Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study

Martin‐McGill, Kirsty J; Marson, Anthony G; Smith, Catrin Tudur; Young, Bridget; Mills, Samantha J.; Cherry, Mary Gemma; Jenkinson, Michael D.

doi:10.1007/s11060-020-03417-8

Cited by 45 publications

(78 citation statements)

References 41 publications

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“…Ketogenic therapy for CNS tumors, including glioma, extends far beyond the originally proposed mechanism of reducing glucose availability and may work through multiple mechanisms such as reducing inflammation and the oxidative stress [ 91 , 92 ]. Some trial was published about this topic [ 93 , 94 ], but further studies are needed to assess the real benefit of ketogenic diet on survival of patients with GBM.…”

Section: Discussionmentioning

confidence: 99%

Clinical Risk and Overall Survival in Patients with Diabetes Mellitus, Hyperglycemia and Glioblastoma Multiforme. A Review of the Current Literature

Montemurro

Perrini

Rapone

2020

IJERPH

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The relationship between type 2 diabetes mellitus (DM2) and hyperglycemia with cancer patients remains controversial also in the setting of patients with glioblastoma multiforme (GBM), the most common and aggressive form of astrocytoma with a short overall survival (OS) and poor prognosis. A systematic search of two databases was performed for studies published up to 19 August 2020, reporting the OS of patients with DM2 or high blood sugar level and GBM and the clinical risk of diabetic patients for development of GBM. According to PRISMA guidelines, we included a total of 20 papers reporting clinical data of patients with GBM and diabetes and/or hyperglycemia. The aim of this review was to investigate the effect of DM2, hyperglycemia and metformin on OS of patients with GBM. In addition, we evaluated the effect of these factors on the risk of development of GBM. This review supports accumulating evidence that hyperglycemia, rather than DM2, and elevated BMI are independent risk factors for poor outcome and shorter OS in patients with GBM. GBM patients with normal weight compared to obese, and diabetic patients on metformin compared to other therapies, seems to have a longer OS. Further studies are needed to understand better these associations.

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Section: Discussionmentioning

confidence: 99%

Clinical Risk and Overall Survival in Patients with Diabetes Mellitus, Hyperglycemia and Glioblastoma Multiforme. A Review of the Current Literature

Montemurro

Perrini

Rapone

2020

IJERPH

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“…In a recent single-center trial performed in the United Kingdom, 12 patients with newly diagnosed GBM were randomized 1:1 to receive either a modified ketogenic diet or medium chain triglyceride ketogenic diet. Recruitment rate was low, and only four patients completed the 3-month diet (Martin-McGill et al, 2020). Studies are further summarized in recent systematic reviews on this topic (Martin-McGill et al, 2018b;Schwartz et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Exploring the Feasibility and Effects of a Ketogenic Diet in Patients With CNS Malignancies: A Retrospective Case Series

et al. 2020

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Background: Recently, the ketogenic diet has been proposed as an adjunct treatment for a range of medical conditions including weight loss, diabetes, cancer, and neurodegenerative diseases. Because malignant CNS tumors are highly dependent on glucose, the use of a ketogenic diet as an adjunct therapy is currently being explored. This case series summarizes our experience implementing a ketogenic diet for patients with CNS malignancies.Methods: Patients diagnosed with CNS malignancies following a ketogenic diet were identified between 2015 and 2017. Malignancies included confirmed diagnoses of glioblastoma (GBM), astrocytoma, or oligodendroglioma. With guidance from a registered dietitian, ketone levels, glucose levels, and weight were regularly collected for several patients along with patient-reported symptoms and adverse effects. Interested patients were asked to follow a 3:1 ketogenic diet for 120 days. The ketogenic diet is a high-fat, moderate protein, and very low carbohydrate diet, where patients limited carbohydrate intake to ≤20 g per day. Brain imaging was reviewed. A series of descriptive analyses were conducted.Results: The ketogenic diet was initiated in 12 patients of which 8 patients contributed data on their blood glucose and ketone levels. The majority of patients were male (n = 10) with a median age of 45 (range 32-62). Diagnoses included GBM (n = 6), grade 2/3 astrocytomas (n = 5) and one patient with a grade 2 spinal cord astrocytoma. Ten of the 12 patients were receiving concurrent treatment; two received supportive care only. The majority of patients with evaluable data (n = 8) maintained ketone levels above 0.5 mM for the duration of 120-day period. Ketone levels generally increased from baseline while glucose levels and BMI decreased. Overall, patients reported improved symptoms over the course of the diet. Imaging also suggested improved disease control and reduction in vasogenic edema. Conclusion:Taking advantage of a tumor's metabolic inflexibility can have a positive impact on patients, particularly those with CNS malignancies. More structured and statistically planned clinical trials are needed to determine the margin of impact of a ketogenic diet.

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“…To date, human data on KD and cancer are mostly single case reports (54,55) or pilot/feasibility studies (56)(57)(58), which have mostly focused on the safety and tolerability of KD. Only 3 randomized controlled trials are available.…”

Section: Discussionmentioning

confidence: 99%

Cancer Treatment With the Ketogenic Diet: A Systematic Review and Meta-analysis of Animal Studies

Zhang

Dai

2021

Front. Nutr.

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Background: The ketogenic diet (KD) has been reported to play an important role in the development of cancer by an abundance of pre-clinical experiments; however, their conclusions have been controversial. We therefore aimed to perform a systematic review and meta-analysis of animal studies evaluating the effects of KD on cancer.Methods: Relevant studies were collected by searching PubMed, Embase, and Web of Science. Outcome measures comprised tumor weight, tumor volume, and survival time. Meta-analysis was performed using the random-effect model according to heterogeneity.Results: The search resulted in 1,254 references, of which 38 were included in the review and 17 included in the meta-analysis. Pooled results indicated that KD supplementation significantly prolonged survival time [standardized mean difference (SMD) = 1.76, 95% CI (0.58, 2.94), p = 0.003], and reduced tumor weight [SMD = −2.459, 95% CI (−4.188, −0.730), p = 0.027] and tumor volume [SMD = −0.759, 95% CI (−1.349, −0.168), p = 0.012]. Meta-regression and subgroup analysis results suggested that KD supplementation at a ratio of 4:1 was associated with remarkable prolongation of survival time in animals with limited tumor types.Conclusion: In summary, the pre-clinical evidence pointed toward an overall anti-tumor effect of the KD in animals studies currently available with limited tumor types.

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Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study

Cited by 45 publications

References 41 publications

Clinical Risk and Overall Survival in Patients with Diabetes Mellitus, Hyperglycemia and Glioblastoma Multiforme. A Review of the Current Literature

Clinical Risk and Overall Survival in Patients with Diabetes Mellitus, Hyperglycemia and Glioblastoma Multiforme. A Review of the Current Literature

Exploring the Feasibility and Effects of a Ketogenic Diet in Patients With CNS Malignancies: A Retrospective Case Series

Cancer Treatment With the Ketogenic Diet: A Systematic Review and Meta-analysis of Animal Studies

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