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:

The Impact of Low-FODMAPs, Gluten-Free, and Ketogenic Diets on Gut Microbiota Modulation in Pathological Conditions.

The gut microbiota performs several essential protective, structural, and metabolic functions for host health. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and between the microorganisms and the host. The gut microbiota composition may be affected by external factors, among them diet habits may be considered most important. In some pathological conditions such as irritable bowel syndrome (IBS), celiac disease (CD), or neurological disorders (ND), specific dietary regimens as low-fermentable, oligo-, di-, mono-saccharides and polyols (FODMAPs), ketogenic (KD), and gluten-free (GFD) diets are considered therapeutic. These kinds of diets are characterized by a reduction or exclusion of a specific nutrient from the entire dietary pattern. Despite these alimentary regimens showing beneficial effects on disease symptoms, they can affect microbiota composition, especially if they are protracted for a long time. To date, only a few studies have reported the effects of these diets on gut microbiota. In this review, we discuss the effects of low-FODMAPs, KD, and GFD on gut microbiota modulation in pathological conditions, advancing the possibility of depicting a balanced diet and developing personalized dietary intervention protocols.

KEYWORDS: dietary patterns, gluten-free diet, ketogenic diet, low-FODMAPs diet, microbiota

Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study.

To estimate the causal association between intake of dairy products and incident type 2 diabetes. The analysis included 21,820 European individuals of the EPIC-InterAct case-cohort study. Participants were genotyped, and rs4988235, a SNP for lactase persistence (LP) which enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. Each additional LP allele was associated with a higher intake of milk and milk beverages but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits, nonalcoholic beverages, and wine. In instrumental variable analysis, LP-associated milk intake was not associated with diabetes. rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations we consider it unlikely that this has caused the observed null result.

Seizures and Epilepsy.

Epilepsy affects 65 million people worldwide, and is a leading neurologic cause of loss of quality-adjusted life years. The diagnosis of seizures and epilepsy often depends on a careful history, and is supported with electroencephalogram and imaging. First-line treatment of epilepsy includes medical management. Antiepileptic drugs must be chosen with the patient's particular comorbidities in mind. Drug-resistant epilepsy cases should be referred to an epilepsy specialist and may be evaluated for additional medications, epilepsy surgery, neurostimulation, or dietary therapy. When caring for women, providers must take into account needs for contraception or pregnancy safety where applicable.

KEYWORDS: Antiepileptic drugs, Epilepsy, Epilepsy surgery, Epilepsy treatment, First seizure, Seizure, Women with epilepsy

Eicosapentaenoic acid/arachidonic acid ratio and weight loss during hospitalization for glycemic control among overweight Japanese patients with type 2 diabetes: a retrospective observational study.

The study aimed to examine the relationship between levels of serum eicosapentaenoic acid (EPA), arachidonic acid (AA), as well as EPA/AA ratio and weight loss during hospitalization in participants considered to be overweight, with type 2 diabetes. The study participants included 142 patients who were hospitalized for treatment of type 2 diabetes. We divided the participants into two groups depending on the achievenemt in reduction of bodyweight 3% or more during hospitalization and examined the relationship between serum levels of EPA and AA, as well as ratio of EPA/AA on admission and effectiveness of weight loss under strict dietary therapy during hospitalization, using Cox proportional hazard models. After adjustment was made for several confounders, the hazard ratio of effective weight loss for logarithmical serum EPA was 1.59 and for logarithmical EPA/AA ratio 1.64, whereas the hazard ratio for effective weight loss for logarithmical serum AA was 1.11. In addition, after dividing EPA/AA ratio and serum EPA into quartiles based on participant number, the hazard ratio for the highest quartile of EPA/AA ratio was 2.33, and for the highest quartile of serum EPA 1.60 compared with the lowest quartile. These results suggest the possibility that EPA is involved in bodyweight change under a caloric-restriction regimen. In addition, EPA/AA ratio was found to be a better predictor of medical intervention for weight loss among overweight patients with type 2 diabetes, compared with serum EPA level.

KEYWORDS: Arachidonic acid, Body weight loss, Eicosapentaenoic acid, Type 2 diabetes

The neurological and psychological phenotype of adult patients with early-treated phenylketonuria: a systematic review.

Newborn screening for phenylketonuria and early introduction of dietary therapy has been remarkably successful in preventing the severe neurological features of phenylketonuria, including mental retardation and epilepsy. However, concerns remain that long-term outcome is still suboptimal, particularly in adult patients who are no longer on strict phenylalanine-restricted diets. With our systematic literature review we aimed to describe the neurological phenotype of adults with early-treated phenylketonuria (ETPKU). The literature search covered the period from 1 January 1990 up to 16 April 2018, using the NLM MEDLINE controlled vocabulary. Of the 643 records initially identified, 83 were included in the analysis. The most commonly reported neurological signs were tremor and hyperreflexia. The overall quality of life (QoL) of ETPKU adults was good or comparable to control populations, and there was no evidence for a significant incidence of psychiatric disease or social difficulties. Neuroimaging revealed that brain abnormalities are present in ETPKU adults, but their clinical significance remains unclear. Generally, IQ appears normal but specific deficits in neuropsychological and social functioning were reported in early-treated adults compared with healthy individuals. However, accurately defining the prevalence of these deficits is complicated by the lack of standardised neuropsychological tests. Future research should employ standardised neurological, neuropsychological and neuroimaging protocols, and consider other techniques such as advanced imaging analyses and the recently validated phenylketonuria-specific QoL questionnaire, to precisely define the nature of the impairments within the adult ETPKU population and how these relate to metabolic control throughout life. This article is protected by copyright. All rights reserved.

KEYWORDS: Phenylketonuria, adult, early-treated, neurological, newborn screening

Ketogenic and anaplerotic dietary modifications ameliorate seizure activity in Drosophila models of mitochondrial encephalomyopathy and glycolytic enzymopathy.

Seizures are a feature not only of the many forms of epilepsy, but also of global metabolic diseases such as mitochondrial encephalomyopathy (ME) and glycolytic enzymopathy (GE). Modern anti-epileptic drugs (AEDs) are successful in many cases, but some patients are refractory to existing AEDs, which has led to a surge in interest in clinically managed dietary therapy such as the ketogenic diet (KD). This high-fat, low-carbohydrate diet causes a cellular switch from glycolysis to fatty acid oxidation and ketone body generation, with a wide array of downstream effects at the genetic, protein, and metabolite level that may mediate seizure protection. We have recently shown that a Drosophila model of human ME responds robustly to the KD; here, we have investigated the mechanistic importance of the major metabolic consequences of the KD in the context of this bioenergetics disease: ketogenesis, reduction of glycolysis, and anaplerosis. We have found that reduction of glycolysis does not confer seizure protection, but that dietary supplementation with ketone bodies or the anaplerotic lipid triheptanoin, which directly replenishes the citric acid cycle, can mimic the success of the ketogenic diet even in the presence of standard carbohydrate levels. We have also shown that the proper functioning of the citric acid cycle is crucial to the success of the KD in the context of ME. Furthermore, our data reveal that multiple seizure models, in addition to ATP6 1 , are treatable with the ketogenic diet. Importantly, one of these mutants is TPI sugarkill , which models human glycolytic enzymopathy, an incurable metabolic disorder with severe neurological consequences. Overall, these studies reveal widespread success of the KD in Drosophila, further cementing its status as an excellent model for studies of KD treatment and mechanism, and reveal key insights into the therapeutic potential of dietary therapy against neuronal hyperexcitability in epilepsy and metabolic disease.

KEYWORDS: Anaplerosis, Drosophila, Ketogenesis, Mitochondrial encephalomyopathy (ME), Seizures, Triose phosphate isomerase (TPI) deficiency

ENOblock inhibits the pathology of diet-induced obesity.

Obesity is a medical condition that impacts on all levels of society and causes numerous comorbidities, such as diabetes, cardiovascular disease, and cancer. We assessed the suitability of targeting enolase, a glycolysis pathway enzyme with multiple, secondary functions in cells, to treat obesity. Treating adipocytes with ENOblock, a novel modulator of these secondary 'moonlighting' functions of enolase, suppressed the adipogenic program and induced mitochondrial uncoupling. Obese animals treated with ENOblock showed a reduction in body weight and increased core body temperature. Metabolic and inflammatory parameters were improved in the liver, adipose tissue and hippocampus. The mechanism of ENOblock was identified as transcriptional repression of master regulators of lipid homeostasis, gluconeogenesis and inflammation. ENOblock treatment also reduced body weight gain, lowered cumulative food intake and increased fecal lipid content in mice fed a high fat diet. Our results support the further drug development of ENOblock as a therapeutic for obesity and suggest enolase as a new target for this disorder.

Diet and Functional Gastrointestinal Disorders in Children. Is the Focus on Food Exaggerated?

Almost all children who consult for irritable bowel syndrome (IBS) report food intolerances.

Dietary Therapy in Conjunction with Immunosuppression to Treat Gastrointestinal Graft-Versus-Host Disease (GVHD).

Elimination Diets for Irritable Bowel Syndrome: Approaching the End of the Beginning.

Dietary interventions have become a mainstay of treating patients with irritable bowel syndrome (IBS). Most of the available studies have focused on the benefits of elimination diets. While elimination diets can be highly effective, they should be avoided in patients with 2 emerging eating disorders: orthorexia nervosa and avoidant/restrictive food intake disorder. Similar to drug therapies, diet interventions are effective for only a subgroup of patients with IBS. They should be viewed as "a" therapy not "the" therapy for patients with IBS. It will be critical to develop strategies that utilize symptoms combined with biomarkers which parse patients with IBS by pathophysiology and in so doing, help providers to pick the right treatment for the right patient. At present, diet interventions are primarily focused on elimination of certain foods but there are an increasing number of supplementation studies which are lending support to the concept of "functional foods."

Oral administration of a lecithin-based delivery form of boswellic acids (Casperome®) for the prevention of symptoms of irritable bowel syndrome: a randomized clinical study.

The purpose of this study was to evaluate the long-term efficacy and the safety of a lecithin-based delivery form of boswellic acids from Boswellia serrata (Casperome®) for the prevention of symptoms in otherwise healthy subjects with mild irritable bowel syndrome (IBS). The study included 69 otherwise healthy participants with a mild form of IBS who completed a 6-month follow-up period. In total, 34 subjects were assigned to the standard management (SM) group: diet and, if needed, hyoscine butylbromide (Buscopan®) or papaverine hydrochloride + 10 mg of Atropa belladonna extract; 35 subjects were assigned to supplementation with the Boswellia serrata lecithin-based delivery form (one tablet/day; Casperome®). IBS signs and symptoms were evaluated at inclusion, after 3 and 6 months. The numbers of patients who needed rescue medication were recorded. Adverse events were also evaluated. At baseline, the groups were comparable in terms of demographic and clinical characteristics. At follow-up, compared with the SM group, the Boswellia group showed lower mean score values for almost all self-assed IBS symptoms. A significantly lower need for rescue medications and consultations or medical evaluation/admissions was found in the Boswellia group compared with the SM group. The incidence of minimal adverse events - mainly stipsis - was significantly higher in the SM group. Oxidative stress at T2 was significantly decreased in Boswellia-supplemented subjects. Boswellia serrata lecithin-based delivery form (Casperome®) appears to be effective and safe in improving signs and symptoms in IBS subjects who are otherwise healthy, particularly in comparison with symptomatic drug treatment that may cause side effects and stiptis.

Patients' views on a new treatment for Bulimia nervosa and binge eating disorder combining physical exercise and dietary therapy (the PED-t). A qualitative study.

A new group based treatment for patients with bulimia nervosa (BN) and binge eating disorder (BED), combining guided Physical Exercise and Dietary therapy (PED-t), has shown the capacity to alleviate BN and BED symptoms. The PED-t is run by therapists with a professional background in sport sciences and nutrition, which in many clinical settings is an uncommon group of professionals. The symptom reduction effects using the PED-t need validation from patients who have been given this kind of treatment, as negative experiences may impinge further clinical implementation. To explore such experiences, semistructural interviews were conducted with 15 participants. The interviews were transcribed and analyzed using a systematic text condensation approach. Overall, patients experienced the format and content of the PED-t as beneficial and as providing tools to manage BN- and BED symptoms. The patients' experiences of therapist credibility was enhanced by their appreciation of the therapists' professional background. Finally, some treatment modifications were suggested. Overall, the PED-t may thus be offered to patients with BN and BED, by a new set of professionals, and in uncommon settings. This possibility calls for future effectiveness studies integrating both parametric and experiential data.

Reduced efficacy of low FODMAPs diet in patients with IBS-D carrying sucrase-isomaltase ( SI ) hypomorphic variants.

KEYWORDS: carbohydrates, genetic polymorphisms, irritable bowel syndrome

Effect of a short-term low fermentable oligiosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet on exercise-related gastrointestinal symptoms.

Research has demonstrated that low fermentable oligiosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diets improve gastrointestinal (GI) symptoms in irritable bowel syndrome sufferers. Exercise-related GI issues are a common cause of underperformance, with current evidence focusing on the use of FODMAP approaches with recreationally competitive or highly trained athletes. However, there is a paucity of research exploring the potential benefit of FODMAP strategies to support healthy, recreational athletes who experience GI  issues during training. This study therefore aimed to assess whether a short-term LOW FODMAP diet improved exercise-related GI symptoms and the perceived ability to exercise in recreational runners. Sixteen healthy volunteers were randomly assigned in a crossover design manner to either a LOW FODMAP or HIGH FODMAP diet for 7 days, with a one week washout period followed by a further 7 days on the alternate diet. Participants rated their gastrointestinal symptoms on an adapted version of the Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) questionnaire before and at the end of each dietary period. Perceived ability to exercise (frequency, intensity and duration) in relation to each dietary period was also rated using a visual analogue scale. Resting blood samples were collected prior to and on completion of each diet to determine plasma intestinal fatty acid binding protein (I-FABP) as a marker of acute GI injury. Overall IBS-SSS score significantly reduced in the LOW FODMAP condition from 81.1 ± 16.4 to 31.3 ± 9.2. Perceived exercise frequency and intensity was significantly improved following a short-term LOW FODMAP approach compared to HIGH FODMAP . No significant differences were reported between dietary conditions for plasma I-FABP. A short-term LOW FODMAP diet under free-living conditions reduced exercise-related GI symptoms and improved the perceived ability to exercise in otherwise healthy, recreational runners. These findings may be explained by a reduction in indigestible carbohydrates available for fermentation in the gut. The therapeutic benefits of LOW FODMAP diets in recreational and trained athletes during sustained training periods warrants further investigation.

KEYWORDS: FODMAP diet, Gastrointestinal symptoms, Nutrition, Recreational athletes

Low-FODMAP Diet Is Associated With Improved Quality of Life in IBS Patients-A Prospective Observational Study.

The low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet is effectively manages irritable bowel syndrome (IBS) symptoms. Long-term low-FODMAP studies rarely report quality of life (QoL). We aimed to determine the effect of low-FODMAP diet on long-term QoL, gastrointestinal (GI) and non-GI symptoms in IBS patients. A prospective observational study of IBS patients referred for low-FODMAP dietary advice was performed. The primary outcome of QoL and secondary outcomes of GI symptoms, anxiety/depression, fatigue, sleep quality, and happiness were obtained at baseline, 6 weeks, and 6 months. 111 patients were recruited. 91.0%, 71.6%, and 50.5% of participants completed baseline, T6, and T26 assessments, respectively. There were significant improvements in QoL from baseline at T6 and T26. Significant reductions were seen in GI symptoms at T6 and T26, fatigue at T6 and T26, and anxiety at T6 and T26, compared with baseline. A significant reduction was seen for depression from baseline at T26, and a significant increase was seen for both happiness and vitality from baseline at T26. There was a significant correlation between GI symptom response and change in QoL, anxiety, depression, and fatigue. Low-FODMAP diet was associated with improved long-term QoL and GI symptoms, reduced fatigue and anxiety/depression, and increased happiness and vitality. These data support a wider range of benefits for IBS patients consuming a low-FODMAP diet.

KEYWORDS: FODMAP, anxiety, depression, diarrhea, diet therapy, fatigue, irritable bowel syndrome, quality of life

Efficacy of the gluten free diet in the management of functional gastrointestinal disorders: a systematic review on behalf of the Italian Society of Paediatrics.

Functional gastrointestinal disorders (FGIDs) are characterized by chronic/recurrent gastrointestinal symptoms not related to organic disorders. Due to the limited treatment options and to the perception of subjects with FGIDs suffering from a food intolerance, in recent years there has been an increase in the self-prescription of elimination diets, especially gluten free diet (GFD), for the treatment of these disorders. For this reason, we decided to perform this systematic review with the aim to evaluate the available evidence on the effects of a GFD on gastrointestinal symptoms, in subjects with FGIDs. Cochrane Library and MEDLINE (via PubMed) databases were searched, from inception to March 2018, using the MeSH terms "functional gastrointestinal disorder OR irritable bowel syndrome AND gluten". We included all the clinical trials published in English and evaluating the effects of a GFD in subjects with FGIDs diagnosed according to the Rome II, III, and IV criteria. Eleven trials were eligible, with 10/11 trials including adult subjects with irritable bowel syndrome (IBS) or FGIDs. Most of the prospective studies found an effect of GFD on gastrointestinal symptoms control. Nevertheless, 1 trial failed to find an association between gluten and GI symptoms when FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) content was simultaneously reduced in the diet, and 2 trials reported a worsening of symptoms during placebo administration. The results of the different trials are difficult to compare due to discrepancies in the study protocols regarding the amount and type of gluten administered, the duration of the gluten challenge, the type of placebo used, and the duration of the challenge itself. According to our results, gluten may contribute to the occurrence of gastrointestinal symptoms in patients with FGIDs, particularly in those with IBS. Nevertheless, the results of the currently available trials are difficult to compare due to the lack of standardization in the study designs. For this reason, it is still not possible to recommend the use of the GFD in the routine management of FGIDs.

KEYWORDS: Abdominal pain, Elimination diet, Gastrointestinal symptoms, Irritable bowel syndrome

Dietary weight loss intervention improves subclinical atherosclerosis and oxidative stress markers in leukocytes of obese humans.

The relationship between caloric restriction-mediated weight loss and the generation of ROS and its effects on atherosclerotic markers in obesity is not fully understood. Therefore, we set out to investigate whether dietary weight loss intervention improves markers of oxidative stress in leukocytes and subclinical parameters of atherosclerosis. This was an interventional study of 59 obese subjects who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical parameters, inflammatory markers-hsCRP, TNFα and NFκB -, oxidative stress parameters-total superoxide, glutathione, catalase activity and protein carbonyl groups-, soluble cellular adhesion molecules-sICAM, sP-selectin, sPSGL-1 -, myeloperoxidase (MPO), leukocyte-endothelium cell interactions-rolling flux, velocity and adhesion-and LDL subfractions, before and after the dietary intervention. After losing weight, an improvement was observed in the patients' anthropometric, blood pressure and metabolic parameters, and was associated with reduced inflammatory response (hsCRP, TNFα and NFκB). Oxidative stress parameters improved, since superoxide production and protein carbonyl content were reduced and antioxidant systems were enhanced. In addition, a significant reduction of subclinical markers of atherosclerosis-small and dense LDL particles, MPO, sP-selectin and leukocyte adhesion-and an increase in soluble PSGL-1 were reported. Our findings reveal that the improvement of subclinical atherosclerotic markers after dietary weight loss intervention is associated with a reduction of oxidative stress in leukocytes and inflammatory pathways, suggesting that these are the underlying mechanisms responsible for the reduced risk of cardiovascular disease in obese subjects after losing weight.

Dietary exclusion of fructose and lactose after positive breath tests improved rapid-transit constipation in children.

Exclusion of f ermentable o ligosaccharides, d isaccharides, m onosaccharides, and p olyols (FODMAPs) from the diet is effective in alleviating symptoms of irritable bowel syndrome (IBS) in adults. Rapid-transit constipation (RTC) is a recently discovered subset of chronic constipation and has been linked to food intolerance. The aim of this study was to audit the effect of specific FODMAP elimination diets in children with RTC. This was an audit of children presenting to a tertiary children's hospital surgeon with refractory chronic constipation who had rapid transit in the proximal colon on nuclear imaging; had hydrogen/methane breath tests for fructose, lactose, and/or sorbitol intolerance; and were advised to exclude positive sugar under clinical supervision. Patients filled in a questionnaire rating severity of constipation, abdominal pain, and pain on defecation with a visual analogue scale and stool consistency for 6 months before and after dietary exclusion. In responses from 29 children, 70% eliminated fructose, and 40% eliminated lactose. There was a significant reduction in the severity of constipation, abdominal pain, pain on defecation, and increase in stool wetness. Children with RTC showed significant improvements in constipation and pain after excluding the sugar indicated by positive breath tests, suggesting that specific sugar-exclusion diets may have a role in the management of RTC in children.

KEYWORDS: FODMAP, exclusion diet, food intolerance, rapid‐transit constipation

Implementation of ketogenic diet in children with drug-resistant epilepsy in a medium resources setting: Egyptian experience.

Even with the extensive use of ketogenic dietary therapies (KD), there still exist many areas of the world that do not provide these treatments. Implementing the ketogenic diet in different countries forms a real challenge in order to match the cultural and economic differences. To assess the feasibility of implementing a ketogenic diet plan in a limited resource setting with identification of the compliance, tolerability and side effects in the target population and to assess the efficacy of the ketogenic diet in children with intractable epilepsy. The medical records of 28 patients with intractable epilepsy, treated at The Children's Hospital - Cairo University from December 2012 to March 2014 with ketogenic dietary therapy were reviewed. The non-fasting protocol was followed without hospital admission. All children were started on a standardized classic ketogenic diet with a ratio ranging from 2.5-4:1 (grams of fat to combined carbohydrate and protein). Patients were followed at 1, 3 and 6 months after diet initiation. The median age was 60 months. After 1 month from diet initiation, 16 patients remained on the diet. One of them had more than 90% reduction in seizure frequency, an additional 6 patients had a 50-90% reduction in seizure frequency. In total, seven out of the 16 patients continuing the diet for 1 month had more than 50% improvement in seizure control from the base line. Despite having 50-90% seizure control, three children discontinued the diet after one month.Three months after diet initiation, 6 patients remained on diet, 4 of them had more than 50% reduction in seizure frequency.At 6 months, only 3 patients remained on diet, 2 of them had 50-90% reduction in seizure frequency, while one patient showed better than 90% decrease in seizure. The current study shows that the ketogenic diet could be implemented in medium resources countries and should be included in the management of children with intractable epilepsy.

KEYWORDS: Intractable epilepsy, Ketogenic diet, Pediatric epilepsy, Seizures

Limiting FODMAP consumption for patients with IBS.

Irritable bowel syndrome (IBS) is a chronic disorder affected by stress and dietary habits. This article explores the role of diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols in reducing IBS symptoms.