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Nutrition

Peer-Reviewed Scientific Articles​

The ketogenic diet as a treatment paradigm for diverse neurological disorders

May 17, 2020 No Comments

URL: https://www.frontiersin.org/articles/10.3389/fphar.2012.00059/full

Journal: Frontiers in Pharmacology

Publication Date: 04/2012

Summary: Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

Key Takeaways

The ketogenic diet has been shown to be neuroprotective and used in the treatment of epilepsy. The exact mechanisms of how the diet is protective against epilepsy is unclear, but it is thought that energy regulation plays a major role. Because the ketogenic diet does not rely on continuous inputs of carbohydrates, blood sugar levels remain constant. Without these large fluctuations in blood sugar, the energy supply to the brain is stable resulting in a reduction in seizures. Additionally, ketone bodies produced by burning fat are neuroprotective in their own way through a variety of actions. This dietary approach has been shown to be helpful in treating other neurologic conditions such as headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis.

Is The Ketogenic Diet The Best Treatment For Neurologic Diseases?

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?

May 17, 2020 No Comments

URL: https://www.sciencedirect.com/science/article/abs/pii/S0920121111002063?via%3Dihub

Journal: Epilepsy Research

Publication Date: 07/2012

Summary: Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As long as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer.

Key Takeaways

Brain cancers can be thought of as a disease of energy regulation. They utilize glucose and glutamine to survive and grow. This is why standards of care may be outperformed by dietary approaches that stabilize the glucose input to the brain such as the ketogenic diet. Additionally a calorie restricted ketogenic diet may target the utilization of glutamine by the cancer. A calorie restricted ketogenic diet in mice with malignant brain cancer was shown to be anti-inflammatory, reduce invasion of the cancer, reduce access of cancer to nutrients by preventing blood vessel formation, and induce death of the cancer cells.

Brain Cancer Goes Away On Ketogenic Diet?!

Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes

May 17, 2020 No Comments

URL: https://www.sciencedirect.com/science/article/abs/pii/S0899900712000731?via%3Dihub

Journal: Nutrition

Publication Date: 10/2012

Summary: Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneficial effects of a low-carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the beneficial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. The LCD and LCKD had beneficial effects on all the parameters examined. Interestingly, these changes were more significant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically significant. This study shows the beneficial effects of a ketogenic diet over the conventional LCD in obese diabetic subjects. The ketogenic diet appears to improve glycemic control. Therefore, diabetic patients on a ketogenic diet should be under strict medical supervision because the LCKD can significantly lower blood glucose levels.

Key Takeaways

363 overweigh or obese patients (102 of them had type 2 diabetes) chose either a low carbohydrate ketogenic diet or a low calorie diet. The study lasted for 24 weeks, and both diets showed improvement in body weight, BMI, waist circumference, Hb-A1C, blood lipids, and kidney function tests. However, the low carb ketogenic group showed greater improvements across the board.

Ketogenic Diet Outperforms Calorie Restriction for Weight Loss and Diabetes Management

Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease

May 16, 2020 No Comments

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679496/

Journal: Current Opinions in Clinical Nutrition and Metabolic Care

Publication Date: 07/2012

Summary: Obesity-associated nonalcoholic fatty liver disease (NAFLD) is highly prevalent, for which weight loss is the generally recommended clinical management. Low-carbohydrate ketogenic diets have been successful in promoting weight loss, but variations in the range of metabolic responses to these diets indicate that the effects of altering macronutrient content are not completely understood. This review focuses on the most recent findings that reveal the relationship between low-carbohydrate diets and NAFLD in rodent models and humans. Low-carbohydrate diets have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity. These ketogenic diets also provoke weight loss in rodents. However, long-term maintenance on a ketogenic diet stimulates the development of NAFLD and systemic glucose intolerance in mice. The relationship between ketogenic diets and systemic insulin resistance in both humans and rodents remains to be elucidated. Because low-carbohydrate ketogenic diets are increasingly employed for treatment of obesity, NAFLD, and neurological diseases such as epilepsy, understanding the long-term systemic effects of low-carbohydrate diets is crucial to the development of efficacious and safe dietary interventions.

Key Takeaways

Low Carbohydrate Ketogenic Diets are shown to be highly effective for weight loss and reduction of fatty liver. However, long term ketogenic diets in mice induced fatty liver. This study calls for further research in long term low carbohydrate diets to assess unintended health consequences. We must ask the question: Are outcomes in mice going to be the same in humans? Likely not as we are different species, which is why this study calls for more long term data in humans to assess safety.

Keto Causes NAFLD in Mice. Can We Assume This To Be True In Humans?

Dietary ketosis enhances memory in mild cognitive impairment

May 16, 2020 No Comments

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116949/

Journal: Nuerobiology of Aging

Publication Date: 02/2012

Summary: We randomly assigned 23 older adults with Mild Cognitive Impairment to either a high carbohydrate or very low carbohydrate diet. Following the six-week intervention period, we observed improved verbal memory performance for the low carbohydrate subjects (p = 0.01) as well as reductions in weight (p < 0.0001), waist circumference (p < 0.0001), fasting glucose (p = 0.009), and fasting insulin (p = 0.005). Level of depressive symptoms was not affected. Change in calorie intake, insulin level, and weight were not correlated with memory performance for the entire sample, although a trend toward a moderate relationship between insulin and memory was observed within the low carbohydrate group. Ketone levels were positively correlated with memory performance (p = 0.04). These findings indicate that very low carbohydrate consumption, even in the short-term, can improve memory function in older adults with increased risk for Alzheimer’s disease. While this effect may be attributable in part to correction of hyperinsulinemia, other mechanisms associated with ketosis such as reduced inflammation and enhanced energy metabolism also may have contributed to improved neurocognitive function. Further investigation of this intervention is warranted to evaluate its preventive potential and mechanisms of action in the context of early neurodegeneration.

Key Takeaways

Low carbohydrate ketogenic diets showed improved memory, weight loss, blood sugar, and fasting insulin in adults with mild cognitive impairment. Further research is needed to determine whether the improvement is due to correction of high insulin levels, or the reduction in inflammation brought about by the ketosis.

Ketogenic Diet Improves Memory in Adults With Cognitive Impairment

Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials

May 16, 2020 No Comments

URL: https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/verylowcarbohydrate-ketogenic-diet-v-lowfat-diet-for-longterm-weight-loss-a-metaanalysis-of-randomised-controlled-trials/6FD9F975BAFF1D46F84C8BA9CE860783

Journal: British Journal of Nutrition

Publication Date: 10/2013

Summary: The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30 % of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect, Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was body weight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure, glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis, five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference − 0·91 (95 % CI − 1·65, − 0·17) kg, 1415 patients), TAG (weighted mean difference − 0·18 (95 % CI − 0·27, − 0·08) mmol/l, 1258 patients) and diastolic blood pressure (weighted mean difference − 1·43 (95 % CI − 2·49, − 0·37) mmHg, 1298 patients) while increased HDL-C (weighted mean difference 0·09 (95 % CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95 % CI 0·04, 0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the long term; hence, a VLCKD may be an alternative tool against obesity.

Key Takeaways

Evidence gathered from multiple trials shows that low carbohydrate ketogenic diets are very effective for long term weight loss. Additionally, low carb ketogenic diets showed lower triglycerides and blood pressure, while HDL and LDL were shown to be increased.

Ketogenic Diets Are An Excellent Approach for Long Term Weight Loss

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects

May 16, 2020 No Comments

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845365/

Journal: Metabolism

Publication Date: 12/2013

Summary: High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity. Obese subjects (29.0–44.6 kg/m2) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12 weeks. The age range of subjects was 21–62 years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2 h oral glucose tolerance test did not differ (P>0.05) between diets after 12 weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet. Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets.

Key Takeaways

This study compared high fat low carb diets to low fat high carb diets for 12 weeks in obese adults. Both diets saw similar levels of change in body weight, lean and fat mass, blood pressure, blood sugar, and insulin. However, the high fat low carb diet led to decreases in triglycerides and CRP (a marker of inflammation). The high fat low carb group also saw increase in HDL and adiponectin (a marker of insulin sensitivity).

High Fat Low Carb Diets Lead to Lower Inflammation and Better Insulin Sensitivity Than Low Fat High Carb Diets

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

May 16, 2020 No Comments

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.

Key Takeaways

The ketogenic diet has been used as a way to control patients' epilepsy for a century, but it has been recently shown to have a therapeutic effect in several other diseases such as diabetes, polycystic ovarian syndrome, acne, neurologic diseases, cardiovascular disease, and cancer. Click the link to the article to read in more detail about the effects of the ketogenic diet on these diseases.

The Ketogenic Diet Has Therapeutic Use Beyond Epilepsy and Weight Loss

Ketosis and appetite-mediating nutrients and hormones after weight loss

May 16, 2020 No Comments

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.

Key Takeaways

Being in ketosis after weight loss gives the benefit of appetite suppression, but when foods are reintroduced that brings individuals out of a ketogenic state, appetite increases, which could lead to regaining weight.

Ketogenic Diets May Prevent Regaining Lost Weight By Keeping Appetite Low

Improvements in Glucose Metabolism and Insulin Sensitivity with a Low-Carbohydrate Diet in Obese Patients with Type 2 Diabetes

May 16, 2020 No Comments

URL: https://www.ncbi.nlm.nih.gov/pubmed/24015695

Journal: Journal of the American College of Nutrition

Publication Date: 04/2013

Summary: The optimal diet for weight loss in type 2 diabetes remains controversial. This study examined a low-carbohydrate, high-fat diet with detailed physiological assessments of insulin sensitivity, glycemic control, and risk factors for cardiovascular disease. Fourteen obese patients (body mass index [BMI] 40.6 ± 4.9 kg/m2) with type 2 diabetes were recruited for an “Atkins”-type low-carbohydrate diet. Measurements were made at 0, 12, and 24 weeks of weight, insulin sensitivity, HbA1c, lipids, and blood pressure. Twelve completers lost a mean of 9.7 ± 1.8 kg over 24 weeks attributable to a major reduction in carbohydrates and resultant reduction in total energy intake. Glycemic control significantly improved (HbA1c −1.1 ± 0.25%) with reductions in hypoglycemic medication. Fasting glucose, homeostasis model assessment (HOMA), and area under the curve (AUC) glucose (intravenous glucose tolerance test [IVGTT]) were significantly reduced by week 12 (p < 0.05). There were nonsignificant improvements in insulin sensitivity (SI) at week 12 ( p = 0.19) and week 24 ( p = 0.31). Systolic blood pressure was reduced (mean −10.0 mmHg between weeks 0 and 24, p = 0.13). Mean high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol all increased. The ratio of total: HDL cholesterol and triglycerides was reduced. A low-carbohydrate diet was well tolerated and achieved weight loss over 24 weeks in subjects with diabetes. Glycemic control improved with a reduction in requirements for hypoglycemic agents.

Key Takeaways

In this study, a low carbohydrate diet was administered to 14 obese type 2 diabetics for 24 weeks. The subjects saw improvements across the board in weight, blood sugar, and blood pressure. Total, HDL, and LDL cholesterol all increased, but with good ratios. Overall glycemic control was improved with a lower requirement for diabetic medications.

Ketogenic Diets Improve Glycemic Control and Reduce Medication Requirement in Type 2 Diabetics

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