Ketogenic Dietary Therapies in Patients with Autism Spectrum Disorder: Facts or Fads? A Scoping Review and a Proposal for a Shared Protocol

Varesio, Costanza; Grumi, Serena; Zanaboni, Martina Paola; Mensi, Martina Maria; Chiappedi, Matteo; Pasca, Ludovica; Ferraris, Cinzia; Tagliabue, Anna; Borgatti, Renato; Giorgis, Valentina De

doi:10.3390/nu13062057

Cited by 18 publications

(15 citation statements)

References 42 publications

(153 reference statements)

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“…They found that probiotic supplementation altered the composition of gut microbiota and the level of plasma cytokines were decreased after treatment. Similarly, Varesio et al(2021) reported that ketogenic diet therapy had bene cial effects in improving behavioral symptoms in autism due to changes in gut microbiota. To the best of our knowledge, this is the rst research assessing the therapeutic effects of UDCA in an experimental autism model.…”

Section: Discussionmentioning

confidence: 99%

Lowering Propionic Acid Levels by Regulating Gut Microbiota with Ursodeoxycholic Acid Appears to Regress Autism Symptoms: An Animal Study

karakas

Solmaz

Bağcıoğlu³

et al. 2022

Preprint

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Background Autism is a complex neurobehavioral disorder that is associated with genetic and environmental factors. Patients with autism have altered gut microbiata, including higher frequency of bacteroidetes and clostridiales that produce of propionic acid (PPA) –a compound that is established as an autism-inducing agent. We hypothesized that lowering the PPA levels by regulating gut microbiata with ursodeoxycholic acid (UDCA) can regress the autism symptoms. Methods Thirty male Wistar albino rats were divided into three groups: controls, PPA-induced (5 days of intraperitoneal 250 mg/kg/day dosage) autism model receiving oral saline, and PPA-induced autism model receiving oral UDCA (100 mg/kg/day). Oral treatments were applied for 15 days. At the end of the 15th day, all rats underwent behavioral tests and MR spectroscopy. At the end of the study, all animals were sacrificed and brain tissue / blood samples were collected for histopathological and biochemical analyses. Results Sociability test, open field test and passive avoidance learning tests were impaired, similar to the autism behavioral pattern, in PPA recipients; however, results were closer to normal patterns in the PPA + UDCA group. Biochemically, MDA, TNF-alpha, IL-2, IL-17, NF-kB, lactate, NGF and NRF2 levels in brain tissues showed significant differences between controls and the PPA + Saline group, and between the PPA + Saline group and the PPA + UDCA group. Histopathology showed that PPA injection caused increased glial activity, neural body degeneration, decreased neural count and dysmorphic changes in hippocampal and cerebellar tissues. UDCA treatment significantly ameliorated these changes. Conclusion UDCA administration has ameliorating effects on PPA-induced autism-like behavioral, biochemical and histopathological changes in rats.

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Section: Discussionmentioning

confidence: 99%

Lowering Propionic Acid Levels by Regulating Gut Microbiota with Ursodeoxycholic Acid Appears to Regress Autism Symptoms: An Animal Study

karakas

Solmaz

Bağcıoğlu³

et al. 2022

Preprint

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“…The researchers of animal model studies proved that KD might be an effective intervention in alleviating ASD symptoms [52,53]. Furthermore, larger cohort studies found that the use of KD results in noticeable improvements in: learning, social behaviour, speech, cooperation and reduction of hyperactivity in ASD patients [5,40,54].…”

Section: Dietary Models In Asdmentioning

confidence: 99%

The importance of nutritional management and education in the treatment of autism

Mandecka

Regulska−Ilow

2022

Rocz Panstw Zakl Hig

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Autism spectrum disorders (ASDs) are an early-onset neurodevelopmental disorders. The key symptoms of ASD include social deficits, verbal and non-verbal communication deficits, and restricted, repetitive patterns of behaviour, interests, or activities. Dietary patterns have been evidenced to be related to maternal nutritional status that might lead to different metabolic conditions, and maternal metabolic dysfunction has been observed to be associated with ASD. Furthermore growing evidence suggests that the gut microbiota has a role in the pathophysiology of ASD. Differences in composition of the gastrointestinal (GI) microbiota in children with ASD compared to unaffected siblings and/or healthy unrelated controls have been reported in various studies. The above-mentioned ASD factors and symptoms can be regulated by proper nutrition. The importance of nutrition and its possible impact on ASD patients is key to integral therapy. According to numerous research studies, various nutritional approaches succeeded in reducing the severity of patients' core ASD symptoms. The numerous options for diet that is used in the ASD therapy, as described in the scientific literature, are related to the problem of choosing an appropriate nutritional treatment. Each nutrition programme needs to be personalised and tailored to an individual patient. The aim of the paper is to review the available literature on dietary interventions in children with ASD and provide up-to-date evidence.

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“…However, ketogenic dieting should be recommended with caution, as the high-fat percentage (65-90%) can be associated with GID and may lead to nutritional deficiencies, due to low tolerability and the high food selectivity in children with ASD [150]. Gastrointestinal side effects of ketogenic diets in children with ASD included constipation, diarrhea, and vomiting, which occurred within 2-4 weeks of the ketogenic diet onset [169].…”

Section: High-fat Dietsmentioning

confidence: 99%

Dietary Fat Effect on the Gut Microbiome, and Its Role in the Modulation of Gastrointestinal Disorders in Children with Autism Spectrum Disorder

et al. 2021

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Children with autism spectrum disorder (ASD) report a higher frequency and severity of gastrointestinal disorders (GID) than typically developing (TD) children. GID-associated discomfort increases feelings of anxiety and frustration, contributing to the severity of ASD. Emerging evidence supports the biological intersection of neurodevelopment and microbiome, indicating the integral contribution of GM in the development and function of the nervous system, and mental health, and disease balance. Dysbiotic GM could be a contributing factor in the pathogenesis of GID in children with ASD. High-fat diets may modulate GM through accelerated growth of bile-tolerant bacteria, altered bacterial ratios, and reduced bacterial diversity, which may increase the risk of GID. Notably, saturated fatty acids are considered to have a pronounced effect on the increase of bile-tolerant bacteria and reduction in microbial diversity. Additionally, omega-3 exerts a favorable impact on GM and gut health due to its anti-inflammatory properties. Despite inconsistencies in the data elaborated in the review, the dietary fat composition, as part of an overall dietary intervention, plays a role in modulating GID, specifically in ASD, due to the altered microbiome profile. This review emphasizes the need to conduct future experimental studies investigating the effect of diets with varying fatty acid compositions on GID-specific microbiome profiles in children with ASD.

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Ketogenic Dietary Therapies in Patients with Autism Spectrum Disorder: Facts or Fads? A Scoping Review and a Proposal for a Shared Protocol

Cited by 18 publications

References 42 publications

Lowering Propionic Acid Levels by Regulating Gut Microbiota with Ursodeoxycholic Acid Appears to Regress Autism Symptoms: An Animal Study

Lowering Propionic Acid Levels by Regulating Gut Microbiota with Ursodeoxycholic Acid Appears to Regress Autism Symptoms: An Animal Study

The importance of nutritional management and education in the treatment of autism

Dietary Fat Effect on the Gut Microbiome, and Its Role in the Modulation of Gastrointestinal Disorders in Children with Autism Spectrum Disorder

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