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Randomised controlled trial: effects of gluten-free diet on symptoms and the gut microenvironment in irritable bowel syndrome.
Algera, JP, Magnusson, MK, Öhman, L, Störsrud, S, Simrén, M, Törnblom, H
Alimentary pharmacology & therapeutics. 2022;56(9):1318-1327
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The majority of irritable bowel syndrome (IBS) patients relate their symptoms to intake of certain foods. The gut microenvironment, where microbiota, food components and the nervous system interact, is suggested to play a key role in gastrointestinal (GI) symptom generation in a subset of IBS patients. The main aim of this study was to assess and compare the efficacy of the gluten-free and gluten-containing diets in terms of effects on GI symptoms in IBS patients. Secondary aims where to identify the putative link between gut microenvironment and the diets´ effect on GI symptoms, and to identify potential predictors of clinical response to the gluten-free diet. This study is a single-centre, double-blind, randomised, placebo-controlled, cross-over trial. Adult sex- and age-matched IBS patients (n=20) and healthy controls (HC) (n=21) were recruited, randomised and challenged with gluten (14 g/day) and rice flour, both for 2 weeks, while adhering to a strict gluten-free diet. Results indicate that a gluten-free diet may affect IBS symptoms in general, and bowel habits in a subset of IBS patients. The gluten-free diet has distinct effect on the gut microenvironment in IBS patients who respond favourably to gluten reduction. Authors conclude that the gut microenvironment may be of importance in the clinical response to the gluten-free diet in IBS, and future studies should aim to further assess these factors in relation to clinical response to the gluten-free diet.
Abstract
BACKGROUND A gluten-free diet reduces symptoms in some patients with irritable bowel syndrome (IBS) through unclear mechanisms. AIMS To assess the effects of gluten-free versus gluten-containing diet on symptoms and the gut microenvironment, and to identify predictors of response to the gluten-free diet in IBS METHODS Twenty patients with IBS and 18 healthy controls (HC) followed a gluten-free diet during two 14-day intervention periods where they sprinkled either gluten (14 g/day) or rice flour powder over their meals. Primary outcomes included effects of the interventions on IBS symptoms (IBS-SSS) and bowel habits. Secondary outcomes included effects of gluten-free diet on faecal microbiota and metabolite profile. RESULTS IBS symptoms improved during the gluten-free (p = 0.02), but not the gluten-containing period, with no difference between the interventions. IBS patients reported fewer loose stools during the gluten-free intervention (p = 0.01). Patients with IBS and HC presented distinct metabolite profiles based on the effects of the gluten-free diet (p < 0.001). True responders (reduced IBS-SSS by ≥50 solely after gluten-free period) and non-responders were discriminated based on the effects of the gluten-free diet on the microbiota (p < 0.01) and metabolite profiles (p < 0.001). The response to the gluten-free diet could be predicted by the metabolite profile before the intervention (p < 0.001). CONCLUSIONS A gluten-free diet may influence symptoms in a subset of patients with IBS, with a particular effect on bowel habits. A gluten-free diet seems to impact the gut microenvironment. Responsiveness to the gluten-free diet may be predicted by the metabolite profile. CLINICALTRIALS gov: NCT03869359.
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Evolution of the Human Diet and Its Impact on Gut Microbiota, Immune Responses, and Brain Health.
González Olmo, BM, Butler, MJ, Barrientos, RM
Nutrients. 2021;13(1)
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One explanation for the increased prevalence in chronic disease and mental illness is from the evolutionary perspective. This suggests the rapid shift in diet towards processed foods in the past 200 years has not allowed for sufficient adaptation of the gut microbiome. The gut microbiome plays an important role in the digestive, immune and nervous systems via the gut-brain axis, and may be a key factor in modulating inflammation and disease. The aim of this review is to discuss how what we eat affects the immune system and impacts our brain health. The literature currently shows significant associations between the Western diet and its impact on the health of the gut microbiome and the brain. Increased intake of saturated fats, refined carbohydrates and sugar, coupled with a reduction in fiber, negatively impacts the digestive system and elicits an immune response. This response can lead to neuroinflammation, which is now found to be associated with deficits in learning and memory, as well as increased rates of neurodegenerative disease and depression. Based on the existing literature, the authors conclude the human gut microbiome has not had sufficient time to adapt to many modern foods, thus leading to inflammation and disease. The authors recommend that a diet composed of natural whole foods with minimal processing can help prevent and alleviate some of the burden caused by chronic disease, and suggest future studies focus on improving techniques to evaluate neuroinflammation in humans.
Abstract
The relatively rapid shift from consuming preagricultural wild foods for thousands of years, to consuming postindustrial semi-processed and ultra-processed foods endemic of the Western world less than 200 years ago did not allow for evolutionary adaptation of the commensal microbial species that inhabit the human gastrointestinal (GI) tract, and this has significantly impacted gut health. The human gut microbiota, the diverse and dynamic population of microbes, has been demonstrated to have extensive and important interactions with the digestive, immune, and nervous systems. Western diet-induced dysbiosis of the gut microbiota has been shown to negatively impact human digestive physiology, to have pathogenic effects on the immune system, and, in turn, cause exaggerated neuroinflammation. Given the tremendous amount of evidence linking neuroinflammation with neural dysfunction, it is no surprise that the Western diet has been implicated in the development of many diseases and disorders of the brain, including memory impairments, neurodegenerative disorders, and depression. In this review, we discuss each of these concepts to understand how what we eat can lead to cognitive and psychiatric diseases.
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Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review.
Aranburu, E, Matias, S, Simón, E, Larretxi, I, Martínez, O, Bustamante, MÁ, Fernández-Gil, MDP, Miranda, J
Nutrients. 2021;13(6)
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There is growing evidence that gluten and FODMAPs, such as fermentable oligosaccharides, disaccharides, monosaccharides and polyols, can cause gastrointestinal symptoms, inflammation, and immune responses in patients with celiac disease and irritable bowel syndrome. In addition, a high intake of gluten and FODMAPs may also be associated with neurological and psychiatric disorders. Thirteen studies were included in this systematic review to examine the relationship between gluten and FODMAP consumption and illnesses affecting the central nervous system. In addition, the studies examined the effects of potential dietary strategies that consider gluten and FODMAP intake on mental disorders, anxiety, depression, schizophrenia, Alzheimer’s disease, and autism spectrum disorders. Several possible mechanisms identified in this systematic review could contribute to neurological and psychiatric disorders, including the release of proinflammatory cytokines, immune responses, gut dysbiosis, intestinal permeability, and interactions between the gut-brain axis. In patients with fibromyalgia, celiac disease, and irritable bowel syndrome, avoiding or limiting gluten may reduce depression, anxiety, and cognitive impairment. However, the effects of a low-FODMAP diet on the central nervous system are inconclusive. There is some evidence that gluten-free diets can improve cognition in schizophrenia patients. In addition, those with autism spectrum disorders may benefit from a gluten-free diet and a low-FODMAP diet. Further robust research is required to evaluate the beneficial effects of interventions that avoid or restrict the consumption of foods high in FODMAPs and gluten. However, healthcare professionals can use the results of this systematic review to understand the potential benefits of therapeutic interventions that consider the intake of FODMAPs and gluten on illnesses affecting the central nervous system and their possible mechanisms of action.
Abstract
Nowadays, gluten and FODMAP food components (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are increasingly studied due to their possible relation with extraintestinal-associated conditions. In recent years, gluten-free diets (GFD) and low-FODMAP diets (LFD) are becoming more popular not only in order to avoid the food components that cause intolerances or allergies in some people, but also due to the direct influence of marketing movements or diet trends on feeding habits. Likewise, neurological and psychiatric diseases are currently of increasing importance in developed countries. For this reason, a bibliographic systematic review has been carried out to analyse whether there is a pathophysiological relationship between the dietary intake of gluten or FODMAPs with mental disorders. This review collects 13 clinical and randomized controlled trials, based on the PRISMA statement, which have been published in the last ten years. Based on these results, limiting or ruling out gluten or FODMAPs in the diet might be beneficial for symptoms such as depression, anxiety (7 out of 7 articles found any positive effect), or cognition deficiency (improvements in several cognition test measurements in one trial), and to a lesser extent for schizophrenia and the autism spectrum. Nevertheless, further studies are needed to obtain completely reliable conclusions.
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The Role of Diet, Eating Behavior, and Nutrition Intervention in Seasonal Affective Disorder: A Systematic Review.
Yang, Y, Zhang, S, Zhang, X, Xu, Y, Cheng, J, Yang, X
Frontiers in psychology. 2020;11:1451
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Seasonal affective disorder (SAD) is a mood disorder characterised by annual depression or bipolar disorder in a seasonal pattern. Recent evidence suggests dietary intervention and nutrition status can affect the symptoms in depressed patients, but none have specifically considered depression among SAD patients. The aim of this review was to assess the associations between diet, eating behaviour and nutrition intervention in SAD patients. Eleven studies were included and found vegetarian diet patterns and alcoholism to be associated with higher SAD prevalence. Additionally, SAD patients tend to consume larger dinners, more snacks, and show more cravings for starch-rich foods. Despite these patterns, dietary supplementation or nutrition intervention did not show benefit for SAD symptoms. Overall, the authors conclude there is a lack of evidence to draw conclusions on dietary pattern and nutritional interventions for preventing and managing SAD. The authors suggest further evidence is needed from larger controlled trials and encourage investigation of the role of the B vitamin group, rather than an isolated B12 supplementation.
Abstract
Background: Seasonal affective disorder (SAD) is a biological and mood disorder with a seasonal pattern. Dietary intervention and nutritional status have been reported to affect SAD severity. The objective of this study was to systematically review the evidence of associations between SAD and diet, eating behavior, and nutrition intervention. Methods: We performed a comprehensive search of MEDLINE, EMBASE, Web of Science, and Google Scholar from inception up to July 1, 2019. Studies that examined diet and eating behaviors in SAD patients and tests of nutrition interventions for SAD were included. Two independent investigators extracted data based on study designs, participants, outcomes, exposures, and association measures. Results: Eleven studies were included: six studies examined distinctive dietary patterns and eating behaviors in SAD patients and five studies explored the efficacy of nutrition interventions for SAD. Vegetarianism and alcoholism were associated with higher SAD prevalence, but normal alcohol intake was not correlated with SAD severity. Compared with non-clinical subjects, SAD patients tended to consume significantly larger dinners and more evening snacks during weekdays and weekends and exhibit a higher frequency of binge eating, external eating, and emotional eating. Additionally, compared to healthy controls, SAD patients presented more cravings for starch-rich food and food with high fiber. However, neither the ingestion of carbohydrate-loaded meals nor Vitamin D/B12 supplementation showed benefit for SAD. Conclusion: Studies suggest that SAD patients may exhibit distinctive diet preferences and eating behaviors, but no current nutrition intervention has demonstrated efficacy for ameliorating SAD symptoms. Further evidence is needed from randomized controlled trials with larger sample sizes and longer durations.
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Gut Microbiome and Depression: How Microbes Affect the Way We Think.
Limbana, T, Khan, F, Eskander, N
Cureus. 2020;12(8):e9966
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Recent findings have shown that a healthy gut microflora transmits signals to the brain through various pathways, namely the gut-brain axis. With the gut and brain working in a bidirectional relationship, emerging research suggests this could potentially impact stress, anxiety, depression and cognition. Therefore the aim of this review was to determine the role of the gut microbiome in mental health and depression. A total of 26 articles were reviewed and based on these articles, a strong link exists between the gut microbiome and its impact on mental health. Additionally, the literature supports the notion that the gut-brain axis serves as an essential pathway. Based on these findings, the authors agree there is a strong association between the gut microbiome and mental health, while also acknowledging the need to establish a causal link between these two entities. The authors conclude that the microbiome is a promising approach when considering the prevention, treatment and management of mental health diseases in the future.
Abstract
The gut microbiome serves an important role in the human body. Reportedly, one of the benefits of these microflora is on mental health. Once established, food and other dietary sources that enhance quality microbiome content in our gastrointestinal system will be a significant consideration in individuals' day to day lives. This literature review conducted a PubMed search for studies about the gut microbiome and its relation to depression. In using several Medical Subject Heading (MeSH) keywords, relevant literature was selected. A total of 26 articles were selected after applying the inclusion and exclusion criteria, and after checking the articles' accessibility. This literature would like to establish the role of the gut microbiome in depression. This study's findings showed that there is a strong association of microbiome function to mental well-being.
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Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease).
Włodarek, D
Nutrients. 2019;11(1)
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The ketogenic diet (KD) is characterised by a low-carbohydrate, high-fat content that induces a fasting-like state in the body. The KD has been used clinically for children with epilepsy and recent studies have shed light on potential neuro-protective effects. The aim of this systematic review was to evaluate the role of the KD in prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Among the existing literature, there is very limited data on long-term application of the KD in patients with neurodegenerative disease. The research using animal models or in-vitro models look very promising however the use of KD in elderly adults with neurodegenerative disease is very complex. Based on these results, the authors conclude there is a need for further research to evaluate the suitability of KD for patients with AD or PD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The studies into the effectiveness of ketogenic diets in neurodegenerative diseases tend to be too small and heterogeneous to draw firm conclusions.
- Specific elements of ketogenic diets may be useful for individual cases, however healthcare practitioners are encouraged to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The role of ketogenic diets for the management of a number of conditions has become a discussion subject, not only for scientists and clinicians, but also for the general public, however the evidence of their effectiveness in neurodegenerative diseases is patchy. Studies are either too small to be good enough to draw conclusions from, or the interventions are too mixed / heterogeneous to be able to attribute any potential benefit to the ketogenic dietary component alone. This highlights the need to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Clinical practice applications:
Specific elements of ketogenic diets might be useful for individual cases. However clinicians should be encouraged to draw from a wide array of approaches and not be limited to one single method when it comes to dealing with complex conditions such as Alzheimer's and Parkinson's Disease. Patient-centred care where dietary recommendations revolve around the individual's needs - based on biochemical markers but also on subjective experience of their own quality of life / wellbeing - should be the basis upon which to tailor nutrition programmes that support those living with neurodegenerative conditions.
Considerations for future research:
Good methodological quality studies with placebo / control groups and clear outcomes are needed in order to contribute to the evidence base of the potential role of ketogenic diets in the support of patients living with neurodegenerative conditions.
Abstract
The goal of this review was to assess the effectiveness of ketogenic diets on the therapy of neurodegenerative diseases. The ketogenic diet is a low-carbohydrate and fat-rich diet. Its implementation has a fasting-like effect, which brings the body into a state of ketosis. The ketogenic diet has, for almost 100 years, been used in the therapy of drug-resistant epilepsy, but current studies indicate possible neuroprotective effects. Thus far, only a few studies have evaluated the role of the ketogenic diet in the prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Single studies with human participants have demonstrated a reduction of disease symptoms after application. The application of the ketogenic diet to elderly people, however, raises certain concerns. Persons with neurodegenerative diseases are at risk of malnutrition, while food intake reduction is associated with disease symptoms. In turn, the ketogenic diet leads to a reduced appetite; it is not attractive from an organoleptic point of view, and may be accompanied by side effects of the gastrointestinal system. All this may lead to further lowering of consumed food portions by elderly persons with neurodegenerative diseases and, in consequence, to further reduction in the supply of nutrients provided by the diet. Neither data on the long-term application of the ketogenic diet in patients with neurodegenerative disease or data on its effects on disease symptoms are available. Further research is needed to evaluate the suitability of the ketogenic diet in the therapy of AD- or PD-affected persons.
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A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial).
Jacka, FN, O'Neil, A, Opie, R, Itsiopoulos, C, Cotton, S, Mohebbi, M, Castle, D, Dash, S, Mihalopoulos, C, Chatterton, ML, et al
BMC medicine. 2017;15(1):23
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While extensive observational evidence linking diet quality and mental health exists, a causal relationship between the two has net yet been examined. The aim of this study was to determine the efficacy of a dietary intervention for treating patients with moderate to severe depression. 56 participants were randomised to attend either seven nutritional consultations delivered by a dietitian or social support groups in 12 weeks, and depressive symptomology was assessed at baseline and 12 weeks. This study found that participants receiving the dietary intervention had significantly greater improvements in depression symptoms than the social support group. Based on these results, the authors conclude that dietary improvement is an effective treatment strategy for the management of depression, and that clinicians should consider promoting the benefits of dietary improvement for their patients with depression. Future large-scale studies in this field are needed to better understand the mechanisms underlying this link.
Abstract
BACKGROUND The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes. METHODS 'SMILES' was a 12-week, parallel-group, single blind, randomised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression. The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician. The control condition comprised a social support protocol to the same visit schedule and length. Depression symptomatology was the primary endpoint, assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at 12 weeks. Secondary outcomes included remission and change of symptoms, mood and anxiety. Analyses utilised a likelihood-based mixed-effects model repeated measures (MMRM) approach. The robustness of estimates was investigated through sensitivity analyses. RESULTS We assessed 166 individuals for eligibility, of whom 67 were enrolled (diet intervention, n = 33; control, n = 34). Of these, 55 were utilising some form of therapy: 21 were using psychotherapy and pharmacotherapy combined; 9 were using exclusively psychotherapy; and 25 were using only pharmacotherapy. There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks. The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group, t(60.7) = 4.38, p < 0.001, Cohen's d = -1.16. Remission, defined as a MADRS score <10, was achieved for 32.3% (n = 10) and 8.0% (n = 2) of the intervention and control groups, respectively (χ 2 (1) = 4.84, p = 0.028); number needed to treat (NNT) based on remission scores was 4.1 (95% CI of NNT 2.3-27.8). A sensitivity analysis, testing departures from the missing at random (MAR) assumption for dropouts, indicated that the impact of the intervention was robust to violations of MAR assumptions. CONCLUSIONS These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder, the benefits of which could extend to the management of common co-morbidities. TRIAL REGISTRATION Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820 . Registered on 29 February 2012.
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Psychological support counselling improves gluten-free diet compliance in coeliac patients with affective disorders.
Addolorato, G, De Lorenzi, G, Abenavoli, L, Leggio, L, Capristo, E, Gasbarrini, G
Alimentary pharmacology & therapeutics. 2004;20(7):777-82
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Currently the only treatment for coeliac disease (CD) is a lifetime adherence to a gluten-free diet (GFD). Several studies report that newly diagnosed coeliac patients find adhering to the GFD difficult and report the occurrence of affective disorders, namely depression and anxiety. The aim of this study was to evaluate the usefulness of psychological support counselling to improve anxiety and depression commonly associated with newly diagnosed CD patients. Sixty-six adults newly diagnosed with CD who reported being affected by anxiety and depression were enrolled in the study and were randomly assigned to either receive psychological counselling or not. This study found that psychological support counselling did not improve anxiety and depression nor increase adherence to a GFD in newly diagnosed CD patients. Based on this study, the authors suggest that affective disorders in newly diagnosed CD patients are related to the presence of the physical symptoms, of which can be relieved by the GFD.
Abstract
BACKGROUND Anxiety and depression are common features of coeliac disease. Depression is cause of non-compliance to treatment in chronic illness. AIM: To evaluate the useful of psychological support counselling to improve affective disorders and gluten-free diet adherence in coeliac disease with anxiety and depression. METHODS A total of 66 coeliac disease patients with state anxiety and current depression were enrolled. Patients were randomized in two groups: in group A psychological support was started at the beginning of gluten-free diet, while group B was free of psychological support. Both groups were followed every 2 weeks for 6 months. State and Trait Anxiety Inventory test Y-1 and the modified Zung self-rating depression scale were administered before (T0) and after 6 months of gluten-free diet (T1). RESULTS At T1 no difference was found between groups in the percentage of state anxiety, while a significant lower percentage of depressed subjects was found in group A with respect to group B (15.1% vs. 78.8%; P=0.001). In the follow-up period, a significant lower compliance to gluten-free diet was found in group B with respect to group A (39.4% vs. 9.1%; P=0.02). CONCLUSIONS In coeliac disease patients with affective disorders psychological support seems to be able to reduce depression and to increase gluten-free diet compliance.