The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study

Abstract

BackgroundPreclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC).MethodsEligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level of γ-H2AX analyzed by flow cytometry.ResultsThirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels of γ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients.ConclusionsSTF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy.Trial registrationClinicalTrials.gov: NCT01304251, March 2011Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1663-5) contains supplementary material, which is available to authorized users.

Short-Term Fasting Induces Cell Cycle Arrest in Immature Hematopoietic Cells and Increases the Number of Naïve T Cells in the Bone Marrow of Mice

“…However, it is not certain whether such effects of fasting on hematopoietic immature cells directly reduce the adverse events of chemotherapy in human patients with various malignancies. The decrease of hemoglobin level by chemotherapy with previous short-term fasting was less in some cases [15] and hematological toxicity was well tolerated following short-term fasting in breast cancer patients [16]. Together with the reduction of gastrointestinal adverse effects of chemotherapy by short-term fasting, such as oral inflammation, nausea, and diarrhea, CR should also have a significantly positive effect on the hematopoietic system.…”

“…In addition, fasting for 48–140 h before chemotherapy administration in human patients diagnosed with various types of cancer reduced adverse effects, including fatigue, weakness, and gastrointestinal symptoms [15]. The reduction of hematological toxicity following short-term fasting in breast cancer patients [16] suggests that CR has a remarkably positive influence on the hematopoietic system, but the detailed mechanism through which it weakens the adverse events of anticancer drugs is not fully understood.…”

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

“…All of the preclinical studies summarized in table 1 have confirmed a reduction of side effects from a variety of chemotherapeutic drugs without interfering with, or even boosting, their anti-tumor effects. To date, 3 small studies in humans have also found evidence of a protective effect of STF against chemotherapy-related toxicity [130,131,132]. These studies and their relevance for patients receiving chemotherapy have been discussed in detail elsewhere [133,134,135,136] and will only briefly be reviewed here.…”

“…In 6 patients who partly had fasted and partly had not, side effects were reduced during those cycles in which chemotherapy had been combined with fasting, in particular fatigue and gastrointestinal problems. The second study, by deGroot et al [131], was a randomized controlled trial in 13 human epidermal growth factor receptor 2 (HER2)-negative stage II and III breast cancer patients who were treated with 6 cycles of combined docetaxel, doxorubicin, and cyclophosphamide. The intervention group who fasted for 24 h prior up to 24 h after chemotherapy administration experienced a significant reduction in IGF-1 levels and lower insulin levels than the control group and exhibited signs of less DNA damage or more efficient DNA double-strand break repair in peripheral blood mononuclear cells [134].…”

An Evolutionary and Mechanistic Perspective on Dietary Carbohydrate Restriction in Cancer Prevention

“…Studies of CR in humans have generally addressed cancer treatment [6][7][8][9] but, most recently, carbohydrate-restricted diets, ketogenic diets, and so-called paleo diets which have de facto reduction of carbohydrate (CHO) as a common feature, have shown much promise for prevention [10]. It is understood, however that the discussion has outstripped both understanding of underlying mechanisms and the limited experimental support [11].…”