The ketogenic diet has the potential to decrease all-cause mortality without a concomitant increase in cardiovascular-related mortality.

The impact of the ketogenic diet (KD) on overall mortality and cardiovascular disease (CVD) mortality remains inconclusive.This study enrolled a total of 43,776 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2018 to investigate the potential association between dietary ketogenic ratio (DKR) and both all-cause mortality as well as cardiovascular disease(CVD) mortality.Three models were established, and Cox proportional hazards regression analysis was employed to examine the correlation. Furthermore, a restricted cubic spline function was utilized to assess the non-linear relationship. In addition, subgroup analysis and sensitivity analysis were performed.In the adjusted Cox proportional hazards regression model, a significant inverse association was observed between DKR and all-cause mortality (HR = 0.76, 95% CI = 0.63-0.9, P = 0.003). However, no significant association with cardiovascular mortality was found (HR = 1.13; CI = 0.79-1.6; P = 0.504). Additionally, a restricted cubic spline(RCS) analysis demonstrated a linear relationship between DKR and all-cause mortality risk. In the adult population of the United States, adherence to a KD exhibits potential in reducing all-cause mortality risk while not posing an increased threat of CVD-related fatalities.

Element Changes Occurring in Brain Point at the White Matter Abnormalities in Rats Exposed to the Ketogenic Diet During Prenatal Life.

A large number of clinical studies demonstrate that the ketogenic diet (KD) may be an effective approach to the reduction of epileptic seizures in children and adults. Such dietary therapy could also help pregnant women with epilepsy, especially since most antiseizure drugs have teratogenic action. However, there is a lack of medical data, considering the safety of using KD during gestation for the progeny. Therefore, we examined the influence of KD used prenatally in rats on the elemental composition of the selected brain regions in their offspring. For this purpose, synchrotron radiation-induced X-ray fluorescence (SR-XRF) microscopy was utilized, and elements such as P, S, K, Ca, Fe, and Zn were determined. Moreover, to verify whether the possible effects of KD are temporary or long-term, different stages of animal postnatal development were taken into account in our experiment. The obtained results confirmed the great applicability of SR-XRF microscopy to track the element changes occurring in the brain during postnatal development as well as those induced by prenatal exposure to the high-fat diet. The topographic analysis of the brains taken from offspring of mothers fed with KD during pregnancy and appropriate control individuals showed a potential influence of such dietary treatment on the brain levels of elements such as P and S. In the oldest progeny, a significant reduction of the surface of brain areas characterized by an increased P and S content, which histologically/morphologically correspond to white matter structures, was noticed. In turn, quantitative elemental analysis showed significantly decreased levels of Fe in the striatum and white matter of 30-day-old rats exposed prenatally to KD. This effect was temporary and was not noticed in adult animals. The observed abnormalities may be related to the changes in the accumulation of sphingomyelin and sulfatides and may testify about disturbances in the structure and integrity of the myelin, present in the white matter.

Is a Meta-Analysis of Clinical Trial Outcomes for Ketogenic Diets Justifiable? A Critical Assessment Based on Systematic Research.

While the macronutrient content of a ketogenic diet specifically utilized for childhood epilepsy is clearly defined in the literature, variations among other ketogenic diets exhibit substantial heterogeneity. Furthermore, studies utilizing ketogenic diets contain several confounders with notable impacts on outcomes, thereby rendering both their findings and those of the meta-analyses less reliable. The objective of this meta-epidemiological assessment was to scrutinize existing clinical trials that investigated the effects of ketogenic diets on patients with obesity and diabetes, thereby determining the feasibility of conducting a meta-analysis. The Ovid Medline, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases were searched from 1946 to 24 September 2024. Of the studies reviewed, none met the predefined inclusion criteria. However, seven articles met these criteria very closely. In the future, studies investigating the effects of ketogenic diets containing significant confounding factors should adopt a single definition of a ketogenic diet. Additionally, accurate measurement of actual macronutrient and caloric intake, along with regularly monitored nutritional ketosis, will be essential to highlight the true effects of a ketogenic diet.

The genetically predicted causal associations between circulating 3-hydroxybutyrate levels and malignant neoplasms: A pan-cancer Mendelian randomization study.

OBJECTIVE: The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers. METHODS: Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer. RESULTS: Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI] = 0.28[0.14-0.57] p = 3.92e-04), biliary malignancies (OR[95%CI] = 0.30[0.15-0.60], p = 7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI] = 0.25[0.09-0.71], p = 9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI] = 0.76[0.58-0.99], p = 0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI] = -0.073[-0.122∼-0.024], p = 0.0034) and enhanced susceptibility to HCC (OR[95%CI] = 13.9[9.76-19.79], p = 3.14e-48), biliary malignancies (OR[95%CI] = 4.04[3.22-5.07], p = 1.64e-33), nasopharyngeal cancer (OR[95%CI] = 3.26[1.10-9.67], p = 0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI] = 1.27[1.13-1.44], p = 1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI] = 1.076[1.01-1.15], p = 0.034). CONCLUSIONS: Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL.

The hydroxycarboxylic acid receptor HCA2 is required for the protective effect of ketogenic diet in epilepsy.

One third of epilepsy patients are resistant to treatment with current anti-seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2-deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.

Weight loss, changes in body composition and inflammatory status after a very low-energy ketogenic therapy (VLEKT): does gender matter?

BACKGROUND: Considering differences in body composition and inflammatory status between sexes, as well as recent recommendations advocating for personalized dietary approaches, this study aimed to explore how sex influences weight loss, changes in body composition, and inflammatory status in subjects with grade I and II obesity undergoing a 45-day of the Very Low-Energy Ketogenic Therapy (VLEKT). METHODS: Participants (21 premenopausal females and 21 males), included in the study adhered to the 45-day of the VLEKT and underwent assessments of anthropometric parameters (weight, height, body mass index-BMI -, and waist circumference), body composition via bioelectrical impedance analysis, and inflammatory status measured by high sensitivity C-reactive protein (hs-CRP) levels at baseline and post-intervention. RESULTS: At baseline, premenopausal females and males did not differ in BMI (p = 0.100) and hs-CRP levels (p = 0.948). Males demonstrated overall larger benefits than premenopausal females from the VLEKT in terms of weight loss (Δ% = - 11.63 ± 1.76 vs - 8.95 ± 1.65 kg, p < 0.001), fat mass (Δ% = - 30.84 ± 12.00 vs -21.36 ± 4.65 kg, p = 0.002), and hs-CRP levels (Δ% = - 41.42 ± 21.35 vs - 22.38 ± 17.30 mg/L, p = 0.003). Of interest, in males phase angle values are statistically improved compared to female (Δ% = 17.11 ± 9.00 vs 7.05 ± 3.30°, p < 0.001). CONCLUSION: These findings underscore the importance of considering sex-specific responses in personalized obesity treatment strategies, particularly dietary interventions like VLEKTs.

Oral Administration of a Novel, Synthetic Ketogenic Compound Elevates Blood ß-Hydroxybutyrate Levels in Mice in Both Fasted and Fed Conditions.

BACKGROUND/OBJECTIVES: Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. METHODS: Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2-3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. RESULTS: Concentration levels of ß-hydroxybutyrate in blood were elevated (ßHB; 2-3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. CONCLUSIONS: Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis.

Effects of a Carbohydrate Meal on Lipolysis.

BACKGROUND: Due to the increasing prevalence of obesity and type 2 diabetes, effective dietary recommendations are needed. Previously, we developed the low-insulin method: by avoiding insulinogenic, i.e., insulin-release-triggering foods, insulin secretion becomes reduced, lipolysis is stimulated, and energy production is shifted to ketosis with excess ketone bodies exhaled in the form of acetone. Now, we investigate how quickly stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm) is achieved, whether and for how long a carbohydrate meal inhibits ketosis, and whether the responses differ in healthy adults with different insulin levels. METHODS: An oral glucose tolerance test was conducted, and body composition and fasting insulin were determined at the beginning and end of the 14-day study. Participants (n = 10) followed a ketogenic diet and performed continuous glucose monitoring. Ketosis levels were determined by measuring breath acetone concentrations. On day 8, two white bread rolls with jam (72 g carbohydrates) were consumed for breakfast. RESULTS: After seven days, all participants achieved stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm), which dropped from 8.2 to 5.7 ppm (p = 0.0014) after the carbohydrate meal. It took five days to achieve stable ketosis again. The stratification of participants into tertiles according to their fasting insulin levels demonstrated that individuals with low fasting insulin levels achieved stable ketosis again after two days and those with medium insulin levels after five days, while those with high baseline values did not reach stable ketosis by the end of the study. CONCLUSIONS: By carbohydrate restriction, stable ketosis can be achieved within one week. However, a single carbohydrate meal inhibits ketosis for several days. This effect is pronounced in individuals with elevated fasting insulin levels.

Ketogenic Diet: A Review of Composition Diversity, Mechanism of Action and Clinical Application.

The ketogenic diet (KD) is a special high-fat, very low-carbohydrate diet with the amount of protein adjusted to one's requirements. By lowering the supply of carbohydrates, this diet induces a considerable change in metabolism (of protein and fat) and increases the production of ketone bodies. The purpose of this article is to review the diversity of composition, mechanism of action, clinical application and risk associated with the KD. In the last decade, more and more results of the diet's effects on obesity, diabetes and neurological disorders, among other examples have appeared. The beneficial effects of the KD on neurological diseases are related to the reconstruction of myelin sheaths of neurons, reduction of neuron inflammation, decreased production of reactive oxygen species, support of dopamine production, repair of damaged mitochondria and formation of new ones. Minimizing the intake of carbohydrates results in the reduced absorption of simple sugars, thereby decreasing blood glucose levels and fluctuations of glycaemia in diabetes. Studies on obesity indicate an advantage of the KD over other diets in terms of weight loss. This may be due to the upregulation of the biological activity of appetite-controlling hormones, or to decreased lipogenesis, intensified lipolysis and increased metabolic costs of gluconeogenesis. However, it is important to be aware of the side effects of the KD. These include disorders of the digestive system as well as headaches, irritability, fatigue, the occurrence of vitamin and mineral deficiencies and worsened lipid profile. Further studies aimed to determine long-term effects of the KD are required.

The role of ketogenic diets in the treatment of status epilepticus.

Status epilepticus is a severe neurological condition, characterized by abnormally, prolonged seizures. Recent studies have explored the use of ketogenic diets (KDs) as a potential therapeutic approach for refractory status epilepticus. This article summarises the recent literature and discussions regarding the practicalities of implementing KDs in the critical care setting. This overview was presented at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in April 2024.

The gut microbiota changed by ketogenic diets contribute to glucose intolerance rather than lipid accumulation.

The ketogenic diet (KD) is a popular option for managing body weight, though its influence on glucose and lipid metabolism was still inconclusive. Gut microbiota is modulated by dietary pattens and has been associated with the changes of metabolic homeostasis induced by KD. Here, we found that two types of KDs, KD1 (8.8% carbohydrate, 73.4% fat, 17.9% protein, 5.7 kcal/g) and KD2 (0.4% carbohydrate, 93.2% fat, 6.4% protein, 6.7 kcal/g), induced changes of gut microbiota and its metabolites, contributing to glucose intolerance but not lipid accumulation in mice. Following a 2-week intervention with KDs, mice fed on KD1 displayed symptoms related to obesity, whereas KD2-fed mice exhibited a decrease in body weight but had severe hepatic lipid accumulation and abnormal fatty acid metabolism, while both KDs led to significant glucose intolerance. Compared to the mice fed on a standard chow diet, the conventional mice fed on both KD1 and KD2 had significant shifted gut microbiota, lower levels of short chain fatty acids (SCFAs) and composition alteration of cecal bile acids. By using an antibiotic cocktail (ABX) to deplete most of the gut microbiota in mice, we found the disturbances induced by KDs in lipid metabolism were similar in the ABX-treated mice to their conventional companions, but the disturbances in glucose metabolism were absent in the ABX-treated mice. In conclusion, these findings suggest that ketogenic diets disrupted glucose and lipid metabolism, at least in mice, and highlight the gut microbial culprits associated with KD induced glucose intolerance rather than lipid accumulation.

Emerging Roles of Ketone Bodies in Cardiac Fibrosis.

Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition within the myocardium, poses a significant challenge in cardiovascular health, contributing to various cardiac pathologies. Ketone bodies (KBs), particularly ß-hydroxybutyrate (ß-OHB), have emerged as subjects of interest due to their potential cardioprotective effects. However, their specific influence on cardiac fibrosis remains underexplored. This literature review comprehensively examines the relationship between KBs and cardiac fibrosis, elucidating potential mechanisms through which KBs modulate fibrotic pathways. A multifaceted interplay exists between KBs and key mediators of cardiac fibrosis. While some studies indicate a pro-fibrotic role for KBs, others highlight their potential to attenuate fibrosis and cardiac remodeling. Mechanistically, KBs may regulate fibrotic pathways through modulation of cellular components such as cardiac fibroblasts, macrophages, and lymphocytes, as well as extracellular matrix proteins. Furthermore, the impact of KBs on cellular processes implicated in fibrosis, including oxidative stress, chemokine and cytokine expression, caspase activation, and inflammasome signaling are explored. While conflicting findings exist regarding the effects of KBs on these processes, emerging evidence suggests a predominantly beneficial role in mitigating inflammation and oxidative stress associated with fibrotic remodeling. Overall, this review underscores the importance of elucidating the complex interplay between KB metabolism and cardiac fibrosis. Insights gained have the potential to inform novel therapeutic strategies for managing cardiac fibrosis and associated cardiovascular disorders, highlighting the need for further research in this area.

Ketogenic ß-hydroxybutyrate regulates ß-hydroxybutyrylation of TCA cycle-associated enzymes and attenuates disease-associated pathologies in Alzheimer's mice.

Lysine ß-hydroxybutyrylation (Kbhb) is a post-translational modification that has recently been found to regulate protein functions. However, whether and how protein Kbhb modification participates in Alzheimer's disease (AD) remains unknown. Herein, we carried out 4D label-free ß-hydroxybutylation quantitative proteomics using brain samples of 8-month-old and 2-month-old APP/PS1 AD model mice and wild-type (WT) controls. We identified a series of tricarboxylic acid (TCA) cycle-associated enzymes including citrate synthase (CS) and succinate-CoA ligase subunit alpha (SUCLG1), whose Kbhb modifications were decreased in APP/PS1 mice at pathological stages. Sodium ß-hydroxybutyrate (Na-ß-OHB) treatment markedly increased Kbhb modifications of CS and SUCLG1 and their enzymatic activities, leading to elevated ATP production. We further found that Kbhb modifications at lysine 393 site in CS and at lysine 81 site in SUCLG1 were crucial for their enzymatic activities. Finally, we found that ß-OHB levels were decreased in the brain of APP/PS1 mice at pathological stages. While ketogenic diet not only significantly increased ß-OHB levels, Kbhb modifications and enzymatic activities of CS and SUCLG1, and ATP production, but also dramatically attenuated ß-amyloid plaque pathologies and microgliosis in APP/PS1 mice. Together, our findings indicate the importance of protein Kbhb modification for maintaining normal TCA cycle and ATP production and provide a novel molecular mechanism underlying the beneficial effects of ketogenic diet on energy metabolism and AD intervention.

Exogenous ketones exert antiseizure effects and modulate the gut microbiome and mycobiome in a clinically relevant murine model of epilepsy.

OBJECTIVE: Despite growing interest in the potential use of exogenous ketones for the treatment of epilepsy, their impact on seizures and the gut microbiome and mycobiome remain unclear. METHODS: Here, we examined the effects of both oral gavage and subcutaneous (SC) injection of a ketone ester (KE) in spontaneously epileptic Kcna1-null (KO) mice that model seminal aspects of human temporal lobe epilepsy. Electroencephalographic recordings and biochemical analyses were performed in KE-treated KO mice. Fecal microbial and fungal communities were profiled to determine whether the antiseizure activity of KE involves changes in the gut microbiome. RESULTS: We found that exogenous KE administration by SC injection was more effective than oral gavage in terms of rendering antiseizure effects while generating similar degrees of ketonemia. However, reductions in mean daily seizure counts were accompanied by overall alterations in the fecal bacterial microbiome. Either oral or SC injection imposed a greater impact on the microbiome in male than female mice. In males, oral KE decreased Bacteroidota phylum and genera of Ligilactobacillus and Muribaculaceae, whereas SC injection decreased Bacteroides, Lactobacillus, and Lachnospiraceae. The fecal mycobiome was affected by KE injection to a greater degree than by oral gavage, and more in females than in males, as reflected by an increase in Ascomycota and Saccharomyces. Correlation analysis between microbiome and seizure counts revealed that in mice receiving KE injection, the seizure count was positively correlated with an amplicon sequencing variant of Lactobacillus (Spearman rho = .64, p = .03) and tended toward a negative correlation with Saccharomyces (Spearman rho = -.57, p = .057). SIGNIFICANCE: Our findings demonstrate that exogenous ketone administration alone can induce antiseizure effects equally via different routes of administration, and that they induce differential shifts in both the bacterial microbiome and mycobiome.

Clinician Understanding, Acceptance and utilization of Ketogenic diet therapy for epilepsy in Australia and New Zealand: An online survey.

Ketogenic diet therapy (KDT) is an established treatment for people with epilepsy. As increasing evidence demonstrates effectiveness and safety of KDT on seizure reduction, cognition and behaviour, it is essential to evaluate factors hindering and supporting neurologists in prescribing KDT to strengthen quality, evidence-based, appropriate and equitable care. A study of Australian and New Zealand (ANZ) neurologists was undertaken via an online survey. Demographics, clinical role characteristics, perceptions of knowledge, use and experiences of KDT for epilepsy treatment were assessed. Responses were analysed using the Capability, Opportunity, Motivation and Behaviour (COM-B) model. 114 neurologists participated (18 % response rate). All were aware of KDT for epilepsy treatment, most (90 %) perceived it as acceptable and 85 % identified suitable patients in their practice. Poor knowledge of the KDT referral processes was a barrier for 64 %. Clinical role characteristics were significantly associated with perceived level of knowledge and use of KDT in practice, being more likely among paediatric neurologists), epileptologists and those in urban practices (p < 0.00001). Most neurologists (90 %) endorsed adoption of a KDT guideline to facilitate use of KDT in epilepsy management. This study established that KDT is accepted as a suitable treatment for epilepsy in ANZ. There is high variability in perceived knowledge and skills related to KDT, which impacts on utilization in clinical practice. Further education and resources for clinicians, allied health and community support agencies are needed to optimise the use of this valuable therapy. Additionally, a clear referral pathway would improve patient access.

Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes.

Background: Drug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs). Objective: This study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs. Materials and methods: This is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly. Results: We enrolled a cohort of 77 patients with a mean current age of 7.94 ± 3.83 years. The mean age of seizure onset was 15.5 months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox-Gastaut syndrome showed the most significant improvement (14/15) followed by patients with Dravet syndrome (6/8), and West syndrome (3/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet. Conclusion: The study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient's age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles.

Human Chorionic Gonadotropin (hCG) Injections Exacerbating Acute Intermittent Porphyria in a 34-Year-Old Woman.

A 34-year-old Asian woman arrived at the emergency department (ED) with complaints of sharp, cramping abdominal pain followed by stabbing chest pain that radiated to her back. She also reported numbness, tingling in both hands and feet, and a burning sensation. Upon examination, she exhibited tachycardia and persistently elevated blood pressure. Her lab results revealed low potassium and sodium levels. Despite testing negative for pregnancy, normal hepatic function test, and nerve conduction study, her symptoms persisted, and she was admitted to the intensive care unit for the monitoring and correction of her electrolyte imbalances. She was later discharged but continued to experience symptoms, prompting multiple ED visits. The patient reported the symptoms following a calorie-restricted ketogenic diet and receiving human chorionic gonadotropin (hCG) injections for weight loss, which led the providers to initially diagnose her with "keto flu" due to inadequate nutrient intake. Despite receiving this diagnosis, her symptoms worsened, and she experienced pain throughout her whole body, along with muscle pain and abnormal sensations. Further assessment revealed that her urine was brown and showed abnormal levels of porphyrins, indicating acute intermittent porphyria. A genetic test confirmed the presence of a pathogenic mutation in hydroxymethylbilane synthase (HMBS), leading to a diagnosis of late-onset acute intermittent porphyria.

Fueling Recovery: The Therapeutic Role of Ketogenic Diet in Neurological Pathologies.

The ketogenic diet (KD) has gained a lot of attraction in the management of neurological disorders. KD therapies are high-fat, low-carbohydrate diets intended to shift energy consumption and metabolism from carbohydrates to fat in ketogenesis. The oxidative phosphorylation of ketone bodies generates energy packets for body cells, especially the central nervous system, replacing the role of glucose. KD can benefit multiple neurologic disorders like migraine, motor neuron disease, autism, multiple sclerosis, neuro-oncology, drug-resistant epilepsy, and neurotrauma. KD can provide significant adjuncts to limited conventional therapies, highlighting the feasibility, safety, and potential efficacy in neurology and neurosurgical disease management.

Carbohydrate Restriction-Induced Elevations in LDL-Cholesterol and Atherosclerosis: The KETO Trial.

Background: Increases in low-density lipoprotein cholesterol (LDL-C) can occur on carbohydrate restricted ketogenic diets. Lean metabolically healthy individuals with a low triglyceride-to-high-density lipoprotein cholesterol ratio appear particularly susceptible, giving rise to the novel "lean mass hyper-responder" (LMHR) phenotype. Objectives: The purpose of the study was to assess coronary plaque burden in LMHR and near-LMHR individuals with LDL-C ≥190 mg/dL (ketogenic diet [KETO]) compared to matched controls with lower LDL-C from the Miami Heart (MiHeart) cohort. Methods: There were 80 KETO individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglyceride levels ≤80 mg/dL, without familial hypercholesterolemia, matched 1:1 with MiHeart subjects for age, gender, race, hyperlipidemia, hypertension, and smoking status. Coronary artery calcium and coronary computed tomography angiography (CCTA) were used to compare coronary plaque between groups and correlate LDL-C to plaque levels. Results: The matched mean age was 55.5 years, with a mean LDL-C of 272 (maximum LDL-C of 591) mg/dl and a mean 4.7-year duration on a KETO. There was no significant difference in coronary plaque burden in the KETO group as compared to MiHeart controls (mean LDL 123 mg/dL): coronary artery calcium score (median 0 [IQR: 0-56]) vs (1 [IQR: 0-49]) (P = 0.520) CCTA total plaque score (0 [IQR: 0-2] vs [IQR: 0-4]) (P = 0.357). There was also no correlation between LDL-C level and CCTA coronary plaque. Conclusions: Coronary plaque in metabolically healthy individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL on KETO for a mean of 4.7 years is not greater than a matched cohort with 149 mg/dL lower average LDL-C. There is no association between LDL-C and plaque burden in either cohort. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT057333255).

Ketogenic diets in clinical psychology: examining the evidence and implications for practice.

Introduction: The application of ketogenic dietary interventions to mental health treatments is increasingly acknowledged within medical and psychiatric fields, yet its exploration in clinical psychology remains limited. This article discusses the potential implications of ketogenic diets, traditionally utilized for neurological disorders, within broader mental health practices. Methods: This article presents a perspective based on existing ketogenic diet research on historical use, biological mechanisms, and therapeutic benefits. It examines the potential application of these diets in mental health treatment and their relevance to clinical psychology research and practice. Results: The review informs psychologists of the therapeutic benefits of ketogenic diets and introduces to the psychology literature the underlying biological mechanisms involved, such as modulation of neurotransmitters, reduction of inflammation, and stabilization of brain energy metabolism, demonstrating their potential relevance to biopsychosocial practice in clinical psychology. Conclusion: By considering metabolic therapies, clinical psychologists can broaden their scope of biopsychosocial clinical psychology practice. This integration provides a care model that incorporates knowledge of the ketogenic diet as a treatment option in psychiatric care. The article emphasizes the need for further research and training for clinical psychologists to support the effective implementation of this metabolic psychiatry intervention.