Very low-calorie ketogenic diet (VLCKD): a therapeutic nutritional tool for acne?

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.

Impact of Ketogenic and Low-Glycemic Diets on Inflammatory Skin Conditions.

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.

Efficacy and Safety of Ketogenic Diet Treatment in Pediatric Patients with Mitochondrial Disease.

Mitochondrial diseases (MDs) are a heterogeneous group of disorders resulting from abnormal mitochondrial function. Currently, there is no causal treatment for MDs. The aim of the study was to assess the effectiveness and safety of the ketogenic diet (KD) in patients with MD and to analyse selected biochemical and clinical parameters evaluating the effectiveness of KD treatment in patients with MDs. A total of 42 paediatric patients were assigned to four groups: group 1-patients with MD in whom KD treatment was started (n = 11); group 2-patients with MD remaining on an ordinary diet (n = 10); group 3-patients without MD in whom KD treatment was initiated (n = 10), group 4-patients without MD on a regular diet (n = 11). Clinical improvement was observed in 9/11 patients with MD treated with KD. Among patients with MD without KD, the clinical condition deteriorated in 7/10 patients, improved in 2/10 patients, and remained unchanged in one patient. Adverse events of KD occurred with a comparable frequency in groups 1 and 3. There was no significant difference in changes in biomarker concentrations over the course of the study among patients treated and untreated with KD.

Tolerance, adherence, and acceptability of a ketogenic 2.5:1 ratio, nutritionally complete, medium chain triglyceride-containing liquid feed in children and adults with drug-resistant epilepsy following a ketogenic diet.

OBJECTIVE: To investigate incorporating a ready-to-use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. METHODS: Following a three-day baseline, patients (n = 19; age: 19 years [SD 13], range: 8-46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready-to-use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß-hydroxybutyrate (BHB) concentration, seizure outcomes, health-related quality of life (HRQoL), acceptability and safety. RESULTS: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). SIGNIFICANCE: These findings provide an evidence-base to support the effective management of children and adults with drug-resistant epilepsy following a KD with the use of a ready-to-use, nutritionally complete, 2.5:1 ratio feed including MCTs. PLAIN LANGUAGE SUMMARY: This study examined the use of a ready-to-use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively.

Ketogenic diet for epilepsy and obesity: Is it the same?

The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet. This terminology is confusing for patients and the medical and scientific community. The term "ketogenic" diet implies a dietary regimen characterized by increased levels of circulating ketone bodies that should be measured in blood (beta-hydroxybutyrate), urine (acetoacetate) or breath (acetone) to verify the "ketogenic metabolic condition". Our viewpoint highlights that KDs used for epilepsy and obesity are not the same; the protocols aimed at weight loss characterized by low-fat, low-CHO and moderate/high protein content are not ketogenic by themselves but may become mildly ketogenic when high calorie restriction is applied. In contrast, there are standardized protocols for neurological diseases treatment for which ketosis has been established to be part of the mechanism of action. Therefore, in our opinion, the term ketogenic dietary therapy (KDT) should be reserved to the protocols considered for epilepsy and other neurological diseases, as suggested by the International Study Group in 2018. We propose to adjust the abbreviations in VLCHKD for Very Low CarboHydrate Ketogenic Diet and VLEKD for Very Low Energy Ketogenic Diet, to clarify the differences in dietary composition. We recommend that investigators describe the researchers describing efficacy or side effects of KDs, to clearly specify the dietary protocol used with its unique acronym and level of ketosis, when ketosis is considered as a component of the diet's mechanism of action.

Effect of ketogenic diet on blood pressure: A GRADE-Assessed systematic review and meta-analysis of randomized controlled trials.

AIMS: Cardiovascular diseases (CVDs) are major causes of mortality around the world. High blood pressure (BP) or hypertension is one of the most significant predisposing factors to CVDs. Ketogenic diets (KDs) have been the center of attention for their possible health benefits. The aim of this analysis is to study the impact of KDs on BP through the existing literature. DATA SYNTHESIS: We investigated the impact of KDs on systolic and diastolic blood pressures (SBP and DBP) conducted in the format of randomized controlled trials (RCTs). Four online databases (PubMed/Medline, SCOPUS, Cochrane Library, and Google Scholar) were searched from inception up to November 2022. Subgroup analyses were carried out to find the sources of heterogeneities. Twenty-three RCTs with 1664 participants were identified. KDs did not exert any significant impacts on SBP (WMD: -0.87 mmHg, 95% CI: -2.05, 0.31) nor DBP (WMD: -0.11 mmHg, 95% CI -1.14, 0.93). Subgroup analyses did not reveal any further information. Also, non-linear dose-response analysis could not detect any associations between the percentage of calorie intake from fat in the KD format and BP levels. CONCLUSION: KDs do not seem to be effective in improving BP. Nonetheless, further investigations are recommended to examine the proportion of fat intake needed to induce favorable clinical impacts.

Ketogenic diet in pharmacoresistant epilepsies: a clinical nutritional assessment.

BACKGROUND: Epilepsies are among the most prevalent chronic neurological diseases, usually beginning in childhood. About 30% of children with epilepsies develop seizures that are difficult to control with medication. Recurrent epileptic seizures hinder diet intake, impairing the nutritional status. Although non-pharmacological interventions (e.g., ketogenic diet therapy) can improve epileptic seizure frequency, few studies analyzed their impact on the nutritional status of children and adolescents with epilepsies. OBJECTIVE: The aim was to evaluate the effects of a ketogenic diet on the nutritional status and clinical course of patients with pharmacoresistant epilepsies. METHODS: This cross-sectional study included patients under 18 years of age followed up at the Ketogenic Diet Ambulatory Clinic of the Instituto de Medicina Integral Prof. Fernando Figueira between December 2015 and December 2021. Socioeconomic, clinical, nutritional, and laboratory data were collected from medical records at different time points during the ketogenic diet. RESULTS: The sample comprised 49 patients aged between 5 months and 17 years (median = 4.4 years), mostly male (62.1%), and from Recife and the metropolitan region (51%). Underweight patients (BMI-for-age) improved their nutritional status in six months. However, patients who were normal weight and overweight maintained their nutritional status. Dyslipidemia was a common and short-term adverse effect. Moreover, the treatment decreased epileptic seizure frequency and antiseizure medication intake. CONCLUSION: The ketogenic diet prevented malnutrition from worsening and reduced epileptic seizures and antiseizure medication intake.

ANTECEDENTES: A epilepsia, uma das doenças neurológicas crônicas mais prevalentes, tem geralmente início na infância. Cerca de 30% das crianças com epilepsia desenvolvem crises de difícil controle medicamentoso. As crises epilépticas recorrentes dificultam a ingestão alimentar, prejudicando o estado nutricional. Intervenções não farmacológicas, como a terapia com dieta cetogênica, podem melhorar a frequência das crises epilépticas, mas existem poucos estudos sobre a repercussão no estado nutricional da criança/adolescente. OBJETIVO: Avaliar o efeito da terapia cetogênica sobre o estado nutricional e a evolução clínica da epilepsia fármaco-resistente. MéTODOS: Estudo tipo corte transversal envolvendo menores de 18 anos acompanhados no Ambulatório de Dieta Cetogênica do Instituto de Medicina Integral Prof. Fernando Figueira entre dezembro de 2015 e dezembro de 2021. Dados socioeconômicos, clínicos, nutricionais e laboratoriais foram coletados nos prontuários dos pacientes em vários momentos da terapia cetogênica. RESULTADOS: A amostra foi composta por 49 pacientes com idades entre cinco meses e 17 anos (mediana = 4,4 anos), a maioria do sexo masculino (62,1%) e procedentes de Recife e região metropolitana (51%). Pacientes com baixo peso (de acordo com o IMC para idade) melhoraram seu estado nutricional em seis meses. No entanto, os pacientes com peso adequado e com sobrepeso mantiveram seu estado nutricional. A dislipidemia foi um efeito adverso frequente e de curta duração. Além disso, o tratamento reduziu a frequência de crises epilépticas e a dose de fármacos anticrises. CONCLUSãO: A dieta cetogênica preveniu o agravamento da desnutrição e reduziu as crises epilépticas e a dosagem de fármacos anticrises.

Long-term effectiveness and tolerability of ketogenic diet therapy in patients with genetic developmental and epileptic encephalopathy onset within the first 6 months of life.

OBJECTIVE: To investigate the effectiveness and tolerability of ketogenic diet therapy (KDT) in patients with developmental and epileptic encephalopathy (DEE) associated with genetic etiology which onset within the first 6 months of life, and to explore the association between response to KDT and genotype/clinical parameters. METHODS: We retrospectively reviewed data from patients with genetic DEE who started KDT at Beijing Children's Hospital between January 1, 2016, and December 31, 2021. RESULTS: A total of 32 patients were included, involving 14 pathogenic or likely pathogenic single genes, and 16 (50.0%) patients had sodium/potassium channel gene variants. The median age at onset of epilepsy was 1.0 (IQR: 0.1, 3.0) months. The median age at initiation of KDT was 10.0 (IQR: 5.3, 13.8) months and the median duration of maintenance was 14.0 (IQR: 7.0, 26.5) months, with a mean blood ß-hydroxybutyrate of 2.49 ± 0.62 mmol/L. During the maintenance period of KDT, 26 (81.3%) patients had a ≥50% reduction of seizure frequency, of which 12 (37.5%) patients achieved seizure freedom. Better responses were observed in patients with STXBP1 variants, with four out of five patients achieving seizure freedom. There were no statistically differences in the age of onset, duration of epilepsy before KDT, blood ketone values, or the presence of ion channel gene variants between the seizure-free patients and the others. The most common adverse effects were gastrointestinal side effects, which occurred in 21 patients (65.6%), but all were mild and easily corrected. Only one patient discontinued KDT due to nephrolithiasis. SIGNIFICANCE: KDT is effective in treating early onset genetic DEE, and no statistically significant relationship has been found between genotype and effectiveness in this study. KDT is well tolerated in most young patients, with mild and reversible gastrointestinal side effects being the most common, but usually not the reason to discontinue KDT. PLAIN LANGUAGE SUMMARY: This study evaluated the response and side effects of ketogenic diet therapy (KDT) in patients who had seizures within the first 6 months of life, and were diagnosed with genetic developmental and epileptic encephalopathy (DEE), a type of severe epilepsy with developmental delay caused by gene variants. Thirty-two patients involving 14 gene variants who started KDT at Beijing Children's Hospital between were included. KDT was effective in treating early onset genetic DEE in this cohort, and patients with STXBP1 variants responded better; however, no statistically significant relationship was found between gene variant and response. Most young patients tolerated KDT well, with mild and reversible gastrointestinal side effects being the most common.

Ketogenic diet and cardiovascular risk - state of the art review.

The ketogenic diet is based on extreme carbohydrate intake reduction and replacing the remaining with fat and has become a popular dietary pattern used for weight loss. The relationship between the ketogenic diet and cardiovascular risk is a controversial topic. This publication aimed to present evidence on the ketogenic diet and cardiovascular risk factors and mortality. The ketogenic diet does not fulfill the criteria of a healthy diet. It presents the potential for rapid short-term reduction of body mass, triglycerides level, Hb1Ac, and blood pressure. Its efficacy for weight loss and the above-mentioned metabolic changes is not significant in long-term observations. In terms of cardiovascular mortality, the low-carb pattern is more beneficial than very low-carbohydrate (including the ketogenic diet). There is still scarce evidence comparing ketogenic to the Mediterranean diet. Other safety concerns in cardiovascular patients such as adverse events related to ketosis, fat-free mass loss, or potential pharmacological interactions should be also taken into consideration in future research.

Use of ketogenic dietary therapy for drug-resistant epilepsy in early infancy.

OBJECTIVE: There is growing evidence that ketogenic dietary therapy (KDT) can be safely and efficiently used in young children, but little evidence exists on its use in newborns. Developmental and epileptic encephalopathies starting in the neonatal period or early infancy usually present a poor prognosis. The aim of this study was to evaluate effectiveness, safety, and survival of infants younger than 3 months of age with drug-resistant epilepsy in whom KDT was used. METHODS: A retrospective study was conducted to evaluate neonates and infants younger than 3 months who started KDT for drug-resistant developmental and epileptic encephalopathies at three referral centers. Data were collected on demographic features, time of epilepsy onset, epilepsy syndrome, seizure type, seizure frequency at diet onset, etiology, details regarding diet initiation, type of ketogenic formula, breastfeeding, route of administration, blood ketones, growth, length of NICU stay, and survival. RESULTS: Nineteen infants younger than 12 weeks of life who received KDT with a minimum follow-up of 1 month were included; 13 had early-infantile developmental and epileptic encephalopathy, four epilepsy of infancy with migrating focal seizures, and two focal epilepsy. A >50% response was observed in 73.7% at 1 month on the diet; 37% achieved a > 75% seizure reduction, and 10.5% became seizure free. At 3 months, a >50% decrease in seizure frequency was observed in 72.2%; 15.8% had a >75% reduction; 21% became seizure free. Overall survival was 76% at 1 year on diet. Incidence of acute and late adverse effects was low and most adverse effects were asymptomatic and manageable. SIGNIFICANCE: Our experience suggests that KDT is safe and effective in newborns and very young infants; however, further studies on the management of the diet in this vulnerable age group are necessary.

Efficacy and safety of a smartphone application-based treatment of ketogenic diet in pediatric refractory epilepsy.

OBJECTIVE: We aimed to find predictors for smartphone application-based ketogenic diet (KD) treatment effectiveness and safety. METHODS: The efficacy was evaluated according to the reduction in seizure frequency after the intervention of KD; safety was evaluated based on adverse effects. The ordinal logistic regression analysis was used to explore the influencing factors of efficacy. RESULTS: The study sample included 116 males and 65 females with a median age of 2.27 years. The baseline frequency of seizure was more than five times/day in 123 children, 50.83% of them received three or more antiepileptic drugs (AEDs). Seventy-two patients' KD initiation mode was outpatient, and 73 completed the 12-month follow-up. A total of 88 (48.62%) patients had reported a reduction in seizure ≥50%. Compared with 12 months, those who had received KD therapy for only 3 (P = 0.009) and 6 months (P = 0.005) were more likely to show negative outcomes. Outpatient initiation had better outcomes (P = 0.029) than inpatient initiation. For the number of AEDs applied, patients on two AEDs were more likely to achieve better outcomes (P = 0.001). Adverse events had been noted among 77 patients; BMI Z-score at KD initiation was associated with adverse effects (P = 0.003). SIGNIFICANCE: Our study suggested that outpatient initiation and long-term treatment of KD should be encouraged. PLAIN LANGUAGE SUMMARY: Our research shows that the KD is a helpful treatment for children with refractory epilepsy, reducing seizures by more than 50% in nearly half of the cases, with some experiencing complete seizure freedom. We used a smartphone app to improve communication between patients and their healthcare teams, resulting in a high retention, and app usage was linked to reduced adverse effects. We recommend early consideration of KD treatment for patients failing two AED, encourage outpatient initiation, and advocate for longer-term KD use.

Ketogenic diets: A systematic review of current scientific evidence and possible applicability in dogs and cats.

Ketogenic diets (KD) have been used in the treatment of epilepsy in humans for around a century and, more recently, they have been implanted for cancer patients, as well as in the treatment of obesity. This type of diet consists of high-fat levels, an adequate amount of protein and restricted carbohydrates, or high medium-chain triglycerides. Recently, the ketogenic diet has gained attention in veterinary medicine and studies were published evaluating the effects of KD in dogs with epilepsy. The objective of this review was to highlight recent studies about the application of KD in dogs and cats, to describe the neurobiochemical mechanisms through which KD improves epilepsy crisis, and their adverse effects. Studies were identified by a systematic review of literature available on PubMed, Embase, and Scopus. All cohort and case-control studies were included, and all articles were exported to Mendeley® citation manager, and duplicates were automatically removed. Seven articles and three conference abstracts conducted with dogs were included in the present study. There is evidence that the consumption of diets with medium-chain triglycerides increases the concentration of circulating ketone bodies and improves epilepsy signs, although these diets have higher carbohydrate and lower fat content when compared to the classic KD.

Effects of Ketogenic Diet Intervention on Metabolic Acidosis in Patients with Obesity and Chronic Kidney Disease.

In this study, we found no significant acid-base changes after six weeks of ketogenic diet in patients with obesity with Chronic kidney disease) 2 or 3. A ketogenic diet was well tolerated overall with no gross changes to serum creatinine, anion gap, serum, or venous bicarbonate, or albumin. We were limited by a small sample size, and we did not confirm whether patients achieved a biochemical ketogenic state.

Classic ketogenic diet versus further antiseizure medicine in infants with drug-resistant epilepsy (KIWE): a UK, multicentre, open-label, randomised clinical trial.

BACKGROUND: Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy. METHODS: In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding. FINDINGS: Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee. INTERPRETATION: In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications. FUNDING: National Institute for Health and Care Research.

Ketogenic Diet and the Skin.

In dermatology, the role of dietary modifications as a means to manage or prevent skin disorders has recently gained special attention among patients and physicians. This is especially true for the currently popular ketogenic diet (KD), which comprises low carbohydrate, high fat, and adequate amount of protein. Recent evidence from basic science research, small clinical trials, population studies, and reports has presented promising potential role of KD as a supplementary or adjuvant treatment in different cutaneous disorders mainly due to its anti-inflammatory properties. This review is directed at raising awareness among dermatologists on the potential uses of KD in managing skin disorders, such as acne, psoriasis, and hidradenitis suppurativa, among others. In addition, cutaneous adverse reactions, such as prurigo pigmentosa and nutritional deficiencies, which have been associated with KD, are also discussed in this review.

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.

Ketogenic diet influence on the elemental homeostasis of internal organs is gender dependent.

The ketogenic diet (KD) is a low-carbohydrate and high-fat diet that gains increasing popularity in the treatment of numerous diseases, including epilepsy, brain cancers, type 2 diabetes and various metabolic syndromes. Although KD is effective in the treatment of mentioned medical conditions, it is unfortunately not without side effects. The most frequently occurring undesired outcomes of this diet are nutrient deficiencies, the formation of kidney stones, loss of bone mineral density, increased LDL (low-density lipoprotein) cholesterol levels and hormonal disturbances. Both the diet itself and the mentioned adverse effects can influence the elemental composition and homeostasis of internal organs. Therefore, the objective of this study was to determine the elemental abnormalities that appear in the liver, kidney, and spleen of rats subjected to long-term KD treatment. The investigation was conducted separately on males and females to determine if observed changes in the elemental composition of organs are gender-dependent. To measure the concentration of P, S, K, Ca, Fe, Cu, Zn and Se in the tissues the method of the total reflection X-ray fluorescence (TXRF) was utilized. The obtained results revealed numerous elemental abnormalities in the organs of animals fed a high-fat diet. Only some of them can be explained by the differences in the composition and intake of the ketogenic and standard diets. Furthermore, in many cases, the observed anomalies differed between male and female rats.

Persistent hypercalcemia mimicking hypophosphatasia after discontinuation of a ketogenic diet: a case report.

OBJECTIVES: Hypercalcemia has been reported as an uncommon complication of the ketogenic diet (KD). Here we present a toddler whose hypercalcemia persisted for 2 months after stopping the KD. CASE PRESENTATION: A 2 year 11-month-old child with global developmental delay, infantile spasms, neuromuscular weakness with limited mobility, tracheostomy and ventilator dependence, and oropharyngeal dysphagia with G-tube dependence presented with hypercalcemia in the setting of recurrent vomiting. At presentation, the patient was adherent to a KD and taking topiramate since infancy for intractable seizures. His laboratory parameters at presentation showed hypercalcemia (11.9 mg/dL), hypercalciuria, acute renal failure, low alkaline phosphatase (76 IU/L [110-302 IU/L]), parathyroid hormone (PTH) <6 pg/mL (18-80 pg/mL), normal thyroid function, cortisol and vitamin D level. The patient's hypercalcemia persisted post-discontinuation of the KD and topiramate. PTH-related protein was mildly elevated at 15.3 pmol/L. Follow-up laboratory and imaging studies ruled out malignancy. He was managed with calcitonin 4 u/kg/dose Q12H × 1 day and 8 u/kg/dose Q8H × 1 day, hydration and low-calcium formula. Post-discontinuation of the KD, normalization of alkaline phosphatase levels preceded the normalization of calcium on day 55 and PTH on day 85. CONCLUSIONS: Hypercalcemia may persist for an extended period after weaning from a KD; lab parameters may mimic that of hypophosphatasia as previously described in the literature. Normalization of alkaline phosphatase, a marker of bone turnover, indicates recovery from the adynamic state induced by the KD and typically precedes the normalization of calcium and PTH.

Propofol for Anesthesia in Pediatric Patients With Epilepsy on the Ketogenic Diet: A Single-Center Experience.

BACKGROUND: Propofol use is contraindicated in patients on ketogenic diet (KD) due to higher risk of propofol infusion syndrome (PIS). This study is intended to provide a descriptive analysis of our experience with propofol bolus and short infusions for anesthetic care in patients on the KD and to evaluate if any signs of PIS were observed. METHODS: All patients on the KD who underwent anesthesia with propofol between 2012 and 2022 were reviewed. Anesthetic encounters and charts were studied for type of surgical procedure; signs of PIS, including new cardiac arrhythmias, acidosis, or rhabdomyolysis in the periprocedural period; hypoglycemia; unplanned admissions within 24 hours of the procedure; if procedure was unexpectedly aborted; and increased seizure frequency within one week. RESULTS: We identified 65 patients, aged from one to 20 years who underwent 165 anesthetic encounters with propofol, of which 123 were boluses and 42 were infusions. In bolus dosing, the average dose was 2.8 mg/kg (0.7 to 12.8 ± 1.8 mg/kg). Of these, four encounters developed acidosis, one developed rhabdomyolysis, and one developed increased seizures. With infusions, the average infusion rate was 9 mg/kg/hour, with mean infusion duration of 83 minutes (10 to 352 ± 75 minutes). Of these, one developed acidosis and one increased seizures. No cases of PIS were identified. None of the adverse effects were attributed to propofol. CONCLUSIONS: Boluses and brief infusions of propofol for anesthetic use in patients on the KD did not cause PIS in our cohort.

Ketogenic Diets in Children With Intractable Epilepsy and its Effects on Gastrointestinal Function, Gut Microbiome, Inflammation, and Quality of Life.

OBJECTIVES: The ketogenic diet (KD) is a treatment for children with intractable epilepsy (IE), can cause gastrointestinal symptoms, and have an adverse effect on growth, nutrition and quality of life (QOL). This study investigated the extent of these side effects by comparing children with IE on KDs to their counterparts on normal diets. METHODS: Patients with IE were categorized into patients with KD or control groups. Gastrointestinal side effects and QOL were assessed using the PedsQL Gastrointestinal Symptoms Module. Cross sectional growth, gut microbiome compositions, and inflammation levels were also analyzed. RESULTS: Fourteen patients on the KD and 13 control patients were enrolled. Patients had been on KD for a median duration of 15 months (interquartile range: 9.8-60 months). The patients on the KD reported a trend to lower total gastrointestinal symptoms scores (more symptoms) compared to control patients, at 71.1 and 84.9, respectively ( P = 0.06, not significant). Patients on the KD had significantly lower QOL scores compared to control patients ( P = 0.01). Patients on the KD were found to have consistently lower median height/length, weight, and body mass index z scores compared to the controls although these were not statistically significant. Patients on the KD had a lower microbial diversity, Both groups had a normal level of S100A12, a marker of gut inflammation. CONCLUSIONS: Patients on the KD reported a trend to more gastrointestinal symptoms and more QOL concerns compared to controls. Although microbial differences were noted in patients on the KD, this did not result in detectable gut inflammation.