Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors: 1H-MRS study

Abstract

Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy (H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD. MR scans included conventional imaging and H-MRS acquired from normal appearing-white-matter (NAWM) and lesion. High adherence to KD was obtained only in two patients, based on high urine ketones; in these two patients ketone bodies, Acetone and Acetoacetate were detected in four MR spectra-three within the NAWM and one in the lesion area -4 and 25 months following initiation of the diet. No ketone-bodies were detected in the control group. In one patient with gliomatosis-cerebri, who adhered to the diet for 3 years and showed stable disease, an increase in glutamin + glutamate and reduction in N-Acetyl-Aspartate and myo-inositol were detected during KD.H-MRS was able to detect ketone-bodies in patients with brain tumors who adhered to KD. Yet it remains unclear whether accumulation of ketone bodies is due to increased brain uptake or decreased utilization of ketone bodies within the brain.

A systematic review of the use of ketogenic diets in adult patients with cancer

“…All studies investigated the effect of oral KD; however, there was considerable variation in how the diet was delivered. Three studies followed a traditional KD with a 4 : 1 or 3 : 1 fat (F) to carbohydrate CHO) + protein (P) kg m –2 (F : CHO + P) , two studies used a ratio of F : CHO + P between 0.7 : 1 and 1.8 : 1 , three studies used a modified Atkins diet (20–40 g day −1 CHO) , two studies used a low glycaemic index diet (<70 g day −1 CHO) and one study used a Paleolithic KD with a F : P ratio of 2 : 1 .…”

“…We included three early-phase single-arm clinical trials (28)(29)(30) , three prospective cohort studies (31)(32)(33) , one retrospective review (34) and four case reports (6,(35)(36)(37) . Only two studies were designed to compare intervention and control groups: one retrospective review (34) and one prospective study (33) . In total, 102 participants followed KD and their age ranged between 34 and 87 years.…”

“…Mean (SD) baseline body mass index (BMI) ranged from 23.5 (6) kg m -2 to 29.46 (5) kg m -2 . Participants in eight studies had an advanced cancer stage (30)(31)(32)(33)(34)(35)37) . In three studies, the cancer stage ranged from an early to a more advanced stage (6,28,36) .…”

“…In three studies, the cancer stage ranged from an early to a more advanced stage (6,28,36) . Five studies involved participants with brain cancer (30,(33)(34)(35)37) , one study involved rectal cancer (6) and five studies had participants with mixed cancer sites (28,29,31,32,36) . The duration of intervention ranged from 2.4 to 134.7 weeks.…”

“…All studies investigated the effect of oral KD; however, there was considerable variation in how the diet was delivered. Three studies followed a traditional KD with a 4 : 1 or 3 : 1 fat (F) to carbohydrate CHO) + protein (P) kg m -2 (F : CHO + P) (28,33,37) , two studies used a ratio of F : CHO + P between 0.7 : 1 and 1.8 : 1 (32,36) , three Full-text articles assessed for eligibility (n = 35)…”