Preclinical studies prove that short-term fasting (STF) secures healthy cells from the side effects of chemotherapy while making cancer cells more vulnerable to it . There has been an interest in investigating the effects of calorie intake and the nutritional composition of the diet on the chance of disease progression or recurrence in patients with cancer diagnoses . STF has been studied to reduce chemotherapy side effects in cancer patients in limited clinical trials [11, 19].
This study was designed to explore the effects of IF on chemotherapy-induced side effects and to evaluate the ability of IF to promote DSR according to the metabolic changes induced in BC patients.
In our study, analysis of hematologic parameters showed no significant differences between the two groups until cycle 4, which showed no significant variations in chemotherapy-related modifications between the two groups.
Our results were in agreement with de Groot et al. , who randomized seven women with HER2-negative BC to fast for 24 h before their chemotherapy regimen of docetaxel, doxorubicin, and cyclophosphamide, and for 24 h after chemotherapy, significant elevation in platelet counts was observed in the STF group, explained by the decreased breakdown of circulating cells and/or less severe bone marrow suppression, but was incompatible with our results concerning erythrocyte counts, which showed significant elevation in the fasting group, explained by the hypothesis that STF may protect against chemotherapy-associated hematological toxicity.
In addition, our results showed no significant differences in median glucose levels in the IF group between baseline and after cycle 4, while there were significant increases in median glucose and median insulin levels in the NF group between the two points. In addition, there were significant increases in median glucose and in median insulin levels in the NF group compared to the IF group after cycle 4, which demonstrates the effect of IF throughout the day for 18 h in 3 consecutive days with the limitation of sugar and fats on the significant reduction of glucose and insulin levels, which may be due to better insulin performance and glucose tolerance [20, 21], despite the administration of dexamethasone as premedication.
In the NF group, the increase in glucose levels may lead to insulin elevation, which may be due to bad insulin performance and glucose intolerance . The significant reduction in insulin levels in the IF group and the significant increase in glucose and insulin levels in the NF group may reflect the ability of IF in this way to promote DSR in BC patients despite the insignificant reduction in median IGF-1 levels in the IF group [10, 23,24,25].
DSR is said to occur when fasting limits the amount of glucose and insulin, among other hormones and metabolites, circulating in the body [10, 25].
Results obtained by de Groot et al.  were in disagreement with our results concerning plasma glucose levels, which increased in the STF group, which was explained by the use of dexamethasone.
Consistently with our results, Dorff et al.  showed that blood glucose levels did not change significantly or reliably among the compliant patients (P = 0.35), where three cohorts fasted for 24, 48, and 72 h before chemotherapy (48 pre-chemo and 24 post-chemo) and recorded all calories ingested. A total of 3/6 participants in each group consumed 200 kcal per 24 h during the fast phase without experiencing any adverse effects. In the 24-h cohort, there were four of six subjects stated fasting enforcement was registered in 200 kcal consumed; insulin levels were decreased in four of those patients by an average of 56% after chemotherapy after completing the first fast. Six compliant participants were included in the 48-h cohort, insulin levels in those patients decreased by 27%, and insulin levels in the seven compliant patients in the 72-h cohort had decreased by 42%.
In addition, Ferroni et al.  and Monzavi-Karbassi et al.  suggested in their studies in nondiabetic BC patients that elevated blood glucose and insulin levels were associated with a poor prognosis of breast cancer.
Lutes et al.  stated in their review concerning IF during chemotherapy that neither Dorff et al.  nor de Groot et al.  were able to show decreased levels of insulin and glucose when analyzing biochemical blood work.
The obvious findings of our study were that IF was well-tolerated, safe, and had a beneficial effect on patient-reported side effects, which may reflect the probability of promotion of DSR observed in the significant reduction in nausea, vomiting, diarrhea, and mouth sores, which may be due to exertion of some protection to gastrointestinal tract (GIT) cells against chemotherapy [8, 28].
Results obtained by Safdie et al.  in their case series study on ten patients suffering from different types of cancer were in agreement with our results concerning nausea, vomiting, diarrhea, and mouth sores which were virtually absent from the records of all ten patients in the fasting cycles which were undertaken prior to and/or following chemotherapy.
Our results demonstrated a significant increase in median CRP levels in NF patients. The lack of protection of GIT cells in the NF group may explain the significant increase in median CRP levels, and the presence of this protection in the IF group may explain the unchanged levels of median CRP in this group .
Poor glycemic control in the NF group may induce metabolic dysregulation, leading to pro-inflammatory conditions. Also, chronic inflammation may cause oxidative stress in the impaired glucose environment, which may accelerate tumor progression .
Our results showed a higher incidence of constipation in IF patients compared to NF patients. This obvious side effect related to IF in this way, which was constipation, may be due to dietary factors such as insufficient fiber intake or may be due to lifestyle factors such as lack of mobility or sedentary lifestyle .
Our results support the role of IF as a new intervention for malignancy treatment that can be utilized as an assistant to traditional treatment modalities, such as chemotherapy, to improve disease control.
Limitations of this study were the possibility of incomplete adherence to exact hours of fasting and the composition of the food consumed during the eating period, despite our encouragement to study subjects to honestly follow instructions about fasting hours and the food consumed regarding the total amount of calories consumed per day.
Examination of medication targets dependent on IGF-1 and IGFBP1 that might be similar to fasting in providing DSR will be a critical zone for future investigation.