The combined treatment with ketogenic diet and metformin slows tumor growth in two mouse models of triple negative breast cancer.
Study Goal
The researchers aimed to determine whether reducing systemic glucose via a ketogenic diet combined with metformin could inhibit tumor proliferation and improve survival in triple-negative breast cancer (TNBC) mouse models.
Results Summary
The combination of a ketogenic diet and metformin reduced tumor burden by two-thirds, slowed tumor growth by 38%, extended latency by 36%, and improved overall survival by 31 days compared to either treatment alone. The findings suggest this approach could be effective for hypoxic and glycolytic tumors.
Population
Mouse models of triple-negative breast cancer (TNBC).
Effective Dosage
Not specified (ketogenic diet composition and metformin dosage not detailed in abstract).
Duration
Not specified (intervention duration not detailed in abstract).
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
combination regimen of ketogenic diet and metformin | decrease | tumor burden | animals with TNBC | by two-thirds | had their tumor burden lowered | #1 |
combination regimen of ketogenic diet and metformin | decrease | tumor growth | animals with TNBC | 38% | displayed slower tumor growth | #2 |
combination regimen of ketogenic diet and metformin | increase | latency | animals with TNBC | 36% | showed longer latency | #3 |
lowering systemic glucose by combined dietary and pharmacologic approach | increase | overall survival | mouse TNBC models | by 31 days | improved overall survival | #4 |
reducing systemic glucose by combining a ketogenic diet and metformin | decrease | tumor proliferation | - | - | significantly inhibits tumor proliferation | #5 |
reducing systemic glucose by combining a ketogenic diet and metformin | increase | overall survival | - | - | increases overall survival | #6 |
BACKGROUND: Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis. This glucose dependency is linked to a metabolic shift in response to hypoxic conditions. METHODS: To leverage the glucose dependency of hypoxic tumor cells, we assessed the effects of a mild reduction in systemic glucose by controlling both dietary carbohydrates with a ketogenic diet and endogenous glucose production by using metformin on two mouse models of triple-negative breast cancer (TNBC). RESULTS: Here, we showed that animals with TNBC treated with the combination regimen of ketogenic diet and metformin (a) had their tumor burden lowered by two-thirds, (b) displayed 38% slower tumor growth, and (c) showed 36% longer latency, compared to the animals treated with a ketogenic diet or metformin alone. As a result, lowering systemic glucose by this combined dietary and pharmacologic approach improved overall survival in our mouse TNBC models by 31 days, approximately equivalent to 3 years of life extension in human terms. CONCLUSION: This preclinical study demonstrates that reducing systemic glucose by combining a ketogenic diet and metformin significantly inhibits tumor proliferation and increases overall survival. Our findings suggest a possible treatment for a broad range of hypoxic and glycolytic tumor types that can augment existing treatment options to improve patient outcomes.