scholarly journals Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Huiyuan Zhu ◽  
Dexi Bi ◽  
Youhua Zhang ◽  
Cheng Kong ◽  
Jiahao Du ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Therapeutic Potential ◽  
Ketone Bodies ◽  
Intractable Epilepsy ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Clinical Implementation ◽  
Research Attention ◽  
Low Carbohydrate Diet ◽  
Underlying Mechanisms

AbstractThe ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.

scholarly journals The Ketogenic Diet Increases In Vivo Glutathione Levels in Patients with Epilepsy

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 504
Author(s):  
Antonio Napolitano ◽  
Daniela Longo ◽  
Martina Lucignani ◽  
Luca Pasquini ◽  
Maria Camilla Rossi-Espagnet ◽  
...  
Keyword(s):  
Blood Serum ◽  
Ketogenic Diet ◽  
Animal Studies ◽  
Ketone Bodies ◽  
Neuroprotective Effect ◽  
Intractable Epilepsy ◽  
Epileptic Seizures ◽  
Resonance Spectroscopy ◽  
Low Carbohydrate Diet

The Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that has been utilized as the first line treatment for contrasting intractable epilepsy. It is responsible for the presence of ketone bodies in blood, whose neuroprotective effect has been widely shown in recent years but remains unclear. Since glutathione (GSH) is implicated in oxidation-reduction reactions, our aim was to monitor the effects of KD on GSH brain levels by means of magnetic resonance spectroscopy (MRS). MRS was acquired from 16 KD patients and seven age-matched Healthy Controls (HC). We estimated metabolite concentrations with linear combination model (LCModel), assessing differences between KD and HC with t-test. Pearson was used to investigate GHS correlations with blood serum 3-B-Hydroxybutyrate (3HB) concentrations and with number of weekly epileptic seizures. The results have shown higher levels of brain GSH for KD patients (2.5 ± 0.5 mM) compared to HC (2.0 ± 0.5 mM). Both blood serum 3HB and number of seizures did not correlate with GSH concentration. The present study showed a significant increase in GSH in the brain of epileptic children treated with KD, reproducing for the first time in humans what was previously observed in animal studies. Our results may suggest a pivotal role of GSH in the antioxidant neuroprotective effect of KD in the human brain.

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

Exploiting metabolic susceptibilities in glioblastoma via glycolytic inhibition and ketogenic therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13558-e13558
Author(s):  
Frederic Anthony Vallejo ◽  
Sumedh Shah ◽  
Winston Walters ◽  
Katrina Kostenko ◽  
Ingrid Torrens ◽  
...  
Keyword(s):  
Stem Cell ◽  
Western Blot ◽  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Combined Treatment ◽  
Glycolytic Enzymes ◽  
Parp Cleavage ◽  
Low Carbohydrate Diet ◽  
Dose Dependent Decrease ◽  
Dose Dependent

e13558 Background: Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Despite enormous efforts to elucidate the genetic and epigenetic drivers of this disease, the prognosis for patients diagnosed with GBM remains dismal. Because tumor cell metabolism differs greatly from that of normal non-cancerous cells, it is possible to develop therapies which more effectively target the cancer cell while sparing normal cells. Growing in popularity is the ketogenic diet, which is a high fat, very low carbohydrate diet resulting in the production of ketone bodies, acetoacetate (AA) and β-hydroxybutyrate (βHB) to generate ATP. Methods: Analysis conducted by open-access GBM patient database, mts assay, Western blot, neurosphere assay, and TEM. Results: Enzymes required for ketone metabolism (BDH1 and OXCT1) were significantly downregulated in GBM while glycolytic enzymes were significantly upregulated (HK2, HK1, SLC2A3, NAMPT, G6PD). GBM stem cell (GSC) markers (CD44, STAT3) positively correlated with glycolytic enzymes. Ultrastructural analysis of GSCs indicated that about half of the mitochondria were missing cristae, highly suggestive of an increased glycolytic dependency. Treatment of patient-derived GSC lines as well as non-stem cell lines SJGBM2 (pediatric) and U87 (adult) resulted in a dose-dependent decrease in viability in response to the glycolytic inhibitor 2-deoxy-D-glucose (2-DG). When cells were exposed to ketone bodies, AA but not βHB induced a dose-dependent decrease in cell viability with 10 mM reducing viability ranging from 20-80% of non-treated controls. Western blot analysis demonstrated robust caspase activation and PARP cleavage in response to AA. Furthermore, AA significantly reduced GSC neurosphere formation at 2.5 mM suggesting inhibition of GSC self-renewal pathways. Combined treatment of low dose 2-DG (50 μM) with increasing concentrations of AA resulted in more cell death than either treatment. The effect was more than additive at the low concentrations of AA (1- 5 mM) suggesting synergy. Conclusions: Glycolytic inhibition in conjunction with the ketogenic diet may be a promising therapeutic route for this difficult-to-treat cancer.

scholarly journals A Ketogenic Diet and the Treatment of Autism Spectrum Disorder

2021 ◽  
Vol 9 ◽  
Author(s):  
Qinrui Li ◽  
Jingjing Liang ◽  
Na Fu ◽  
Ying Han ◽  
Jiong Qin
Keyword(s):  
Autism Spectrum Disorder ◽  
Ketogenic Diet ◽  
Mammalian Target Of Rapamycin ◽  
Stereotyped Behavior ◽  
Autism Spectrum ◽  
The Body ◽  
Spectrum Disorder ◽  
Brain Diseases ◽  
Low Carbohydrate Diet ◽  
Underlying Mechanisms

Autism spectrum disorder (ASD) is characterized by stereotyped behavior and deficits in communication and social interaction. There are no curative treatments for children with ASD. The ketogenic diet (KD) is a high-fat, appropriate-protein, and low-carbohydrate diet that mimics the fasting state of the body and is proven beneficial in drug-resistant epilepsy and some other brain diseases. An increasing number of studies demonstrated that a KD improved autistic behavior, but the underlying mechanisms are not known. We reviewed the neuroprotective role of a KD in ASD, which is likely mediated via improvements in energy metabolism, reductions in antioxidative stress levels, control of neurotransmitters, inhibition of the mammalian target of rapamycin (mTOR) signaling pathway, and modulation of the gut microbiota. A KD is likely a safe and effective treatment for ASD.

scholarly journals Ketogenic Diet in Alzheimer’s Disease

2019 ◽  
Vol 20 (16) ◽  
pp. 3892 ◽  
Author(s):  
Marta Rusek ◽  
Ryszard Pluta ◽  
Marzena Ułamek-Kozioł ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ketogenic Diet ◽  
Neurodegenerative Disorder ◽  
Ketone Bodies ◽  
Amyloid Β ◽  
The Body ◽  
Aging Brain ◽  
Effective Prevention ◽  
Low Carbohydrate Diet

At present, the prevalence of Alzheimer’s disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer’s disease. This review aims to examine the role of the ketogenic diet in Alzheimer’s disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer’s disease.

scholarly journals Crosstalk between the Ketogenic Diet and Epilepsy: From the Perspective of Gut Microbiota

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yuying Fan ◽  
Hua Wang ◽  
Xueyan Liu ◽  
Junmei Zhang ◽  
Gang Liu
Keyword(s):  
Gut Microbiota ◽  
Ketogenic Diet ◽  
Gut Microbiome ◽  
Ketone Bodies ◽  
Positive Impact ◽  
Neurological Diseases ◽  
Dietary Therapy ◽  
Neuroprotective Effects ◽  
Wide Range ◽  
Underlying Mechanisms

Given the association between a range of neurological disorders and changes in the gut microbiota, interest in the gut microbiota has recently increased. In particular, the significant involvement of the autoimmune processes in the development of epilepsy, one of the most serious and widespread neurological diseases, has led to a suggested link with the gut microbiome. Because the constitution of the gut microbiome can be influenced by diet, dietary therapy has been shown to have a positive impact on a wide range of conditions via alteration of the gut microbiota. An example of one such diet is the ketogenic diet (KD), which promotes a diet that contains high levels of fat, adequate levels of protein, and low levels of carbohydrate. Due to the near-total elimination of carbohydrates from the individual’s food in this ultra-high-fat diet, ketone bodies become an important source of energy. Although the ketogenic diet has proven successful in the treatment of refractory epilepsy and other illnesses, the underlying mechanisms of its neuroprotective effects have yet to be fully elucidated. Nevertheless, recent studies strongly indicate a role for the gut microbiota in the effective treatment of epilepsy with the ketogenic diet. The latest advances regarding the links between the ketogenic diet, gut microbiota, and epilepsy are reviewed in this article, with a particular focus on the role of the gut microbiota in the treatment outcome.

Predictors of Psychedelic Experience: A Thematic Analysis

2021 ◽  
Author(s):  
Annie McCartney ◽  
Hugh McGovern ◽  
Alexander De Foe
Keyword(s):  
Harm Reduction ◽  
Thematic Analysis ◽  
Adverse Reactions ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
First Person ◽  
Online Database ◽  
Early Step ◽  
Nuanced Understanding

Research on the therapeutic potential of psychedelic substances is rapidly expanding. A major limitation within this field is the unpredictability of individual responses to psychedelic substances. A better understanding of factors that can predict psychedelic experience is essential to both clinical progress and wider harm reduction frameworks. Ketamine, MDMA, LSD and psilocybin were selected for comparison due to their promising therapeutic effects and different mechanisms of action. The current study aimed to (a) identify factors that predict both positive and adverse psychedelic experience, and (b) compare these predictors across the four psychedelic substances. A thematic analysis was conducted on twenty-four subjective, first-person reports of psychedelic use (six per substance), sourced from the Erowid online database. The analysis revealed three external predictors (nature, music and preparation) and three internal predictors (understanding, mindset and motivation). Each predictor contained two sub-themes that further elucidated their meaning and impact. Nature and music emerged as potential tools for de-escalating adverse reactions to psychedelics, which was a novel finding. A comparison between substances further revealed that these predictors actually had different impacts, depending on the substance being taken. Finally, the importance of, and interrelationship between, preparation, mindset, understanding and motivation was made clear. The broader clinical and sociological implications of this were discussed, with particular reference to developing harm reduction frameworks. As psychedelic therapy and research continues to gain momentum, these findings constitute an early step in developing a more nuanced understanding of the factors shaping psychedelic experience.

scholarly journals NMR-Based Metabonomic Study Reveals Intervention Effects of Polydatin on Potassium Oxonate-Induced Hyperuricemia in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bin Han ◽  
Mengjuan Gong ◽  
Zhong Li ◽  
Yuqin Qiu ◽  
Zhongjie Zou
Keyword(s):  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
Therapeutic Effects ◽  
Holistic View ◽  
Branched Chain Amino Acid ◽  
Metabolic Mechanism ◽  
Branched Chain ◽  
Underlying Mechanisms ◽  
Natural Precursor ◽  
Potassium Oxonate

Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive. The present study was undertaken to evaluate the therapeutic effects and the underlying mechanisms of polydatin on potassium oxonate-induced hyperuricemia in rats through metabonomic technology from a holistic view. Nuclear magnetic resonance (NMR) spectroscopy was applied to capture the metabolic changes in sera and urine collected from rats induced by hyperuricemia and polydatin treatment. With multivariate data analysis, significant metabolic perturbations were observed in hyperuricemic rats compared with the healthy controls. A total of eleven and six metabolites were identified as differential metabolites related to hyperuricemia in serum and urine of rats, respectively. The proposed pathways primarily included branched-chain amino acid (BCAA) metabolism, glycolysis, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, purine metabolism, and intestinal microflora metabolism. Additionally, some metabolites indicated the risk of renal injury induced by hyperuricemia. Polydatin significantly lowered the levels of serum uric acid, creatinine, and blood urea nitrogen and alleviated the abnormal metabolic status in hyperuricemic rats by partially restoring the balance of the perturbed metabolic pathways. Our findings shed light on the understanding of the pathophysiological process of hyperuricemia and provided a reference for revealing the metabolic mechanism produced by polydatin in the treatment of hyperuricemia.

scholarly journals An effective medical replacement therapy: ketogenic diet for intractable childhood epilepsy

2021 ◽  
Vol 9 (4) ◽  
pp. 1234
Author(s):  
Ansh Chaudhary ◽  
Bhupendra Chaudhary
Keyword(s):  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Intractable Epilepsy ◽  
Coconut Oil ◽  
Epileptic Seizures ◽  
High Fat ◽  
Low Carbohydrate ◽  
History Of ◽  
Restrictive Diet ◽  
Long Chain Triglycerides

Ketogenic diet (KD) a high fat, adequate protein and low carbohydrate restrictive diet has a long history of its use in intractable epilepsy of childhood. The diet produces biochemical changes mimicking that of starvation. The high levels of ketone bodies produced by KD act as a major source of energy for brain replacing the usual glucose.1 Comprising the ratio of 4:1 (fat:carbohydrate and protein) by weight, the diet produces state of ketonemia or ketosis that leads to reduction in frequency of epileptic seizures by is unique mode of action. To increase the palatability medium chain triglycerides (as coconut oil) in ratio of 3:1 is used which is more efficiently absorbed and have lesser gastro intestinal side effects as compared to traditional 4:1 ratio diet with long chain triglycerides like PUFA

scholarly journals Dahuang Zhechong Pills Suppress Silicosis Fibrosis Progression via p38 MAPK/TGF-β1/Smad Pathway In Vitro

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Li-Juan Wu ◽  
Xiao-Yan He ◽  
Wen-Xiang Wang ◽  
Jie Liang ◽  
Yu-Die Zhang ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Therapeutic Potential ◽  
Blood Stasis ◽  
Therapeutic Effects ◽  
Smad Pathway ◽  
Nourishing Yin ◽  
Underlying Mechanisms ◽  
Smad3 Expression ◽  
Tgf Β1

Background. Dahuang Zhechong pills (DHZCP) is a classic Chinese medicinal prescription in “Treatise on Cold Pathogenic and Miscellaneous Diseases (Shanghan Zabing Lun),” and it has the function of tonifying blood, nourishing Yin, and removing blood stasis. Previous studies have shown that DHZCP could alleviate SiO2 induced pulmonary fibrosis in mice. This study aims to further explore the preventive and therapeutic effects of DHZCP against silicosis fibrosis and the underlying mechanisms in vitro. Methods. We used the experimental model of SiO2-induced MH-S cells to evaluate the therapeutic potential of DHZCP. MH-S cells induced by SiO2 were intervened with the drug-containing serum of DHZCP, and the effects of drug-containing serum of DHZCP on the MH-S cells were detected by CCK8, ELISA, flow cytometry, western blot, and immunofluorescence. Results. DHZCP improved cell viability by reducing apoptosis. It also decreased the levels of TNF-α, IL-1β, IL-6 in the supernatant of MH-S cells induced by SiO2, inhibited the expression of p38 MAPK, blocked the activation of NF-κB, and controlled the upstream inflammatory response by multiple targeting. Concomitantly, we observed upregulation of Smad7 and a marked decline in TGF-β1, α-SMA, Smad2, Smad3 expression in MH-S cells treated with DHZCP. Conclusion. To sum up, we conclude that DHZCP protects against SiO2-induced silicosis by reducing the persistent irritation of inflammation, regulating the p38 MAPK/TGF-β1/Smad pathway.

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