PMID: 

Int J Mol Sci. 2020 May 5 ;21(9). Epub 2020 May 5. PMID: 32380723

Abstract Title: 

Aberrant Mitochondrial Morphology and Function in the BTBR Mouse Model of Autism Is Improved by Two Weeks of Ketogenic Diet.

Abstract: 

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder that exhibits a common set of behavioral and cognitive impairments. Although the etiology of ASD remains unclear, mitochondrial dysfunction has recently emerged as a possible causative factor underlying ASD. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that augments mitochondrial function, and has been shown to reduce autistic behaviors in both humans and in rodent models of ASD. The aim of the current study was to examine mitochondrial bioenergetics in the BTBR mouse model of ASD and to determine whether the KD improves mitochondrial function. We also investigated changes in mitochondrial morphology, which can directly influence mitochondrial function. We found that BTBR mice had altered mitochondrial function and exhibited smaller more fragmented mitochondria compared to C57BL/6J controls, and that supplementation with the KD improved both mitochondrial function and morphology. We also identified activating phosphorylation of two fission proteins, pDRP1and pMFF, in BTBR mice, consistent with the increased mitochondrial fragmentation that we observed. Intriguingly, we found that the KD decreased pDRP1levels in BTBR mice, likely contributing to the restoration of mitochondrial morphology. Overall, these data suggest that impaired mitochondrial bioenergetics and mitochondrial fragmentation may contribute to the etiology of ASD and that these alterations can be reversed with KD treatment.

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PMID: 

Curr Probl Cardiol. 2020 Mar 19:100582. Epub 2020 Mar 19. PMID: 32389436

Abstract Title: 

A Comparative Review of Established Diets for Prevention of Cardiovascular Disease and Newer Dietary Strategies.

Abstract: 

As part of a population-based approach to combating obesity, the American Heart Association has published specific dietary guidelines for the management of obesity and cardiovascular disease prevention. These guidelines give a primary view of healthy dietary changes and goals which may reduce cardiovascular risk. The American Heart Association guideline on Cardiovascular Prevention focuses on the benefits of a Plant-Based Diet and the Mediterranean diet. In addition to these recommendations, several other diets exist with variable long-term cardiovascular outcomes. In recent years, the ketogenic and intermittent fasting diets have been emerging and have garnered their own respective followings as weight loss strategies, and we will include them in our discussion of the potential long-term benefits related to cardiovascular risks. As the guidelines emphasize, all of the diets we will cover throughout this review must be discussed at the level of the individual patient with their primary care provider, and cannot be exercised without informed consent regarding the potential outcomes. Further research is required, and caution is advised before prescribing any of these diets to patients in the long-term, due to the potential to exacerbate cardiovascular risk factors.

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PMID: 

Brain Dev. 2020 May 7. Epub 2020 May 7. PMID: 32389449

Abstract Title: 

Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG.

Abstract: 

BACKGROUND: Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far.CASE: Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions.RESULTS: We studied two siblings by whole exome sequencing. A pathogenic variant in ALG3 (NM_005787.6: c.165C > T; p.Gly55=) that had been previously associated with congenital glycolysis defect type 1d was identified. Their intractable seizures were controlled by ketogenic diet.CONCLUSION: Although prominent findings of growth retardation and microcephaly seen in our patients have been extensively reported before, presence of hemangioma is a novel finding that may be used as an indication for ALG3-CDG diagnosis. Our patients are the first reported cases whose intractable seizures were controlled with ketogenic diet. This report adds ketogenic diet as an option for treatment of intractable epilepsy in ALG3-CDG.

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PMID: 

Rev Neurosci. 2020 May 15. Epub 2020 May 15. PMID: 32406387

Abstract Title: 

Exploring the mechanisms of action of the antidepressant effect of the ketogenic diet.

Abstract: 

The ketogenic diet (KD) is characterized by a diet ratio of 4:1 fat to non-fat energy sources. For decades KD has been successfully used to control seizures in epilepsy patients. Investigations into its mechanism of action suggest that it may have an effect on the metabolic, nervous, immune, and digestive systems. In this review, we postulate that KD may also improve depressive symptoms – for that, we highlight the similarities between depression and epilepsy, describe the extent to which body systems involved in both conditions are affected by the KD, and ultimately hypothesize how KD could improve MDD outcomes. Research into animal models and human patients have reported that KD can increase mitochondrial biogenesis and increase cellular resistance to oxidative stress both at the mitochondrial and genetic levels. Its effect on neurotransmitters alters cell-to-cell communication in the brain and may decrease hyperexcitability by increasing Gamma Aminobutyric Acid (GABA) and decreasing excitatory neurotransmitter levels. Its anti-inflammatory effects are mediated by decreasing chemo- and cytokine levels, including TNF-alpha and IL-1 levels. Finally, KD can alter gut microbiota (GM). Certain strains of microbiota predominate in major depressive disorder (MDD) when compared to healthy individuals. Recent evidence points to Bacteroidetes as a potential treatment predictor as it seems to increase in KD treatment responders for epilepsy. Each of these observations contributes to the presumed modulatory effects of KD on mood and supports its potential role as antidepressant.

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PMID: 

Brain Behav Immun. 2020 May 12. Epub 2020 May 12. PMID: 32413556

Abstract Title: 

Anti-depression effects of ketogenic diet are mediated via the restoration of microglial activation and neuronal excitability in the lateral habenula.

Abstract: 

Depression is a severe neuropsychiatric disorder, of which the underlying pathological mechanisms remain unclear. The ketogenic diet (KD) has been reported to exhibit preventative effects on depressive-like behaviors in rodents. However, the therapeutic effects of KD on depressive-like behaviors have not been illustrated thus far. Here, we found that KD treatment dramatically ameliorated depressive-like behaviors in both repeated social defeat stress (R-SDS) and lipopolysaccharide (LPS) models, indicating the potential therapeutic effects of KD on depression. Our electrophysiological studies further showed that neuronal excitability was increased in the lateral habenula (LHb) of mice exposed to R-SDS or LPS, which can be reversed in the presence of KD treatment. Moreover, R-SDS and LPS were also found to induce robust microglial inflammatory activation in the LHb. Importantly, these phenotypes were rescued in mice fed with KD. In addition, we found that the protein level of innate immune receptor Trem2 in the LHb was significantly decreased in depression models. Specific knockdown of Trem2 in LHb microglia induced depressive-like behaviors, increased neuronal excitability as well as robust microglial inflammatory activation. Altogether, we demonstrated the therapeutic effects of KD on depressive-like behaviors, which are probably mediated via the restoration of microglial inflammatory activation and neuronal excitability. Besides, we also proposed an unrecognized function of Trem2 in the LHb for depression. Our study sheds light on the pathogenesis of depression and thereby offers a potential therapeutic intervention.

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PMID: 

Epilepsy Res. 2020 Apr 29 ;164:106348. Epub 2020 Apr 29. PMID: 32413817

Abstract Title: 

Long-term outcomes of ketogenic diet in patients with tuberous sclerosis complex-derived epilepsy.

Abstract: 

OBJECTIVE: For epilepsy with tuberous sclerosis complex (TSC), ketogenic diet (KD) therapy has been consistently reported to be more beneficial than the average KD therapy response. Herein, we aimed to investigate the long-term outcomes of a KD on patients with TSC and intractable epilepsy.METHODS: This study included 31 patients with intractable epilepsy and TSC who were treated with the KD, and an intention-to-treat analysis was performed.RESULTS: Overall, 21 of the 31 patients (67.7%) had>50% reduction in seizures at 3 months after initiating the KD. Thirteen of the 31 patients (41.9%) were seizure-free for at least 3 months, but 10 of these 13 patients (76.9%) experienced seizure recurrence during the 24-month follow-up period. Finally, at 24 months of the KD observational period, there was>50% response in 10 of the 31 patients (32.3%), including seizure-free patients (6 of 31 patients, 19.4%). Most of the patients (12 of 13, 92.3%) who experienced seizure freedom had>50% reduction in seizures within 1 month after initiating the KD, and this result was the only factor associated with seizure freedom in the current study.CONCLUSION: The KD appeared to be an effective therapeutic modality for intractable pediatric epilepsy in TSC, but it did not exhibit guaranteed efficacy over a long-term period.

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PMID: 

Medicine (Baltimore). 2020 Apr ;99(16):e19857. PMID: 32312010

Abstract Title: 

Effects of hyperbaric oxygen therapy on the expression levels of the inflammatory factors interleukin-12p40, macrophage inflammatory protein-1β, platelet-derived growth factor-BB, and interleukin-1 receptor antagonist in keloids.

Abstract: 

BACKGROUND: Our study aimed to screen and explore the expression of inflammatory factors in keloid patients and to investigate how hyperbaric oxygen (HBO) therapy affects the expression levels of interleukin-12p40 (IL-12p40), macrophage inflammatory protein-1β (MIP-1β), platelet-derived growth factor-BB (PDGF-BB), and interleukin-1 receptor antagonist (IL-1Ra).OBJECTIVE: 30 patients were randomly selected and divided into the following 3 groups: keloid samples from keloid patients treated with HBO therapy (A), keloid samples from keloid patients treated without HBO therapy (B), and normal control skin samples derived from individuals who had no clear scarring (C). Each group included 10 samples.METHODS: Inflammatory factors in the keloid tissues were measured with the MILLIPLEX multiplexed Luminex system. Hematoxylin and eosin staining, immunohistochemical staining, and Western blotting were used to observe the morphological differences in different tissues and the expression levels.RESULTS: The expression levels of inflammatory mediators, including IL-12p40, MIP-1β, PDGF-BB, and IL-1Ra, in keloid tissues were significantly different from those in samples of normal skin. Hematoxylin and eosin staining showed significantly greater inflammatory infiltration in keloid tissue. Significantly different expression levels were observed in group A, B, and C.CONCLUSION: Significantly altered levels of inflammatory factors in the samples from keloid patients were observed, suggesting that formation of a keloid is potentially related to inflammatory responses. HBO therapy could significantly affect the expression levels of IL-12p40, MIP-1β, PDGF-BB, and IL-1Ra, indicating that the effects of HBO therapy are associated with the attenuation of inflammatory responses.

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PMID: 

Front Oncol. 2020 ;10:390. Epub 2020 Apr 9. PMID: 32328454

Abstract Title: 

The Effects of Hyperbaric Oxygen Therapy on Pelvic Radiation Induced Gastrointestinal Complications (Rectal Bleeding, Diarrhea, and Pain): A Meta-Analysis.

Abstract: 

Radiotherapy is a routine treatment for pelvic cancer patients. While it had been proven effective, gastrointestinal side effects remain a concern, impairing the quality of life. A few studies focused on the effects of hyperbaric oxygen (HBO) treatment to alleviate radiation-induced gastrointestinal complications. This meta-analysis aimed to critically review and summarize existing literature, assessing the effectiveness of HBO therapy for the treatment of radiation-induced gastrointestinal side effects.Medical literature search was performed with PubMed, Cochrane Library, and EMBASE up to March 14, 2019. Literatures about HBO treatment upon patients undergoing pelvic cancer (endometrial, cervix, rectum, or prostate cancers) radiotherapy were collected, and the effects of HBO treatment on radiotherapy-induced gastrointestinal complications were evaluated. A random-effects model was used to calculate the pooled effect size. Subgroup analyses were performed to search for sources of heterogeneity. Publication bias was detected with Funnel plots and Egger's test.Three different radiotherapy-related gastrointestinal complications, including rectal bleeding, diarrhea, and pain, were analyzed after screening. It was revealed that the improvement rates were considerable in rectal bleeding (0.81, 95% CI: 0.74-0.89) and diarrhea (0.75, 95% CI: 0.61-0.90) and slightly in pain (0.58, 95% CI: 0.38-0.79). Subgroup analysis revealed factors that significantly influenced the heterogeneity of rectal bleeding, diarrhea, and pain (evaluation criteria, follow-up time, and scoring system, respectively). No significant publication bias was detected.HBO treatment might have the potential to alleviate radiotherapy-related gastrointestinal complications, including rectal bleeding, diarrhea, and pain, but more data are needed for further conclusions. Other symptoms were not further analyzed, as the number of studies was insufficient. More large-scale and prospective studies are needed for better evaluation of HBO's therapeutic values.

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PMID: 

Med Hypotheses. 2020 Apr 22 ;140:109760. Epub 2020 Apr 22. PMID: 32344310

Abstract Title: 

Respiratory conditions in coronavirus disease 2019 (COVID-19): Important considerations regarding novel treatment strategies to reduce mortality.

Abstract: 

A novel virus named 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) causes symptoms that are classified as coronavirus disease (COVID-19). Respiratory conditions are extensively described among more serious cases of COVID-19, and the onset of acute respiratory distress syndrome (ARDS) is one of the hallmark features of critical COVID-19 cases. ARDS can be directly life-threatening because it is associated with low blood oxygenation levels and can result in organ failure. There are no generally recognized effective treatments for COVID-19, but treatments are urgently needed. Anti-viral medications and vaccines are in the early developmental stages and may take many months or even years to fully develop. At present, management of COVID-19 with respiratory and ventilator support are standard therapeutic treatments, but unfortunately such treatments are associated with high mortality rates. Therefore, it is imperative to consider novel new therapeutic interventions to treat/ameliorate respiratory conditions associated with COVID-19. Alternate treatment strategies utilizing clinically available treatments such as hyperbaric oxygen therapy (HBOT), packed red blood cell (pRBC) transfusions, or erthropoiesis-stimulating agent (ESA) therapy were hypothesized to increase oxygenation of tissues by alternative means than standard respiratory and ventilator treatments. It was also revealed that alternative treatments currently being considered for COVID-19 such as chloroquine and hydroxychloroquine by increasing hemoglobin production and increasing hemoglobin availability for oxygen binding and acetazolamine (for the treatment of altitude sickness) by causing hyperventilation with associated increasing levels of oxygen and decreasing levels of carbon dioxide in the blood may significantly ameliorate COVID-19 respiratory symptoms. In conclusion, is recommend, given HBOT, pRBC, and ESA therapies are currently available and routinely utilized in the treatment of other conditions, that such therapies be tried among COVID-19 patients with serious respiratory conditions and that future controlled-clinical trials explore the potential usefulness of such treatments among COVID-19 patients with respiratory conditions.

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PMID: 

Biomed Pharmacother. 2020 May 17 ;127:110227. Epub 2020 May 17. PMID: 32434144

Abstract Title: 

Ketogenic diet improves and restores redox status and biochemical indices in monosodium glutamate-induced rat testicular toxicity.

Abstract: 

This study investigated the effect of ketogenic diet on monosodium glutamate (MSG)-induced testicular dysfunction. Forty-six male rats (180 ± 40 g) were grouped into two groups (23 rats each); control group and MSG-induced group (4 mg/kg bw) for 28 days. At the 29th day, 5 rats from both group were sacrificed to establish testicular dysfunction. The remaining animals from the control group was further divided into three sub-groups and treated for 42 days; untreated group, ketogenic diet only and curcumin only as the standard drug (150 mg/kg bw). In the pre-treatment, the administration of MSG resulted in a significant (p 

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