Ketogenic metabolic therapy in conjunction with standard treatment for glioblastoma: A case report
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ABSTRACT:
SUBMITTER: Phillips M
PROVIDER: S-EPMC10996027 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:Background Mast cell tumors (MCT) are common neoplasms in dogs and are similar to most other malignant cancers in requiring glucose for growth, regardless of histological grade. Ketogenic metabolic therapy (KMT) is emerging as a non-toxic nutritional intervention for cancer management in animals and humans alike. We report the case of a 7 years-old Pit Bull terrier that presented in 2011 with a cutaneous mast cell tumor under the right nostril. Methods The patient’s parent refused standard of care (SOC) and steroid medication after initial tumor diagnosis due to the unacceptable adverse effects of these treatments. Following tumor diagnosis, the patient’s diet was switched from Ol’Roy dog food to raw vegetables with cooked fish. The tumor continued to grow on this diet until July, 2013 when the diet was switched to a carbohydrate free, raw calorie restricted ketogenic diet consisting mostly of chicken and oils. A dog food calculator was used to reduce calories to 60% (40% calorie restriction) of that consumed on the original diet. A total of 444 kilocalories were given twice/day at 12 h intervals with one medium-sized raw radish given as a treat between each meal. Results The tumor grew to about 3–4 cm and invaded surrounding tissues while the patient was on the raw vegetable, cooked fish diet. The tumor gradually disappeared over a period of several months when the patient was switched to the carbohydrate free calorie restricted ketogenic diet. The patient lost 2.5 kg during the course of the calorie restriction and maintained an attentive and active behavior. The patient passed away without pain on June 4, 2019 (age 15 years) from failure to thrive due to an enlarged heart with no evidence of mast cell tumor recurrence. Conclusion This is the first report of a malignant cutaneous mast cell tumor in a dog treated with KMT alone. The resolution of the tumor in this canine patient could have been due to the diet-induced energy stress and the restriction of glucose-driven aerobic fermentation that is essential for the growth of most malignant tumors. Further studies are needed to determine if this non-toxic dietary therapeutic strategy could be effective in managing other canine patients with malignant mast cell tumors.
| S-EPMC10086349 | biostudies-literature
Project description:Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a universally lethal prognosis despite maximal standard therapies. Here, we present a consensus treatment protocol based on the metabolic requirements of GBM cells for the two major fermentable fuels: glucose and glutamine. Glucose is a source of carbon and ATP synthesis for tumor growth through glycolysis, while glutamine provides nitrogen, carbon, and ATP synthesis through glutaminolysis. As no tumor can grow without anabolic substrates or energy, the simultaneous targeting of glycolysis and glutaminolysis is expected to reduce the proliferation of most if not all GBM cells. Ketogenic metabolic therapy (KMT) leverages diet-drug combinations that inhibit glycolysis, glutaminolysis, and growth signaling while shifting energy metabolism to therapeutic ketosis. The glucose-ketone index (GKI) is a standardized biomarker for assessing biological compliance, ideally via real-time monitoring. KMT aims to increase substrate competition and normalize the tumor microenvironment through GKI-adjusted ketogenic diets, calorie restriction, and fasting, while also targeting glycolytic and glutaminolytic flux using specific metabolic inhibitors. Non-fermentable fuels, such as ketone bodies, fatty acids, or lactate, are comparatively less efficient in supporting the long-term bioenergetic and biosynthetic demands of cancer cell proliferation. The proposed strategy may be implemented as a synergistic metabolic priming baseline in GBM as well as other tumors driven by glycolysis and glutaminolysis, regardless of their residual mitochondrial function. Suggested best practices are provided to guide future KMT research in metabolic oncology, offering a shared, evidence-driven framework for observational and interventional studies.
| S-EPMC11622503 | biostudies-literature
Project description:Background: Successful treatment of glioblastoma (GBM) remains futile despite decades of intense research. GBM is similar to most other malignant cancers in requiring glucose and glutamine for growth, regardless of histological or genetic heterogeneity. Ketogenic metabolic therapy (KMT) is a non-toxic nutritional intervention for cancer management. We report the case of a 32-year-old man who presented in 2014 with seizures and a right frontal lobe tumor on MRI. The tumor cells were immunoreactive with antibodies to the IDH1 (R132H) mutation, P53 (patchy), MIB-1 index (4-6%), and absent ATRX protein expression. DNA analysis showed no evidence of methylation of the MGMT gene promoter. The presence of prominent microvascular proliferation and areas of necrosis were consistent with an IDH-mutant glioblastoma (WHO Grade 4). Methods: The patient refused standard of care (SOC) and steroid medication after initial diagnosis, but was knowledgeable and self-motivated enough to consume a low-carbohydrate ketogenic diet consisting mostly of saturated fats, minimal vegetables, and a variety of meats. The patient used the glucose ketone index calculator to maintain his Glucose Ketone Index (GKI) near 2.0 without body weight loss. Results: The tumor continued to grow slowly without expected vasogenic edema until 2017, when the patient opted for surgical debulking. The enhancing area, centered in the inferior frontal gyrus, was surgically excised. The pathology specimen confirmed IDH1-mutant GBM. Following surgery, the patient continued with a self-administered ketogenic diet to maintain low GKI values, indicative of therapeutic ketosis. At the time of this report (May 2021), the patient remains alive with a good quality of life, except for occasional seizures. MRI continues to show slow interval progression of the tumor. Conclusion: This is the first report of confirmed IDH1-mutant GBM treated with KMT and surgical debulking without chemo- or radiotherapy. The long-term survival of this patient, now at 80 months, could be due in part to a therapeutic metabolic synergy between KMT and the IDH1 mutation that simultaneously target the glycolysis and glutaminolysis pathways that are essential for GBM growth. Further studies are needed to determine if this non-toxic therapeutic strategy could be effective in providing long-term management for other GBM patients with or without IDH mutations.
| S-EPMC8200410 | biostudies-literature
Project description:BackgroundHigh-grade glioma cells consume mainly glucose and cannot compensate for glucose restriction. Apoptosis may potentially occur under carbohydrate restriction by a ketogenic diet (KD). We explored the feasibility and safety of KD during standard treatment of chemoradiation in patients with glioblastoma multiforme.MethodsA full liquid KD induced ketosis within 2 weeks before start of chemoradiation. After 6 weeks, the KD was modified with solid foods and medium-chain-triglyceride emulsions and used for an additional 6 weeks while maintaining ketosis. During the total study period (14 weeks), feasibility, safety, coping (both patient and partner), quality of life (QoL), neurological functioning and impairment were measured. Overall survival was analyzed with actuarial estimates.ResultsEleven patients started the study protocol, nine reached ketosis and six (67%) completed the study. Severe adverse effects did not occur. The majority of coping scores ranged from 3 to 6 on a 10-point scale at all timepoints; QoL, neurological functioning, and impairment did not essentially change over time; overall survival ranged between 9.8 and 19.0 months.ConclusionKD was feasible and safe as an adjuvant to standard chemoradiation treatment of glioblastoma multiforme. A supportive partner and intensive counseling were essential for coping. Future research should identify possible beneficial effects on overall survival.Clinical trial registrationNetherlands Trial Registry: NTR5167 (registration date 29-01-2015), http://www.trialregister.nl/trialreg/index.asp.
| S-EPMC6589986 | biostudies-literature
Project description: Not available
| S-EPMC11346312 | biostudies-literature
Project description:Background: Language and communication impairments are among the most frequently reported long-term behavioral consequences of brain tumor. Such deficits may persist long after a patient has been discharged from the hospital and can significantly impact return to work, resumption of prior social roles, and interpersonal relations, as well as full engagement in leisure activities. While considerable research has centered on identifying and describing communication impairments in brain tumor survivors, relatively little research has investigated language therapy for this population. Aims: This report (1) reviews the literature and describes the language and cognitive-communicative profile of a 35-year-old man 6 years post glioblastoma excision with subsequent chemo- and radiation therapies; (2) presents cognitive-communication outcome data for this individual following an integrated discourse therapy; and (3) assesses treatment feasibility in face-to-face (F2F) and tele-neurorehabilitation (TNR) contexts. Methods: A battery of tests and weekly conversation probes were administered to evaluate baseline performance and potential changes associated with F2F and TNR treatment delivery. Integrated Conversation Therapy (ICT) was administered across four alternating (F2F and TNR) treatment blocks over 2 months. ICT is a solution-focused discourse intervention that simultaneously targets word finding, sentence processing, and authentic patient-selected conversational interactions. Results: Although the participant presented with long term-language impairments that were clinically distinct from stroke-associated aphasia, statistically significant post-treatment gains (>2 SEM) were evident following F2F and TNR treatment delivery on standardized measures of apraxia, discourse production, verbal memory, and self-ratings of discourse production, communication, and living with aphasia. While objective measures of treatment effect size (probes of CIU discourse data) were consistent across F2F and TNR delivery models, results of a satisfaction survey indicated a slight but statistically significant participant preference for TNR treatment delivery. Conclusions: This study provides preliminary support for F2F and TNR delivery of ICT discourse intervention for glioblastoma survivors. It also highlights the need for more research specifically dedicated to language therapy for this population.
| S-EPMC7710897 | biostudies-literature
Project description:BackgroundVery-low-carbohydrate diets, including ketogenic and carnivore diets, are gaining popularity for the experimental treatment of a wide range of disorders, including inflammatory bowel disease (IBD).MethodsParticipants were recruited through a social media survey. Final inclusion required a histologically confirmed diagnosis of ulcerative colitis (UC) or Crohn's disease that was responsive to treatment with a ketogenic or carnivore diet without medication or with successful medication cessation on the diet. Clinical improvement was measured with the Inflammatory Bowel Disease Questionnaire (IBDQ).ResultsWe report on 10 cases of IBD responsive to ketogenic, mostly carnivore, diets. Clinical presentations were diverse, including six cases of UC and four of Crohn's disease. Clinical improvements were universal, with clinical improvement scores ranging between 72 and 165 points on the IBDQ. Patients' diets comprised mostly meat, eggs, and animal fats. Patients report their diets are pleasurable, sustainable, and unequivocally enhance their quality of life.ConclusionKetogenic and carnivore diets hold promise for the treatment of IBD, including UC and Crohn's disease. These cases are consistent with clinical literature that shows an inverse association between intestinal ketone levels and IBD activity, as well as the therapeutic effects of low residue elimination diets on colonic microbiota metabolism.
| S-EPMC11409203 | biostudies-literature
Project description:Aspergillary rhinopharyngitis in an equine patient
| PRJEB46193 | ENA
Project description:BackgroundEpidemiological data from the COVID-19 pandemic report that patients with pre-existing cardiovascular disease have worse outcomes and higher mortality, and that pregnant women should be considered at high risk.Case summaryA 25-year-old pregnant woman on the waiting list for a heart transplant, with a history of complete atrioventricular canal surgery, mitral mechanical prosthetic implant (St Jude-27), and cardiac resynchronization therapy (Boston Scientific) was hospitalized at 30 weeks of gestation for treatment of heart failure. After 7 days of hospitalization, she had a positive RT-PCR test for severe acute respiratory syndrome coronavirus 2 with progressive worsening of her clinical condition and acute foetal distress. Hence emergency caesarean section was performed. After the birth, the patient required mechanical ventilation, progressing to multiple organ system failures. Conventional inotropic drugs, antibiotics, and mechanical ventilation for 30 days in the intensive care unit provided significant clinical, haemodynamic, and respiratory improvement. However, on the 37th day, she suddenly experienced respiratory failure, gastrointestinal and airway bleeding, culminating in death.DiscussionProgressive physiological changes during pregnancy cause cardiovascular complications in women with severe heart disease and higher susceptibility to viral infection and severe pneumonia. COVID-19 is known to incite an intense inflammatory and prothrombotic response with clinical expression of severe acute respiratory syndrome, heart failure, and thromboembolic events. The overlap of these COVID-19 events with those of pregnancy in this woman with underlying heart disease contributed to an unfortunate outcome and maternal death.
| S-EPMC8557342 | biostudies-literature
Project description:The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.
| S-EPMC7794443 | biostudies-literature