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Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826507/

Journal: European Journal of Clinical Nutrition

Publication Date: 08/2013

Summary: Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician’s hand.

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Ketosis and appetite-mediating nutrients and hormones after weight loss

URL: https://www.nature.com/articles/ejcn201390

Journal: European Journal of Clinical Nutrition

Publication Date: 05/2013

Summary: Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss. Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding. During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding. The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.

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Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

URL: https://www.ncbi.nlm.nih.gov/pubmed/25402637

Journal: Obesity Reviews

Publication Date: 01/2015

Summary: Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.

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Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis.

URL: https://www.ncbi.nlm.nih.gov/pubmed/26559897

Journal: Obesity Research & Clinical Practice

Publication Date: 05/2016

Summary: Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the vis- ceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relaps- ing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis.

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Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus

URL: https://www.ncbi.nlm.nih.gov/pubmed/28179470

Journal: Neurology

Publication Date: 03/2017

Summary: To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults. We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility. Secondary measures included resolution of SRSE, disposition at discharge, KD-related side effects, and long-term outcomes. Twenty-four adults were screened for participation at 5 medical centers, and 15 were enrolled and treated with a classic KD via gastrostomy tube for SRSE. Median age was 47 years (interquartile range [IQR] 30 years), and 5 (33%) were male. Median number of antiseizure drugs used before KD was 8 (IQR 7), and median duration of SRSE before KD initiation was 10 days (IQR 7 days). KD treatment delays resulted from intravenous propofol use, ileus, and initial care received at a nonparticipating center. All patients achieved ketosis in a median of 2 days (IQR 1 day) on KD. Fourteen patients completed KD treatment, and SRSE resolved in 11 (79%; 73% of all patients enrolled). Side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, hyponatremia, and weight loss. Five patients (33%) ultimately died. KD is feasible in adults with SRSE and may be safe and effective. Comparative safety and efficacy must be established with randomized placebo-controlled trials.

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Implementing a low carbohydrate, ketogenic diet to manage type 2 diabetes mellitus

URL: https://www.ncbi.nlm.nih.gov/pubmed/30289048

Journal: Expert Review of Endocrinology and Metabolism

Publication Date: 09/2018

Summary: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the modern world. For individuals affected by obesity-related T2DM, clinical studies have shown that carbohydrate restriction and weight loss can improve hyperglycemia, obesity and T2DM. Reducing carbohydrate intake to a certain level, typically below 50 grams per day, leads to increased ketogenesis in order to provide fuel for the body. Such low- carbohydrate, ketogenic diets were employed to treat obesity and diabetes in the 19th and early 20th centuries. Recent clinical research has reinvigorated the use of the ketogenic diet for individuals with obesity and diabetes. Although characterized by chronic hyperglycemia, the underlying cause of T2DM is hyperinsulinemia and insulin resistance, typically as a result of increased energy intake leading to obesity. The ketogenic diet substantially reduces the glycemic response that results from dietary carbohydrate as well as improves the underlying insulin resistance. This review combines a literature search of the published science and practical guidance based on clinical experience. While the current treatment of T2DM emphasizes drug treatment and a higher carbohydrate diet, the ketogenic diet is an effective alternative that relies less on medication, and may even be a preferable option when medications are not available.

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Nutritional Ketosis for Weight Management and Reversal of Metabolic Syndrome

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472268/pdf/nihms-1015199.pdf

Journal: Current Nutrition Reports

Publication Date: 09/2018

Summary: The goal of this paper is to review current literature on nutritional ketosis within the context of weight management and metabolic syndrome—namely insulin resistance, lipid profile and cardiovascular disease risk, and development of non-alcoholic fatty liver disease. We provide background on the mechanism of ketogenesis and describe nutritional ketosis. Nutritional ketosis has been found to improve metabolic and inflammatory markers, including lipids, HbA1c, high-sensitivity CRP, fasting insulin and glucose levels, and aid in weight management. We discuss these findings and elaborate on potential mechanisms of ketones for promoting weight loss, decreasing hunger, and increasing satiety. Humans have evolved with the capacity for metabolic flexibility and the ability to use ketones for fuel. During states of low dietary carbohydrate intake, insulin levels remain low and ketogenesis takes place. These conditions promote breakdown of excess fat stores, sparing of lean muscle, and improvement in insulin sensitivity.

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Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study

URL: https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-018-0698-8

Journal: Cardiovascular Diabetology

Publication Date: 05/2018

Summary: Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a con- tinuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort. We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-rand- omized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomark- ers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-fac- torial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons. The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m−2). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (− 4.9%, P = 0.02), small LDL-P (− 20.8%, P = 1.2 × 10−12), LDL-P size (+ 1.1%, P = 6.0 × 10−10), ApoB (− 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10−16), ApoB/ApoA1 ratio (− 9.5%, P = 1.9 × 10−7), triglyceride/HDL-C ratio (− 29.1%, P < 10−16), large VLDL-P (− 38.9%, P = 4.2 × 10−15), and LDL-C (+ 9.9%, P = 4.9 × 10−5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10−7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased − 11.9% (P = 4.9 × 10−5). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10−5). The UC group of 87 participants [base- line mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m−2] showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C.

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Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up

URL: https://www.frontiersin.org/articles/10.3389/fnut.2018.00020/full

Journal: Frontiers in Nutrition

Publication Date: 03/2018

Summary: Few advances have been made in overall survival for glioblastoma multiforme (GBM) in more than 40 years. Here, we report the case of a 38-year-old man who presented with chronic headache, nausea, and vomiting accompanied by left partial motor seizures and upper left limb weakness. Enhanced brain magnetic resonance imaging revealed a solid cystic lesion in the right partial space suggesting GBM. Serum testing revealed vitamin D deficiency and elevated levels of insulin and triglycerides. Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast. Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day. In addition to radiotherapy, temozolomide chemotherapy, and the KD (increased to 1,500 kcal/day at day 22), the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA). The patient also received levetiracetam (1,500 mg/day). No steroid medication was given at any time. Post-surgical histology confirmed the diagnosis of GBM. Reduced invasion of tumor cells and thick-walled hyalinized blood vessels were also seen suggesting a therapeutic benefit of pre-surgical metabolic therapy. After 9 months treatment with the modified SOC and complimentary ketogenic metabolic therapy (KMT), the patient’s body weight was reduced by about 19%. Seizures and left limb weakness resolved. Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D. This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies. As rapid regression of GBM is rare following subtotal resection and SOC alone, it is possible that the response observed in this case resulted in part from the modified SOC and other novel treatments. Additional studies are needed to validate the efficacy of KMT administered with alternative approaches that selectively increase oxidative stress in tumor cells while restricting their access to glucose and glutamine. The patient remains in excellent health (Karnofsky Score, 100%) with continued evidence of significant tumor regression.

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The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed

URL: http://www.ncbi.nlm.nih.gov/pubmed/31825066

Journal: The Journal of Nutrition

Publication Date: 12/2019

Summary: For >50 y, dietary guidelines in the United States have focused on reducing intakes of saturated and total fat. However, rates of obesity and diabetes rose markedly throughout this period, with potentially catastrophic implications for public health and the economy. Recently, ketogenic diets have received substantial attention from the general public and nutrition research community. These very-low-carbohydrate diets, with fat comprising >70% of calories, have been dismissed as fads. However, they have a long history in clinical medicine and human evolution. Ketogenic diets appear to be more effective than low-fat diets for treatment of obesity and diabetes. In addition to the reductions in blood glucose and insulin achievable through carbohydrate restriction, chronic ketosis might confer unique metabolic benefits of relevance to cancer, neurodegenerative conditions, and other diseases associated with insulin resistance. Based on available evidence, a well-formulated ketogenic diet does not appear to have major safety concerns for the general public and can be considered a first-line approach for obesity and diabetes. High-quality clinical trials of ketogenic diets will be needed to assess important questions about their long-term effects and full potential in clinical medicine.