Phenotype assessment in neurologically impaired paediatric patients: Impact of a nutrition intervention protocol.

BACKGROUND: Deficits in nutritional status and functional feeding disorders are common in Neurologically Impaired Paediatric Patients (NIPP). Interventions addressing these problems could offer better overall health status and quality of life in this group of patients, but the extent of their effectiveness is yet to be determined. Recent guidelines concerning the nutritional care of NIPP have been published from ESPGHAN but compliance to them has not been assessed. AIM: The study aimed to assess the phenotypic profile of a group of NIPP attending the outpatient clinic of a pediatric department, and to implement, for the first time to our knowledge, an individualized nutritional intervention protocol following ESPGHAN guidelines 2017 as well as to assess the impact on phenotypic parameters and nutritional status. PATIENTS AND METHODS: 68NIPP and their caregivers aged 1m-17 years (83.8% suffering from cerebral palsy (CP) were invited to assess their phenotypic parameters and to implement in a nutrition intervention protocol in order to improve their dietary intake and nutritional status. Anthropometry (weight, height, triceps skinfold thickness, mid upper arm circumference) was expressed as z-scores for age and sex using WHO Anthro software and classified following the WHO criteria. Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Dysphagia Disorder Survey (DDS), Saliva Severity Scale (SSS), gastrointestinal complications, energy and nutrient intake were assessed at the beginning (zero point), after 6 (point 1) and 12 (point 2) months period. Intake to Requirement ratio (I/R) was derived. At zero point, following the baseline evaluation, caregivers were advised and educated on nutrition protocol and customized nutrition plans were handed out. The impact of the nutritional intervention on the phenotypic parameters was recorded on follow up visits (points 1, 2).The primary outcomes analyzed were anthropometric parameters (Waz), as indicators of nutritional status. GMFCS, MACS, DDS, SSS, FA were evaluated as possible predictors of this outcome. Secondary outcomes included the impact of the intervention protocol on the phenotypic parameters during the study period. RESULTS: Based on weight for age z-score (Waz ≤ -2) (WHO) 17 patients (32.1%) were undernourished, 5/68 (10, 4%) were with triceps skinfold thickness z-score (TSTz) <-2 and 3/68 (7%) with mid upper arm circumference z-score (MUACz) <-2. Z-scores (WHO) for weight (p1 = 0, 036) (p2 = 0, 003), body mass index (BMI) (p2 = 0,000), MUAC (p1 = 0, 029) and TST (p1 = 0, 021) (p3 = 0, 044) were significantly improved in follow-up evaluations compared to the baseline. Less NIPP were found to be underweight according to Waz from point 1 to point 2 (p3 = 0, 006), as well as stunding according to height for age z-score (Haz) from point 1 to point 2 (p ≤ 0,001). Patients with higher levels of GMFCS (p1 = 0,040), MACS (p1 = 0,028) DDS (p1 = 0,001) and SSS (p1 = 0,005) had significantly lower Haz. Patients with higher levels of SSS (p1 = 0,002) had significantly lower TSTz scores. There were no significant changes in the classification of NIPP according to DDS or the patients' feeding ability. The energy (kcals) intake/kg of body weight (bw) was significantly higher at point 2 compared to point zero (p3 = 0,028), protein intake/kg of body weight was significantly higher at points 1 and 2 compared to point zero (p1 = 0,026, p3 = 0,003), and fat intake/kg of body weight (bw) was significantly higher at point 2 compared to point zero (p3 = 0,012). Intake of energy (kcals)/bw (p1 = 0,026), (p2 = 0,046), (p3 = 0,048) carbs/bw (p1 = 0,014) (p2 = 0,042), I/R of pro (p1 = 0,032), (p3 = 0,013), and fat/kg (p2 = 0, 033) (p3 = 0,037) were found to be significantly lower in higher GMFCS levels. DQI did not improve during the study period nor correlated to any of the anthropometric parameters. Gastrointestinal complications correlated with Waz (r = -, 285 p1 = 0, 011). Feeding Ability (FA) was found to be the only strong predictor for Waz at baseline evaluation (p = 0,012) when a multiple regression was run along with DDS. CONCLUSION: Underweight was detected in one third of the patients, some degree of dysphagia in 69% and gastrointestinal complications in 58.8% of the sample. Height for age z-score (Haz) was the anthropometric parameter most sensitive to the changes in ranking on motor and functional feeding scores. The implementation of a customized nutrition intervention protocol in line with ESPGHAN's guidelines had a beneficial effect on improving dietary intake and nutritional status of NIPP after a 12 months period. Better results could be expected if dysphagia and feeding ability were also addressed by appropriate intervention protocols. Patients' feeding ability is of importance for predicting Waz.

Impact of Newborn Screening and Early Dietary Management on Clinical Outcome of Patients with Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency and Medium Chain Acyl-CoA Dehydrogenase Deficiency-A Retrospective Nationwide Study.

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.

Rice bran, an off-shoot to newer therapeutics in neurological disorders.

Normal brain functioning involves the interaction of interconnected molecular and cellular activities, which appear to alter normal to abnormal brain functioning when worsened, contributing to the emergence of neurological disorders. There are currently millions of people who are living with brain disorders globally and this will rise if suitable prevention strategies are not explored. Nutraceutical intended to treat numerous health goals with little adverse effect possible together can be more beneficial than pharmaceutical monotherapy for fostering balanced brain functioning. Nutraceutical provides a specific composition of effective macronutrients and micronutrients that are difficult to synthesize in the laboratory. Numerous elements of rice fibers in rice bran are characterized as natural anti-oxidant and having potential anti-inflammatory activity. The rice bran captures interest among the researchers as it is widespread, affordable, and rich in nutrients including protein, fat, carbohydrates, bioactive components, and dietary fiber. This review covers the neuroprotective multiplicity of rice bran and its constituents to deter pathological conditions of the brain and to facilitate balanced brain functioning at the same time.

Dietary nutrition for neurological disease therapy: Current status and future directions.

Adequate food intake and relative abundance of dietary nutrients have undisputed effects on the brain function. There is now substantial evidence that dietary nutrition aids in the prevention and remediation of neurologic symptoms in diverse pathological conditions. The newly described influences of dietary factors on the alterations of mitochondrial dysfunction, epigenetic modification and neuroinflammation are important mechanisms that are responsible for the action of nutrients on the brain health. In this review, we discuss the state of evidence supporting that distinct dietary interventions including dietary supplement and dietary restriction have the ability to tackle neurological disorders using Alzheimer's disease, Parkinson's disease, stroke, epilepsy, traumatic brain injury, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis as examples. Additionally, it is also highlighting that diverse potential mechanisms such as metabolic control, epigenetic modification, neuroinflammation and gut-brain axis are of utmost importance for nutrient supply to the risk of neurologic condition and therapeutic response. Finally, we also highlight the novel concept that dietary nutrient intervention reshapes metabolism-epigenetics-immunity cycle to remediate brain dysfunction. Targeting metabolism-epigenetics-immunity network will delineate a new blueprint for combating neurological weaknesses.

Ketogenic diet and cognition in neurological diseases: a systematic review.

CONTEXT: In recent years, the ketogenic diet has gained special relevance as a possible therapeutic alternative to some neurological and chronic diseases. OBJECTIVE: The aim of this systematic review was to answer the following question: Does a ketogenic diet improve cognitive skills in patients with Alzheimer's disease, Parkinson's disease, refractory epilepsy, and type 1 glucose deficiency syndrome? To define the research question, the PICOS criteria were used, following the guidelines of the PRISMA method. DATA SOURCES: Medline/PubMed, Elsevier Science Direct, Dialnet, EBSCOhost, Mediagraphic, Sage Journals, ProQuest, and Wiley Online Library databases were used. DATA EXTRACTION: After applying inclusion and exclusion criteria in accordance with the PRISMA method, a total of 63 entries published between 2004 and 2019 were used. DATA ANALYSIS: The records extracted were analyzed from a qualitative approach, so no statistical analysis was carried out. CONCLUSION: Although scientific literature on the subject is scarce and there has tended to be a lack of scientific rigor, the studies reviewed confirmed the effectiveness of this diet in improving the cognitive symptomatology of the aforementioned diseases.

[Neurological pathology by liposoluble vitamin-related disorders]. / Patología neurológica por desequilibrio de vitaminas liposolubles.

INTRODUCTION: Background: the clinicians rarely have to cope with diseases of nutritional origin and scarcely, although possible, vitamins alterations produce neurological symptoms. Objectives: to show, based on two clinical cases, the neurological symptoms due to liposoluble vitamins alterations, focusing on vitamins E and A. Conclusions: it is important to consider liposoluble vitamin alterations as a cause of neurological symptoms, despite their rarity, after rolling out the most probable entities.

INTRODUCCIÓN: Introducción: en la práctica clínica hospitalaria nos enfrentamos a algunas patologías que tienen origen nutricional. Aunque rara vez, las alteraciones vitamínicas pueden desencadenar trastornos neurológicos graves. Objetivos: mostrar los síntomas neurológicos que pueden darse por alteraciones en los niveles de las vitaminas liposolubles, centrándonos en las vitaminas E y A, mediante la exposición de dos casos clínicos. Conclusiones: es importante tener en mente las alteraciones de vitaminas liposolubles como origen de un trastorno neurológico, a pesar de su escasa frecuencia, habiendo descartado primero las causas más probables.

Ketogenic diet ­ mechanism of action and perspectives for the use in the therapy: data from clinical studies / Dieta ketogeniczna - mechanizm dzialania i perspektywy zastosowania w terapii: dane z badan klinicznych.

Ketogenic diet is a high fat and very low-carbohydrate nutritional approach that induces increased production of ketone bodies, which serve as an alternative to glucose energetic substrates. Since almost a century ketogenic diet has been used in the therapy of refractory epilepsy, especially in children. Because of the pleiotropic effect of ketogenic diet on physiology, including inflammation, oxidative stress, energy balance and signaling pathways, in recent years scientists have been intensively exploring the use of it in the treatment of other diseases. In the present article current clinical studies regarding the possibility of using the ketogenic diet in the treatment of obesity, diabetes, neurological disorders and cancer has been reviewed alongside with potential mechanisms responsible for the therapeutic effect of ketogenic diet in these diseases. The metabolic processes engaged in nutritional ketosis and practicals aspects of ketogenic dieting have been also discussed.

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review.

Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "on demand" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

Mens Sana in Corpore Sano: Does the Glycemic Index Have a Role to Play?

Although diet interventions are mostly related to metabolic disorders, nowadays they are used in a wide variety of pathologies. From diabetes and obesity to cardiovascular diseases, to cancer or neurological disorders and stroke, nutritional recommendations are applied to almost all diseases. Among such disorders, metabolic disturbances and brain function and/or diseases have recently been shown to be linked. Indeed, numerous neurological functions are often associated with perturbations of whole-body energy homeostasis. In this regard, specific diets are used in various neurological conditions, such as epilepsy, stroke, or seizure recovery. In addition, Alzheimer's disease and Autism Spectrum Disorders are also considered to be putatively improved by diet interventions. Glycemic index diets are a novel developed indicator expected to anticipate the changes in blood glucose induced by specific foods and how they can affect various physiological functions. Several results have provided indications of the efficiency of low-glycemic index diets in weight management and insulin sensitivity, but also cognitive function, epilepsy treatment, stroke, and neurodegenerative diseases. Overall, studies involving the glycemic index can provide new insights into the relationship between energy homeostasis regulation and brain function or related disorders. Therefore, in this review, we will summarize the main evidence on glycemic index involvement in brain mechanisms of energy homeostasis regulation.

Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD.

BACKGROUND: The plasma acylcarnitine profile is frequently used as a biochemical assessment for follow-up in diagnosed patients with fatty acid oxidation disorders (FAODs). Disease specific acylcarnitine species are elevated during metabolic decompensation but there is clinical and biochemical heterogeneity among patients and limited data on the utility of an acylcarnitine profile for routine clinical monitoring. METHODS: We evaluated plasma acylcarnitine profiles from 30 diagnosed patients with long-chain FAODs (carnitine palmitoyltransferase-2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), and long-chain 3-hydroxy acyl-CoA dehydrogenase or mitochondrial trifunctional protein (LCHAD/TFP) deficiencies) collected after an overnight fast, after feeding a controlled low-fat diet, and before and after moderate exercise. Our purpose was to describe the variability in this biomarker and how various physiologic states effect the acylcarnitine concentrations in circulation. RESULTS: Disease specific acylcarnitine species were higher after an overnight fast and decreased by approximately 60% two hours after a controlled breakfast meal. Moderate-intensity exercise increased the acylcarnitine species but it varied by diagnosis. When analyzed for a genotype/phenotype correlation, the presence of the common LCHADD mutation (c.1528G > C) was associated with higher levels of 3-hydroxyacylcarnitines than in patients with other mutations. CONCLUSIONS: We found that feeding consistently suppressed and that moderate intensity exercise increased disease specific acylcarnitine species, but the response to exercise was highly variable across subjects and diagnoses. The clinical utility of routine plasma acylcarnitine analysis for outpatient treatment monitoring remains questionable; however, if acylcarnitine profiles are measured in the clinical setting, standardized procedures are required for sample collection to be of value.

Home Enteral Nutrition in Adults-Nationwide Multicenter Survey.

Home enteral nutrition (HEN) is an important part of the health care system, with a growing population of patients around the world. The aim of our study was to analyze one of the largest cohorts of HEN patients to provide the most recent data available in European literature. A multicenter, nation-wide survey in the period of 1 January 2018-1 January 2019 was performed in Poland. Data concerning adult patients on HEN in 2018 during 1 year of observation time were analyzed: demographic characteristics, primary disease, technique of enteral feeding, diet formulation and amount of energy provided. A total of 4586 HEN patients (F: 46.7%, M: 53.3%) were included in the study. The primary diseases were: 54.5% neurological (17.4%-neurovascular, 13.7%-neurodegenerative), 33.9% cancer (20.2%-head and neck, 11.7%-gastrointestinal cancer), 2.5%-gastroenterology, 1.5%-inherited diseases. Of new registrations in 2018-cancer patients 46.3%, neurological patients 45.1%. The median age overall was: 64 yr., BMI-20.2 kg/m2, NRS 2002 score-4.28. A total of 65% of patients were treated with PEG, 11.6% with surgical gastrostomy, 14.3% with naso-gastric tube and 7% with jejunostomy. Boluses were the most common method of feeding (74.4%). Gravity flow was used in 17.6% and peristaltic pump was used in 8% patients. The median energy provision was 1278 kcal/day and 24 kcal/kg/day. The most commonly used diets were: isocaloric (28.1%), protein-enriched isocaloric (20%) and protein-enriched hypercaloric (12%). The median overall duration of HEN was 354 days, 615 days for neurological and 209 days for cancer patients. A number of new registrations of cancer patients was significant and long duration of HEN in this group is encouraging. A developing spectrum of enteral formulas available enables more specified nutritional interventions.

Nutraceuticals in Neurological Disorders.

Neurological diseases are one of the major healthcare issues worldwide. Posed lifestyle changes are associated with drastically increased risk of chronic illness and diseases, posing a substantial healthcare and financial burden to society globally. Researchers aim to provide fine treatment for ailing disorders with minimal exposed side effects. In recent decades, several studies on functional foods have been initiated to obtain foods that have fewer side effects and increased therapeutic activity. Hence, an attempt has been made to unravel several extraction techniques to acquire essential bioactive compounds or phytochemicals from therapeutically active food products. This has led to the conception of the term functional foods being meddled with other similar terms like "pharmafoods," "medifoods", "vitafoods", or "medicinal foods". With a dire need to adhere towards healthy options, the demand of nutraceuticals is widely increasing to combat neurological interventions. An association between food habits and the individual lifestyle with neurodegeneration has been manifested, thereby proposing the role of nutraceuticals as prophylactic treatment for neurological interventions. The current review covers some of the major neurological disorders and nutraceutical therapy in the prevention of disease.

Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States.

Ketone bodies (KBs), comprising ß-hydroxybutyrate, acetoacetate and acetone, are a set of fuel molecules serving as an alternative energy source to glucose. KBs are mainly produced by the liver from fatty acids during periods of fasting, and prolonged or intense physical activity. In diabetes, mainly type-1, ketoacidosis is the pathological response to glucose malabsorption. Endogenous production of ketone bodies is promoted by consumption of a ketogenic diet (KD), a diet virtually devoid of carbohydrates. Despite its recently widespread use, the systemic impact of KD is only partially understood, and ranges from physiologically beneficial outcomes in particular circumstances to potentially harmful effects. Here, we firstly review ketone body metabolism and molecular signaling, to then link the understanding of ketone bodies' biochemistry to controversies regarding their putative or proven medical benefits. We overview the physiological consequences of ketone bodies' consumption, focusing on (i) KB-induced histone post-translational modifications, particularly ß-hydroxybutyrylation and acetylation, which appears to be the core epigenetic mechanisms of activity of ß-hydroxybutyrate to modulate inflammation; (ii) inflammatory responses to a KD; (iii) proven benefits of the KD in the context of neuronal disease and cancer; and (iv) consequences of the KD's application on cardiovascular health and on physical performance.

Neurological manifestations in adults with phenylketonuria: new cases and review of the literature.

OBJECTIVE: Phenylketonuria (PKU) is a rare autosomal recessive disease characterised by high plasma phenylalanine levels inducing, if untreated, serious neurological manifestations in children but also, rarely, in adults who stopped their diet. The objective of the study was to describe the neurological manifestations observed in adults with PKU. METHODS: We analysed cases reported in French reference centres for inborn errors of metabolism and cases already reported in the literature. RESULTS: We report 8 new cases of neurological manifestations and 22 cases in the literature, which occurred in adult PKU patients, associated with chronic or rapid increase of phenylalanine levels, mostly when strict low-phenylalanine diet was stopped early in life. Neurological symptoms consisted in cerebellar ataxia, tremor, brisk reflexes, visual loss, sensory manifestations, and/or headaches. Visual loss was more frequent in the new cases (4/8) of the present series than in the literature (4/22). These neurological complications were associated with leucopathy on brain magnetic resonance imaging (27/29). The start of a low-phenylalanine diet improved or fully reversed neurological manifestations, even in patients with late diagnosis during adulthood. CONCLUSION: Neurological manifestations can complicate PKU in adult patients with elevated phenylalanine levels, after long or short period of diet discontinuation. Neurologists should be aware of this diagnosis, and measure phenylalaninemia in case of neurological symptoms associated with non-specific leucopathy on brain MRI. PKU patients should be systematically encouraged to continue their diet and their medical follow-up to avoid neurological complications.

Fasting as a Therapy in Neurological Disease.

Fasting is deeply entrenched in evolution, yet its potential applications to today's most common, disabling neurological diseases remain relatively unexplored. Fasting induces an altered metabolic state that optimizes neuron bioenergetics, plasticity, and resilience in a way that may counteract a broad array of neurological disorders. In both animals and humans, fasting prevents and treats the metabolic syndrome, a major risk factor for many neurological diseases. In animals, fasting probably prevents the formation of tumors, possibly treats established tumors, and improves tumor responses to chemotherapy. In human cancers, including cancers that involve the brain, fasting ameliorates chemotherapy-related adverse effects and may protect normal cells from chemotherapy. Fasting improves cognition, stalls age-related cognitive decline, usually slows neurodegeneration, reduces brain damage and enhances functional recovery after stroke, and mitigates the pathological and clinical features of epilepsy and multiple sclerosis in animal models. Primarily due to a lack of research, the evidence supporting fasting as a treatment in human neurological disorders, including neurodegeneration, stroke, epilepsy, and multiple sclerosis, is indirect or non-existent. Given the strength of the animal evidence, many exciting discoveries may lie ahead, awaiting future investigations into the viability of fasting as a therapy in neurological disease.

[Aspects of nutrition for prevention and treatment of chronic neurological diseases]. / Aspekte der Ernährung zur Prävention und Therapie chronisch neurologischer Erkrankungen.

Chronic neurodegenerative and neuroinflammatory diseases, such as idiopathic Parkinson's syndrome, amyotrophic lateral sclerosis and multiple sclerosis, represent a therapeutic challenge. Their pathophysiology is not well understood and a cure for any of these diseases is not possible. Over the past decades lifestyle and nutritional habits in modern industrial nations have changed and evidence is increasing that the prevalence of chronic diseases as well their clinical presentation are also changing. Epidemiological investigations indicate that nutritional components might have an impact on the pathogenesis of chronic neurological diseases. A profound understanding of these correlations could foster a better prevention as well as treatment of such chronic disabling diseases. This continuing medical education article summarizes the current understanding of selected nutritional components and their effect on the development and clinical course of chronic neurological disorders.

Going Against the Grains: Gluten-Free Diets in Patients Without Celiac Disease-Worthwhile or Not?

While the gluten-free diet (GFD) is the only known effective therapy for celiac disease, in recent years it has become increasingly popular in the USA and worldwide, with many believing it to be more "healthful" and others claiming that it has beneficial effects for health conditions, many extraintestinal, other than celiac disease. This review examines the evidence for use of the GFD in patients without celiac disease who self-report intestinal and/or extraintestinal symptoms (non-celiac gluten sensitivity), as well as for enhancement of athletic performance and treatment of autism, rheumatoid arthritis, and psychiatric disorders. Overall, the evidence for use of GFDs in conditions other than celiac disease is poor. Though non-celiac gluten sensitivity may ultimately emerge as a biomarker-defined condition, a large proportion of patients with apparent non-celiac gluten sensitivity have, after careful investigation, an alternative diagnosis. In light of this, and coupled with the potential physical and psychological harms associated with the avoidance of gluten, initiating a GFD should not be encouraged for people who have these other conditions or are seeking physical/athletic enhancement.