PMID: 

J Nutr. 2020 Feb 6. Epub 2020 Feb 6. PMID: 32027752

Abstract Title: 

Lactobacillus rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction by Regulating MAPK/NF-κB Signaling and Modulating Metabolome in the Piglet Intestine.

Abstract: 

BACKGROUND: Probiotic Lactobacillius rhamnosus GG (LGG) shows beneficial immunomodulation on cultured cell lines in vitro and in mouse models.OBJECTIVE: The aim was to investigate the effects of LGG on intestinal injury and the underlying mechanisms by elucidating inflammatory signaling pathways and metabolomic response to LPS stimulation in the piglet intestine.METHODS: Piglets (Duroc × Landrace × Large White, including males and female; 8.6 ± 1.1 kg) aged 28 d were assigned to 3 groups (n = 6/group): oral inoculation with PBS for 2 wk before intraperitoneal injection of physiological saline [control (CON)] or LPS (25 μg/kg body weight; LPS) or oral inoculation with LGG for 2 wk before intraperitoneal injection of LPS (LGG+LPS). Piglets were killed 4 h after LPS injection. Systemic inflammation, intestinal integrity, inflammation signals, and metabolomic characteristics in the intestine were determined.RESULTS: Compared with CON, LPS stimulation significantly decreased ileal zonula occludens 1 (ZO-1; 44%), claudin-3 (44%), and occludin (41%) expression; increased serum diamineoxidase (73%), D-xylose (19%), TNF-α (43%), and IL-6 (55%) concentrations; induced p38 mitogen-activated protein kinase (p38 MAPK; 85%), extracellular signal-regulated kinase (ERK; 96%), and NF-κB p65 phosphorylation (37%) (P

read more

PMID: 

Pediatr Res. 2020 Feb 13. Epub 2020 Feb 13. PMID: 32053825

Abstract Title: 

NEC-like intestinal injury is ameliorated by Lactobacillus rhamnosus GG in parallel with SIGIRR and A20 induction in neonatal mice.

Abstract: 

BACKGROUND: Exaggerated Toll-like receptor (TLR) signaling and intestinal dysbiosis are key contributors to necrotizing enterocolitis (NEC). Lactobacillus rhamnosus GG (LGG) decreases NEC in preterm infants, but underlying mechanisms of protection remain poorly understood. We hypothesized that LGG alleviates dysbiosis and upregulates TLR inhibitors to protect against TLR-mediated gut injury.METHODS: Effects of LGG (low- and high-dose) on intestinal pro-inflammatory TLR signaling and injury in neonatal mice subjected to formula feeding (FF) and NEC were determined. 16S sequencing of stool and expression of anti-TLR mediators SIGIRR (single immunoglobulin interleukin-1-related receptor) and A20 were analyzed.RESULTS: FF induced mild intestinal injury with increased expression of interleukin-1β (IL-1β) and Kupffer cell (KC) (mouse homolog of IL-8) compared to controls. LGG decreased IL-1β and KC in association with attenuated TLR signaling and increased SIGIRR and A20 expression in a dose-dependent manner. Low- and high-dose LGG had varying effects on gut microbiome despite both dosesproviding gut protection. Subsequent experiments of LGG on NEC revealed that pro-inflammatory TLR signaling and intestinal injury were also decreased, and SIGIRR and A20 expression increased, in a dose-dependent manner with LGG pre-treatment.CONCLUSIONS: LGG protects against intestinal TLR-mediated injury by upregulating TLR inhibitors without major changes in gut microbiome composition.

read more

PMID: 

Molecules. 2019 Jul 9 ;24(13). Epub 2019 Jul 9. PMID: 31323907

Abstract Title: 

Ketogenic Diet-Induced Weight Loss is Associated with an Increase in Vitamin D Levels in Obese Adults.

Abstract: 

Vitamin D is an important micronutrient involved in several processes. Evidence has shown a strong association between hypovitaminosis D and cardio-metabolic diseases, including obesity. A ketogenic diet has proven to be very effective for weight loss, especially in reducing fat mass while preserving fat-free mass. The aim of this study was to investigate the effect of a ketogenic diet-induced weight loss on vitamin D status in a population of obese adults. We enrolled 56 obese outpatients, prescribed with either traditional standard hypocaloric Mediterranean diet (SHMD) or very low-calorie ketogenic diet (VLCKD). Serum 25(OH)D concentrations were measured by chemiluminescence. The mean value of serum 25-hydroxyvitamin D (25(OH)D) concentrations in the whole population at baseline was 17.8± 5.6 ng/mL, without differences between groups. After 12 months of dietetic treatment, in VLCKD patients serum 25(OH)D concentrations increased from 18.4 ± 5.9 to 29.3 ± 6.8 ng/mL (

read more

PMID: 

Diabetes Metab Syndr. 2019 Mar – Apr;13(2):1187-1191. Epub 2019 Jan 24. PMID: 31336463

Abstract Title: 

Ketogenic diet rescues cognition in ApoE4+ patient with mild Alzheimer's disease: A case study.

Abstract: 

It has been established that there is a correlation between Alzheimer's disease and apolipoprotein E, specifically the ApoE4 genetic variant. However, the correlation between Apoe4, insulin resistance and metabolic syndrome (MetS) pathologies still remains elusive. As apolipoprotein E has many important physiological functions, individuals with the ApoE4 allele variant, also known as the Alzheimer's disease gene, are primarily at a greater risk for physiological consequences, specifically cognitive impairment (Chan et al., 2016). In this case study, a 71-year old female, heterozygous for ApoE4 with a family history of Alzheimer's Disease (AD) and the dual diagnosis of mild AD/metabolic syndrome (MetS) was placed on a 10-week nutrition protocol purposed at raising plasma ketones through carbohyrdrate restricted,high fat ketogenic diet (KD), time- restricted eating and physical/cognitive exercise. Primary biomarkers for MetS were measured pre/mid-/post intervention. The MoCA (Montreal Cognitive Assessment) was administered pre/post intervention by a licensed clinical therapist. The results were statistically significant. The HOMA-IR decreased by 75% from 13.9 to 3.48. Triglycerides decreased by 50% from 170mg/dL to 85mg/dL. VLDL dropped by 50% from 34mg/dL to 17mg/dL, and HgA1c decreased from 5.7% to 4.9%. The baseline MoCA score was 21/30; post treatment score was 28/30. The significant results in both MetS biomarkers and the MoCA score suggest that a ketogenic diet may serve to rescue cognition in patients with mild AD. The results of this case study are particularly compelling for ApoE4 positive (ApoE4+) subjects as ketogenic protocols extend hope and promise for AD prevention.

read more

PMID: 

Diabetes Metab Syndr. 2019 Mar – Apr;13(2):1475-1479. Epub 2019 Feb 6. PMID: 31336509

Abstract Title: 

Ketogenic diets potentially reverse Type II diabetes and ameliorate clinical depression: A case study.

Abstract: 

Efficacious adherence to treatment protocol predicts metabolic control among Type 2 diabetics (T2DM) [1-4]; however, few healthcare systems employ individualized strategies to mediate the comorbidity of T2DM with other chronic disease states. A clinically prescribed ketogenic diet, patient-centered nutritional education and high intensity interval training (HIIT), girded by solution-focused psychotherapy, modulate significant improvements in the clinical biomarkers associated with concurring T2DM and clinical depression [5-15]. Relevant metabolic change was noted in the following measures: HOMA-IR, triglyceride/HDL ratio, HgA1c, fasting insulin, fasting glucose, fasting triglycerides, LDL, VLDL, HDL, total cholesterol and C-reactive protein. The Patient Health Questionnaire 9 (PHQ-9) along with clinical interview and the mental status exam showed notable change in the patient's depressive symptoms; likewise, her self-efficacy score normalized, as measured by the General Self-Efficacy Questionnaire (GSE) and the Metabolic Syndrome Compliance Questionnaire (MSC). The case study highlights a 65-year old female who presented with a 26-year history of dually-diagnosed Type 2 diabetes (T2DM) and major depressive disorder (MDD). The patient was prescribed a ketogenic diet (KD), clinically formulated from her resting metabolic rate, body fat percentage and lean body mass, together with weekly nutrition education, high intensity interval training (matched to her cardiovascular conditioning), and eight 45-minute solution-focused psychotherapy sessions. Intervention goals included improved insulin sensitivity evaluated by the HOMA-IR, sustained glycemic control measured via HgA1c, reduced cardiovascular risk via the triglyceride/HDL ratio, and improved depressive symptoms with increased self-efficacy monitored by the PHQ-9 and GSE/MSC. The results of the 12-week intervention were statistically significant. The patient's HgA1c dropped out of diabetic range (8.0%) and normalized at 5.4%. Her average daily glucose measurements declined from 216 mg/dL to 96 mg/dL; the HOMA-IR and triglyceride/HDL ratios improved by 75%. Her marker for clinical depression and measurement of self-efficacy normalized. The 12-week individualized treatment intervention served to functionally reverse 26 years of T2DM, ameliorate two and half decades of chronic depressive disorder and empower/equip the patient with a new experience of hope and success.

read more

PMID: 

Nutr Cancer. 2019 Jul 27:1-11. Epub 2019 Jul 27. PMID: 31352797

Abstract Title: 

A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: a Randomized, Controlled Trial.

Abstract: 

Ketogenic diets (KDs) are emerging as effective therapies for several chronic diseases, including cancer. However, concerns regarding safety and adherence may prevent clinicians from prescribing KDs. We hypothesized that a KD does not negatively affect blood lipid profile compared to a lower-fat diet in ovarian and endometrial cancer patients, and that KD subjects would demonstrate acceptable adherence. Subjects were randomized to either a KD (70% fat, 25% protein, 5% carbohydrate), or the American Cancer Society diet (ACS; high-fiber and lower-fat). Blood lipids and ketones were measured at baseline and after 12 weeks of the assigned intervention. Adherence measures included urinary ketones in the KD and 4 days' diet records. Diet records were also examined to identify general patterns of consumption. Differences between the diets on blood lipids and dietary intake were assessed with Analysis of covariance and independent-tests. Correlation analyses were used to estimate associations between dietary intake and serum analytes. At 12 weeks, there were no significant differences between diet groups in blood lipids, after adjusting for baseline values and weight loss. Adherence among KD subjects ranged from 57% to 80%. These findings suggest that KDs may be a safe and achievable component of treatment for some cancer patients.

read more

PMID: 

Mol Metab. 2019 Jul 27. Epub 2019 Jul 27. PMID: 31399389

Abstract Title: 

Ketogenic diet in the treatment of cancer – Where do we stand?

Abstract: 

BACKGROUND: Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy.SCOPE OF REVIEW: To critically evaluate available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy. Furthermore, we highlight important mechanisms that could explain the potential antitumor effects of the ketogenic diet.MAJOR CONCLUSIONS: The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.

read more

PMID: 

Int J Mol Sci. 2019 Aug 9 ;20(16). Epub 2019 Aug 9. PMID: 31405021

Abstract Title: 

Ketogenic Diet in Alzheimer's Disease.

Abstract: 

At present, the prevalence of Alzheimer's disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloidβ-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrialfunction, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer's disease. This review aims to examine the role of the ketogenic diet in Alzheimer's disease progression and to outline specificaspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer's disease.

read more

PMID: 

Acta Med Port. 2019 Dec 2 ;32(12):760-766. Epub 2019 Dec 2. PMID: 31851885

Abstract Title: 

Ketogenic Diet for Refractory Childhood Epilepsy: Beyond Seizures Control, the Experience of a Portuguese Pediatric Centre.

Abstract: 

INTRODUCTION: Ketogenic diet is a low carbohydrate diet, which can be used as a treatment for refractory childhood epilepsy. The first aim of this study was to evaluate its efficacy, in patients receiving ketogenic diet for at least three months, on epilepsy control, behaviour and awareness. The secondary aims were to evaluate the variation in the number of antiepileptic drugs, reasons for discontinuing the diet and adverse effects.MATERIAL AND METHODS: Retrospective analysis of clinical records of patients who underwent ketogenic diet for refractory epilepsy, from October 2007 to January 2018, in a tertiary pediatric hospital.RESULTS: In the twenty-nine eligible patients, the mean age of initiation was 7.9 years-old (+/- 5.6). Of those, 18 had a≥ 50% reduction of seizure activity, 19 a marked behaviour improvement and 18 improved awareness. The median number of antiepileptic drugs remained equal for the 15 patients who completed 18 months of treatment (three drugs). The main reason for discontinuing ketogenic diet was a familiar decision. The main adverse effects were hypercholesterolemia (n = 23) and hypertriglyceridemia (n = 21).DISCUSSION: Results were comparable to those of other cohorts, namely age of initiation, proportion of patients completing ketogenic diet, most frequent reasons for stopping and significant improvement of alertness and behavior.CONCLUSION: Beyond seizure control, patients experienced a marked improvement in behavior and awareness. It is necessary to develop strategies to increase the adherence of families to the diet.

read more

PMID: 

Mol Nutr Food Res. 2020 Jan 8:e1900535. Epub 2020 Jan 8. PMID: 31914235

Abstract Title: 

Ketogenic Diet Potentiates Electrical Stimulation-induced Peripheral Nerve Regeneration after Sciatic Nerve Crush Injury in Rats.

Abstract: 

SCOPE: Recent findings indicate that ketogenic diet is neuroprotective and electrical stimulation can improve functional recovery from peripheral nerve injury. However, it is not clear whether ketogenic diet and electrical stimulation play synergistical role in the peripheral nerve recovery following injury.METHODS AND RESULTS: We used ketogenic diet consisting of 3:1 ratio of fat to carbohydrate+protein and coupled it with electrical stimulation treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery was evaluated by electromyography, and axonal regeneration and myelination by histological methods. We also investigated the effects on IGF-1 and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury. Combination of ketogenic diet and electrical stimulation synergistically increased muscle force in biceps femoris and gluteus maximus and prevented development of hypersensitivity in biceps femoris. It promoted peripheral nerve regeneration by increasing total axons, axons density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects were due to modulation of IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue.CONCLUSION: Our results establish that ketogenic diet and electrical stimulation promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach. This article is protected by copyright. All rights reserved.

read more