Decline of Lactate in Tumor Tissue After Ketogenic Diet: In Vivo Microdialysis Study in Patients with Head and Neck Cancer

Abstract

In head and neck squamous cell carcinoma (HNSCC) aerobic glycolysis is the key feature for energy supply of the tumor. Quantitative microdialysis (μD) offers an online method to measure parameters of the carbohydrate metabolism in vivo. The aim was to standardize a quantitative μD-study in patients with HNSCC and to prove if a ketogenic diet would differently influence the carbohydrate metabolism of the tumor tissue. Commercially available 100 kDa-CMA71-μD- catheters were implanted in tumor-free and in tumor tissue in patients with HNSCC for simultaneous measurements up to 5 days. The metabolic pattern and circadian rhythm of urea, glucose, lactate, and pyruvate was monitored during 24 h of western diet and subsequent up to 4 days of ketogenic diet. After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose metabolism.

Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

“…Based on the literature a synergistic effect of a carbohydrate-restricted diet with an anti-mitochondrial therapy can be concluded, since carbohydrate-restricted diets may induce enhanced OXPHOS and lead to inhibition of mTOR [218], which is responsible for synthesis of glycolytic enzymes [30,31]. Specifically observed in patients with head and neck cancer a ketogenic diet decreased the in vivo production of lactate in tumor cells [213]. …”

Dietary and pharmacological modification of the insulin/IGF-1 system: exploiting the full repertoire against cancer

“…This would be of special value for patients undergoing several week long radiotherapy during which prolonged fasting is no option. The state of ketosis, induced by low insulin levels, may generally benefit cancer patients, as KBs have been shown to inhibit glycolysis in various tumor cell lines 73, 74 and probably also patients, 75, 76, 77 and tumor cells often lack the enzymes 78, 79, 80, 81 or oxygenation 82 to effectively use ketones for energy production. Furthermore, in glioblastoma xenografts it was shown that KBs can partly reverse the genetic alterations that occur in these tumors.…”

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

“…A decrease in tumor lactate production has also been observed in mice kept on a KD [82,83] and in cultured cancer cells treated with ketone bodies [84,85] or fasting-mimicking conditions [86,87]. The decreased tumor lactate concentrations after a few days on a KD in head-and-neck cancer patients measured by Schroeder et al [81] are of particular interest, as tumor lactate concentrations have been directly linked to radioresistance in a variety of xenografted head-and-neck tumors that were irradiated using a clinically relevant schedule of 30 fractions over 6 weeks [88,89]. …”

“…In a case study of cancer patients, those who kept a strict KD showed reduced levels of the tumor marker TKTL-1 (transketolase-like 1), which is supposed to be associated with the pentose phosphate pathway [79]. Studies using FDG-PET imaging [25,80] or microdialysis measurements [81] have shown that a KD can downregulate the glycolytic tumor metabolism in some patients. A decrease in tumor lactate production has also been observed in mice kept on a KD [82,83] and in cultured cancer cells treated with ketone bodies [84,85] or fasting-mimicking conditions [86,87].…”