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

Schreck, Karisa C.; Hsu, Fang Chi; Berrington, Adam; Henry-Barron, Bobbie J.; Vizthum, Diane; Blair, Lindsay; Kossoff, Eric H.; Easter, Linda; Whitlow, Christopher T.; Barker, Peter B.; Cervenka, Mackenzie C.; Blakeley, Jaishri O.; Strowd, Roy

doi:10.1212/wnl.0000000000012386

Cited by 35 publications

(50 citation statements)

References 41 publications

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“…Cerebral metabolic activity was assessed using MRS at baseline and week 8. The result obtained was increased ketone concentrations, including bHB and acetone in both lesional and contralateral brain that correlated with average ketonuria (bHB R s 0.52; p=0.05) [19].…”

Section: Cerebral Metabolism Shifts In Mrs In Patients With Neurological Disorders On a Ketogenic Dietmentioning

confidence: 88%

“…Biological activity of KD was evaluated in a study by Schreck et al [19] in which 25 patients with WHO Grade 2-4 astrocytoma with stable disease following adjuvant chemotherapy, participated in a GLioma Atkins-based Diet (GLAD) for 8 weeks. This diet is based 2 days of fasting (calories <20% calculated estimated needs) and 5 days of modified Atkins diet each week.…”

Section: Cerebral Metabolism Shifts In Mrs In Patients With Neurological Disorders On a Ketogenic Dietmentioning

confidence: 99%

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Magnetic resonance spectroscopy as a promising modality for assessing ketogenic diet impact on the level of cerebral metabolites in the treatment of certain neurological disorders

Machowiec¹,

Maksymowicz²,

Piecewicz‐Szczęsna³

2021

Ann Agric Environ Med.

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Section: Cerebral Metabolism Shifts In Mrs In Patients With Neurological Disorders On a Ketogenic Dietmentioning

confidence: 88%

Section: Cerebral Metabolism Shifts In Mrs In Patients With Neurological Disorders On a Ketogenic Dietmentioning

confidence: 99%

Magnetic resonance spectroscopy as a promising modality for assessing ketogenic diet impact on the level of cerebral metabolites in the treatment of certain neurological disorders

Machowiec¹,

Maksymowicz²,

Piecewicz‐Szczęsna³

2021

Ann Agric Environ Med.

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show abstract

“…Strict adherence to KD is notoriously difficult [15, 41]. Most prescribed KD includes caloric restriction, which can lead to undesired weight loss and introduce confounding effects on metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Even adjusting dietary supplementation based on measured body weight has been shown to significantly affect overall body weight [13]. A recent patient-based study showed that KD does cause similarly elevated ketones within IDH wt and IDH mut gliomas by magnetic resonance spectroscopy [15], but patient survival was not a part of that analysis. Other recent preclinical and clinical studies have suggested that gliomas can metabolically adapt to ketogenesis, and even use ketones to facilitate disease progression [25, 27].…”

Section: Discussionmentioning

confidence: 99%

The efficacy of a ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma

Javier¹,

Wang²,

Drumm³

et al. 2021

Preprint

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Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 ( IDH1 ) or, less commonly, IDH2 (together called “IDH mut ”). These mutations alter cellular biochemistry, and IDH mut gliomas are generally less aggressive than IDH wild-type (IDH wt ) gliomas. Some preclinical studies and clinical trials have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, not all studies have shown promising results, and to date, no study has addressed whether IDH mut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of KD in preclinical models of IDH wt versus IDH mut gliomas. In vitro , simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDH wt or IDH mut glioma cells. Likewise, a cycling KD, wherein mice alternated between KD and a standard diet (SD), had no effect on the in vivo growth of patient-derived IDH wt or IDH mut gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDH mut glioma. These data suggest that neither IDH wt nor IDH mut gliomas are particularly responsive to KD.

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“…A recent clinical study found that 8 weeks of KD did indeed elevate urinary ketones in glioma patients, with no significant change in fasting glucose or hemoglobin A1c. Additionally, the levels of intratumoral ketones were similar between IDH wt and IDH mut glioma patients [ 15 ]. However, that study was not designed to evaluate antitumor efficacy.…”

Section: Introductionmentioning

confidence: 99%

The efficacy of an unrestricted cycling ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma

et al. 2022

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Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut) or, less commonly, IDH2 (together called “IDHmut”). These mutations alter cellular biochemistry, and IDHmut gliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas. Some preclinical studies and clinical trials have suggested that various forms of a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, adherence to a strict KD is difficult, and not all studies have shown promising results. Furthermore, no study has yet addressed whether IDHmut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of a unrestricted, cycling KD (weekly alternating between KD and standard diet) in preclinical models of IDHwt versus IDHmut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDHwt or IDHmut glioma cells, either in low or normal glucose conditions. Likewise, an unrestricted, cycling KD had no effect on the in vivo growth of patient-derived IDHwt or IDHmut gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, this KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDHmut or IDHwt glioma. These data suggest that neither IDHwt nor IDHmut gliomas are particularly responsive to an unrestricted, cycling form of KD.

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

Cited by 35 publications

References 41 publications

Magnetic resonance spectroscopy as a promising modality for assessing ketogenic diet impact on the level of cerebral metabolites in the treatment of certain neurological disorders

Magnetic resonance spectroscopy as a promising modality for assessing ketogenic diet impact on the level of cerebral metabolites in the treatment of certain neurological disorders

The efficacy of a ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma

The efficacy of an unrestricted cycling ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma

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