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List of ongoing clinical trials using ketogenic diets in cancer treatment
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Background:
The employment of dietary strategies such as ketogenic diets, which force cells to alter their energy source, has shown efficacy in the treatment of several diseases. Ketogenic diets are composed of high fat, moderate protein and low carbohydrates, which favor mitochondrial respiration rather than glycolysis for energy metabolism.
Des...
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Context 1
... remaining available completed trials focused mostly on the safety and feasibility of ketogenic diets in the oncological population, reporting for the most part favourable and encouraging results [50,67,68]. Ongoing trials using ketogenic diets as mono-or adjuvant therapies in cancer treatment are summarized in Table 1. ...
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Mitochondrial disorders are genetically and clinically heterogeneous, mainly affecting high energy-demanding organs due to impaired oxidative phosphorylation (OXPHOS). Currently, effective treatments for OXPHOS defects, with complex I deficiency being the most prevalent, are not available. Yet, clinical practice has shown that some complex I defici...
Citations
... These findings indicate that a metabolic-based treatment that bypasses damaged glycolytic pathways and impaired mitochondrial activity may have beneficial therapeutic effects [35]. By bypassing glycolysis, providing alternative energy substrates in the form of ketone bodies, and resetting the processes underlying glucose and energy metabolism, the KD positively impacts normalization of brain energy metabolism [46][47][48]. Additionally, it inhibits histone deacetylases and promotes metabolic regulation [35]. ...
The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics the physiological state of fasting. The potential therapeutic effects in many chronic conditions have led to the gaining popularity of the KD. The KD has been demonstrated to alleviate inflammation and oxidative stress, modulate the gut microbiota community, and improve metabolic health markers. The modification of these factors has been a potential therapeutic target in serious mental illness (SMI): bipolar disorder, major depressive disorder, and schizophrenia. The number of clinical trials assessing the effect of the KD on SMI is still limited. Preliminary research, predominantly case studies, suggests potential therapeutic effects, including weight gain reduction, improved carbohydrate and lipid metabolism, decrease in disease-related symptoms, increased energy and quality of life, and, in some cases, changes in pharmacotherapy (reduction in number or dosage of medication). However, these findings necessitate further investigation through larger-scale clinical trials. Initiation of the KD should occur in a hospital setting and with strict care of a physician and dietitian due to potential side effects of the diet and the possibility of exacerbating adverse effects of pharmacotherapy. An increasing number of ongoing studies examining the KD’s effect on mental disorders highlights its potential role in the adjunctive treatment of SMI.
... To date, there have been very few studies dedicated to exploring the mineral composition of fig seeds, despite their importance in providing essential nutrients that cannot be synthesized by the human body and must be obtained through dietary sources or supplements to meet daily nutritional requirements (Chongtham et al., 2020). Scientific evidence suggests that a diet rich in minerals can play a crucial role in preventing and treating various diseases, such as diabetes, heart disease, stroke, and cancer (Tolonen, 1990;Branco et al., 2016). Macro-elements, including calcium, phosphorus, sodium, magnesium, and potassium, are involved in vital cellular transmission and signaling processes. ...
Introduction
Ficus carica L. seeds are a substantial source of minor oil with high unsaturation levels and potent antioxidant properties. The study aims to evaluate the mineral composition, lipodomic profile, and vibrational fingerprints of 22 fig genotypes utilizing FTIR-ATR techniques and chemometrics.
Methods
FTIR-ATR spectroscopy and chemometric techniques were employed to examine the phenotypic diversity of fig seeds. The investigation was performed in detail. The research analyzed twenty-two fig genotypes to assess their nutritional properties, genetic relationships, and potential applications.
Results
The results demonstrate substantial nutritional benefits related to fig seeds, which could serve as genetic resources for selection programs for extracting vegetable oil and functional ingredients. Additionally, a detailed lipodomic profile analysis led to the categorization of the genotypes into four unique clusters. The study uncovered new insights regarding the nutritional composition of the samples, while also highlighting significant similarities and differences. The findings showcased the phenotypic diversity within the studied fig germplasm, which is likely attributed to underlying genetic factors. These accessions offer a valuable gene pool for future breeding programs and diverse applications involving fig seeds.
Discussion
This work contributes to the selection of potential genotypes for scientific and industrial purposes. Furthermore, the application of FTIR and chemometrics revealed a noteworthy diversity of patterns, emphasizing the previously underestimated significance of this aspect in evaluating the chemodiversity of the species.
... KD treatment may attenuate the effects of DM-dysregulated Na + and Ca 2+ homeostasis, contributing to its cardioprotection in DM. fat will be transformed into ketones, including beta-hydroxybutyrate (BHB), acetoacetate, acetone, and fatty acids (FAs). Evidence of the KD's possible health advantages includes neurological illnesses, cancer, and mitochondrial diseases [3][4][5], as well as BHB improved endogenous antioxidant defense and mitochondrial performance [5]. Moreover, increased circulating ketone levels in patients with heart failure may also improve their cardiac health [4,6] because, as oxygen-efficient, highly energetic fuel, ketone bodies may enhance the work capacity of the myocardium at risk [7,8]. ...
A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM.
... 11 There are clinical parallels between bipolar disorder and epilepsy, such as the pharmacological treatments that are effective, which could indicate similarities in underlying disease processes. 12 Case series have suggested benefits of a ketogenic diet in several psychiatric disorders, including bipolar disorder 13,14 and schizophrenia. 15,16 Analysis of data from online bipolar disorder forums (165 people with bipolar disorder adhering to a ketogenic diet) found that 56% reported either remission of symptoms or significant mood stabilisation. 4 Recent narrative reviews have indicated that a ketogenic diet may affect metabolic and biochemical features of bipolar disorder, including: reduction in oxidative stress; improved mitochondrial function and biogenesis; improved glutamate/GABA transmission; and reductions in intracellular sodium and calcium. ...
Background
Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.
Aims
To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.
Method
Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.
Results
Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).
Conclusions
The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.
... KD has been shown to improve survival, reduce tumor growth, and work in combination with cancer therapies in a variety of cancers, including malignant glioma, colon cancer, gastric cancer, and prostate cancer [6,8,9]. A strict KD consisting of 90% fat, 2% carbohydrates, and 8% proteins induces a metabolic state of glucose depletion, ketone body elevation (ketogenesis), increased fatty acid oxidation, and altered amino acid metabolism [10][11][12]. Some of the proposed anti-tumor benefits of KD include inhibition of the insulin/insulin growth factor (IGF) pathway, alteration in cancer stem cell properties, and upregulation of metabolic signaling pathways, such as AMP kinase activation [6,13]. ...
The ketogenic diet (KD) is hypothesized to impact tumor progression by altering tumor metabolism. In this study, we assessed the impact of an unrestricted KD on epithelial ovarian cancer (EOC) tumor growth, gene expression, and metabolite concentration in a mouse model. ID8 EOC cells, which were syngeneic with C57Bl/6J mouse strain and transfected with luciferase (ID8-luc), were injectedand monitored for tumor development. Female mice were fed either a strict KD, a high fat/low carbohydrate (HF/LC) diet, or a low fat/high carbohydrate (LF/HC) diet (n = 10 mice per group) ad libitum. EOC tumor growth was monitored weekly, and tumor burden was determined based on luciferase fluorescence (photons/second). At the endpoint (42 days), tumors were collected and processed for RNA sequencing. Plasma and tumor metabolites were evaluated using LC-MS. The KD-fed mice exhibited a statistically significant increase in tumor progression in comparison to the HF/LC- and LF/HC-fed groups (9.1 vs. 2.0 vs. 3.1-fold, respectively, p < 0.001). The EOC tumors of the KD-fed mice exhibited significant enrichment of the peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid metabolism pathways based on the RNA sequencing analysis when compared to the LF/HC- and HF/LC-fed mice. Thus, unrestricted KD diet enhanced tumor progression in our mouse EOC model. KD was associated with the upregulation of fatty acid metabolism and regulation pathways, as well as enrichment of fatty acid and glutamine metabolites.
... This metabolic shift reduces seizures by 50% in around half of children with drug-resistant epilepsy (11). There are clinical parallels between bipolar disorder and epilepsy, which could indicate similarities in underlying disease processes (12). ...
Background
Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. To date, no clinical trials have been conducted.
Aims
To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.
Methods
Euthymic individuals with bipolar disorder were recruited to a 6-8 week trial of a modified ketogenic diet and a range of clinical, economic and functional outcome measures were assessed.
Results
Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet at 6-8 weeks. The completeness of the outcomes dataset was 95% for daily ketone measures, 95% for daily glucose measures and 95% for daily Ecological Momentary Assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (SD= 0.77, Median = 1.1), and 91% of all readings indicated ketosis indicating a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).
Conclusions
The recruitment and retention of euthymic individuals with bipolar disorder to a 6-8 week ketogenic diet intervention was feasible, with high outcome measure completion rates. The majority of participants reached and maintained ketosis and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.
... It has been shown that the ketogenic diet increases the concentration of γ-aminobutyric acid affecting the action of glutamate in the central nervous system (in patients with autism, increased concentration of glutamate and increased expression of genes related to glutamatergic pathways) and also affects the function of mitochondria. It is assumed that this may play a beneficial role in patients with the autism spectrum (1,(21)(22)(23)(24)(25). There is only one study in the scientific literature addressing the impact of the ketogenic diet on the clinical aspects of autism. ...
The role of diet and supplementation in the prevention and treatment of autism spectrum disorders There is evidence indicating the positive effects of dietary intervention in the prevention and treatment of autism spectrum disorders. There are studies linking maternal vitamin D deficiency with ASD in offspring. Children and adolescents on the autism spectrum are also supposed to have significantly lower concentrations of vitamin D than healthy children and adolescents. This indicates the role of vitamin D supplementation in the prevention and treatment of ASD(5). Diets most commonly used in the therapy of autism spectrum disorders are: dairy-free and gluten-free, specific carbohydrate diet, low phenol, low oxalate and ketogenic diet(4). The most popular of them are dairy-free and gluten-free. However, studies conducted by Dr. James Adams attribute the highest effectiveness to a diet of specific carbohydrates(7). After applying the ketogenic diet, improvements in concentration, learning ability and social behavior were observed(1,26). However, it should be remembered that the scientific literature contains a small number of reliably conducted studies confirming the effectiveness of individual diets and supplementation in the prevention and treatment of ASD. Therefore, the positive impact of dietary intervention is still referred to as "potential". In addition, the use of certain diets may be associated with side effects, such as vomiting and hypoglycemia in the case of a ketogenic diet (1,28) and underweight in the case of elimination diets(16). Therefore, the introduction of dietary changes for therapeutic purposes should be carried out under the constant supervision of doctors and dieticians.
... The metabolic transformation leading to the Warburg effect we observe in cancer also underlies neuronal degeneration in sporadic AD (Traxler et al., 2022). Strategies intervening in this metabolic switch, inhibiting glycolysis and glutaminolysis, and promoting OXPHOS-keeping mitochondria healthy-could be interesting strategies in the fight against these conditions and others related to the Warburg effect (Manzi et al., 2015;Branco et al., 2016;Smyl, 2016;Cusso et al., 2019;Tran et al., 2020). ...
Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.
... Acetyl CoA is used to form ketones, which easily enter the brain, convert back to acetyl-CoA, and feed back into the Krebs cycle to produce more energy [6,7]. The KD content shares the same mechanism of ketone production as in starvation, allowing the body to thrive by using it as an alternative source of energy [8,9]. Despite an increase in fatty acid and ketone production the level of nutritional ketosis in the KD is relatively low, and not life-threatening, unlike diabetic ketoacidosis (DKA), which is an unbalanced state of high uncontrolled ketone production, as seen in type 1 diabetes cases [10]. ...
... Furthermore, several studies have recently been published on the benefits of KD in various neurological disorders. The proposed mechanisms include metabolic regulation, improved neurotransmission, increased neuroprotection and antiinflammatory properties, and a reduction in oxidative stress [9,12,13]. Intracellular signaling pathways are also involved in the metabolism of glucose, proteins, and fatty acids. Fasting and the KD can improve insulin and glucose balance by increasing SIRT1, inhibiting AMPK and PI3K/AKT/mammalian target of rapamycin (mTOR) signaling, and restoring mitochondrial function [14][15][16][17]. ...
... The KD has been found to be effective against cancer in a variety of ways as a co-adjuvant therapy [9]. There is growing interest in the effects of KD on brain cancer [65][66][67][68][69], particularly glioblastoma multiforme (GBM), based on the hypothesis that tumor cells require more glucose and have a limited ability to utilize ketone bodies. ...
The ketogenic diet (KD) is currently well known in the lay media as a quick way to lose weight. However, the KD is not a new medical concept. The KD was used in the early 1900s to control seizures. However, as we developed more effective pharmacological agents, we used the KD less until it became practically obscure by the 1980s. Similar to the effects of fasting, the KD leads to the production of ketones as an alternative energy source to glucose. Therefore, the KD has many beneficial metabolic effects, such as an improved immune response, regulation of signal transduction, inflammatory pathways, and neurotransmission. There is growing evidence that KD can be used in the management of various disorders, such as mitochondrial diseases, metabolic disorders, and even cancer. From a neurological standpoint, the KD may have therapeutic benefits in multiple sclerosis, traumatic brain injury, dementia, and stroke. The purpose of this brief narrative review is to outline the current research in the literature on the great potential of the KD as part of a comprehensive neurological treatment plan covering multiple neurological disorders such as status epilepticus, traumatic brain injuries, neurodegenerative diseases, autoimmune disorders, neuropathies, and cancers.
... Low carbohydrate content in ketogenic diet leads to increased fat metabolism and elevated levels of fatderived ketone in the blood. Since glucose is the main source of energy for cancer cells (the Warburg effect), a reduction in the availability of this fuel can be beneficial, controlling the proliferation and metastatic capacity (Branco et al., 2016). Low calorie diet, such as fasting inducing a state of ketosis, has been shown to enhance the responsiveness of cancer cells to chemotherapy in pre-clinical cancer therapy models and to ameliorate some of chemotherapy-induced side effects in normal tissues (Lee et al., 2012). ...
Cancer is a complex disease that results from multiple interactions between genes and the environment, and considered as leading causes of mortality in dogs and cats. Decreased food intake and metabolic abnormalities are seen in cancer patients, which in turn are associated with delayed recovery, as well as increased mortality. Metabolic condition called cachexia, is normally seen in cancer patients and is characterized by systemic inflammation, negative protein and energy balance, and weight loss. Nutrition therapy helps cancer patients to maintain healthy body weight, keep body tissue healthy, and decrease side effects both during and after treatment. Nutritional intervention in cancer patients aim to identify, prevent and treat malnutrition through the use of nutritional supplements. Foods that are low in simple carbohydrates with moderate amounts of high-quality protein, fiber, and fat (especially fats of the omega-3 fatty acid series) have been reported beneficial for cancer patients. The objective of the present review was to bring to light the most recent literature, summarise it and discuss the findings focusing on the benefits of appropriate nutritional inventions during oncological disease conditions in dogs and cats.
