Effects of Ketogenic metabolic therapy on patients with breast cancer: A randomized controlled clinical trial

Khodabakhshi, Adeleh; Akbari, Mohammad Esmaeil; Mirzaei, Hamid Reza; Seyfried, Thomas N.; Kalamian, Miriam; Davoodi, Sayed Hossein

doi:10.1016/j.clnu.2020.06.028

Cited by 74 publications

(71 citation statements)

References 38 publications

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“…Winter and colleagues coined the term "Ketogenic Metabolic Therapy (KMT)" to describe an anti-neoplastic nutritional strategy, using ketogenic or low-glycemic diets, for the management of malignant gliomas (45). KMT is gaining recognition as a complementary therapeutic strategy for the management of a broad range of cancers in addition to malignant gliomas (17,19,(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Low carbohydrate, high fat ketogenic diets (KD) reduce the glucose needed to drive aerobic fermentation (Warburg effect) while also elevating ketone bodies, which cannot be effectively metabolized for energy in tumor cells due to defects in mitochondrial OxPhos (17,26,45,56,(61)(62)(63)(64)(65)(66)(67).…”

Section: Introductionmentioning

confidence: 99%

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

et al. 2021

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Background: Successful treatment of glioblastoma (GBM) remains futile despite decades of intense research. GBM is similar to most other malignant cancers in requiring glucose and glutamine for growth, regardless of histological or genetic heterogeneity. Ketogenic metabolic therapy (KMT) is a non-toxic nutritional intervention for cancer management. We report the case of a 32-year-old man who presented in 2014 with seizures and a right frontal lobe tumor on MRI. The tumor cells were immunoreactive with antibodies to the IDH1 (R132H) mutation, P53 (patchy), MIB-1 index (4–6%), and absent ATRX protein expression. DNA analysis showed no evidence of methylation of the MGMT gene promoter. The presence of prominent microvascular proliferation and areas of necrosis were consistent with an IDH-mutant glioblastoma (WHO Grade 4).Methods: The patient refused standard of care (SOC) and steroid medication after initial diagnosis, but was knowledgeable and self-motivated enough to consume a low-carbohydrate ketogenic diet consisting mostly of saturated fats, minimal vegetables, and a variety of meats. The patient used the glucose ketone index calculator to maintain his Glucose Ketone Index (GKI) near 2.0 without body weight loss.Results: The tumor continued to grow slowly without expected vasogenic edema until 2017, when the patient opted for surgical debulking. The enhancing area, centered in the inferior frontal gyrus, was surgically excised. The pathology specimen confirmed IDH1-mutant GBM. Following surgery, the patient continued with a self-administered ketogenic diet to maintain low GKI values, indicative of therapeutic ketosis. At the time of this report (May 2021), the patient remains alive with a good quality of life, except for occasional seizures. MRI continues to show slow interval progression of the tumor.Conclusion: This is the first report of confirmed IDH1-mutant GBM treated with KMT and surgical debulking without chemo- or radiotherapy. The long-term survival of this patient, now at 80 months, could be due in part to a therapeutic metabolic synergy between KMT and the IDH1 mutation that simultaneously target the glycolysis and glutaminolysis pathways that are essential for GBM growth. Further studies are needed to determine if this non-toxic therapeutic strategy could be effective in providing long-term management for other GBM patients with or without IDH mutations.

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Section: Introductionmentioning

confidence: 99%

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

et al. 2021

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“…The protocol used in this trial [16] and part of the results from this trial have been previously published [17,18].…”

Section: Introductionmentioning

confidence: 99%

Does a ketogenic diet have beneficial effects on quality of life, physical activity or biomarkers in patients with breast cancer: a randomized controlled clinical trial

Khodabakhshi

Seyfried

Kalamian

et al. 2020

Nutr J

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Introduction: Despite recent interest in the use of ketogenic diets (KDs) for cancer, evidence of beneficial effects is lacking. This study examined the impact of a randomly assigned KD on quality of life, physical activity and biomarkers in patients with breast cancer. Method: A total of 80 patients with locally advanced or metastatic breast cancer and without a history of renal disease or diabetes were randomly assigned to either a KD or a control group for this 12-week trial. Concurrent with the first, third, and fifth chemotherapy sessions, quality of life, physical activity, and biomarkers (thyroid function tests, electrolytes, albumin, ammonia, ALP, lactate and serum ketones) were assessed. Dietary intake was also recorded on admission and the end of the treatment. Results: No significant differences were seen in quality of life or physical activity scores between the two groups after 12 weeks; however, the KD group showed higher global quality of life and physical activity scores compared to the control group at 6 weeks (P = 0.02 P = 0.01). Also, serum lactate and ALP levels decreased significantly in the KD group compared to the control group at the end of the intervention (10.7 ± 3 vs 13.3 ± 4, 149 ± 71 vs 240 ± 164, P = 0.02 and P = 0.007, respectively). A significant inverse association was observed between total carbohydrate intake and serum beta-hydroxybutyrate at 12 weeks (r = − 0.77 P < 0.001). No significant differences between groups were observed in thyroid hormones, electrolytes, albumin, LDH or ammonia. Compliance among KD subjects ranged from 66.7 to 79.2% as assessed by dietary intake and serum ketones levels of > 0.5.

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“…TNF-α also exhibits a multi-function in breast cancer such as tumor markers, promotion, progression, and metastasis [131][132][133]. Khodabakhshi et al, in a randomized control trial on breast cancer patients, showed a significant diminish of TNF-α level after 12 weeks of KD intake that is explained by the suppression of MMP-9 expression [134] and activation of PPARγ [135,136].…”

Section: Tumor Necrosis Factor Alpha (Tnf-α)mentioning

confidence: 99%

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities

Talib

Mahmod

Kamal

et al. 2021

CIMB

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Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.

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Effects of Ketogenic metabolic therapy on patients with breast cancer: A randomized controlled clinical trial

Cited by 74 publications

References 38 publications

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

Does a ketogenic diet have beneficial effects on quality of life, physical activity or biomarkers in patients with breast cancer: a randomized controlled clinical trial

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities

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