Review: Ketogenic diet in the treatment of cancer – Where do we stand? 評論:生酮飲食治療癌症-我們的立場是什麼?

中文版谷歌中文翻譯(90% 準確率) | English translation
Buy/Sell Your Domains Here。在這裡購買/出售您的域名
Contact Dr. Lu for information about cancer treatments。聯繫盧博士,獲取有關癌症治療資訊。

5. Future potential of the ketogenic diet as an adjuvant cancer therapy

As elucidated in this review, the KD seems to create an unfavorable metabolic environment for cancer cell proliferation and, thus, represents a promising adjuvant for a multifactorial patient-specific therapeutic regime. One clear benefit of the KD is its potential to increase the response to therapeutic drugs, which has been widely demonstrated in vitro and in vivo [51], [52], [53], [56], [176]. Thus, combining the KD with standard therapy or even novel treatment approaches to enhance the therapeutic response in humans should be a research focus in this field [177]. Limitations of the available evidence (Table 1, Table 2) include heterogeneous study designs and divergent dietary regimes in preclinical as well as clinical studies. For better comparability of the studies, it would be important to have uniform formulations of the KD as well as proper control diets matched in vitamins and minerals. However, since unification of the KD regime in clinical trials might be limited by individual diet preferences of patients, uniform KDs may be feasible only in preclinical studies. Further limitations are the small number of patients plus the lack of proper randomization and control groups within most human studies. Therefore, even though preclinical evidence clearly points toward an overall antitumor effect of the KD, it remains hard to draw generalizable conclusions about the actual effect of the KD on cancer growth and survival in humans [178], [179], [180].

Several clinical trials to elucidate the effect of the KD on cancer patients are ongoing [181] [https://clinicaltrials.gov/], and the results from these trials will be essential to further evaluate the feasibility of the KD in clinical practice. However, future clinical trials with a large number of patients are required to better understand important questions regarding the optimal diet (composition and ratio), calorie consumption as well as the optimal blood glucose and blood ketone concentrations to maximize the antitumor effect [76]. Klement and colleagues initiated a phase I clinical trial investigating whether a part-time KD, for example as a ketogenic breakfast, after radiotherapy delivers similar effects as a complete KD on the body composition of cancer patients [181]. Interim results indicate significant favorable effects of the KD with concurrent radiotherapy on the body composition of colorectal, breast, as well as head and neck cancer patients [88]. Thus, the optimal time point of the KD (before, during and/or after standard therapy) and the stage of disease are further important factors which may influence KD efficacy [79], [84], [177], [181]. Martin-McGill et al. investigated the feasibility and deliverability of a modified KD in glioblastoma patients within the National Health Service in the UK [80]. Interestingly, the study revealed from 172 completed questionnaires that 73% would be willing to try a KD for three months and 66% would be inclined to participate in a clinical study to analyze efficacy and tolerability of the dietary intervention. Moreover, 25% of the respondents stated they would prefer to start the KD before surgery, 22% right after surgery, 15% after surgery during chemotherapy, and 27% after treatment during the monitoring phase [80]. In our opinion, such questionnaire data are highly relevant to guiding the design of clinical trials to maximize their effectiveness.

In conclusion, most preclinical and some clinical studies support the use of the KD as an adjuvant cancer therapy. The mechanisms underlying the KD seem to involve a broad spectrum, ranging from targeting tumor metabolism, gene expression and the tumor microenvironment. To further elucidate the mechanisms behind KD therapy and its use in clinical practice, more molecular as well as well-designed randomized controlled trials are needed. The available scientific literature indicates that, based on controlled preclinical trials, strict KDs could be beneficial in a range of cancers. However, enthusiasm is currently tempered by the lack of clinical trials to warrant routine use of a strict KD as an adjuvant therapy in cancer patients. Nonetheless, it has been shown that a low-carbohydrate diet increased the quality of life in type 2 diabetic patients [182]. Thus, cancer patients may already benefit from moderate low-carbohydrate regimes not leading to a dramatic induction of ketosis without risking adverse effects from the growth of certain types of cancers. In any case, close guidance by clinicians and dieticians is crucial for patients who are changing their diets.
Acknowledgement

This work was supported by the European Union H2020-MSCA-ITN-2016-722605 (TRANSMIT), the Austrian Science Fund (P31228-B33) and the Children’s Cancer Foundation Salzburg.
Conflict of interest

Julia Tulipan is founder of naehrsinn GmbH (Vienna, Austria) and coach for low-carb and ketogenic diets. The other authors have no conflicts of interest to declare.

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