A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

A ketogenic diet rich in fish oil is superior to other fats in preventing NNK-induced lung cancer in A/J mice.

Given that ketogenic diets (KDs) are extremely high in dietary fat, we compared different fats in KDs to determine which was the best for cancer prevention. Specifically, we compared a Western and a 15% carbohydrate diet to seven different KDs, containing either Western fats or fats enriched in medium chain fatty acids (MCTs), milk fat (MF), palm oil (PO), olive oil (OO), corn oil (CO) or fish oil (FO) for their ability to reduce nicotine-derived nitrosamine ketone (NNK)-induced lung cancer in mice. While all the KDs tested were more effective at reducing lung nodules than the Western or 15% carbohydrate diet, the FO-KD was most effective at reducing lung nodules. Correlating with this, mice on the FO-KD had low blood glucose and the highest ß-hydroxybutyrate level, lowest liver fatty acid synthase/carnitine palmitoyl-1a ratio and a dramatic increase in fecal Akkermansia. We found no liver damage induced by the FO-KD, while the ratio of total cholesterol/HDL was unchanged on the different diets. We conclude that a FO-KD is superior to KDs enriched in other fats in reducing NNK-induced lung cancer, perhaps by being the most effective at skewing whole-body metabolism from a dependence on glucose to fats as an energy source.

Icariin promotes bone marrow mesenchymal stem cells osteogenic differentiation via the mTOR/autophagy pathway to improve ketogenic diet-associated osteoporosis.

BACKGROUND: Icariin, a traditional Chinese medicine, has demonstrated anti-osteoporotic properties in ovariectomized mice. However, its effectiveness in preventing bone loss induced by ketogenic diet (KD), which mimics osteoporosis in human, remains unexplored. This study aims to investigate icariin's impact on KD-induced bone loss in mice. METHODS: Thirty mice were divided into: sham, KD, and KD + icariin groups. Post a 12-week intervention, evaluation including bone microstructures, serum concentrations of tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (ALP), and femoral tissue expression levels of osteocalcin (OCN) and TRAP. The expression levels of mammalian target of rapamycin (mTOR), ALP, peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphorylated mTOR (p-mTOR), and the autophagy adaptor protein (p62) were also analyzed. Alizarin granule deposition and cellular ALP levels were measured following the induction of bone marrow mesenchymal stem cells (BMSCs) into osteogenesis. RESULTS: The study found that KD significantly impaired BMSCs' osteogenic differentiation, leading to bone loss. Icariin notably increased bone mass, stimulated osteogenesis, and reduced cancellous bone loss. In the KD + icariin group, measures such as bone tissue density (TMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly higher than in the KD group. Additionally, bone trabecular separation (Tb.Sp) was markedly lower in the KD + icariin group. Moreover, icariin increased OCN and ALP levels while suppressing PPAR-γ, TRAP, p62, and p-mTOR. In cellular studies, icariin encouraged osteogenic development in BMSCs under KD conditions. CONCLUSIONS: Icariin effectively counteracts bone thinning and improves bone microstructure. Its mechanism likely involves stimulating BMSCs osteogenic differentiation and inhibiting bone resorption, potentially through mTOR downregulation. These findings suggest icariin's potential as an alternative treatment for KD-induced bone loss.

The Role of Diet in Parkinson's Disease.

The aim of this review is to examine the intersection of Parkinson's disease (PD) with nutrition, to identify best nutritional practices based on current evidence, and to identify gaps in the evidence and suggest future directions. Epidemiological work has linked various dietary patterns and food groups to changes in PD risk; however, fewer studies have evaluated the role of various diets, dietary components, and supplements in the management of established PD. There is substantial interest in exploring the role of diet-related interventions in both symptomatic management and potential disease modification. In this paper, we evaluate the utility of several dietary patterns, including the Mediterranean (MeDi), Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), Alternative Healthy Eating Index (AHEI), vegan/vegetarian, and ketogenic diet in persons with PD. Additionally, we provide an overview of the evidence relating several individual food groups and nutritional supplements to PD risk, symptoms and progression.

Ketogenic nutritional therapy (KeNuT)-a multi-step dietary model with meal replacements for the management of obesity and its related metabolic disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-diet therapies in endocrinology and metabolism.

PURPOSE: The ketogenic nutritional therapy (KeNuT) is an effective dietary treatment for patients with obesity and obesity-related comorbidities, including type 2 diabetes, dyslipidaemia, hypertension, coronary artery disease, and some type of cancers. However, to date an official document on the correct prescription of the ketogenic diet, validated by authoritative societies in nutrition or endocrine sciences, is missing. It is important to emphasize that the ketogenic nutritional therapy requires proper medical supervision for patient selection, due to the complex biochemical implications of ketosis and the need for a strict therapeutic compliance, and an experienced nutritionist for proper personalization of the whole nutritional protocol. METHODS: This practical guide provides an update of main clinical indications and contraindications of ketogenic nutritional therapy with meal replacements and its mechanisms of action. In addition, the various phases of the protocol involving meal replacements, its monitoring, clinical management and potential side effects, are also discussed. CONCLUSION: This practical guide will help the healthcare provider to acquire the necessary skills to provide a comprehensive care of patients with overweight, obesity and obesity-related diseases, using a multistep ketogenic dietary treatment, recognized by the Club of the Italian Society of Endocrinology (SIE)-Diet Therapies in Endocrinology and Metabolism.

Triheptanoin, an odd-medium-chain triglyceride, impacts brain cognitive function in young and aged mice.

ABSTRACTThe brain aging process triggers cognitive function impairment, such as memory loss and compromised quality of life. Cognitive impairment is based on bioenergetic status, with reduced glucose uptake and metabolism in aged brains. Anaplerotic substrates are reported to promote mitochondrial ATP generation, having been tested in clinical trials for the treatment of neurological disorders and metabolic diseases.Objectives and Methods: To assess whether the improvement in oxidative capacity ameliorates cognitive function in adults (12 weeks), and aged (22-month-old) C57/6BJ mice, they received (1) a ketogenic diet, (2) a ketogenic diet supplemented with the anaplerotic substance, triheptanoin, or (3) a control diet for 12 weeks. Spontaneous alternation and time spent in a previously closed arm in the Y-maze test and time interacting with an unknown object in the novel object recognition test (NORT) were used to evaluate working memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain left hemisphere, and cerebellum was also evaluated. Glucose transporter 3 (GLUT3) expression in the prefrontal lobe was analyzed by western blotting.Results: The ketogenic diet (KD) reduced spontaneous alternation in aged mice, leading to lower AChE activity in the aged prefrontal lobe and cerebellum, and in the parieto-temporal-occipital lobe of adult mice. Furthermore, KD decreased GLUT3 protein expression in the frontal lobe of the adults.Discussion: Supplementation of KD with triheptanoin prevented memory impairment and showed similar values of AChE activity and GLUT3 expression compared to the controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, improving cognitive function.

Tolerability and Acceptability of an Exogenous Ketone Monoester and Ketone Monoester/Salt Formulation in Humans.

Exogenous ketone ester and ketone ester mixed with ketone free acid formulations are rapidly entering the commercial marketspace. Short-term animal and human studies using these products suggest significant potential for primary or secondary prevention of a number of chronic disease conditions. However, a number of questions need to be addressed by the field for optimal use in humans, including variable responses among available exogenous ketones at different dosages; frequency of dosing; and their tolerability, acceptability, and efficacy in long-term clinical trials. The purpose of the current investigation was to examine the tolerability, acceptability, and circulating R-beta-hydroxybutyrate (R-ßHB) and glucose responses to a ketone monoester (KME) and ketone monoester/salt (KMES) combination at 5 g and 10 g total R-ßHB compared with placebo control (PC). Fourteen healthy young adults (age: 21 ± 2 years, weight: 69.7 ± 14.2 kg, percent fat: 28.1 ± 9.3%) completed each of the five study conditions: placebo control (PC), 5 g KME (KME5), 10 g KME (KME10), 5 g (KMES5), and 10 g KMES (KMES10) in a randomized crossover fashion. Circulating concentrations of R-ßHB were measured at baseline (time 0) following an 8-12 h overnight fast and again at 15, 30, 60, and 120 min following drink ingestion. Participants also reported acceptability and tolerability during each condition. Concentrations of R-ßHB rose to 2.4 ± 0.1 mM for KME10 after 15 min, whereas KMES10 similarly peaked (2.1 ± 0.1 mM) but at 30 min. KME5 and KMES5 achieved similar peak R-ßHB concentrations (1.2 ± 0.7 vs. 1.1 ± 0.5 mM) at 15 min. Circulating R-ßHB concentrations were similar to baseline for each condition by 120 min. Negative correlations were observed between R-ßHB and glucose at the 30 min time point for each condition except KME10 and PC. Tolerability was similar among KME and KMES, although decreases in appetite were more frequently reported for KMES. Acceptability was slightly higher for KMES due to the more frequently reported aftertaste for KME. The results of this pilot investigation illustrate that the KME and KMES products used increase circulating R-ßHB concentrations to a similar extent and time course in a dose-dependent fashion with slight differences in tolerability and acceptability. Future studies are needed to examine variable doses, frequency, and timing of exogenous ketone administration for individuals seeking to consume ketone products for health- or sport performance-related purposes.

Ketogenic Diet: A Nutritional Therapeutic Tool for Lipedema?

PURPOSE OF REVIEW: This review aims to provide an overview of the current evidence on the efficacy, also considering the anti-inflammatory properties and safety of very low-calorie ketogenic diet (VLCKD) as a potential treatment for lipedema, particularly in the context of obesity. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal and painful fat buildup on the legs and/or arms. It is often misdiagnosed as obesity or lymphedema. However, although lipedema and obesity can coexist, unlike obesity, lipedema usually affects the legs and thighs without affecting the feet or hands, and the abnormal deposition of adipose tissue in lipedema is painful. The current lifestyle interventions are often unsuccessful in the management of lipedema. There is no consensus on the most effective nutritional approach for managing lipedema. Recent studies have suggested that VLCKD may be an effective treatment for lipedema, demonstrating that it is also superior to other nutritional approaches such as Mediterranean diet or intermittent fasting. Lipedema is a chronic and debilitating disease characterized by abnormal and painful accumulation of adipose tissue in the legs. VLCKD has been shown to be an effective treatment for lipedema, especially in the context of obesity, due to its anti-inflammatory properties. However, further research is needed to determine the long-term safety and efficacy of VLCKD as a treatment for lipedema.

Ketogenic effects of medium chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers: a randomized, double-blinded, placebo-controlled, single dose-response study.

The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, ß-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy. Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.

Exogenous Ketone Supplementation and Ketogenic Diets for Exercise: Considering the Effect on Skeletal Muscle Metabolism.

In recent years, ketogenic diets and ketone supplements have increased in popularity, particularly as a mechanism to improve exercise performance by modifying energetics. Since the skeletal muscle is a major metabolic and locomotory organ, it is important to take it into consideration when considering the effect of a dietary intervention, and the impact of physical activity on the body. The goal of this review is to summarize what is currently known and what still needs to be investigated concerning the relationship between ketone body metabolism and exercise, specifically in the skeletal muscle. Overall, it is clear that increased exposure to ketone bodies in combination with exercise can modify skeletal muscle metabolism, but whether this effect is beneficial or detrimental remains unclear and needs to be further interrogated before ketogenic diets or exogenous ketone supplementation can be recommended.

Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate.

The ketogenic diet (KD) has emerged as a popular weight-loss regimen in recent years. However, it has been confirmed to elicit a mild inflammatory response in the intestinal epithelium and exacerbate various digestive disorders. The severity of acute pancreatitis (AP) is closely associated with the permeability of the intestinal epithelium and gut microbiota, yet the impact of KD on acute pancreatitis remains unclear. In this study, we induced acute pancreatitis using L-arginine in mice fed with KD. The consumption of KD resulted in an elevation of lipopolysaccharide-binding protein (LBP), accompanied by upregulated cytokines (IL-1a, IL-5, IL-12, MIP-1a, and Rantes) and dysfunction of the intestinal barrier both in control and AP groups. The bloom of Lachnospirales and Erysipelotrichales was observed as a specific profile of gut microbiota in KD-fed mice with AP, along with downregulation of carbohydrate metabolism and depletion of short-chain fatty acids (SCFAs). Antibiotic decontamination reduced the cytokine storm and tissue necrosis but did not significantly improve the integrity of the intestinal barrier in KD-fed mice with AP. The overgrowth of Mycoplasmatales in feces and Enterobacterales in colonic tissue appears to explain the limitation of antibiotic treatment to aggravate acute pancreatitis. Butyrate supplementation attenuated the depletion of SCFAs, promoted the intestinal barrier, and reduced the necrotic area in AP mice. The bloom of Bacteroidales and the correlated increase in tryptophan metabolism explain the therapeutic potential of butyrate supplements for acute pancreatitis. In conclusion, our findings suggest that the ketogenic diet exacerbates acute pancreatitis through its impact on the gut microbiota and subsequent disruption of the intestinal barrier, while butyrate supplementation reverses this effect.

Circadian Oscillations of Minimal Erythema Dose (MED) are Also Influenced by Diet in Patients with Psoriasis: A Chronomedical Study.

INTRODUCTION: Minimal erythema dose (MED) remains a parameter of paramount importance to orient narrow-band (NB)-UVB phototherapy in psoriatic (PsO) patients. Recently, circadian rhythm and diet were recognized as potential MED modulators, but their mutual interaction remains understudied. Thus, we aimed to evaluate the potential diet modulation of MED circadian oscillations. METHODS: In the first phase, a cohort study was performed comparing potential MED oscillations (morning, afternoon, and evening) among omnivorous psoriatic patients before and after a phototherapy cycle and omnivorous healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Then, in the second phase, another cohort study was carried out comparing MED oscillations 24 h after the last phototherapeutic session only in psoriatic patients cleared with NB-UVB and undergoing different diets (vegan, vegetarian, paleo , ketogenic, intermittent circadian fasting, and omnivore). Patients with different diets were age-, gender-, and skin-type matched. RESULTS: In the first phase, we enrolled only omnivores, specifically 54 PsO patients and 54 healthy individuals. Their MED before and after NB-UVB therapy changed significantly among the three different time-points (morning, afternoon, and evening) (p < 0.001). The time effect was statistically significant in both groups before and after phototherapy. In the second phase, we enrolled 144 PsO patients (vegan, vegetarian, paleo, ketogenic, intermittent circadian fasting, and omnivore). MED circadian oscillations preserved a significant difference also after clearance and were influenced by diet type and time of day (p < 0.001). In particular, vegans displayed the lowest MED values, whilst Ramadan fasting showed the highest values in morning, afternoon, and evening. CONCLUSIONS: Diet, like other ongoing therapies, should be reported in the medical records of patients with psoriasis undergoing NB-UVB and patients with lower MEDs should be preferentially treated in the morning when the MED is higher.

The Ketogenic Diet and Cardiovascular Diseases.

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 comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area.

Dietary interventions and precision nutrition in cancer therapy.

In recent years dietary interventions have become a promising tool in cancer treatment and have demonstrated a powerful ability to alter metabolism and tumor growth, development, and therapeutic response. However, because the mechanisms underlying dietary therapeutics are poorly understood, they are frequently ignored as a potential line of treatment for cancer. We discuss the proposed mechanisms behind the anticancer effects of various diets and their development for clinical use. This review aims to provide researchers and clinicians in the field of oncology with a complete overview of the contemporary landscape of nutritional interventions and precision nutrition as cancer therapeutics, and offers a perspective on the steps necessary to establish nutritional interventions as a standard line of treatment.

Cannabidiol-Decorated Berberine-Loaded Microemulsions Improve IBS-D Therapy Through Ketogenic Diet-Induced Cannabidiol Receptors Overexpression.

Background: Berberine (BR) shows promise as a candidate for treating irritable bowel syndrome with diarrhea (IBS-D). However, the undesired physicochemical properties and poor oral absorption limit its clinical translation. A ketogenic diet (KD) can induce intestinal overexpression of cannabidiol (CB) receptors, which may offer a potential target for IBS-D-specific delivery of BR. Methods: The microemulsions loaded with BR and decorated with cannabidiol (CBD/BR-MEs) were developed through a one-step emulsion method. The pharmaceutical behaviors of the CBD/BR-MEs were measured using dynamic light scattering and high-performance liquid chromatography. The efficacy of the anti-IBS-D therapy was evaluated by assessing fecal water content, Bristol score, and AWR score. The intestinal permeability were assessed through immunofluorescent staining of CB1 and ZO-1, respectively. The signaling of CREB/BDNF/c-Fos was also studied along with immunofluorescent and immunohistochemical examination of brain sections. Results: The CBD/BR-MEs, which had a particle size of approximately 30 nm and a surface density of 2% (wt%) CBD, achieved greater than 80% (wt%) encapsulation efficiency of BR. The pharmacokinetics performance of CBD/BR-MEs was significantly improved in the KD-fed IBS-D rats than the standard diet-fed ones, which is highly related to intestinal expression of CB1 receptors. The treatment with CBD/BR-MEs and KD exhibited evident comprehensive advantages over the other groups in terms of anti-IBS-D efficacy. CBD/BR-MEs and KD synergistically decreased intestinal permeability. Moreover, the treatment with CBD/BR-MEs and KD not only blocked the CREB/BDNF/c-Fos signaling in the brain but also decreased the levels of neurotrophic factors, neurotransmitters, and inflammatory cytokines in the serum of IBS-D model rats. Conclusion: Such a design represents the first attempt at IBS-D-targeted drug delivery for improved oral absorption and efficacy through KD-induced target exposure, which holds promising potential for the treatment of IBS-D.

Nummular headache: a case report of remission following ketogenic diet and botulinum toxin type A injections.

Nummular headache is an unusual facial pain disorder with no evidence-based therapy recommendations. The ketogenic diet is an alternative therapy that demonstrated to be effective in migraineurs, but it was never used in the setting of nummular headache. We describe a 58-years old female patient with nummular headache successfully treated with a 6-months ketogenic diet and botulinum toxin type A injections. Ketogenic diet could be an effective alternative/complementary therapy in nummular headache patients although more studies are needed to confirm our results.

Ketogenic diet in children and adolescents: The effects on growth and nutritional status.

The ketogenic diet is known to be a possible adjuvant treatment in several medical conditions, such as in patients with severe or drug-resistant forms of epilepsy. Its use has recently been increasing among adolescents and young adults due to its supposed weight-loss effect, mediated by lipolysis and lowered insulin levels. However, there are still no precise indications on the possible use of ketogenic diets in pediatric age for weight loss. This approach has also recently been proposed for other types of disorder such as inherited metabolic disorders, Prader-Willi syndrome, and some specific types of cancers. Due to its unbalanced ratio of lipids, carbohydrates and proteins, a clinical evaluation of possible side effects with a strict evaluation of growth and nutritional status is essential in all patients following a long-term restrictive diet such as the ketogenic one. The prophylactic use of micronutrients supplementation should be considered before starting any ketogenic diet. Lastly, while there is sufficient literature on possible short-term side effects of ketogenic diets, their possible long-term impact on growth and nutritional status is not yet fully understood, especially when started in pediatric age.

Ketogenic diet in action: Metabolic profiling of pyruvate dehydrogenase deficiency.

The pyruvate dehydrogenase complex serves as the main connection between cytosolic glycolysis and the tricarboxylic acid cycle within mitochondria. An infant with pyruvate dehydrogenase complex deficiency was treated with vitamin B1 supplementation and a ketogenic diet. These dietary modifications resolved the renal tubular reabsorption, central apnea, and transfusion-dependent anemia. A concurrent metabolome analysis demonstrated the resolution of the amino aciduria and an increased total amount of substrates in the tricarboxylic acid cycle, reflecting the improved mitochondrial energetics. Glutamate was first detected in the cerebrospinal fluid, accompanied by a clinical improvement, after the ketogenic ratio was increased to 3:1; thus, glutamate levels in cerebrospinal fluid may represent a biomarker for neuronal recovery. Metabolomic analyses of body fluids are useful for monitoring therapeutic effects in infants with inborn errors of carbohydrate metabolism.

The Role of Ketogenic Diet in the Treatment of Neuroblastoma.

The ketogenic diet (KD) was initially used in 1920 for drug-resistant epileptic patients. From this point onward, ketogenic diets became a pivotal part of nutritional therapy research. To date, KD has shown therapeutic potential in many pathologies such as Alzheimer's disease, Parkinson's disease, autism, brain cancers, and multiple sclerosis. Although KD is now an adjuvant therapy for certain diseases, its effectiveness as an antitumor nutritional therapy is still an ongoing debate, especially in Neuroblastoma. Neuroblastoma is the most common extra-cranial solid tumor in children and is metastatic at initial presentation in more than half of the cases. Although Neuroblastoma can be managed by surgery, chemotherapy, immunotherapy, and radiotherapy, its 5-year survival rate in children remains below 40%. Earlier studies have proposed the ketogenic diet as a possible adjuvant therapy for patients undergoing treatment for Neuroblastoma. In this study, we seek to review the possible roles of KD in the treatment of Neuroblastoma.

Nutraceuticals as Supportive Therapeutic Agents in Diabetes and Pancreatic Ductal Adenocarcinoma: A Systematic Review.

The correlation between pancreatic ductal adenocarcinoma (PDAC) and diabetes-related mechanisms support the hypothesis that early therapeutic strategies targeting diabetes can contribute to PDAC risk reduction and treatment improvement. A systematic review was conducted, using PubMed, Embase and Cochrane Library databases, to evaluate the current evidence from clinical studies qualitatively examining the efficacy of four natural products: Curcumin-Curcuma longa L.; Thymoquinone-Nigella sativa L.; Genistein-Glycine max L.; Ginkgo biloba L.; and a low-carbohydrate ketogenic diet in type 2 diabetes (T2D) and PDAC treatment. A total of 28 clinical studies were included, showing strong evidence of inter-study heterogeneity. Used as a monotherapy or in combination with chemo-radiotherapy, the studied substances did not significantly improve the treatment response of PDAC patients. However, pronounced therapeutic efficacy was confirmed in T2D. The natural products and low-carbohydrate ketogenic diet, combined with the standard drugs, have the potential to improve T2D treatment and thus potentially reduce the risk of cancer development and improve multiple biological parameters in PDAC patients.