Effects of a Ketogenic Diet on the Quality of Life in 16 Patients With Advanced Cancer

A Pilot Trial

Melanie Schmidt; Nadja Pfetzer; Micheal Schwab; Ingrid Strauss; Ulrike Kämmerer

Disclosures

Nutr Metab. 2011;8(54) 

In This Article

Abstract and Introduction

Abstract

Background Tumor patients exhibit an increased peripheral demand of fatty acids and protein. Contrarily, tumors utilize glucose as their main source of energy supply. Thus, a diet supplying the cancer patient with sufficient fat and protein for his demands while restricting the carbohydrates (CHO) tumors thrive on, could be a helpful strategy in improving the patients' situation. A ketogenic diet (KD) fulfills these requirements. Therefore, we performed a pilot study to investigate the feasibility of a KD and its influence on the quality of life of patients with advanced metastatic tumors.
Methods Sixteen patients with advanced metastatic tumors and no conventional therapeutic options participated in the study. The patients were instructed to follow a KD (less than 70 g CHO per day) with normal groceries and were provided with a supply of food additives to mix a protein/fat shake to simplify the 3-month intervention period. Quality of life [assessed by EORTC QLQ-C30 (version 2)], serum and general health parameters were determined at baseline, after every two weeks of follow-up, or after drop out. The effect of dietary change on metabolism was monitored daily by measuring urinary ketone bodies.
Results One patient did not tolerate the diet and dropped out within 3 days. Among those who tolerated the diet, two patients died early, one stopped after 2 weeks due to personal reasons, one felt unable to stick to the diet after 4 weeks, one stopped after 6 and two stopped after 7 and 8 weeks due to progress of the disease, one had to discontinue after 6 weeks to resume chemotherapy and five completed the 3 month intervention period. These five and the one who resumed chemotherapy after 6 weeks report an improved emotional functioning and less insomnia, while several other parameters of quality of life remained stable or worsened, reflecting their very advanced disease. Except for temporary constipation and fatigue, we found no severe adverse side effects, especially no changes in cholesterol or blood lipids.
Conclusions These pilot data suggest that a KD is suitable for even advanced cancer patients. It has no severe side effects and might improve aspects of quality of life and blood parameters in some patients with advanced metastatic tumors.

Introduction

In the recent past, a remarkable growing interest could be observed in scientific literature concerning the striking carbohydrate metabolism of tumor tissue. In contrast to normal tissues, which can metabolize glucose, fatty acids and ketone bodies, according to Warburg's observations, many tumors depend heavily on glucose for their metabolic demands and ferment it to lactate - even under sufficient oxygen supply.[1,2] For this purpose, tumor cells have a remarkable up regulation of glucose transporter molecules on their surface. In addition, there is a frequent over expression of several key enzymes of glycolysis and attached pathways.[3,4] This prominent change in metabolism and associated enzymes/receptors could provide attractive targets for tumor-specific therapies. Several substances such as specific drugs interfering with the Warburg effect are under investigation.[5–7] However, to date, no safe and established therapy is available that targets tumor metabolism to fight cancer.

Hence, the search for alternatives to drugs is reasonable. Since 1885, when E. Freund observed that patients with malignant disease can develop spontaneous hyperglycaemia,[8] there has been episodic interest in the association of the altered glucose metabolism with the path of nutrition and neoplasia in man. As early as 1924, Händel and Tadeuma summarized the findings in those days as: "a diet rich in carbohydrates has a pronounced stimulating impact on tumor growth".[9] Reckoning the metabolic situation in the tumor patient's body, it could not be overseen, that increasing insulin resistance[10] and fatty acid oxidation[11] is characteristic for healthy tissue. In contrast, tumor cells often lack the ability to use fatty acids or ketone bodies (acetoacetate, beta-hydroxybutyrate) as an energy source and could even be harmed by them.[12–15] In an elegant in vivo setting, Holm et al have proven the different substrate utilization rates of tumor tissue and peripheral tissue in colon cancer patients. They clearly demonstrated that the peripheral tissue of the patients preferably utilized fatty acids and ketone bodies for energy demands, while the tumour showed the Warburg effect.[16] Thus, supporting fatty acid metabolism and inhibiting glucose metabolism should "feed" the body while neither supporting nor harming the tumor. LowCarb/HighFat (LCHF) diets and the strictly carbohydrate restricted ketogenic diet (KD) fulfill this purpose. Here, ketone bodies are produced as intermediate catabolic products of fatty acid breakdown by the liver.These ketone bodies can substitute glucose as an energy source in nearly every healthy tissue including the brain, even in a nutritional situation completely devoid of carbohydrates (CHO). This was impressively shown nearly one hundred years ago by the arctic explorer Vilhjalmur Stefansson, whose clinically controlled one year meat only diet impaired neither his nor his partner's physical and mental fitness.[17]

Ketogenic diets have been used for the treatment of epilepsy in children since the 1920s.[18] Currently, the number of centers applying a KD to treat children with drug resistant epilepsy and the number of clinical studies have dramatically increased.[19–21] Other than classical KDs for the treatment of epilepsy which are in general 80% fat, 15% protein and 5% CHO, a KD with 60% fat, 30% protein and 10% carbohydrate was introduced by Atkins in the 1970s to combat obesity.[22] Nowadays, the Atkins diet is very popular and although it's long-term effect on weight loss is discussed controversially[23] undoubtedly it has a positive effect on the triglyceride and insulin levels[24,25] and no adverse side effects.

In 1995, two female pediatric patients with advanced stage astrocytoma tumors were treated at the Case Western Reserve University, Cleveland, Ohio with a KD based on medium chain triglycerides (MCT) as fat source.[26] The glucose uptake of the tumor decreased remarkably in both children and one of the patients was free of disease progression for 12 months of follow up and was still alive 10 years later (Nebeling L, personal communication). Several groups in the first decades of the last century reported that a diet low in carbohydrates and rich in fat and protein was an effective treatment in animal settings.[9,27,28] Although different in experimental details, all three groups agreed that withdrawal of carbohydrates and enrichment of fat in the chow fed ad libitum to tumor bearing animals led to a strong reduction in tumor growth. In this respect, data from the Seyfried lab demonstrated, that a calorie reduced KD was able to considerably reduce the intracerebral growth of malignant brain cancer cells in mice[13] and a tumor in a female glioblastoma patient,[29] however, at the expense of a dramatic weight loss. Earlier, it was shown, that the ketone body beta-hydroxybutyrate not only inhibited the growth of several tumor cells in vitro, but also reduced the number of B16 melanoma deposits in the lungs of C57BL/6 mice by two thirds.[30] This inhibitory effect of beta-hydroxybutyrate and acetoacetate on tumor cell growth was confirmed in colon and breast cancer cell lines,[14] as well as in neuroblastoma cells.[15]

It has been shown recently, that a KD significantly decreased tumor volume and increased survival time in a mouse model for prostate cancer, compared to animals fed the standard "Western diet".[31] Of importance, this effect was observed without restricting total calories and the mice did not lose body weight, a situation desirable in humans, especially in advanced cancer patients. In addition, a chow enriched in Omega-3 fatty acids, even if it was non-ketogenic, has been shown to reduce tumor growth rate and tumor cell proliferation significantly in animal models.[32] Our own preliminary experiments have shown that the application of an unrestricted ketogenic diet enriched with Omega-3 fatty acids and MCT delayed tumor growth in a mouse xenograft model.[33]

Based on data from literature and our own observations, an LCHF diet was established to treat advanced cancer patients that restricted CHO to a maximum of 70 g/day, was enriched in fat - with emphasis on Omega-3 fatty acids - and nonrestricted in overall calories. The aims of the pilot study presented here were a) to prove the tolerability of such a diet in advanced tumor patients with no further established (classical) therapeutic options b) to see which effect it has on the quality of life, as determined by EORTC QLQ-C30 (version 2)[34] and c) to analyze the effects of such a diet on classical blood parameters and the course of disease. No specific tumor entity was chosen, the diet was offered to all patients who fulfilled the inclusion criteria.

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