Figure - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Source publication
Ketogenic diets and orally administered exogenous ketone supplements are strategies to increase serum ketone bodies serving as an alternative energy fuel for high energy demanding tissues, such as the brain, muscles, and the heart. The ketogenic diet is a low-carbohydrate and fat-rich diet, whereas ketone supplements are usually supplied as esters...
Contexts in source publication
Context 1
... refeeding, the presence of insulin and reduction of glucagon will reduce lipolysis and diminish the ketogenetic flux in the liver (8). Besides starvation, also diets low in carbohydrate content can be used to reach a state of ketosis (see Table 1). The latter carbohydrate restricted diets vary in their proportion of carbohydrates. ...Context 2
... recent years, the effectiveness of exogenous KB supplementation has been explored (15). Oral administered exogenous KB supplementation rapidly elevate plasma levels of KB during a ketogenic diet, but can also be taken as a supplement on top of a normal diet (see Table 1). The metabolic response, due to the presence of glucose, is however different. ...Similar publications
The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a compreh...
Background: Raspberry ketone (RK: [4-(4-Hydroxyphenyl)-2-butanone]) is a dietary supplement marketed for weight control. RK is structurally unrelated to the ketone bodies elevated with a ketogenic diet (KD). This study aims to determine whether RK oral supplementation with KD improves the weight loss outcomes in high-fat diet (HFD; 45% fat)-fed mic...
Background
The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending ¹⁸ F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using ¹⁸ F-FDG uptake as a surrogat...
Brain glucose hypometabolism is an early sign of Alzheimer’s disease (AD), and interventions which offset this deficit, such as ketogenic diets, show promise as AD therapeutics. Conversely, high-fat feeding may exacerbate AD risk. We analyzed the metabolomic profile of cerebrospinal fluid (CSF) in a pilot study of older adults who underwent saline...
There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for se...
Citations
... Increased ketone bodies in resistant cancer cells disrupt their survival and proliferation, inhibit glycolysis, and block the main pathway of energy production (22,24). Ketone supplementation or a ketogenic diet has shown positive therapeutic advantages in various malignancies, potentially targeting tumour metabolism as a new area for drug discovery (25). The molecular pathways affected by ketone body treatment in cancer cells include the JAK-STAT and mTOR pathways, which lead to decreased cell migration and inhibition of cellular growth and proliferation. ...
Background: The PI3K signalling pathway regulates the metabolic activity of cells. Disruption by PI3K inhibitors causes an aerobic/anaerobic imbalance that decreases energy production and cell growth. Cancer cells adapt to PI3K inhibitors in order to reduce their effectiveness. Resistance to apitolisib could be due to intrinsic factors or acquired adaptation. Oncologists often ask whether to discontinue apitolisib, increase its dose, or use a drug combination.
Methods: We observed the proliferation of resistant cells in (H1975R+) and out (H1975R-) of apitolisib treatment, cell cycle pattern, energy phenotyping/reprogramming, and the effects of combining Apitolisib with Vorinostat on the acquired proliferation of H1975R- cells.
Results: The Proliferation of H1975R- cells increased, while that of H1975R+ cells remained suppressed. Both conditions showed a 5x decrease in the number of cells at the Go/G1 phase and doubled at S and G2/M phases (p< 0.0001). H1975R- cell survival was 80% compared with 20% in H975R+ cells treated with 7 μM vorinostat. Vorinostat effectively controlled acquired hyperproliferation of H1975R- cells.
Conclusion: If a tumour becomes unresponsive to apitolisib, it is advisable to continue the inhibitor and consider a combination with non-tyrosine kinase inhibitors.
... Ketone salts, and sometimes ketone esters, are often racemic mixtures of the two optical isoforms of BHB, D-BHB and L-BHB, and the metabolism and function of L-BHB are poorly understood (43). D-BHB is the predominant circulating KB and is better oxidized than L-BHB, which only accounts for 2-3% of endogenous BHB production in the fasted state (49,50). This has led to L-BHB being thought of as not important, which might not be the case (50)(51)(52). ...
... Commercial ketone meters and standard laboratory analysis only detect D-BHB, and most do not test for AcAc (49). ...
ABSTRACT
Background: Post-Traumatic Stress Disorder (PTSD) is a severe and pervasive mental disorder, and patients experience numerous distressing symptoms and impairments that significantly impact their lives. In addition to being a mental disorder, PTSD is strongly associated with a wide range of metabolic abnormalities that affect the entire body. Existing treatment options of psychotherapy and medications are often ineffective. Exploring other potential treatments is necessitated. The ketogenic diet has shown potential as a metabolic therapy in certain neurological and mental disorders and is a promising intervention in the treatment of PTSD.
Aim: This study aimed to examine if a 4-week ketogenic diet intervention supplemented with exogenous ketones was feasible in adult patients with PTSD, to what extent it was possible to recruit patients, attain and maintain ketosis, the occurrence of serious adverse reactions and adverse reactions to KD-KS, and acceptance of treatment. Our exploratory aims were changes in PTSD symptoms and health-related quality of life (QoL) from baseline to 4 weeks.
Methods: Patients 18 ≤ 65 years old, diagnosed with PTSD, and receiving outpatient treatment for PTSD at Southern Oslo District Psychiatric Centre (DPC), Oslo University Hospital, Oslo, Norway, were included. The intervention consisted of a ketogenic diet supplemented with β-hydroxybutyrate salt (KD-KS) to obtain ketosis (plasma concentration of β-hydroxybutyrate (BHB) ≥ 0,5 mmol/L). PTSD symptoms were measured with the PTSD Checklist for DSM-5 (PCL-5) and QoL was measured with the RAND 36-Item Health Survey 1.0.
Results: During a 21-week inclusion period, three of four eligible patients (75% [95% CI: 30% to 95%]) were included. Two patients (67% [95% CI: 21% to 94%]) completed the 4-week intervention and one patient (33% [95% CI: 6% to 79%]) completed 2 weeks of intervention before discontinuing. Ketosis was achieved on day 1 in one patient, and on day 2 in two patients, and was maintained in 87% of the intervention. There were no serious adverse reactions. Adverse reactions were reported in a total of 70% of intervention days, the most frequent being headache followed by fatigue. The participant-perceived degree of adverse reactions was low to moderate. The treatment was accepted by patients on all intervention days. PCL-5 decreased by 20 points (70 to 50) in patient 1 and by 10 points (50 to 40) in patient 2, from baseline to 4 weeks, which is a reliable and clinically meaningful improvement. QoL improved in six of eight RAND-36 subscales in patient 1 and three of eight in patient 2. Patient 3 did not complete assessments after week 2.
Conclusion: To the best of our knowledge, this feasibility study is the first study examining a ketogenic diet intervention in patients with PTSD. Three of four predefined feasibility criteria were achieved. Ketosis was attained fast and maintained, patients were compliant and there were clinically meaningful improvements in PTSD symptoms and QoL. Despite the small sample size, the knowledge obtained in this study is important for the planning of future studies with ketogenic diet interventions in this patient group. It is a first step for potential dietary and metabolic therapies in PTSD. Further feasibility and pilot studies with larger sample sizes are needed to determine feasibility and safety before planning future randomised controlled trials investigating an effect.
Keywords: Post-Traumatic Stress Disorder (PTSD), ketogenic diet (KD), ketosis, ketogenic metabolic therapy (KMT), β-hydroxybutyrate (BHB), exogenous ketones, ketone salts (KS), metabolism
... During this metabolic state, known as ketosis, the circulating KBs become the main metabolic fuel. In addition to this primary metabolic role, KBs have been shown to influence a variety of cellular processes, including gene transcription, inflammation, and oxidative stress [17,18]. These mechanisms seem to be responsible for the beneficial effects of ketosis on a wide array of pathologies, such as neurodegenerative diseases, heart failure, and cancer. ...
Ursodeoxycholic acid (UDCA) and acetoacetate are natural compounds present in the human intestine and blood, respectively. A number of studies highlighted that besides their well-known primary biological roles, both compounds possess the ability to influence a variety of cellular processes involved in the etiology of various diseases. These reasons suggested the potential of acetoacetate–UDCA hybrids as possible therapeutic agents and prompted us to develop a synthetic strategy to selectively derivatize the hydroxyl groups of the bile acid with acetoacetyl moieties. 3α-acetoacetoxy UDCA was obtained (60% isolated yield) via the regioselective transesterification of methyl acetoacetate with UDCA promoted by the Candida antarctica lipase B (CAL-B). 3α,7β-bis-acetoacetoxy UDCA was obtained instead by thermal condensation of methyl acetoacetate and UDCA (80% isolated yield). This bis-adduct was finally converted to the 7β-acetoacetoxy UDCA (82% isolated yield) via CAL-B catalyzed regioselective alcoholysis of the ester group on the 3α position. In order to demonstrate the value of the above new hybrids as UDCA-based scaffolds, 3α-acetoacetoxy UDCA was subjected to multicomponent Biginelli reaction with benzaldehyde and urea to obtain the corresponding 4-phenyl-3,4-dihydropyrimidin-2-(1H)-one derivative in 65% isolated yield.
... The low-carbohydrate and fat-rich (typically about 80~90% energy from fat) ketogenic diet (KD) induces nutritional ketosis [6], and helps reduce the frequency and extent of seizures in patients with epilepsy [7]. Moreover, KD, or a very low-calorie KD, is protective against weight gain and cancers [8][9][10]. ...
... Nutritional ketosis can be induced by various dietary modifications, including KD, ketone supplementation, intermittent fasting, or calorie restriction [6], and is considered effective for weight loss, improved cognitive function, and cancer protection [6]. It has an inverse association between the blood ketone concentration and insulin resistance in subjects with T2DM [13], suggesting a relationship between nutritional ketosis and insulin resistance. ...
... Nutritional ketosis can be induced by various dietary modifications, including KD, ketone supplementation, intermittent fasting, or calorie restriction [6], and is considered effective for weight loss, improved cognitive function, and cancer protection [6]. It has an inverse association between the blood ketone concentration and insulin resistance in subjects with T2DM [13], suggesting a relationship between nutritional ketosis and insulin resistance. ...
Diabetes is often associated with reduced muscle mass and function. The ketogenic diet (KD) may improve muscle mass and function via the induction of nutritional ketosis. To test whether the KD is able to preserve muscle mass and strength in a mouse model of type 2 diabetes (T2DM), C57BL/6J mice were assigned to lean control, diabetes control, and KD groups. The mice were fed a standard diet (10% kcal from fat) or a high-fat diet (HFD) (60% kcal from fat). The diabetic condition was induced by a single injection of streptozotocin (STZ; 100 mg/kg) and nicotinamide (NAM; 120 mg/kg) into HFD-fed mice. After 8-week HFD feeding, the KD (90% kcal from fat) was fed to the KD group for the following 6 weeks. After the 14-week experimental period, an oral glucose tolerance test and grip strength test were conducted. Type 2 diabetic condition induced by HFD feeding and STZ/NAM injection resulted in reduced muscle mass and grip strength, and smaller muscle fiber areas. The KD nutritional intervention improved these effects. Additionally, the KD altered the gene expression of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome- and endoplasmic reticulum (ER) stress-related markers in the muscles of diabetic mice. Collectively, KD improved muscle mass and function with alterations in NLRP3 inflammasome and ER stress.
... Nonsurgical protocols for treating intractable epilepsy, drugresistant epilepsy and mitochondrial and pediatric epileptic seizures rely largely on ketogenic-related diets (Dyńka et al., 2022;Kim et al., 2022;Kocatürk et al., 2022;Lopriore et al., 2022a;Mu et al., 2022;Rho and Boison, 2022;Saris and Timmers, 2022;Zhou et al., 2023;Zhu et al., 2022). Ketogenic-related diets, which include fasting and intermittent fasting have proven therapeutic value, especially in pediatric epilepsy syndromes (Perucca et al., 2023;Rho and Boison, 2022). ...
Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging. Diagnosis and monitoring of childhood epilepsy add to the need for non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms of epileptogenesis are not fully understood, evidence for mitochondrial involvement is substantial. Seizures affect 35%-60% of patients diagnosed with mitochondrial diseases. Mitochondrial dysfunction is pathophysiological in various epilepsies, including those of non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads to altered neuronal bioenergetics, metabolism and neurological complications, including seizures. Iron-dependent lipid peroxidation initiates ferroptosis, a cell death pathway that aligns with altered mitochondrial bioenergetics, metabolism and morphology found in neurodegenerative diseases (NDDs). Studies in mouse genetic models with seizure phenotypes where the function of an essential selenoprotein (GPX4) is targeted suggest roles for ferroptosis in epilepsy. GPX4 is pivotal in NDDs, where selenium protects interneurons from ferroptosis. Selenium is an essential central nervous system micronutrient and trace element. Low serum concentrations of selenium and other trace elements and minerals, including iron, are noted in diagnosing childhood epilepsy. Selenium supplements alleviate intractable seizures in children with reduced GPX activity. Copper and cuproptosis, like iron and ferroptosis, link to mitochondria and NDDs. Connecting these mechanistic pathways to selenoproteins provides new insights into treating seizures, pointing to using medicines including prodrugs of lipoic acid to treat epilepsy and to potential alternative therapeutic approaches including transcranial magnetic stimulation (transcranial), photobiomodulation and vagus nerve stimulation.
... The increase in blood or urine levels of ketone bodies, namely ketosis, is a metabolic condition that takes place in course of low glucose availability, generally deriving from low-carbohydrate diets or a fasting state [23]. Ketosis, by itself, is a condition of metabolic stress which may exacerbate the clinical risk of pre-existing disease conditions such as ...
... The increase in blood or urine levels of ketone bodies, namely ketosis, is a metabolic condition that takes place in course of low glucose availability, generally deriving from low-carbohydrate diets or a fasting state [23]. Ketosis, by itself, is a condition of metabolic stress which may exacerbate the clinical risk of pre-existing disease conditions such as liver, kidney, or pancreatic insufficiency [24]. ...
Background Calorie restriction is recognized as a useful nutritional approach to improve the endocrine derangements and low fertility profile associated with increased body weight. This is particularly the case for dietary regimens involving ketosis, resulting in increased serum levels of ketone bodies such as β-hydroxy-butyrate (β-HB). In addition to serum, β-HB is detected in several biofluids and β-HB levels in the follicular fluid are strictly correlated with the reproductive outcome in infertile females. However, a possible direct role of ketone bodies on sperm function has not been addressed so far. Methods Semen samples were obtained from 10 normozoospermic healthy donors attending the University Andrology Unit as participants in an infertility survey programme. The effect of β-HB on cell motility in vitro was evaluated on isolated spermatozoa according to their migratory activity in a swim-up selection procedure. The effect of β-HB on spermatozoa undergone to capacitation was also assessed. Results Two hours of exposure to β-HB, 1 mM or 4 mM, proved to be ineffective in modifying the motility of freshly ejaculated spermatozoa isolated according to the migratory activity in a swim-up procedure (all p values > 0.05). Differently, sperm maintenance in 4 mM β-HB after capacitation was associated with a significantly higher percentage of sperm cells with progressive motility compared to β-HB-lacking control (respectively, 67.6 ± 3.5% vs. 55.3 ± 6.5%, p = 0.0158). Succinyl-CoA transferase inhibitor abolished the effect on motility exerted by β-HB, underpinning a major role for this enzyme. Conclusion Our results suggest a possible physiological role for β-HB that could represent an energy metabolite in support of cell motility on capacitated spermatozoa right before encountering the oocyte.
... βHB delivers more adenosine triphosphate (ATP) per mole of substrate as compared to pyruvate. Ketosis is achieved when blood βHB reaches concentrations ≥ 0.5 mmol/L [28]. The metabolic enzyme succinyl-CoA:3-ketoacid CoA transferase (SCOT) is not present in the liver, thus liver cells cannot use ketone bodies for energy and therefore acetoacetate and βHB can leave the liver and enter the bloodstream to be distributed to different body tissues including the brain with the help of monocarboxylate transporters [29,30]. ...
Some diets, such as high lipid and high glucose diets, are known to increase the risk of colorectal cancer. On the other hand, little is known about diets that prevent colonic carcinogenesis. The ketogenic diet, which is characterized by high fat and very low carbohydrate content, is one such diet. The ketogenic diet decreases the amount of available glucose for tumors and shifts to the production of ketone bodies as an alternative energy source for healthy cells. Cancer cells are unable to use the ketone bodies for energy thus depriving them of the energy needed for progression and survival. Many studies reported the beneficial effects of the ketogenic diet in several types of cancers. Recently, the ketone body β-hydroxybutyrate has been found to possess anti-tumor potential in colorectal cancer. Despite its beneficial effects, the ketogenic diet also has some drawbacks, some of which are related to gastrointestinal disorders and weight loss. Thus, studies are being directed at this time towards finding alternatives to following a strict ketogenic diet and supplementing patients with the ketone bodies responsible for its beneficial effects in the hope of overcoming some potential setbacks. This article discusses the mechanism by which a ketogenic diet influences growth and proliferation of tumor cells, it sheds the light on the most recent trials regarding its use as an adjunctive measure to chemotherapy in patients with metastatic colorectal cancer, and it explains the limitations of its usage in metastatic patients and the promising role of exogenous ketone supplementation in this setting.
The surge in popularity of fad diets has raised concerns about compromised health among individuals due to their beliefs and intentions regarding consumption. The aim of this study was to examine the prevalence of fad dieting among persons who are dieting and to determine the different factors influencing the inclination to adopt fad diets. Specifically, this study explored the ways in which individual openness to following fad diets, participation in diet trends, and characteristics may influence attitudes towards fad diet adoption. Data from 407 participants aged 18–34, collected via Google Forms, were analyzed using a high-ordered construct approach between the theory of planned behavior (TPB) and health belief model (HBM). Employing partial least squares structural equation modeling, significant results were obtained. The key findings revealed that knowledge about dieting, perceived benefits, and health motivation significantly influenced individuals’ intentions to adopt fad diets. Additionally, the study demonstrated significant impacts of health motivation on attitude and perceived behavioral control, subsequently affecting individuals’ intention to adopt dietary practices. Practical implications include the development of tailored health communication strategies for government agencies and informed decision-making support for individuals considering adopting fad diets. This research contributes valuable insights into the perception and psychological and social factors shaping dietary decisions, laying the groundwork for enhanced health education and intervention strategies. Furthermore, the study’s theoretical framework offers potential for extension and application to health-related food consumption behaviors across diverse cultural contexts.
We consider a heterogeneous, globally coupled population of excitatory quadratic integrate-and-fire neurons with excitability adaptation due to a metabolic feedback associated with ketogenic diet, a form of therapy for epilepsy. Bifurcation analysis of a three-dimensional mean-field system derived in the framework of next-generation neural mass models allows us to explain the scenarios and suggest control strategies for the transitions between the neurophysiologically desired asynchronous states and the synchronous, seizure-like states featuring collective oscillations. We reveal two qualitatively different scenarios for the onset of synchrony. For weaker couplings, a bistability region between the lower- and the higher-activity asynchronous states unfolds from the cusp point, and the collective oscillations emerge via a supercritical Hopf bifurcation. For stronger couplings, one finds seven co-dimension two bifurcation points, including pairs of Bogdanov–Takens and generalized Hopf points, such that both lower- and higher-activity asynchronous states undergo transitions to collective oscillations, with hysteresis and jump-like behavior observed in vicinity of subcritical Hopf bifurcations. We demonstrate three control mechanisms for switching between asynchronous and synchronous states, involving parametric perturbation of the adenosine triphosphate (ATP) production rate, external stimulation currents, or pulse-like ATP shocks, and indicate a potential therapeutic advantage of hysteretic scenarios.
