Ketogenic Diet Research Articles

P-641 A prospective observational case series on the effects of a very low-calorie ketogenic diet (VLCKD) in overweight and obese infertile women

Abstract Study question What is the compliance level of overweight/obese infertile patients to VLCKD? Is therapeutic adherence associated with weight loss and increased pregnancy rates? Summary answer Compliance level to VLCKD was surprisingly high. Participants experienced weight loss and pregnancy rates improved. What is known already Obesity and overweight are associated with infertility. They can adversely affect the hypothalamic-pituitary-gonadal axis, compromise oocyte quality and reduce endometrial receptivity. In addition, obesity exposes women at increased risk of obstetric complications. Although not always consistent, some evidence suggests a beneficial effect of diet in this setting, both for natural conception and in the context of ART. However, these studies also show low compliance, with many patients failing to lose enough weight to be clinically significant. VLCKD is a more aggressive approach to treating severe obesity and may represent a more effective option for these patients. Study design, size, duration This case-series prospective study has been performed at Unit of Obesity and Occupational medicine, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico Milano between May 2019 and September 2023 and involved 42 infertile women aged ≤ 40 years, affected by overweight-obesity (BMI 27.5-35), but without other relevant systemic pathologies. Participants/materials, setting, methods Treatment firstly included 3 months of VLCKD followed by 12 months of Low-Calorie Diet (LCD). The occurrence of any natural pregnancy led to the discontinuation of treatment. These cases were counted as successes. Throughout the study period, patients underwent regular dietary and anthropometric evaluations. Main results and the role of chance Of the 42 recruited patients, 36 adhered to the VLCKD. The median treatment duration was 5.5 months [Interquartile Range (IQR) 3-9]. The compliance rate was 86% (95% CI: 72-93%). A significant reduction in BMI was observed: at recruitment, patients had a median BMI of 36.6 [IQR 33.4-39.9], and at the end, it was 29.5 [IQR 27.3-32.7], with a weight loss of 19.9 kg [IQR 12.7-24.4]. Regarding pregnancy, 8 women (22%) achieved a natural pregnancy, while of the remaining 28 patients, 25 underwent ART treatments. Among these, 16 achieved pregnancy (13 by homologous cycles, two donor cycles, and one with ovulation induction). In total, 24 women achieved pregnancy. The intention-to-treat success rate was 57% (95% CI: 42-71%), and the protocol success rate was 67% (95% CI: 50-80%). Limitations, reasons for caution The case-series study design, by definition, does not require a control group and this could be considered a “weakness”. However, it should be noted that patients were likely to be highly motivated to lose weight and health-conscious, thus creating a sample group with distinctive characteristics. Wider implications of the findings The use of VLCKD in obese infertile women allows high compliance to be achieved. The probability of pregnancy also appears very promising. VLCKD could be considered as a first approach for the treatment of obese women who do not have contraindications to ketosis. Trial registration number not applicable

Can the ketogenic diet improve the hamstring muscle rupture? A narrative review

The ketogenic diet has garnered significant attention for its potential benefits in various health areas, including weight loss, neurological conditions, and metabolic diseases. Characterized by high fat, moderate protein, and low carbohydrate intake, the ketogenic diet induces a state of ketosis, where the body shifts its primary energy source from glucose to ketones derived from fat. This metabolic shift leads to numerous physiological changes, some of which may benefit muscle health and recovery. Hamstring muscle ruptures, common among athletes and physically active individuals, require a combination of rest, physical therapy, and nutritional interventions to reduce inflammation, promote muscle repair, and enhance overall recovery outcomes. Given the known anti-inflammatory and muscle-sparing effects of the ketogenic diet, there is growing interest in exploring its potential role in the recovery of hamstring muscle ruptures. The primary objective of this research is to investigate and potentially validate the ketogenic diet's potential benefits in improving hamstring muscle rupture recovery. This article will explore the underlying mechanisms through which the ketogenic diet may influence muscle healing, review existing studies and clinical evidence, and discuss the potential benefits and challenges of integrating the ketogenic diet into rehabilitation protocols for muscle injuries.

Anticancer restrictive diets and the risk of psychological distress: Review and perspectives.

The most studied anticancer restrictive diets include fasting, fasting-mimicking diets (FMDs) and ketogenic diets (KDs). Besides the current lack of established clinical benefit and the significant risk of malnutrition and micronutrient deficiencies, dietary restrictions in cancer patients might have relevant psychological effects. We reviewed the randomized and non-randomized controlled clinical trials (CCTs) reporting data on the psychological impact of fasting, FMDs and KDs in cancer patients. We excluded trials on restrictive diets performed for weight reduction in obese or overweight patients, studies on dietary restrictions lasting less than 24 h, and studies on fasting related to cultural or religious beliefs. Three CCTs on fasting or FMDs and eight CCTs on KDs in cancer patients were included. In terms of diet-related distress, emotional, social, and family well-being, none of these studies showed a detrimental impact of fasting, FMDs and KDs. However, clinical trials specifically assessing the psychological aspects in the long term are lacking. In the absence of a conclusive evidence on the clinical benefits of restrictive diets, which carry significant risks especially if unsupervised, further studies are needed to clarify their psychological impact in cancer patients. Multidisciplinary approaches including psychological evaluations should be used to ameliorate patient selection for clinical trials, identify early distress symptoms, and increase patient compliance to dietary recommendations.

Impact of the ketogenic diet as a dietary approach on cardiovascular disease risk factors: a meta-analysis of randomized clinical trials

BackgroundCardiovascular diseases (CVD) remain the leading cause of mortality globally, and the scarcity of scientific evidence regarding the impact of ketogenic diets on CVD risk factors necessitates urgent attention and redress. ObjectivesThis meta-analysis evaluates the impact of the ketogenic diet on CVD risk factors compared with control diets through randomized controlled trials (RCTs). MethodsThe study was registered in advance in the PROSPERO database (CRD42023491853). A systematic search was conducted across PubMed, Web of Science, EMBASE, and Cochrane Library to identify relevant RCTs. Fixed and random effects were employed to calculate the mean differences and 95% confidence intervals (CIs) for changes in CVD risk factors pre- and postketogenic diet intervention. ResultsA total of 27 RCTs with 1278 participants were analyzed. The ketogenic diet intervention presented increase in total cholesterol (mean differences: 0.36 mmol/L; 95% CI: 0.15, 0.57; I2: 85.1%), low-density lipoprotein cholesterol (mean differences: 0.35 mmol/L; 95% CI: 0.20, 0.50; I2: 73.9%) and high-density lipoprotein cholesterol (mean differences: 0.16 mmol/L; 95% CI: 0.09, 0.23; I2: 86.7%) concentrations. Reductions were observed in the triglyceride (mean differences: −0.20 mmol/L; 95% CI: −0.29, −0.11; I2: 72.2%), blood glucose (mean differences: −0.18 mmol/L; 95% CI: −0.33, −0.02; I2: 76.4%), blood insulin (mean differences: −8.32 pmol/L; 95% CI: −14.52, −2.12; I2: 81.5%), diastolic blood pressure (mean differences: −1.41 mmHg; 95% CI: −2.57, −0.26; I2: 49.1%), weight (mean differences: −2.59 kg; 95% CI: −3.90, −1.28; I2: 87.4%), and body mass index (mean differences: −1.59 kg/m2; 95% CI: −2.32, −0.86; I2: 84.5%) concentrations after implementing ketogenic diets. ConclusionsAlthough the ketogenic diet demonstrates benefits in terms of triglyceride, blood pressure, weight, and glycemic control, its impact on CVD risk factors, especially the elevated total cholesterol and low-density lipoprotein cholesterol concentrations, warrants a cautious approach.

Serum and CSF metabolomics analysis shows Mediterranean Ketogenic Diet mitigates risk factors of Alzheimer’s disease

Alzheimer’s disease (AD) is influenced by a variety of modifiable risk factors, including a person’s dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD’s metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean Ketogenic Diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.

Ketogenic Diets With Disparate Fat Sources Protect From Experimental Colitis With Pronounced Benefit From Linoleic Acid Over Saturated Fatty Acids

Ketogenic Diets With Disparate Fat Sources Protect From Experimental Colitis With Pronounced Benefit From Linoleic Acid Over Saturated Fatty Acids

Differences in the Effect of Beta-Hydroxybutyrate on the Mitochondrial Biogenesis, Oxidative Stress and Inflammation Markers in Tissues from Young and Old Rats.

One of the therapeutic approaches to age-related diseases is modulation of body cell metabolism through certain diets or their pharmacological mimetics. The ketogenic diet significantly affects cell energy metabolism and functioning of mitochondria, which has been actively studied in various age-related pathologies. Here, we investigated the effect of the ketogenic diet mimetic beta-hydroxybutyrate (BHB) on the expression of genes regulating mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam), quality control (Sqstm1), functioning of the antioxidant system (Nfe2l2, Gpx1, Gpx3, Srxn1, Txnrd2, Slc6a9, Slc7a11), and inflammatory response (Il1b, Tnf, Ptgs2, Gfap) in the brain, lungs, heart, liver, kidneys, and muscles of young and old rats. We also analyzed mitochondrial DNA (mtDNA) copy number, accumulation of mtDNA damage, and levels of oxidative stress based on the concentration of reduced glutathione and thiobarbituric acid-reactive substances (TBARS). In some organs, aging disrupted mitochondrial biogenesis and functioning of cell antioxidant system, which was accompanied by the increased oxidative stress and inflammation. Administration of BHB for 2 weeks had different effects on the organs of young and old rats. In particular, BHB upregulated expression of genes coding for proteins associated with the mitochondrial biogenesis and antioxidant system, especially in the liver and muscles of young (but not old) rats. At the same time, BHB contributed to the reduction of TBARS in the kidneys of old rats. Therefore, our study has shown that administration of ketone bodies significantly affected gene expression in organs, especially in young rats, by promoting mitochondrial biogenesis, improving the functioning of the antioxidant defense system, and partially reducing the level of oxidative stress. However, these changes were much less pronounced in old animals.

Innovative and Emerging Treatments for Anorexia Nervosa.

Unlike psychopharmacologic interventions for other psychiatric conditions, few medications have emerged as helpful in improving eating disorder cognitions and evidence-based psychotherapies fail many patients. Novel treatments are urgently needed to address anorexia nervosa (AN), which is increasingly prevalent and difficult to treat. This article provides an overview of preliminary investigations into cannabidiol, psilocybin therapy, ketamine and the ketogenic diet, transcranial magnetic stimulation, and vagus nerve stimulation in individuals with AN. These pilot studies underscore the need for larger clinical trials that include more participant diversity in order to rapidly translate findings to real-world clinical practice.

Ketogenic Diets as an Adjunctive Therapy Against Cancer: Potential Mechanism

Ketogenic Diets as an Adjunctive Therapy Against Cancer: Potential Mechanism

Impact of a Ketogenic Diet as an Adjuvant Therapy in Adults With Brain Metastases

Impact of a Ketogenic Diet as an Adjuvant Therapy in Adults With Brain Metastases

Soluble Fiber-Supplemented Ketogenic Diet Attenuated Hepatic Lipid Accumulation and Inflammation

Soluble Fiber-Supplemented Ketogenic Diet Attenuated Hepatic Lipid Accumulation and Inflammation

Ketogenic Diet Worsens the Yo-Yo Effect Compared With an Isocaloric-Low Fat Diet by Inducing Metabolic Adaptation in Lipid Metabolism

Ketogenic Diet Worsens the Yo-Yo Effect Compared With an Isocaloric-Low Fat Diet by Inducing Metabolic Adaptation in Lipid Metabolism

Ketogenic Diet Enhances the Anti-Tumor Effect of Mifepristone in a Breast Cancer Mouse Model

Ketogenic Diet Enhances the Anti-Tumor Effect of Mifepristone in a Breast Cancer Mouse Model

Impact of an 8-Week Well-Formulated Ketogenic Diet on Advanced Lipid Biomarkers Associated With Atherosclerotic Cardiovascular Disease Risk in Healthy Adults

Impact of an 8-Week Well-Formulated Ketogenic Diet on Advanced Lipid Biomarkers Associated With Atherosclerotic Cardiovascular Disease Risk in Healthy Adults

Dietary Fibers in Clinical Ketogenic Diets Promotes Seizure Resistance in Mice Through Modulation of Gut Microbiome

Dietary Fibers in Clinical Ketogenic Diets Promotes Seizure Resistance in Mice Through Modulation of Gut Microbiome

Study Protocol: Investigating the Mechanisms by Which Ketogenic Diet Mediates Alleviation of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)

Study Protocol: Investigating the Mechanisms by Which Ketogenic Diet Mediates Alleviation of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)

Ketogenic diet therapy leads to antiseizure medication reduction in children and adults with drug-resistant epilepsy.

This study aimed to evaluate the safety of reducing or withdrawing anti-seizure medications (ASMs) in a cohort comprising both adults and children with drug-resistant epilepsy (DRE) undergoing ketogenic diet therapy (KDT). We conducted a comprehensive analysis of clinical profiles in adults and children with DRE who had adhered to KDT for at least 6 months. Successful withdrawal or reduction of an ASM was defined as discontinuation or dose reduction without subsequent resumption or increase and without initiation of any new ASM throughout the entire follow-up period. Changes in the ASM load were calculated specifically for adult patients. The study enrolled 56 participants (34 children and 22 adults) with DRE, with 64.3% achieving successful withdrawal of at least one ASM. The probability of ASM withdrawal remained consistent for children (64.7%) versus adults (63.6%), as well as for responders (62.5%) versus non-responders (68.8%), and it was not associated with other clinical factors. Early ASM reduction (including withdrawal) after diet initiation occurred in 15 patients (26.8%), with treatment outcomes comparable to those of the remaining participants. Among the 22 adults, the mean values of ASM load reduced by 24.5%, with a similar magnitude observed for responders (24.2%) versus non-responders (25.1%). In addition, adults tend to have a slower elevation in serum ketone levels compared to children. This study demonstrates the safe achievability of ASM withdrawal through KDT in most patients with DRE, irrespective of age or seizure frequency reduction.

Comparison between Ketogenic and Diabetic Conventional Diet on Wound Closure in Diabetic Rat Model

Background: Managing diabetic ulcers should be multimodal; nutrition is one of the modalities to improve wound healing. This study therefore aimed to compare ketogenic diet and conventional diabetic diet in closing the wounds of diabetic rat models.Methods: Diabetes mellitus was induced in 30 rats which were divided equally into three groups. Group I was given a ketogenic diet (60% fat, 24% carbohydrate, and 16% protein). Group II was given a conventional diabetic diet (43% carbohydrate, 15% fat, and 42% protein). Group III was the control group with a normal diet (13% water, 18.5%–20.5% protein, fat ≥4%, fiber ≤6%, ash ≤8%, 0.9% calcium, and 0.7% phosphor). A 1 cm-diameter wound was made with the Mason-Walker model as a guideline. The rate of wound closure was measured on days 1, 7, 14, and 21 to represent each wound healing phase.Results: On day 7, comparison between wound areas in the ketogenic diet, conventional diet, and normal diet yielded significant differences (mean, 0.664, 0.717, 0.747; P=0.051). There was also a significant difference on day 14 (mean, 0.564, 0.817, 0.647; P<0.001) and day 21 (mean, 0.164, 0.517, 0.447; P<0.001).Conclusion: Compared to a conventional diabetic diet, a ketogenic diet significantly enhanced the wound closure rate in the diabetic rat model. Further studies are needed to confirm this finding.

Dynamics of glucose concentration changes during ketogenic diet initiation in pediatric patients with drug-resistant epilepsy – analysis of glucose values in individual patients

Dynamics of glucose concentration changes during ketogenic diet initiation in pediatric patients with drug-resistant epilepsy – analysis of glucose values in individual patients

Metagenomic and metabolomic analysis showing the adverse risk–benefit trade-off of the ketogenic diet

BackgroundKetogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity.MethodsMale mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents.ResultsObese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity.ConclusionsThe study suggest that the ketogenic diet had an unfavorable risk–benefit trade-off and may compromise metabolic homeostasis in obese mice.