high-carbohydrate Drosophila diet with the KD metabolite beta-hydroxybutyrate (β-HB)-a ketone body (KB). Banged flies raised on a KB-supplemented diet exhibited a marked reduction in aggression, whereas aggression in unbanged flies was equivalent whether dieted with KB supplements or not. Pharmacological blockade of the ATP-sensitive potassium (K ATP ) channel abrogated KB effects reducing post-TBI aggression while pharmacological activation mimicked them, suggesting a mechanism by which KBs act in this model. KBs did not significantly extend lifespan in banged flies, but markedly extended lifespan in unbanged flies. We have thus developed a functional model for the study of post-TBI elevations of aggression. Further, we conclude that dietary interventions may be a fruitful avenue for further exploration of treatments for TBI- and CTE-related cognitive-behavioral symptoms.

KEYWORDS: Drosophila, KATP channel, aggression, chronic traumatic encephalopathies (CTE), ketogenic diet (KD), neuroprotection, traumatic brain injuries (TBI)

Possible role of peptide YY (PYY) in the pathophysiology of irritable bowel syndrome (IBS).

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder of unknown aetiology for which there is no effective treatment. Although IBS does not increase mortality, it reduces the quality of life and is an economic burden to both the patients themselves and society as a whole. Peptide YY (PYY) is localized in endocrine cells located in the ileum, colon and rectum. The concentration of PYY and the density of PYY cells are decreased in both the colon and rectum but unchanged in the ileum of patients with IBS. The low density of PYY cells in the large intestine may be caused by a decreased number of stem cells and their progeny toward endocrine cells. PYY regulates the intestinal motility, secretion and absorption as well as visceral sensitivity via modulating serotonin release. An abnormality in PYY may therefore contribute to the intestinal dysmotility and visceral hypersensitivity seen in IBS patients. Diet management involving consuming a low-FODMAP diet restores the density of PYY cells in the large intestine and improves abdominal symptoms in patients with IBS. This review shows that diet management appears to be a valuable tool for correcting the PYY abnormalities in the large intestine of IBS patients in the clinic.

KEYWORDS: IBS, Motility, NPY, Secretion, stem cells, Visceral hypersensitivity

Lactose and Fructo-oligosaccharides Increase Visceral Sensitivity in Mice via Glycation Processes, Increasing Mast Cell Density in Colonic Mucosa.

Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and erratic bowel habits. A diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) can reduce symptoms of IBS, possibly by reducing microbial fermentation products. We investigated whether ingestion of FODMAPs can induce IBS-like visceral hypersensitivity mediated by fermentation products of intestinal microbes in mice. C57Bl/6 mice were gavaged with lactose, with or without the anti-glycation agent pyridoxamine, or saline (controls) daily for 3 weeks. A separate group of mice were fed a diet containing fructo-oligosaccharides, with or without pyridoxamine in drinking water, or a normal chow diet (controls) for 6 weeks. Feces were collected and analyzed by 16S rRNA gene sequencing and bacterial community analyses. Abdominal sensitivity was measured by electromyography and mechanical von Frey filament assays. Colon tissues were collected from some mice and analyzed by histology and immunofluorescence, to quantify mast cells and expression of advanced glycosylation end-product specific receptor (AGER). Mice gavaged with lactose or fed fructo-oligosaccharides had increased abdominal sensitivity compared with controls, associated with increased numbers of mast cells in colon and expression of the receptor for AGER in proximal colon epithelium. These effects were prevented by administration of pyridoxamine. Lactose and/or pyridoxamine did not induce significant alterations in the composition of the fecal microbiota. Mass spectrometric analysis of carbonyl compounds in fecal samples identified signatures associated with mice given lactose or fructo-oligosaccharides vs controls. We found that oral administration of lactose or fructo-oligosaccharides to mice increases abdominal sensitivity, associated with increased numbers of mast cells in colon and expression of AGER; these can be prevented with an anti-glycation agent. Lactose and/or pyridoxamine did not produce alterations in fecal microbiota of mice. Our findings indicate that preventing glycation reactions might reduce abdominal pain in patients with IBS with sensitivity to FODMAPs.

KEYWORDS: advanced glycation end products, functional bowel disorder, mastocytes, mouse model

Adherence to the pro-inflammatory diet in relation to prevalence of irritable bowel syndrome.

There is no prior study that examined the association between nutrient-based dietary inflammatory index (DII) and odds of Irritable Bowel Syndrome (IBS). We examined the association between DII score and odds of IBS and its severity among Iranian adults. In this cross-sectional study, dietary intakes of 3363 Iranian adults were examined using a validated Dish-based 106-item Semi-quantitative Food Frequency Questionnaire (DS-FFQ). DII was calculated based on dietary intakes derived from DS-FFQ. IBS was assessed using a modified Persian version of Rome III questionnaire. After adjustment for potential confounders, we found that participants in the highest quintile of DII score had greater chance for IBS compared with those in the lowest quintile. By gender, we found a significant association between DII score and IBS among women. By BMI status, overweight or obese individuals in top quintile of DII score had greater odds for IBS than those in the bottom quintile. No significant association was observed between a pro-inflammatory diet and severity of IBS symptoms. Consumption of a pro-inflammatory diet was associated with increased odds of IBS, in particular among women and those with BMI ≥ 25 kg/m 2 .

KEYWORDS: DII, Dietary inflammatory index, IBS, Inflammation, Irritable bowel syndrome

A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study.

The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS). A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC. Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS. Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.

KEYWORDS: Cohort study, Diet, Epidemiology, Nutrition, Prostate cancer