scholarly journals Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors

2015 ◽  
Vol 2 (3) ◽  
pp. 127-136 ◽  
Author(s):  
Roy E. Strowd ◽  
Mackenzie C. Cervenka ◽  
Bobbie J. Henry ◽  
Eric H. Kossoff ◽  
Adam L. Hartman ◽  
...  

Dietary glycemic modulation through high-fat, low-carbohydrate diets, which induce a state of systemic ketosis and alter systemic metabolic signaling, have been incorporated into the clinical management of patients with neurological disease for more than a century. Mounting preclinical evidence supports the antitumor, proapoptotic, and antiangiogenic effects of disrupting glycolytic metabolism through dietary intervention. In recent years, interest in incorporating such novel therapeutic strategies in neuro-oncology has increased. To date, 3 published studies incorporating novel dietary therapies in oncology have been reported, including one phase I study in neuro-oncology, and have set the stage for further study in this field. In this article, we review the biochemical pathways, preclinical data, and early clinical translation of dietary interventions that modulate systemic glycolytic metabolism in the management of primary malignant brain tumors. We introduce the modified Atkins diet (MAD), a novel dietary alternative to the classic ketogenic diet, and discuss the critical issues facing future study.

2016 ◽  
Vol 74 (10) ◽  
pp. 842-848 ◽  
Author(s):  
Letícia Pereira de Brito Sampaio

ABSTRACT The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Deirdre K Tobias ◽  
Mu Chen ◽  
Walter Willett ◽  
Frank B Hu

Introduction: The effectiveness of low-fat diets for weight loss has been debated for decades. Dozens of randomized control trials (RCTs) have assessed whether decreasing the intake of total fat leads to weight loss, giving mixed results. Hypothesis: We hypothesized that low-fat dietary interventions do not lead to greater weight loss when comparator diet intervention intensity is considered. Methods: We conducted a systematic review and meta-analysis. RCTs were included if they compared a low-fat dietary intervention to any control diet with at least 1 year of follow-up. We estimated the combined fixed effect inverse variance weighted mean difference of low-fat vs. comparison diets. Several a priori stratified analyses were considered to explore heterogeneity. Results: Fifty studies met inclusion criteria, reporting 1-10 years of follow-up on 70,054 participants. Overall, low-fat dietary interventions resulted in 0.51kg greater weight loss compared to other diets (95% CI = -0.62, -0.40, p<0.001; I2 = 83%). However, when trials where greater attention was given to the low-fat group were excluded, comparator diets led to greater weight loss than low-fat diets (n=30; WMD=0.87, 95% CI=0.56, 1.17, p<0.001). Similarly, when the type of comparator diet was considered, low-fat diets were only beneficial compared to control groups who were simply asked to maintain their usual diet (n=18; WMD = -1.03, 95% CI = -1.18, -0.88, p<0.001). When equal attention was given to intervention groups, low-carbohydrate diets (n=15; WMD = 1.13kg, 95% CI = 0.53, 1.73, p<0.001) and other “healthy” diets without a low-fat component (n=20; WMD = 0.77kg, 95% CI = 0.42, 1.13, p<0.001) led to greater weight loss than low-fat diets. Comparison diets, irrespective of type, were associated with 1.30kg greater weight loss than low-fat diets when the interventions were intended to be isocaloric (n=19; 95% CI = 0.92, 1.69, p<0.001). Conclusions: Low-fat dietary interventions are not more effective than other diets for weight loss when differences in intervention intensity between treatment groups are considered. Rather, evidence from long-term (>=1 year) randomized trials indicates low-carbohydrate or other healthful dietary pattern interventions without a low-fat focus may be more effective for weight loss than low-fat dietary interventions. Further evidence is needed to establish the role of these interventions in longer-term weight loss and weight maintenance.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi23-vi23
Author(s):  
Karisa Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie J Henry-Barron ◽  
Lindsay Blair ◽  
...  

Abstract INTRODUCTION Exploiting metabolic vulnerabilities via ketosis is a promising approach for gliomas. The modified Atkins diet is a ketogenic diet therapy efficacious in adults with refractory epilepsy. We evaluated the feasibility, pharmacokinetics/pharmacodynamics(PK/PD), and cerebral activity of this dietary intervention intended to induce ketosis. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 ‘intermittent fasting’ days(IF; calories < 20% of recommended daily allowance) interleaved between 5 modified-Atkins diet days(MAD; carbohydrates < 20 gm/day) each week. The primary outcome was dietary compliance. Secondary outcomes were PK assessed by urine ketones post-FAST and post-MAD, PD assessed by serum insulin and IGF-1, and cerebral activity measured by MR spectroscopy at baseline and week 8. RESULTS Grade 2(n=2;8%), Grade 3(n=11;44%) and GBMs(n=12;48%) were enrolled. While only 48% of participants satisfied pre-defined compliance criteria, overall compliance with MAD(80%) was higher than IF(72%). Weight loss was observed (-4.8 + 2.2kg,p< 0.0001) consisting primarily of decreased fat mass (-2.5 + 3.1%,p< 0.0001), with increased lean body mass (2.4 + 3.2%,p< 0.0001), stable nutritional status (phase angle, -0.26 + 0.94%,p=0.22), and normalization of BMI. Urine acetoacetate significantly increased with 55% achieving moderate ketosis at week 8 (p=0.0005). Serum insulin and IGF-1 significantly decreased indicating systemic dietary response and were associated with higher ketones post-IF, but not post-MAD. MRS demonstrated cerebral activity with increased ketones in lesional (0.06±0.03- >0.27±0.06i.u,p=0.005) and contralateral brain at week 8 (0.041±0.01- >0.16±0.04i.u.,p=0.004). Higher cerebral acetone correlated with higher urine ketones (r >0.75,p< 0.02) and lower fasting glucose (r >-0.74,p< 0.05). CONCLUSIONS The GLAD diet was challenging to maintain but demonstrated quantifiable biologic effects systemically and intratumorally. MAD was more feasible than IF, but changes in PD markers correlated most strongly with IF. The role of ketogenic diet therapy for preventing glioma growth remains uncertain.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Soodeh Razeghi Jahromi ◽  
◽  
Zeinab Ghorbani ◽  
Paolo Martelletti ◽  
Christian Lampl ◽  
...  

AbstractThe global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.


Pain Medicine ◽  
2019 ◽  
Vol 21 (1) ◽  
pp. 150-160 ◽  
Author(s):  
Larissa J Strath ◽  
Catherine D Jones ◽  
Alan Philip George ◽  
Shannon L Lukens ◽  
Shannon A Morrison ◽  
...  

Abstract Objective Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA. Design A randomized controlled pilot study to test the efficacy of two dietary interventions. Subjects Adults 65–75 years of age with KOA. Methods Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress. Results Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also significantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain. Conclusions We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.


Author(s):  
Suvasini Sharma

The Ketogenic Diet (KD) is a high fat, low carbohydrate and restricted protein diet which has been used for the treatment of drug resistant epilepsy in children. It is considered the treatment of choice for refractory nonsurgical epilepsy in children. However, despite this being a very useful and relatively simple treatment, children from developing countries have not been able to benefit as much as their counterparts in more privileged settings. In this article, the challenges faced by pediatric neurologists and parents who wish to use the diet in children with refractory epilepsy are discussed, and also the simple low cost innovations which can be used to overcome these challenges are suggested. The evolution from the use of the classic ketogenic diet to the flexible use of the modified Atkins diet in low resource settings will be discussed.


2013 ◽  
Vol 29 (3) ◽  
pp. 437-442 ◽  
Author(s):  
Eric H. Kossoff ◽  
Mackenzie C. Cervenka ◽  
Bobbie J. Henry ◽  
Courtney A. Haney ◽  
Zahava Turner

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2645
Author(s):  
Alberto Verrotti ◽  
Giulia Iapadre ◽  
Ludovica Di Francesco ◽  
Luca Zagaroli ◽  
Giovanni Farello

Epilepsy is a chronic and debilitating neurological disorder, with a worldwide prevalence of 0.5–1% and a lifetime incidence of 1–3%. An estimated 30% of epileptic patients continue to experience seizures throughout life, despite adequate drug therapy or surgery, with a major impact on society and global health. In recent decades, dietary regimens have been used effectively in the treatment of drug-resistant epilepsy, following the path of a non-pharmacological approach. The ketogenic diet and its variants (e.g., the modified Atkins diet) have an established role in contrasting epileptogenesis through the production of a series of cascading events induced by physiological ketosis. Other dietary regimens, such as caloric restriction and a gluten free diet, can also exert beneficial effects on neuroprotection and, therefore, on refractory epilepsy. The purpose of this review was to analyze the evidence from the literature about the possible efficacy of different dietary regimens on epilepsy, focusing on the underlying pathophysiological mechanisms, safety, and tolerability both in pediatric and adult population. We believe that a better knowledge of the cellular and molecular biochemical processes behind the anticonvulsant effects of alimentary therapies may lead to the development of personalized dietary intervention protocols.


2013 ◽  
Vol 111 (4) ◽  
pp. 586-597 ◽  
Author(s):  
Gerald E. Lobley ◽  
Alexandra M. Johnstone ◽  
Claire Fyfe ◽  
Graham W. Horgan ◽  
Grietje Holtrop ◽  
...  

Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m2, took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30 % of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An18fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n4) or 4 h after consumption of a test meal (n8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-13C]acetoacetate, [2,4-13C]3-hydroxybutyrate and [6,6-2H2]glucose. The composite hunger score was 14 % lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5 % lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.


2019 ◽  
Vol 21 (1) ◽  
pp. 69-82 ◽  

Dietary intervention is an enticing approach in the fight against cognitive impairment. Nutritional supplements and dietetic counseling are relatively easy and benign interventions, but research has not yet yielded irrefutable evidence as to their clinical utility. Heterogeneity in the results of available clinical studies, as well as methodological and practical issues, does not allow replication and generalization of findings. The paper at hand reviews only randomized clinical trials of single nutrients, multi-nutrient formulations and dietary counseling in mild cognitive impairment and dementia of the Alzheimer's type focusing on both cognitive and functional outcomes. Thus far, folate, vitamin E, Ω-3 fatty acids, and certain multi-nutrient formulations have shown some preliminary promising results; larger, well-designed trials are needed to confirm these findings before nutritional elements can be incorporated in recommended clinical guidelines.


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