Fasting and Cancer Treatment

Abstract
Fasting-based diets are a popular approach used by thousands to aid weight control, gut rest, and other health benefits. Recent studies suggest fasting can reduce risk factors and even improve symptoms of serious diseases like cancer. This observational study reviews the latest medical research on fasting’s role in preventing and treating cancer, exploring its compatibility with Islamic fasting as a religious duty alongside medical fasting (e.g., FMD, STF, PFCR, IF). Results indicate that while fasting combined with systemic cancer treatments shows potential, extensive clinical trials are needed for definitive conclusions.

1. Introduction

Fasting is one of the most important religious practices and a divine obligation for Muslims during the holy month of Ramadan, as stated in verses 183 and 184 of Surah Al-Baqarah. This emphasis aims to draw closer to God and purify the body and soul. Islamic fasting, in terms of food, entails abstaining from eating and drinking during specific hours of the day (from dawn to sunset). The Quran commands Muslims to fast in verse 183 of Surah Al-Baqarah and, in verse 184, encourages fasting even for the sick or those unable to fast, using the phrase “And fasting is better for you, if only you knew.” Many researchers have studied the effects of fasting on physical health, cellular aging, lifespan, neurological, autoimmune, cardiovascular, and metabolic diseases, proving its benefits [1]. Among these studies, Yoshinori Ohsumi, a Japanese cell biologist, won the Nobel Prize in Medicine in 2016 for demonstrating that fasting activates autophagy (the process of cellular recycling and regeneration) and slows aging [2]. However, a critical point in this research is fasting’s impact on sick individuals, as existing studies have not conclusively shown its positive or negative effects in a coherent manner.

Cancer is recognized as one of the most challenging diseases of the modern era, and patients are typically advised to maintain a complete and varied diet. However, the situation becomes more complex for Muslim patients during Ramadan, where recommendations for or against fasting have always raised concerns. Physicians often advise against fasting during treatment and even up to two years post-treatment. Yet, the potential positive or negative effects globally require further investigation. While some studies focus on the harms of fasting on cancer cells and their proliferation, other pioneering studies suggest its safety and even benefits for cancer patients. Thus, the question arises: Which findings are more reliable, and under what conditions can fasting be used as a preventive or therapeutic agent for cancer? This observational article reviews existing research to determine under what circumstances fasting may benefit the prevention or treatment of severe diseases like cancer.

2. Research Background

Fasting or intermittent fasting, whether for several days a week or several hours a day, is a popular approach used by thousands to aid weight control, gut rest, and other health benefits [3]. Various diets mimicking fasting styles, such as FMD, STF, PFCR, and IF, have emerged worldwide, categorized by duration and dietary changes. While some studies suggest fasting may stimulate cancer cells and promote metastasis [4] and that starving a tumor is ineffective due to all cells’ (cancerous or non-cancerous) reliance on glucose for respiration [5], other pioneering studies report striking results on its safety and even benefits for cancer patients. However, these findings have been highlighted very cautiously [6]. Some research indicates fasting can, in certain cases, serve as a method for preventing and treating specific types of solid tumors [7]. When combined with cancer treatments, dietary restrictions may limit cancer cell adaptation, survival, and growth, potentially playing a key role in cancer remission [8-11]. It may also enhance therapies like chemotherapy, immunotherapy, and hormone therapy [12-13] and reduce side effects of treatments such as radiotherapy [14-15]. These positive effects appear linked to factors like reduced blood glucose production, stimulation of stem cells for immune system regeneration, and balanced nutrition [11]. Additionally, fasting significantly impacts fat metabolism, gut bacteria activity, and caloric intake [16], promoting cholesterol excretion from cancer cells [17]. Thus, combining fasting with chemotherapy slows the progression of cancers like breast and skin cancer [18-19] and increases the production of lymphoid progenitor cells (CLPs) and tumor-infiltrating lymphocytes, which aid in tumor elimination. Therefore, caloric restriction in fasting-based diets not only reduces the toxicity of cancer treatments in healthy cells [12-13] but also significantly damages cancer cells [6, 10].

Overall, a review of scientific literature shows that while dietary manipulation of many metabolites demonstrates clear preclinical advantages and some show promise in clinical trials, no clear guidelines or recommended dietary modifications exist for cancer patients. For preventing or treating various cancers, appropriate dietary recommendations or combinations are needed, as the effects of these diets may vary depending on metabolic activity, energy sources, and nutritional dependencies of each cancer type [14].

3. Research Methodology

3-1. Religious and Quranic Research Methodology:

This study references verses 183 and 184 of Surah Al-Baqarah, consulting authoritative Quranic translations and interpretations. Fasting was examined as a keyword, and extracted studies were compared with Islamic rulings on the subject.

3-2. Scientific Research Methodology:

This study relies on reputable scientific sources, primarily from PubMed (MEDLINE), Scopus, Embase, and Nature journals (2014-2024). Keywords included Fasting, FMD, STF, PFRC, DR, IF, Cancer, etc. Highly cited articles with significant impact were prioritized.

4. Research Execution, Results, and Discussion

4-1. Metabolic Vulnerabilities of Cancer

Nutrient metabolism pathways in cancer cells reveal how they alter metabolism to meet energy and structural needs [21]. These changes include increased nutrient uptake and activation of intracellular anabolic pathways. The three primary nutrient sources for cancer cells are glucose, amino acids, and fats.

• Glucose Metabolism: Glucose, as the primary energy source, is obtained from diet or synthesized in the liver. It is metabolized via:
  1. Glycolysis: Glucose breaks down into pyruvate in the cytosol, producing ATP and NADH. Cancer cells prefer glycolysis even in oxygen-rich conditions (the Warburg effect) [22].
  2. Oxidative Phosphorylation: Pyruvate enters mitochondria, generating more ATP via the TCA cycle and electron transport chain. This pathway is more efficient but oxygen-dependent [23].
• Lactate’s Role: Once considered a waste product, lactate is now recognized as an important energy source for many tumors, sometimes surpassing glucose in TCA cycle utilization [24].
• Fructose Metabolism: Fructose also serves as an energy source, broken down via glycolytic pathways. It can reprogram metabolic pathways for biosynthesis and cell survival.
• Amino Acid Metabolism:

• Glutamine: A non-essential amino acid obtained from diet, muscle breakdown, or intracellular pathways. It converts to α-ketoglutarate, supplying TCA intermediates and aiding fatty acid synthesis [25].
• Branched-Chain Amino Acids (BCAAs): Leucine, isoleucine, and valine are used for protein synthesis or energy.

• Fatty Acid Metabolism: Fats, as dense energy sources, come from diet or body stores. During food scarcity, fats break down into fatty acids and glycerol. Fatty acids oxidize for ATP, contribute to phospholipid/cholesterol synthesis, or are stored. In the liver, fatty acids convert to ketones, which some tumors utilize [26].
• Hypoxia’s Impact: In low oxygen, cancer cells increase glycolysis and reduce NADH production to meet energy demands. This metabolic flexibility is also observed in some immune cells [22].
• Metabolic Vulnerabilities: Cancer cells depend on specific metabolic pathways for survival, which can be targeted therapeutically—e.g., limiting glucose or glutamine or targeting pathways like the pentose phosphate pathway. Understanding these pathways is crucial for designing effective cancer treatments.

Tissue-Specific Metabolism.4-2

Tumors exhibit distinct metabolic changes based on their tissue origin, reflecting adaptation to varying environments [27]. Key examples:

• Brain:
  • Normal Metabolism: The brain relies heavily on glucose and, during fasting, ketones. Fatty acids are rarely used by neurons [28-32].
  • Cancer Changes: Gliomas favor glycolysis but may use glutamine/ketones. IDH1/IDH2 mutations increase nutrient dependency, offering therapeutic opportunities.
• Breast:
  • Normal Metabolism: Mammary glands consume glucose, fatty acids, and amino acids for milk production, regulated by insulin/estrogen [33-38].
  • Cancer Changes:
    • ER+ tumors use oxidative pathways (lactate/citrate).
    • Triple-negative tumors are highly glycolytic. Their reliance on external fatty acids makes them targets for fat-restricted diets.
• Liver:
  • Normal Metabolism: Processes fructose, lactate, and fatty acids via the portal vein and gluconeogenesis [39-45].
  • Cancer Changes: Hepatocellular carcinoma (HCC) upregulates glycolysis/lipogenesis, depending on fatty acids/fructose—potential dietary intervention targets.
• Colon:
  • Normal Metabolism: Active in nutrient absorption/metabolism (e.g., fructose → glucose/organic acids) [46-53].
  • Cancer Changes: Colorectal cancer (CRC) with WNT/PI3K/KRAS mutations increases glycolysis/fatty acid synthesis. Dietary fructose may fuel growth.
• Prostate:
  • Normal Metabolism: Produces/secrets citrate but has limited oxidative capacity [54-56].
  • Cancer Changes: Tumors regain oxidative metabolism, consuming citrate, lactate, and fatty acids. Fructose plays a key role.
• Lung:
  • Normal Metabolism: Utilizes glucose, ketones, and fatty acids with less systemic hormone sensitivity [57-61].
  • Cancer Changes: NSCLC activates glycolysis/fatty acid oxidation. KRAS mutations increase BCAA dependency.
• Pancreas:
  • Normal Metabolism: Requires amino acids for digestive enzymes; uses fatty acids/ketones during fasting [62-65].
  • Cancer Changes: Tumors depend on glutamine/fatty acids, even scavenging unsaturated fats in hypoxia.
• Endometrium:
  • Normal Metabolism: Glucose uptake regulated by estrogen/progesterone [66-69].
  • Cancer Changes: Tumors activate PI3K, relying on glucose.

Therapeutic Outlook: Tissue-specific metabolic traits offer opportunities for targeted dietary interventions (e.g., restricting glucose, specific amino acids, or fats) alongside drugs, opening new avenues in cancer therapy.

4-3. Classification of Studies by Diet Type

Dietary interventions may improve cancer treatment by:

• Depleting tumor-fueling nutrients.
• Enhancing radiotherapy/chemotherapy by nutrient deprivation.
• Modifying growth factors or systemic immunity [3].

Approaches include:

1. Caloric Restriction (CR): Reducing daily calories by 15–30% while maintaining macronutrient balance. CR lowers body weight, fat mass, insulin, thyroid hormones, and metabolic rate [71-73]. Since the 1900s, CR has shown anti-tumor effects in mice, reducing incidence/progression/metastasis [74-77]. Limited human data exists [78-80]. A Phase III trial (BWEL) is evaluating CR in early breast cancer [83].
2. Fasting-Mimicking Diets (FMD):
   • CR’s benefits may stem from fasting periods, not just calorie reduction [84-85].
   • Small clinical trials show fasting reduces pro-tumorigenic hormones, side effects, and improves quality of life [86-87]. It also alters immune cells, potentially aiding anti-tumor responses [88].
   • Challenges: Long-term fasting adherence is difficult [89]. FMD (e.g., 5-day plant-based, 300–600 kcal/day) mimics fasting benefits [91].
   • In mice, FMD cycles boost therapy efficacy [93-95]. Human trials are ongoing [96-122].
3. Very Low-Carbohydrate Diets (VLCD):
   • A 12-week VLCD trial in ovarian/uterine cancer showed fat loss, preserved lean mass, and no lipid changes [124-126].
   • In breast cancer, VLCD reduced tumor size during chemotherapy, though results need cautious interpretation [124].
4. Low-Fat Diets (LFD):
   • LFDs (<30% fat) emphasize vegetables, fruits, and whole grains. They safely reduce weight, cholesterol, and food intake [127-130].
   • In breast cancer, LFDs improved survival post-diagnosis in subgroups (WHI, WINS, WHEL trials) [131-136].
   • For prostate cancer, LFDs show unclear benefits, possibly due to tumor metabolic adaptation [137].
5. Other Interventions:
   • Restricting specific amino acids (e.g., serine, glycine, cysteine, methionine) shows preclinical promise but lacks clinical data.

4-4. Dietary Interventions as Radiotherapy Adjuvants

Fasting may enhance radiotherapy by impairing tumor DNA repair. Examples:

• Methionine restriction sensitizes tumors to radiation in mice [138].
• Low-carb diets/ketosis improved survival in recurrent glioma (ERGO2 trial) for patients achieving low glucose [141].

5. Conclusion and Future Research Directions

Public perception emphasizes nutrition’s importance, especially for patients. Yet, modern medicine, focused on drugs/radiation, often relegates diet to a supportive role. Recent research revisits cancer’s metabolic vulnerabilities:

Key Question: Is high cancer cell metabolism a weakness exploitable by dietary restriction?

Subsidiary questions include:

• Which nutrients fuel specific cancers?
• Should those nutrients be restricted?

Mouse studies support dietary interventions, but confounding variables (e.g., meal timing) complicate findings. Fasting-mimicking diets have emerged to address this. However, it remains unclear which approach (e.g., LFD, CR, FMD) is most effective. While LFD and CR are more advanced clinically, FMD awaits larger trials.

Given Quranic recommendations, we urge randomized controlled trials to test Islamic fasting’s efficacy alongside site-specific metabolic interventions.

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