Paper - Successful application of dietary ketogenic metabolic therapy in patients with glioblastoma: a clinical study - 2025

Notes:

Monitoring of adherence should be performed by quantitative, unbiased biomarkers, such as the glucose-ketone index (GKI)

In particular, recent advancements in our understanding of cancer metabolism have led to renewed interest in Warburg’s theory of carcinogenesis (7–9). According to this theory, malignant cells are characterized by distinct structural and functional mitochondrial abnormalities, leading to compensatory metabolic dependencies

Unlike normal brain cells, that have evolved to metabolize ketone bodies for energy when glucose availability is low, GBM cells depend on glycolysis for growth and are unable to efficiently metabolize ketones due to impaired mitochondrial function

^^This sentence has a assumption, incorrect, that the brain preferences glucose. I think this is reversed, in the absence of ketones the brain can use glucose. In people with both ketones and elevated glucose levels in the blood a healthy brain burns ketones at a 70:30 preference.

3.3 Patient 3

After 6 months the patient decided to abandon the diet due to perceived dietary restrictiveness. On April 2022, 4 months after KD discontinuation, GBM recurrence

This is super interesting, she recovers, quits keto, the GBM comes back, and gets back into keto and has a ECOG of 0.

Of the 12 patients who did not adhere to the diet, only one reached 36 months of survival, while the rest have died in an average time of 15.7 ± 6.7 months, with a 3-year survival rate of 8.3%

This applied to three of our patients who had already undergone surgical resection, radiation, and chemotherapy. They felt reassured that they had done everything possible and saw no need to adhere to a demanding diet. Another reason was a lack of trust in the diet; four of our patients did not believe that, following conventional therapies, a simple diet could be beneficial, despite initially agreeing to follow it. Older patients, in particular, struggled to adjust their eating habits and discontinued the diet shortly after starting. Additionally, two patients stopped the diet due to the absence of a supportive environment, while another two discontinued it due to financial constraints, as they found the ketogenic diet to be relatively costly to implement

^^This is just sad

Tumor recurrence despite diet adherence can be explained by secondary metabolic dependencies of tumor cells (58–61). It is important to acknowledge that dietary strategies alone, such as ketogenic diets or fasting, cannot fully deplete glucose from the tumor microenvironment.

The liver makes glucose, steroids increase glucose levels, etc

Thoughts

This was a dietary ketogenic intervention, I wonder how the outcomes would differ with exogenous ketones? Since compliance with the intervention was so low (33%), could we have seen the other 66% benefit from a ketogenic diet + exogenous ketones? The one patient in the study (patient 5) who took exogenous ketones did suffer a relapse, i would have liked to see their GKI history.

Several of the patients reported constipation when starting the keto diet, probably because they increased fiber consumption. It would be interesting to see the same intervention without fiber. We have other papers indicating full resolution of constipation with the removal of fiber.

The theme amongst the patients is that the lower the GKI, and the better adherence, the better the outcomes and fewer recurrences.