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"In humans, both acute and chronic increases in ketone body availability to the central nervous system cause massive changes in cerebral fuel metabolism. In healthy middle-aged subjects, an i.v. infusion of BHB caused approximately 14% decrease in cerebral glucose consumption while oxygen use was unchanged, suggesting that ketone bodies, even when supplied acutely, enter the brain and may be utilized immediately as an alternative fuel to glucose. Similar cerebral metabolic changes have also been demonstrated in young individuals, however, at lower infusion rates, and thus lower BHB concentrations, glucose uptake does not seem to be affected. Together, this suggests an acute cerebral glucose-sparing effect when ketone availability is high." - "Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases" (2020)
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"Recent evidence suggests that myelin lipids may act as glial energy reserves when glucose is lacking, a hypothesis yet to be solidly proven. Hereby, we examined the effects of running a marathon on the myelin content by MRI. Our findings show that marathon runners undergo widespread robust myelin decrease at completion of the effort. This reduction involves white and gray matter, and includes primary motor and sensory cortical areas and pathways, as well as the entire corpus callosum and internal capsule. Notably, myelin levels partially recover within two weeks after the marathon. These results reveal that myelin use and replenishment is an unprecedented form of metabolic plasticity aimed to maintain brain function during extreme conditions." - "Widespread drastic reduction of brain myelin content upon prolonged endurance exercise" (2023)
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"Ketogenic diet improved mood including calmness, contentedness and alertness compared to other diet controls.
Individuals on ketogenic diet are less anxious and depressed compared to other diet controls.
Cognitive and emotional stress is lower in individuals on ketogenic diet compared to other diet controls." - "Ketogenic Diet has a positive association with mental and emotional well-being in the general population" (2024)
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"This review presents the available evidence for the use of the KD in the treatment of several psychiatric disorders. The results are positive, and all studies that met the inclusion criteria showed some form of benefit in those who were able to remain on the diet, regardless of the disease state." - "The use of the ketogenic diet in the treatment of psychiatric disorders" (2021)
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"Ketogenic diet therapy resulted in metabolic syndrome reversal in this cohort of serious mental illness. Participants with schizophrenia showed an average of 32 % improvement according to the brief psychiatric rating scale. The percentage of participants with bipolar who showed >1 point improvement in clinical global impression was 69 %. Greater biomarker benefits observed with ketogenic dietary adherence. Pilot trial suggests dual metabolic–psychiatric benefits from ketogenic therapy." - "Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial" (2024)
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"Complete remission of major depression and generalized anxiety disorder occurred within 7-12 weeks of therapeutic nutritional ketosis during treatment with a personalized animalbased ketogenic diet (ratio 1.5:1) in adults with complex comorbid depression and anxiety engaged in a specialized metabolic psychiatry program." - "Complete Remission of Depression and Anxiety using a Ketogenic Diet: Case Series" (2024)
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"After 4 months follow up, we found that the KD led to decreased plasma levels of proinflammatory cytokines (IL-12p70 and IL-1b) and brain-derived neurotrophic factor (BDNF). Additionally, we observed changes in the gut microbiome, increased expression of butyrate kinase in the gut, and altered levels of BDNF-associated miRNAs in the plasma. These cohort findings suggest that the KD may positively influence ASD sociability, as previously observed, by reducing inflammation, reversing gut microbial dysbiosis, and impacting the BDNF pathway related to brain activity." - "Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder" (2024)
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"As we previously observed an increase in life span and muscle function in aging mice on a ketogenic diet (KD), we aimed to investigate the effect of a KD on the maintenance of skeletal muscle mass with age [...]"
"Skeletal muscle mass was significantly greater at 26 months in the gastrocnemius of mice on the KD. This result in KD mice was associated with a shift in fiber type from type IIb to IIa fibers and a range of molecular parameters including increased markers of NMJ remodeling, mitochondrial biogenesis, oxidative metabolism, and antioxidant capacity, while decreasing endoplasmic reticulum (ER) stress, protein synthesis, and proteasome activity. Overall, this study shows the effectiveness of a long-term KD in mitigating sarcopenia. The diet preferentially preserved oxidative muscle fibers and improved mitochondrial and antioxidant capacity. These adaptations may result in a healthier cellular environment, decreasing oxidative and ER stress resulting in less protein turnover. These shifts allow mice to better maintain muscle mass and function with age." - "The ketogenic diet preserves skeletal muscle with aging in mice" (2021)
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"This study investigated the impact of an isocaloric and isonitrogenous ketogenic diet (KD) versus a traditional western diet (WD) on changes in body composition, performance, blood lipids, and hormonal profiles in resistance-trained athletes. Twenty-five college-aged men were divided into a KD or traditional WD from weeks 1 to 10, with a reintroduction of carbohydrates from weeks 10 to 11, while participating in a resistance training program. Body composition, strength, power, and blood lipid profiles were determined at weeks 0, 10, and 11. A comprehensive metabolic panel and testosterone levels were also measured at weeks 0 and 11. Lean body mass (LBM) increased in both the KD and WD groups (2.4% and 4.4%, p < 0.01) at week 10. However, only the KD group showed an increase in LBM between weeks 10 and 11 (4.8%, p < 0.0001). Finally, fat mass decreased in both the KD (−2.2 ± 1.2 kg) and WD groups (−1.5 ± 1.6 kg). Strength and power increased to the same extent in the WD and KD conditions from weeks 1 to 11. No changes in any serum lipid measures occurred from weeks 1 to 10; however, a rapid reintroduction of carbohydrate from weeks 10 to 11 raised plasma triglyceride levels in the KD group. Total testosterone increased significantly from weeks 0 to 11 in the KD diet (118 ng·dl−1) as compared to the WD (−36 ng·dl−1) from pre to post while insulin did not change. The KD can be used in combination with resistance training to cause favorable changes in body composition, performance, and hormonal profiles in resistance-trained men." - "Effects of Ketogenic Dieting on Body Composition, Strength, Power, and Hormonal Profiles in Resistance Training Men" (2020)
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"there was an overall greater anti-inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF-α, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1"
"a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet" - "Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation" (2007)
- "The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the findings of various studies, long-term AS consumption has effects on the gut microbiota and intestinal nutrient-sensing receptors in modulating incretin hormones, antimicrobial peptides, and cytokine secretion. These effects contribute to the regulation of glucose metabolism, ion transport, gut permeability, and inflammation and modulate the gut–brain, and gut–kidney axes. Based on the conflicting findings of several in vitro, in vivo, and randomized and controlled studies, artificial sweeteners may have a role in the pathogenesis of IBDs, functional bowel diseases, metabolic syndrome, and cancers via the modulation of nutrient-sensing receptors." - "The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde?" (2023)
- "Glioblastoma (GBM) is an aggressive primary human brain tumour that has resisted effective therapy for decades. Although glucose and glutamine are the major fuels that drive GBM growth and invasion, few studies have targeted these fuels for therapeutic management. The glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), was administered together with a calorically restricted ketogenic diet (KD-R) to treat late-stage orthotopic growth in two syngeneic GBM mouse models: VM-M3 and CT-2A. DON targets glutaminolysis, while the KD-R reduces glucose and, simultaneously, elevates neuroprotective and non-fermentable ketone bodies. The diet/drug therapeutic strategy killed tumour cells while reversing disease symptoms, and improving overall mouse survival. The therapeutic strategy also reduces edema, hemorrhage, and inflammation. Moreover, the KD-R diet facilitated DON delivery to the brain and allowed a lower dosage to achieve therapeutic effect. The findings support the importance of glucose and glutamine in driving GBM growth and provide a therapeutic strategy for non-toxic metabolic management." - "Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma" (2019)