Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012386
Author(s):  
Karisa C. Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie Henry-Barron ◽  
Diane Vizthum ◽  
...  
Keyword(s):  
Biological Activity ◽  
Body Mass ◽  
Mr Spectroscopy ◽  
Hemoglobin A1c ◽  
Dietary Intervention ◽  
Intermittent Fasting ◽  
Cerebral Activity ◽  
Food Records ◽  
Systemic Activity ◽  
Patient Reported

OBJECTIVE:To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma.METHODS:25 patients with biopsy-confirmed WHO Grade 2-4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories<20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, IGF-1, and MR spectroscopy at baseline and week 8.RESULTS:21 patients completed the study (84%). 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% of patients were adherent by food record. The diet was well-tolerated with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity including hemoglobin A1c, insulin, and fat body mass decreased significantly, while lean body mass increased. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs 0.52, p=0.05). Sub-group analysis of IDH-mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria.CONCLUSIONS:The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appear to be a better indicator of systemic activity than patient-reported food records.

scholarly journals DDRE-31. FEASIBILITY AND BIOLOGIC ACTIVITY OF A KETOGENIC / INTERMITTENT FASTING DIET IN GLIOMA PATIENTS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Karisa Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie Henry-Barron ◽  
Diane Vizthum ◽  
...  
Keyword(s):  
Body Mass ◽  
Mr Spectroscopy ◽  
Hemoglobin A1c ◽  
Dietary Intervention ◽  
Intermittent Fasting ◽  
Who Grade ◽  
Cerebral Activity ◽  
Food Records ◽  
Systemic Activity ◽  
Patient Reported

Abstract BACKGROUND There has been increasing interest in exploring ketogenic diet therapies (KDT) in patients with glioma given the poor prognosis. The purpose of this single-arm, open label phase 2 study was to rigorously examine the feasibility, safety, systemic biological activity, and cerebral activity of a KDT in patients with glioma. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories&lt;20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, IGF-1, and MR spectroscopy at baseline and week 8. RESULTS 21 patients completed the study. 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% of patients were adherent by food record. The diet was well-tolerated with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity including hemoglobin A1c, insulin, and fat body mass decreased significantly, while lean body mass increased. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Higher total choline (tCho) and glutamine (Gln) levels were observed in lesional as compared to contralateral brain at baseline, and both decreased following intervention. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs0.52, p=0.05). There were no differences in cerebral metabolites in IDH-mutant glioma after controlling for ketonuria. CONCLUSIONS The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Participant ketonuria correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.

scholarly journals ACTR-44. FEASIBILITY, PHARMACODYNAMICS, AND BIOLOGIC ACTIVITY OF THE GLIOMA ATKINS-BASED DIET (GLAD) FOR PREVENTING TUMOR RECURRENCE IN GLIOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi23-vi23
Author(s):  
Karisa Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie J Henry-Barron ◽  
Lindsay Blair ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Dietary Intervention ◽  
Serum Insulin ◽  
Diet Therapy ◽  
Intermittent Fasting ◽  
Who Grade ◽  
Dietary Compliance ◽  
Cerebral Activity ◽  
Modified Atkins Diet ◽  
Atkins Diet

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.

Predictors of nonroutine discharge among patients undergoing surgery for grade I spondylolisthesis: insights from the Quality Outcomes Database

2020 ◽  
Vol 32 (4) ◽  
pp. 523-532 ◽  
Author(s):  
Praveen V. Mummaneni ◽  
Mohamad Bydon ◽  
John Knightly ◽  
Mohammed Ali Alvi ◽  
Anshit Goyal ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Acute Care ◽  
Body Mass ◽  
Care Facility ◽  
Older Age ◽  
Quality Outcomes ◽  
Acute Care Facility ◽  
Factors Associated ◽  
Patient Reported ◽  
The Impact

OBJECTIVEDischarge to an inpatient rehabilitation facility or another acute-care facility not only constitutes a postoperative challenge for patients and their care team but also contributes significantly to healthcare costs. In this era of changing dynamics of healthcare payment models in which cost overruns are being increasingly shifted to surgeons and hospitals, it is important to better understand outcomes such as discharge disposition. In the current article, the authors sought to develop a predictive model for factors associated with nonroutine discharge after surgery for grade I spondylolisthesis.METHODSThe authors queried the Quality Outcomes Database for patients with grade I lumbar degenerative spondylolisthesis who underwent a surgical intervention between July 2014 and June 2016. Only those patients enrolled in a multisite study investigating the impact of fusion on clinical and patient-reported outcomes among patients with grade I spondylolisthesis were evaluated. Nonroutine discharge was defined as those who were discharged to a postacute or nonacute-care setting in the same hospital or transferred to another acute-care facility.RESULTSOf the 608 patients eligible for inclusion, 9.4% (n = 57) had a nonroutine discharge (8.7%, n = 53 discharged to inpatient postacute or nonacute care in the same hospital and 0.7%, n = 4 transferred to another acute-care facility). Compared to patients who were discharged to home, patients who had a nonroutine discharge were more likely to have diabetes (26.3%, n = 15 vs 15.7%, n = 86, p = 0.039); impaired ambulation (26.3%, n = 15 vs 10.2%, n = 56, p < 0.001); higher Oswestry Disability Index at baseline (51 [IQR 42–62.12] vs 46 [IQR 34.4–58], p = 0.014); lower EuroQol-5D scores (0.437 [IQR 0.308–0.708] vs 0.597 [IQR 0.358–0.708], p = 0.010); higher American Society of Anesthesiologists score (3 or 4: 63.2%, n = 36 vs 36.7%, n = 201, p = 0.002); and longer length of stay (4 days [IQR 3–5] vs 2 days [IQR 1–3], p < 0.001); and were more likely to suffer a complication (14%, n = 8 vs 5.6%, n = 31, p = 0.014). On multivariable logistic regression, factors found to be independently associated with higher odds of nonroutine discharge included older age (interquartile OR 9.14, 95% CI 3.79–22.1, p < 0.001), higher body mass index (interquartile OR 2.04, 95% CI 1.31–3.25, p < 0.001), presence of depression (OR 4.28, 95% CI 1.96–9.35, p < 0.001), fusion surgery compared with decompression alone (OR 1.3, 95% CI 1.1–1.6, p < 0.001), and any complication (OR 3.9, 95% CI 1.4–10.9, p < 0.001).CONCLUSIONSIn this multisite study of a defined cohort of patients undergoing surgery for grade I spondylolisthesis, factors associated with higher odds of nonroutine discharge included older age, higher body mass index, presence of depression, and occurrence of any complication.

scholarly journals Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner

GeroScience ◽  
2021 ◽  
Author(s):  
Yoko O. Henderson ◽  
Nazmin Bithi ◽  
Christopher Link ◽  
Jie Yang ◽  
Rebecca Schugar ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Dietary Intervention ◽  
Caloric Intake ◽  
Production Capacity ◽  
Late Life ◽  
Model Organisms ◽  
Intermittent Fasting ◽  
Sexually Dimorphic ◽  
Average Life Expectancy ◽  
Multiple Components

AbstractGlobal average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan. However, DR is not widely implemented in the clinic due to patient compliance and its lack of mechanistic underpinnings. Thus, the present study tested the effects of a somewhat more clinically applicable and adoptable DR regimen, every-other-day (EOD) intermittent fasting, on frailty in 20-month-old male and female C57BL/6 mice. Frailty was determined by a series of metabolic, musculoskeletal, and cognitive tasks performed prior to and toward the end of the 2.5-month dietary intervention. Late-life EOD fasting attenuated overall energy intake, hypothalamic inflammatory gene expression, and frailty in males. However, it failed to reduce overall caloric intake and had a little positive effect in females. Given that the selected benefits of DR are dependent on augmented production of the gasotransmitter hydrogen sulfide (H2S) and that renal H2S production declines with age, we tested the effects of EOD fasting on renal H2S production capacity and its connection to frailty in males. EOD fasting boosted renal H2S production, which positively correlated with improvements in multiple components of frailty tasks. Therefore, late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the effects of late-life EOD fasting on frailty.

scholarly journals The Effects of Intermittent Fasting Combined with Resistance Training on Lean Body Mass: A Systematic Review of Human Studies

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2349
Author(s):  
Stephen Keenan ◽  
Matthew B. Cooke ◽  
Regina Belski
Keyword(s):  
Body Composition ◽  
Resistance Training ◽  
Lean Body Mass ◽  
Body Mass ◽  
Fat Mass ◽  
Energy Restriction ◽  
Human Studies ◽  
Future Research ◽  
Intermittent Fasting ◽  
Eligibility Criteria

Diets utilising intermittent fasting (IF) as a strategic method to manipulate body composition have recently grown in popularity, however, dietary practices involving fasting have also been followed for centuries for religious reasons (i.e., Ramadan). Regardless of the reasons for engaging in IF, the impacts on lean body mass (LBM) may be detrimental. Previous research has demonstrated that resistance training promotes LBM accrual, however, whether this still occurs during IF is unclear. Therefore, the objective of this review is to systematically analyse human studies investigating the effects of variations of IF combined with resistance training on changes in LBM in previously sedentary or trained (non-elite) individuals. Changes in body weight and fat mass, and protocol adherence were assessed as a secondary objective. This review followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. MEDLINE, CINAHL, PubMed and SportDiscus databases were searched for articles investigating IF, combined with resistance training that reported measures of body composition. Eight studies met the eligibility criteria. LBM was generally maintained, while one study reported a significant increase in LBM. Body fat mass or percentage was significantly reduced in five of eight studies. Results suggest that IF paired with resistance training generally maintains LBM, and can also promote fat loss. Future research should examine longer-term effects of various forms of IF combined with resistance training compared to traditional forms of energy restriction. Prospero registration CRD42018103867.

scholarly journals Predictors of deterioration of symptoms and quality of life in patients with sarcoidosis

2013 ◽  
Vol 66 (suppl. 1) ◽  
pp. 77-83
Author(s):  
Branislav Gvozdenovic ◽  
Violeta Mihailovic-Vucinic ◽  
Mira Vukovic ◽  
Aleksandar Gvozdenovic ◽  
Aleksandra Dudvarski-Ilic ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Body Mass Index ◽  
Body Mass ◽  
Linear Regression Analysis ◽  
Forced Expiratory Volume ◽  
Measuring Instruments ◽  
Multivariate Linear Regression Analysis ◽  
Everyday Functioning ◽  
Patient Reported

Introduction. The most frequent clinical outcomes in sarcoidosis patients are typically focused on the objective measurements of functions of the involved organs, but, generally, they do not take into account the individual perception of patients? everyday functioning. The aim of this study was to determine the type of association between the subjective disease outcomes and other objective conventional parameters in patients with sarcoidosis. Material and Methods. In the cross-sectional study including 172 sarcoidosis patients (122 females), quality of life was measured by a generic instrument, i.e. fifteen-dimensional measure of health-related quality of life together with a respiratory specific instrument, i.e. St George?s Respiratory Questionnaire; symptoms of fatigue were measured by Fatigue Scale and dyspnea was measured by the Basal Dyspnea Index. Body-mass index and the course of the disease (acute vs. chronic) were also evaluated. Pulmonary function was assessed by spirometry. Results. Acute sarcoidosis was present in 48 (28%) patients. Mean body mass index was 27.01?5.2. Only 20 (12%) patients had lower forced expiratory volume in one second values (<80%) that indicated the existance of obstructive ventilatory impairment. Multivariate linear regression analysis revealed that body mass index, clinical course of disease and spirometric parameter forced expiratory volume in one second were the significant predictors (R2=0.929, p<0.01) of sarcoidosis related fatigue (B=0.061, B=0.406, B=0.452; respectively). Body mass index and forced expiratory volume in one second were the only parameters that significantly predicted both patients? quality of life (R2=0.932; B=0.017, B=0.263) and dyspnea (R2=0.847; B=0.025, B=0.668). Conclusions. It is important to measure both subjective patient-reported outcomes and objective disease parameters in sarcoidosis since they represent different aspects of the disease. All applied measuring instruments for the examined subjective outcomes demonstrated good measuring properties.

scholarly journals Coccydynia – could age, trauma and body mass index be independent prognostic factors for outcomes of intervention?

2018 ◽  
Vol 100 (1) ◽  
pp. 12-15 ◽  
Author(s):  
P Kodumuri ◽  
S Raghuvanshi ◽  
R Bommireddy ◽  
Z Klezl
Keyword(s):  
Body Mass Index ◽  
Prognostic Factors ◽  
Body Mass ◽  
Female Gender ◽  
World Health ◽  
Long Term Results ◽  
Significant Difference ◽  
Patient Reported ◽  
Group A ◽  
Manipulation Under Anaesthesia

Introduction The aetiology of coccydynia can be multifactorial, with several associated factors such as obesity, female gender and low mood. The long-term results of operative interventions, such as manipulation under anaesthesia and coccygectomy are variable, ranging from 63–90%. Materials and methods Our aim was to identify whether age, trauma and body mass index (BMI) were independent prognostic factors in coccydynia treatment. All patients who presented to the Royal Derby Hospital with a primary diagnosis of coccydynia between January 2011 and January 2015 who had injections, manipulation under anaesthesia or coccygectomy were included. We used patient-reported satisfaction score as the primary outcome measure. We hypothesised that patients with preceding history of trauma and with high BMI (> 25) would be less satisfied. We divided patient BMI into four groups, following World Health Organization guidelines: group A (18.5–24.9), group B (25–29.9), group C (30–39.9) and group D (> 40). Results A total of 748 patients were diagnosed with coccydynia. Of these, 201 patients had 381 injections, 40 had 98 manipulations under anaesthesia and 9 had coccygectomy. Mean age was 46.4 years; 26% of patients had trauma to the coccyx. The mean time to follow-up was 7.3 months. We found a statistically significant difference (P = 0.03) between satisfaction scores in groups B and D. Patients who had trauma improved significantly (P = 0.04). The odds ratio calculation of coccygectomy and BMI revealed a higher risk of coccygectomy in Group A. Discussion This is the first study to establish BMI and trauma as independent prognostic factors for coccydynia treatment. Our hypothesis that patients with higher BMI would have lower satisfaction levels has been proven true.

scholarly journals Factors Predicting the Response to a Vitamin D-Fortified Milk in Healthy Postmenopausal Women

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2641 ◽  
Author(s):  
Rebeca Reyes-Garcia ◽  
Antonia Garcia-Martin ◽  
Santiago Palacios ◽  
Nancy Salas ◽  
Nicolas Mendoza ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Vitamin D ◽  
Postmenopausal Women ◽  
Body Mass ◽  
Body Fat ◽  
Dietary Intervention ◽  
The Body ◽  
Hydroxyvitamin D ◽  
Percentage Of Body Fat ◽  
Fortified Milk

Background: Milk products fortified with vitamin D may constitute an alternative to pharmacological supplements for reaching the optimal levels of serum 25-hydroxyvitamin D [25(OH)D]. Our aim was to analyze the response of serum 25(OH)D and its predictive factors in postmenopausal healthy women after a dietary intervention with a milk fortified with vitamin D and calcium. Methods: We designed a prospective study including 305 healthy postmenopausal women who consumed a fortified milk with calcium (900 mg/500 mL) and vitamin D3 (600 IU/500 mL) daily for 24 months. Results: The 25(OH)D concentrations at 24 months were correlated to weight, to body mass index, to the percentage of fat, triglycerides and to baseline 25(OH)D levels. We found significant differences in the levels of 25(OH)D at 24 months according to baseline 25(OH)D levels (p < 0.001) and body mass index (p = 0.019) expressed at quartiles. Multivariate analysis showed an association between levels of 25(OH)D after the intervention and at baseline 25(OH)D (Beta = 0.47, p < 0.001) and percentage of body fat (Beta = −0.227, p = 0.049), regardless of the body mass index. Conclusions: In healthy postmenopausal women, the improvement in 25(OH)D after an intervention with a fortified milk for 24 months depends mainly on the baseline levels of serum 25(OH)D and on the percentage of body fat.

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