ABSTRACT
Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.
Subject(s)
Heart Arrest , Ketone Bodies , Ketone Bodies/metabolism , Humans , Heart Arrest/metabolism , Animals , Diet, KetogenicABSTRACT
Epilepsy is one of the most disabling neurological diseases. Despite proper pharmacotherapy and the availability of 2nd and 3rd generation antiepileptic drugs, deep brain stimulation, and surgery, up to 30-40% of epilepsy patients remain drug-resistant. Consequences of this phenomenon include not only decreased a quality of life, and cognitive, behavioral, and personal disorders, but also an increased risk of death, i.e., in the mechanism of sudden unexpected death in epilepsy patients (SUDEP). The main goals of epilepsy treatment include three basic issues: achieving the best possible seizure control, avoiding the undesired effects of treatment, and maintaining/improving the quality of patients' lives. Therefore, numerous attempts are made to offer alternative treatments for drug-resistant seizures, an example of which is the ketogenic diet. It is a long-known but rarely used dietary therapy for intractable seizures. One of the reasons for this is the unpalatability of the classic ketogenic diet, which reduces patient compliance and adherence rates. However, its antiseizure effects are often considered to be worth the effort. Until recently, the diet was considered the last-resort treatment. Currently, it is believed that a ketogenic diet should be used much earlier in patients with well-defined indications. In correctly qualified patients, seizure activity may be reduced by over 90% or even abolished for long periods after the diet is stopped. A ketogenic diet can be used in all age groups, although most of the available literature addresses pediatric epilepsy. In this article, we focus on the mechanisms of action, effectiveness, and adverse effects of different variants of the ketogenic diet, including its classic version, a medium-chain triglyceride diet, a modified Atkins diet, and a low glycemic index treatment.
Subject(s)
Diet, Ketogenic , Epilepsy , Diet, Ketogenic/methods , Humans , Epilepsy/diet therapy , Treatment Outcome , Drug Resistant Epilepsy/diet therapy , Quality of Life , Anticonvulsants/therapeutic use , Anticonvulsants/administration & dosage , ChildABSTRACT
While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.
Subject(s)
Colitis , Colon , Dextran Sulfate , Diet, Ketogenic , Dietary Fats , Disease Models, Animal , Fluorescein-5-isothiocyanate/analogs & derivatives , Mice, Inbred C57BL , Animals , Colitis/chemically induced , Colitis/diet therapy , Male , Mice , Dietary Fats/adverse effects , Colon/pathology , Colon/metabolism , Permeability , Tight Junction Proteins/metabolism , Interleukin-1beta/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , Tumor Necrosis Factor-alpha/metabolism , Fatty Acids , DextransABSTRACT
It is widely acknowledged that the ketogenic diet (KD) has positive physiological effects as well as therapeutic benefits, particularly in the treatment of chronic diseases. Maintaining nutritional ketosis is of utmost importance in the KD, as it provides numerous health advantages such as an enhanced lipid profile, heightened insulin sensitivity, decreased blood glucose levels, and the modulation of diverse neurotransmitters. Nevertheless, the integration of the KD with pharmacotherapeutic regimens necessitates careful consideration. Due to changes in their absorption, distribution, metabolism, or elimination, the KD can impact the pharmacokinetics of various medications, including anti-diabetic, anti-epileptic, and cardiovascular drugs. Furthermore, the KD, which is characterised by the intake of meals rich in fats, has the potential to impact the pharmacokinetics of specific medications with high lipophilicity, hence enhancing their absorption and bioavailability. However, the pharmacodynamic aspects of the KD, in conjunction with various pharmaceutical interventions, can provide either advantageous or detrimental synergistic outcomes. Therefore, it is important to consider the pharmacokinetic and pharmacodynamic interactions that may arise between the KD and various drugs. This assessment is essential not only for ensuring patients' compliance with treatment but also for optimising the overall therapeutic outcome, particularly by mitigating adverse reactions. This highlights the significance and necessity of tailoring pharmacological and dietetic therapies in order to enhance the effectiveness and safety of this comprehensive approach to managing chronic diseases.
Subject(s)
Diet, Ketogenic , Food-Drug Interactions , Ketosis , Humans , Biological Availability , Cardiovascular Agents/pharmacokinetics , Chronic Disease/drug therapy , Chronic Disease/therapy , Drug Interactions , Hypoglycemic Agents/pharmacokinetics , Ketosis/metabolismABSTRACT
Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of Cryptococcus neoformans and Candida albicans infection in combination with fluconazole-a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies. In this series of experiments, mice fed a ketogenic diet prior to infection with C. neoformans and treated with fluconazole had a significant decrease in fungal burden in both the brain (mean 2.66 ± 0.289 log10 reduction) and lung (mean 1.72 ± 0.399 log10 reduction) compared to fluconazole treatment on a conventional diet. During C. albicans infection, kidney fungal burden of mice in the keto-fluconazole combination group was significantly decreased compared to fluconazole alone (2.37 ± 0.770 log10-reduction). Along with higher concentrations of fluconazole in the plasma and brain tissue, fluconazole efficacy was maximized at a significantly lower concentration on a keto diet compared to a conventional diet, indicating a dramatic effect on fluconazole pharmacodynamics. Our findings indicate that a ketogenic diet potentiates the effect of fluconazole at multiple body sites during both C. neoformans and C. albicans infection and could have practical and promising treatment implications.IMPORTANCEInvasive fungal infections cause over 2.5 million deaths per year around the world. Treatments for fungal infections are limited, and there is a significant need to develop strategies to enhance antifungal efficacy, combat antifungal resistance, and mitigate treatment side effects. We determined that a high-fat, low-carbohydrate ketogenic diet significantly potentiated the therapeutic effect of fluconazole, which resulted in a substantial decrease in tissue fungal burden of both C. neoformans and C. albicans in experimental animal models. We believe this work is the first of its kind to demonstrate that diet can dramatically influence the treatment of fungal infections. These results highlight a novel strategy of antifungal drug enhancement and emphasize the need for future investigation into dietary effects on antifungal drug activity.
Subject(s)
Antifungal Agents , Candida albicans , Candidiasis , Cryptococcosis , Cryptococcus neoformans , Diet, Ketogenic , Disease Models, Animal , Fluconazole , Animals , Fluconazole/pharmacology , Fluconazole/administration & dosage , Mice , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacology , Candidiasis/drug therapy , Candidiasis/diet therapy , Candidiasis/microbiology , Candida albicans/drug effects , Cryptococcus neoformans/drug effects , Cryptococcosis/drug therapy , Cryptococcosis/microbiology , Cryptococcosis/diet therapy , Cryptococcosis/prevention & control , Female , Brain/metabolism , Brain/drug effects , Lung/microbiology , Lung/drug effectsABSTRACT
Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer poses a challenge for ICB therapy due to its immunosuppressive features. A ketogenic diet (KD) has been reported to enhance response to ICB therapy in some other cancer models. However, adverse effects associated with continuous KD were also observed, demanding better mechanistic understanding and optimized regimens for using KD as an immunotherapy sensitizer. In this study, we established a series of ICB-resistant prostate cancer cell lines and developed a highly effective strategy of combining anti-PD1 and anti-CTLA4 antibodies with histone deacetylase inhibitor (HDACi) vorinostat, a cyclic KD (CKD), or dietary supplementation of the ketone body ß-hydroxybutyrate (BHB), which is an endogenous HDACi. CKD and BHB supplementation each delayed prostate cancer tumor growth as monotherapy, and both BHB and adaptive immunity were required for the antitumor activity of CKD. Single-cell transcriptomic and proteomic profiling revealed that HDACi and ketogenesis enhanced ICB efficacy through both cancer cell-intrinsic mechanisms, including upregulation of MHC class I molecules, and -extrinsic mechanisms, such as CD8+ T-cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen-presenting cells, and diminished neutrophil infiltration. Overall, these findings illuminate a potential clinical path of using HDACi and optimized KD regimens to enhance ICB therapy for prostate cancer. SIGNIFICANCE: Optimized cyclic ketogenic diet and 1,3-butanediol supplementation regimens enhance the efficacy of immune checkpoint blockade in prostate cancer through epigenetic and immune modulations, providing dietary interventions to sensitize tumors to immunotherapy.
Subject(s)
Diet, Ketogenic , Drug Resistance, Neoplasm , Epigenesis, Genetic , Immune Checkpoint Inhibitors , Prostatic Neoplasms , Male , Diet, Ketogenic/methods , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/immunology , Prostatic Neoplasms/diet therapy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Humans , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Mice , Epigenesis, Genetic/drug effects , Animals , Cell Line, Tumor , Vorinostat/pharmacology , Vorinostat/therapeutic use , Vorinostat/administration & dosage , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , 3-Hydroxybutyric Acid , Xenograft Model Antitumor Assays , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/antagonists & inhibitorsABSTRACT
Se han popularizado diversas dietas para perder peso, incrementar la capacidad física y para el manejo de múltiples enfermedades crónicas: cardiovasculares, neurológicas o cutáneas. Destacan la dieta cetogénica y el ayuno intermitente, con resultados prometedores en la medicina tradicional y deportiva. Además, la dieta mediterránea se ha consolidado como una forma de alimentación de impacto positivo muy significativo en la salud. Otras dietas populares son la dieta «paleo», la dieta vegana y la libre de gluten. La dieta cetogénica, el ayuno intermitente y la dieta mediterránea aportan resultados favorables en dermatosis inflamatorias como la psoriasis, dermatitis atópica, hidradenitis supurativa o acné. La dieta mediterránea podría actuar también como factor protector para el desarrollo de algunas neoplasias cutáneas. En este artículo presentamos una revisión del papel de diversas dietas populares en el manejo de dermatosis. (AU)
Numerous diets for losing weight, building strength, and managing a range of cardiovascular, neurologic, and skin diseases have become popular in recent years. The ketogenic diet and intermittent fasting in particular have shown promising results in clinical and sports medicine. The Mediterranean diet, in turn, is widely recognized for its numerous health benefits. Also popular are the paleo diet and vegan and gluten-free diets. Positive effects on inflammatory conditions, such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne, have been observed in patients who practice intermittent fasting or follow ketogenic or Mediterranean diets. This last choice may also protect against certain skin cancers. We review the role of several popular diets in the management of skin disorders. (AU)
Subject(s)
Humans , Diet, Ketogenic , Fasting , Diet, Vegan , Diet, Mediterranean , Diet, Gluten-Free , DermatologyABSTRACT
Numerous diets for losing weight, building strength, and managing a range of cardiovascular, neurologic, and skin diseases have become popular in recent years. The ketogenic diet and intermittent fasting in particular have shown promising results in clinical and sports medicine. The Mediterranean diet, in turn, is widely recognized for its numerous health benefits. Also popular are the paleo diet and vegan and gluten-free diets. Positive effects on inflammatory conditions, such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne, have been observed in patients who practice intermittent fasting or follow ketogenic or Mediterranean diets. This last choice may also protect against certain skin cancers. We review the role of several popular diets in the management of skin disorders. (AU)
Se han popularizado diversas dietas para perder peso, incrementar la capacidad física y para el manejo de múltiples enfermedades crónicas: cardiovasculares, neurológicas o cutáneas. Destacan la dieta cetogénica y el ayuno intermitente, con resultados prometedores en la medicina tradicional y deportiva. Además, la dieta mediterránea se ha consolidado como una forma de alimentación de impacto positivo muy significativo en la salud. Otras dietas populares son la dieta «paleo», la dieta vegana y la libre de gluten. La dieta cetogénica, el ayuno intermitente y la dieta mediterránea aportan resultados favorables en dermatosis inflamatorias como la psoriasis, dermatitis atópica, hidradenitis supurativa o acné. La dieta mediterránea podría actuar también como factor protector para el desarrollo de algunas neoplasias cutáneas. En este artículo presentamos una revisión del papel de diversas dietas populares en el manejo de dermatosis. (AU)
Subject(s)
Humans , Diet, Ketogenic , Fasting , Diet, Vegan , Diet, Mediterranean , Diet, Gluten-Free , DermatologyABSTRACT
La dieta cetogénica constituyó desde su inicio un planteamiento sorprendente para el tratamiento de la epilepsia. Someter al organismo a un cambio en la obtención de energía, pasando de depender de los carbohidratos a hacerlo de las grasas, pone en marcha toda una serie de rutas bioquímicas que, de forma independiente pero también complementaria, dan lugar a un conjunto de efectos que benefician al paciente. Esta búsqueda de su mecanismo de acción, de idear cómo mejorar el cumplimiento y de aprovecharla para otras enfermedades ha marcado su trayectoria. En este artículo se revisan someramente estos aspectos, haciendo hincapié en la importancia de seguir realizando investigación básica y clínica para que este tratamiento pueda aplicarse con bases científicas sólidas.(AU)
The ketogenic diet was an amazing approach to treating epilepsy from its beginning. The body undergoes a change in obtaining energy, going from depending on carbohydrates to depending on fats, and then a whole series of biochemical routes are launched that, independently but also complementary, give rise to a set of effects that benefit the patient. This search for its mechanism of action, of devising how to improve compliance and take advantage of it for other diseases has marked its trajectory. This article briefl y reviews these aspects, emphasizing the importance of continuing to carry out basic and clinical research so that this treatment can be applied with solid scientific bases.(AU)
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Diet, Ketogenic/methods , Steroid Metabolism, Inborn Errors , Epilepsy/therapy , Diet TherapyABSTRACT
BACKGROUND: The effectiveness of ketogenic diet (KD) in ameliorating fatty liver has been established, although its mechanism is under investigation. Fibroblast growth factor 21 (FGF21) positively regulates obesity-associated metabolic disorders and is elevated by KD. FGF21 conventionally initiates its intracellular signaling via receptor ß-klotho (KLB). However, the mechanistic role of FGF21-KLB signaling for KD-ameliorated fatty liver remains unknown. This study aimed to delineate the critical role of FGF21 signaling in the ameliorative effects of KD on hepatic steatosis. METHODS: Eight-week-old C57BL/6 J mice were fed a chow diet (CD), a high-fat diet (HFD), or a KD for 16 weeks. Adeno-associated virus-mediated liver-specific KLB knockdown mice and control mice were fed a KD for 16 weeks. Phenotypic assessments were conducted during and after the intervention. We investigated the mechanism underlying KD-alleviated hepatic steatosis using multi-omics and validated the expression of key genes. RESULTS: KD improved hepatic steatosis by upregulating fatty acid oxidation and downregulating lipogenesis. Transcriptional analysis revealed that KD dramatically activated FGF21 pathway, including KLB and fibroblast growth factor receptor 1 (FGFR1). Impairing liver FGF21 signaling via KLB knockdown diminished the beneficial effects of KD on ameliorating fatty liver, insulin resistance, and regulating lipid metabolism. CONCLUSION: KD demonstrates beneficial effects on diet-induced metabolic disorders, particularly on hepatic steatosis. Liver FGF21-KLB signaling plays a critical role in the KD-induced amelioration of hepatic steatosis.
Subject(s)
Diet, Ketogenic , Fatty Liver , Fibroblast Growth Factors , Insulin Resistance , Animals , Mice , Mice, Inbred C57BLABSTRACT
Polycystic ovary syndrome (PCOS) is a multifaceted and heterogeneous disorder, linked with notable reproductive, metabolic, and psychological outcomes. During adolescence, key components of PCOS treatment involve weight loss achieved through lifestyle and dietary interventions, subsequently pursued by pharmacological or surgical therapies. Nutritional interventions represent the first-line therapeutic approach in adolescents affected by PCOS, but different kinds of dietary protocols exist, so it is necessary to clarify the effectiveness and benefits of the most well-known nutritional approaches. We provided a comprehensive review of the current literature concerning PCOS definition, pathophysiology, and treatment options, highlighting nutritional strategies, particularly those related to high-fat diets. The high-fat nutritional protocols proposed in the literature, such as the ketogenic diet (KD), appear to provide benefits to patients with PCOS in terms of weight loss and control of metabolic parameters. Among the different types of KD studies, very low-calorie ketogenic diets (VLCKD), can be considered an effective dietary intervention for the short-term treatment of patients with PCOS. It rapidly leads to weight loss alongside improvements in body composition and metabolic profile. Even though extremely advantageous, long-term adherence to the KD is a limiting factor. Indeed, this dietary regimen could become unsustainable due to the important restrictions required for ketosis development. Thus, a combination of high-fat diets with more nutrient-rich nutritional regimens, such as the Mediterranean diet, can amplify positive effects for individuals with PCOS.
Subject(s)
Diet, Ketogenic , Polycystic Ovary Syndrome , Female , Adolescent , Humans , Diet, High-Fat , Polycystic Ovary Syndrome/therapy , Body Composition , Weight LossABSTRACT
BACKGROUND: Acne, a chronic inflammatory disease impacting the pilosebaceous unit, is influenced significantly by inflammation and oxidative stress, and is commonly associated with obesity. Similarly, obesity is also associated with increased inflammation and oxidation. The role of diet in acne remains inconclusive, but the very low-calorie ketogenic diet (VLCKD), known for weight loss and generating anti-inflammatory ketone bodies, presents promising potential. Despite this, the effects of VLCKD on acne remain underexplored. This study aimed to investigate the efficacy of a 45-day active phase of VLCKD in reducing the clinical severity of acne in young women with treatment-naïve moderate acne and grade I obesity. METHODS: Thirty-one women with treatment-naïve moderate acne, grade I obesity (BMI 30.03-34.65 kg/m2), aged 18-30 years, meeting inclusion/exclusion criteria, and consenting to adhere to VLCKD were recruited. Baseline and post-intervention assessments included anthropometric measurements, body composition, phase angle (PhA), trimethylamine N-oxide (TMAO) levels, and reactive oxygen metabolite derivatives (dROMs) as markers of inflammation, dysbiosis, and oxidative stress, respectively. A comprehensive dermatological examination, incorporating the Global Acne Grading System (GAGS) and the Dermatology Life Quality Index (DLQI), was conducted for all women. RESULTS: VLCKD resulted in general improvements in anthropometric and body composition parameters. Significantly, there were significant reductions in both the GAGS score (Δ%: - 31.46 ± 9.53, p < 0.001) and the DLQI score (Δ%: - 45.44 ± 24.02, p < 0.001) after the intervention. These improvements coincided with significant decreases in TMAO (p < 0.001) and dROMs (p < 0.001) levels and a significant increase in PhA (Δ%: + 8.60 ± 7.40, p < 0.001). Changes in the GAGS score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjusting for Δ% FM. Changes in the DLQI score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjustment for Δ% FM. CONCLUSION: Given the side effects of drugs used for acne, there is an increasing need for safe, tolerable, and low-cost treatments that can be used for acne disease. The 45-day active phase of VLCKD demonstrated notable improvements in acne severity, and these improvements seemed to be attributable to the known antioxidant and anti-inflammatory effects of VLCKD.
Subject(s)
Acne Vulgaris , Diet, Ketogenic , Methylamines , Humans , Female , Diet, Ketogenic/adverse effects , Obesity/complications , Inflammation/complications , Anti-Inflammatory AgentsABSTRACT
Ketogenic dietary therapies (KDT) are diets that induce a metabolic condition comparable to fasting. All types of KDT comprise a reduction in carbohydrates whilst dietary fat is increased up to 90% of daily energy expenditure. The amount of protein is normal or slightly increased. KDT are effective, well studied and established as non-pharmacological treatments for pediatric patients with refractory epilepsy and specific inherited metabolic diseases such as Glucose Transporter Type 1 Deficiency Syndrome. Patients and caregivers have to contribute actively to their day-to-day care especially in terms of (self-) calculation and (self-) provision of dietary treatment as well as (self-) measurement of blood glucose and ketones for therapy monitoring. In addition, patients often have to deal with ever-changing drug treatment plans and need to document occurring seizures on a regular basis. With this review, we aim to identify existing tools and features of telemedicine used in the KDT context and further aim to derive implications for further research and development.
Subject(s)
Diet, Ketogenic , Telemedicine , Humans , Drug Resistant Epilepsy/diet therapy , Epilepsy/diet therapy , Child , Metabolism, Inborn Errors/diet therapyABSTRACT
Ketogenic diets have been widely used for weight loss and are increasingly used in the management of type 2 diabetes. Despite evidence that ketones have multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content and acid load, have prevented their widespread use in individuals with impaired kidney function. Clinical trial evidence focusing on major adverse kidney events is sparse. The aim of this review is to explore the effects of a ketogenic diet, with an emphasis on the pleiotropic actions of ketones, on kidney health. Given the minimal concerns in relation to the potential renoprotective effects of a ketogenic diet, future studies should evaluate the safety and efficacy of ketogenic interventions in kidney disease.
Subject(s)
Diabetes Mellitus, Type 2 , Diet, Ketogenic , Diet, Ketogenic/methods , Humans , Diabetes Mellitus, Type 2/diet therapy , Diabetic Nephropathies/diet therapy , Ketones , Kidney Diseases/diet therapyABSTRACT
Studies suggest that ketogenic diets (KD) may improve memory in mouse models of aging and Alzheimer's disease (AD). This study determined whether a continuous or intermittent KD (IKD) enhanced cognitive behavior in the TgF344-AD rat model of AD. At 6 months-old, TgF344-AD and wild-type (WT) littermates were placed on a control (CD), KD, or IKD (morning CD and afternoon KD) provided as two meals per day for 2 or 6 months. Cognitive and motor behavior and circulating ß-hydroxybutyrate (BHB), AD biomarkers and blood lipids were assessed. Animals on a KD diet had elevated circulating BHB, with IKD levels intermediate to CD and KD. TgF344-AD rats displayed impaired spatial learning memory in the Barnes maze at 8 and 12 months of age and impaired motor coordination at 12 months of age. Neither KD nor IKD improved performance compared to CD. At 12 months of age, TgF344-AD animals had elevated blood lipids. IKD reduced lipids to WT levels with KD further reducing cholesterol below WT levels. This study shows that at 8 or 12 months of age, KD or IKD intervention did not improve measures of cognitive or motor behavior in TgF344-AD rats; however, both IKD and KD positively impacted circulating lipids.
Subject(s)
Alzheimer Disease , Cognition , Diet, Ketogenic , Lipids , Animals , Rats , Cognition/physiology , Male , Alzheimer Disease/diet therapy , Alzheimer Disease/blood , Lipids/blood , Rats, Inbred F344 , Disease Models, Animal , 3-Hydroxybutyric Acid/blood , Maze Learning , Motor Activity , Rats, Transgenic , Behavior, AnimalABSTRACT
Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases (HDACs), reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality.
Subject(s)
Diet, Ketogenic , Humans , Ketone Bodies/metabolism , Fasting , Oxidative Stress/physiology , InflammationABSTRACT
Diet plays an emerging role in dermatologic therapy. The ketogenic and low-glycemic diets have potential anti-inflammatory and metabolic effects, making them attractive for treating inflammatory skin conditions. We provide an overview of the current evidence on the effects of ketogenic and low-glycemic diets on inflammatory skin conditions including acne, psoriasis, seborrheic dermatitis (SD), atopic dermatitis (AD), and hidradenitis suppurativa (HS). We conclude that low-glycemic diets show promise for treating acne, while the evidence for ketogenic diets in treating other inflammatory skin conditions is limited. Randomized clinical trials are needed to explore the efficacy of these diets as stand-alone or adjunctive treatments for inflammatory skin conditions.
