NCT07440784

Impact Of Intermittent And Water-Only Fasting On Gene Expression And Tumor Markers In Breast Cancer

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Khyber Medical University Peshawar · Academic / Other
• Sex: Female
• Age: 18 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

This randomized controlled trial investigates the effects of intermittent fasting and water-only fasting on gene expression, tumor markers, quality of life, and chemotherapy tolerance in breast cancer patients receiving chemotherapy. Breast cancer remains the most commonly diagnosed cancer worldwide, and while chemotherapy constitutes standard treatment, it is frequently accompanied by significant adverse effects including cachexia and immunosuppression. Fasting has emerged as a promising complementary approach that may enhance chemotherapy efficacy while protecting healthy cells from treatment-related toxicity. The study will enroll 60 female breast cancer patients from INOR, Abbottabad, who will be randomly assigned to one of four groups: conventional chemotherapy alone, chemotherapy combined with intermittent fasting (23:1 hour fasting to eating ratio) plus routine diet, chemotherapy combined with intermittent fasting plus ketogenic diet, or chemotherapy combined with water-only fasting for two weeks. Blood samples will be collected before and after interventions to assess tumor marker CA 15-3, CD4+ and CD8+ T cell counts, oxidative stress marker malondialdehyde, inflammatory markers including TNF-α and neutrophil-lymphocyte ratio, Glasgow Prognostic Score, and metabolic regulators AMPK and pyruvate dehydrogenase. Quality of life will be evaluated using the validated FACT-B questionnaire, while chemotherapy tolerance will be assessed through symptom severity surveys. The study hypothesizes that combining fasting regimens with standard chemotherapy will enhance anti-tumor effects, improve immune surveillance mechanisms, and ultimately contribute to better prognostic outcomes in breast cancer patients.

Detailed description

This prospective randomized controlled intervention trial is designed to comprehensively evaluate the molecular, immunological, and clinical effects of intermittent and water-only fasting in breast cancer patients undergoing chemotherapy, and will be conducted at the Institute of Nuclear Medicine Oncology and Radiotherapy in Abbottabad in collaboration with the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar. The scientific rationale underlying this investigation stems from the understanding that cancer functions as a metabolic disease characterized by dysfunctional mitochondria and reliance on aerobic glycolysis for energy production, as described by the Warburg hypothesis. By restricting glucose availability through fasting regimens, cancer cells may be selectively starved while normal cells undergo metabolic adaptation, potentially enhancing chemotherapy sensitivity and reducing treatment-related toxicity. Furthermore, fasting has demonstrated immunomodulatory properties through increasing cytotoxic CD8+ T cell precursors and enhancing immune response, while triggering autophagy and inducing differential stress resistance that sensitizes cancer cells to chemotherapy. The study objectives include assessing the effects of intermittent fasting and water-only fasting on quality of life, chemotherapy tolerance, gene expression patterns, and tumor biomarkers, as well as comparing the relative efficacy of these two fasting approaches in improving clinical outcomes. The four study groups will each comprise 15 participants, with group 1 receiving conventional chemotherapy only as the control arm, group 2 undergoing 30 days of intermittent fasting with one routine meal daily, group 3 following 30 days of intermittent fasting with one ketogenic meal daily accompanied by comprehensive dietary guidance and food lists, and group 4 completing a 14-day water-only fast allowing only water, zero-calorie herbal tea, or black coffee without sugar followed by gradual refeeding with juices, broths, and progressive introduction of solid foods. Blood sampling of approximately 10 milliliters will be performed at baseline and following completion of the respective interventions, with serum analyzed for malondialdehyde levels using the thiobarbituric acid method, CD4 and CD8 T cell enumeration through flow cytometry, and quantification of pyruvate dehydrogenase, tumor necrosis factor-alpha, AMPK, albumin, and C-reactive protein using commercially available ELISA kits, while ketone bodies will be measured using a ketone meter. Statistical analysis will be performed using SPSS version 20 with data presented as mean values plus or minus standard error of the mean, analysis of variance applied to identify differences among groups followed by Tukey post-hoc tests, and Pearson correlation coefficients calculated to examine relationships between variables, with statistical significance established at p-values less than 0.05. Ethical approval has been obtained from the Ethics Committee of INOR Abbottabad, and all participants will provide written informed consent after receiving comprehensive information about study procedures, potential benefits, and possible risks including dizziness, weakness, or difficulty tolerating dietary interventions, with assurance of their right to withdraw at any time without providing explanation and without affecting their medical care.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Conventional Chemotherapy	Participants receive standard chemotherapy treatment according to institutional protocols at INOR. The specific chemotherapy regimen, dosage, frequency, and duration are determined by the treating oncologist based on the patient's histological
BEHAVIORAL	Intermittent Fasting (23:1 Regimen)	Participants undergo an intermittent fasting regimen consisting of 23 consecutive hours of fasting followed by a 1-hour eating period daily for 30 days. During the fasting period, participants consume no food or calorie-containing beverages; only water and zero-calorie drinks (plain water, zero-calorie herbal tea, black coffee without sugar) are permitted. During the 1-hour eating window, participants consume one meal. This regimen is implemented alongside standard chemotherapy.
DIETARY_SUPPLEMENT	Ketogenic Diet	Participants follow a ketogenic diet during their 1-hour eating window as part of the intermittent fasting regimen. The diet consists of high fat content (approximately 75% of calories from fat), moderate to low protein (approximately 20% of calories), and very low carbohydrates (approximately 5% of calories). Participants receive comprehensive dietary resources including ketogenic food lists (meat, fish, eggs, nuts, high-fat dairy, above-ground vegetables, berries, and natural fats such as coconut oil and olive oil), daily meal plans, and lists of prohibited high-carbohydrate foods. This dietary intervention aims to induce and maintain nutritional ketosis throughout the 30-day study period.
BEHAVIORAL	Water-Only Fasting	Participants undergo a water-only fasting regimen for 14 consecutive days. During this period, participants consume only water, zero-calorie herbal tea, or black coffee without sugar or milk. No food or calorie-containing beverages are permitted. Limited physical exertion is advised. Following completion of the 14-day fast, participants undergo a structured gradual refeeding protocol: initial introduction of fruit juices and vegetable broths, followed by raw fruits and steamed vegetables, and progressively transitioning back to a normal diet. This intervention is administered alongside standard chemotherapy.

Timeline

• Start date: 2022-08-01
• Primary completion: 2023-07-31
• Completion: 2026-03-30
• First posted: 2026-02-27
• Last updated: 2026-02-27

Locations

1 site across 1 country: Pakistan