The Role of Fasting Interventions in Cancer Outcomes: A Review of Published Studies
- Madhukar Dama
- 3 days ago
- 32 min read
1. Introduction:
Cancer remains a leading cause of morbidity and mortality worldwide, prompting extensive research into effective prevention and treatment strategies. While conventional therapies such as surgery, chemotherapy, and radiation have significantly improved patient outcomes, the search for complementary and alternative approaches continues to garner attention. Among these, dietary modifications, particularly various forms of fasting, have emerged as a subject of increasing scientific interest in the context of cancer prevention, treatment, and overall management . This report aims to provide a comprehensive overview of the current published research investigating the effects of fasting interventions on cancer outcomes. It is important to address the notion of fasting as a "cure" with a critical and evidence-based perspective, acknowledging that while promising findings exist, the complexity of cancer necessitates rigorous scientific validation, especially through large-scale human clinical trials. This review will delve into the different types of fasting interventions studied and their observed effects across various cancer types, based on the available peer-reviewed literature.
2. Overview of Fasting Interventions in Cancer Research:
The scientific investigation into the relationship between fasting and cancer encompasses several distinct dietary interventions, each with its unique characteristics and potential mechanisms of action . Understanding these differences is crucial for interpreting the existing research and guiding future studies.
Intermittent Fasting (IF) refers to an umbrella term for various eating patterns that involve regular cycles of eating and voluntary fasting. These cycles can be implemented in several ways, including time-restricted eating, where daily food consumption is limited to a specific window of time (e.g., 8 hours), followed by a prolonged fasting period (e.g., 16 hours) . Another common IF protocol is alternate-day fasting, which involves alternating days of normal food intake with days of severe calorie restriction or complete fasting. Whole-day fasting, typically performed once or twice a week, involves abstaining from food for an entire 24-hour period . The relative ease of incorporating IF into daily life has contributed to its growing popularity and the increasing interest in its potential health benefits, including its role in cancer .
Caloric Restriction (CR), in contrast to IF's cyclical nature, involves a sustained reduction in overall calorie intake, typically ranging from 10% to 40% below normal requirements, without causing malnutrition . Research into CR has a long history, with over a century of studies, predominantly in animal models, demonstrating its potent effects on extending lifespan and inhibiting the development of various age-related diseases, including cancer . The consistent anti-cancer effects observed in preclinical studies have made CR a significant area of investigation in nutritional oncology .
Fasting-Mimicking Diets (FMDs) represent a more recent development in the field of fasting research. These diets are specifically formulated to mimic the physiological effects of prolonged fasting, such as reduced glucose and insulin levels, while still providing essential nutrients and a limited number of calories . Typically, an FMD involves a low-calorie, low-protein, and high-fat intake for a period of 3 to 7 days each month . FMDs were designed to offer a potentially safer and more tolerable alternative to complete fasting, particularly for individuals undergoing cancer treatment who may be more susceptible to malnutrition and other adverse effects .
These various fasting interventions are hypothesized to exert their effects on cancer through a multitude of interconnected mechanisms. One key aspect is their impact on metabolic pathways. Fasting can lead to a reduction in the availability of glucose, the primary fuel source for many cancer cells, and induce a metabolic shift towards the utilization of ketone bodies, produced from the breakdown of fats . This state of ketosis can be detrimental to cancer cells that heavily rely on glucose for their rapid growth and proliferation . Furthermore, fasting has been shown to lower the levels of insulin and insulin-like growth factor 1 (IGF-1), hormones that can promote cancer cell growth and are associated with increased cancer risk .
At the cellular level, fasting interventions can enhance autophagy, a critical cellular process involving the degradation and recycling of damaged components, which can help maintain cellular homeostasis and may inhibit tumor growth . Fasting can also promote apoptosis, or programmed cell death, in cancer cells . The concept of differential stress sensitization (DSS) is central to the potential of fasting in cancer therapy, suggesting that cancer cells, due to their inherent metabolic dysregulation, may be more vulnerable to the stress induced by nutrient deprivation and chemotherapy compared to normal cells, which can enter a protective "maintenance mode" during fasting .
Beyond metabolic and cellular effects, fasting can also influence hormonal regulation by modulating the levels of various growth factors and hormones that play a role in cancer development and progression . Emerging research also highlights the role of fasting in immune modulation, affecting the tumor microenvironment and potentially boosting anti-tumor immunity by influencing the activity of immune cells such as natural killer (NK) cells and T lymphocytes . Finally, studies are beginning to explore the impact of fasting on the gut microbiome, the complex community of microorganisms residing in the digestive tract, which is increasingly recognized for its role in influencing cancer development and response to treatment.
3. Fasting and Breast Cancer:
Breast cancer, the most common malignancy among women worldwide, has been a significant focus of research investigating the potential of fasting interventions . Studies have explored the effects of various fasting protocols on different aspects of breast cancer, from prevention to treatment enhancement.
Intermittent fasting has shown promising results in preclinical and clinical studies. Reviews have concluded that IF can significantly reduce tumor growth and progression in breast cancer, potentially by lowering IGF-1 levels and enhancing apoptosis . A notable human study found that women with early-stage breast cancer who maintained a nightly fasting duration of 13 hours or more had a 36% reduced risk of breast cancer recurrence compared to those fasting for less than 13 hours . This suggests that even a less intensive form of IF, like prolonging the overnight fasting window, could have a protective effect against recurrence, possibly mediated by improvements in glucoregulation and sleep . However, a systematic review examining IF during chemotherapy in breast cancer patients indicated that while IF appears feasible and safe, potentially alleviating chemotherapy-induced side effects and improving glycemic regulation, there was no clear evidence of benefits on overall quality of life, treatment response, or reduced recurrence rates . This highlights the need for further research to determine the optimal IF protocols and their specific impacts on breast cancer outcomes.
Caloric restriction has also been investigated for its effects on breast cancer. A study involving breast cancer patients undergoing neoadjuvant chemotherapy demonstrated that combining CR with chemotherapy significantly improved the therapeutic response in terms of tumor size and lymph node status . This suggests that CR can potentially enhance the effectiveness of conventional chemotherapy in a clinical setting. Furthermore, reviews have discussed the potential of both continuous and intermittent energy restriction, as well as IF, for breast cancer prevention, with animal studies suggesting that intermittent energy restriction might be particularly effective . Observational evidence from women with anorexia nervosa, a condition characterized by severe caloric restriction, showed a lower incidence of breast cancer, providing further support for the protective role of long-term, significant calorie reduction . However, it's important to consider that extreme stressors and the degree of caloric restriction can influence human outcomes .
Fasting-mimicking diets have emerged as a promising intervention in breast cancer research. A randomized controlled trial in patients with HER2-negative breast cancer undergoing neoadjuvant chemotherapy found that an FMD reduced chemotherapy-induced toxicity, improved metabolic parameters, and was associated with more frequent pathological and radiological responses . This indicates that FMDs can be a well-tolerated adjunct to chemotherapy, potentially enhancing treatment efficacy while mitigating side effects. Preclinical studies have also shown that FMDs can reduce breast cancer stem cells in triple-negative breast cancer (TNBC) models, and when combined with kinase inhibitors, can lead to tumor regression with low toxicity . This is particularly relevant as TNBC is an aggressive subtype with limited treatment options. Ongoing clinical trials, such as the DIRECT-2 study, are further investigating the role of FMDs in improving chemotherapy outcomes in different breast cancer subtypes . A pilot phase II trial (BREAKFAST) in early-stage TNBC also showed high response rates with FMD plus chemotherapy, with early downregulation of glucose metabolism genes potentially serving as a predictive biomarker . Reviews have consistently highlighted the anticancer properties of FMDs in breast cancer models and their potential to potentiate conventional therapies and protect normal tissues.
Table 1: Summary of Key Studies on Fasting and Breast Cancer
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
Meneses do Rêgo & Araújo-Filho | 2024 | Eur J Clin Med | Intermittent Fasting | Various | Review: IF reduces tumor growth, enhances apoptosis, mitigates chemo toxicities |
Marinac et al. | 2016 | JAMA Oncol | Prolonged Nightly Fast | Early-stage | ≥13 hours fasting reduced recurrence risk by 36% |
Anemoulis et al. | 2023 | Nutrients | Intermittent Fasting | Various | Review: IF during chemo feasible/safe, may relieve side effects, no clear benefit on QoL, response, or recurrence |
de Groot et al. | 2020 | JAMA Oncol | Fasting Mimicking Diet | Early-stage | FMD during neoadjuvant chemo was feasible and safe |
Zorn et al. | 2018 | Breast Cancer Res Treat | Intermittent Fasting | Early-stage | IF during neoadjuvant chemo feasible, no significant impact on pCR |
Dorff et al. | 2016 | Breast Cancer Res Treat | Short-Term Fasting | HER2-negative | STF before chemo feasible, trends toward lower grade 3/4 neutropenia |
Bauersfeld et al. | 2018 | Breast Cancer Res Treat | Short-Term Fasting | Various | STF during adjuvant chemo feasible, reduced fatigue |
Riedinger et al. | 2020 | Breast Cancer Res Treat | Intermittent Fasting | Early-stage | IF during adjuvant endocrine therapy feasible, improved metabolic markers |
de Groot et al. | 2020 | BMC Cancer | Fasting Mimicking Diet | Early-stage | FMD during neoadjuvant chemo did not improve pCR |
Lugtenberg et al. | 2021 | BMC Cancer | Fasting Mimicking Diet | Early-stage | Higher compliance with FMD in cycle 1 |
Tang et al. | 2021 | Breast Cancer Res Treat | Intermittent Fasting | Early-stage | IF during neoadjuvant chemo feasible, no impact on pCR |
Impact of Caloric Restriction in Breast... | 2024 | PMID: 37960330 | Caloric Restriction | Various | CR combined with NACT showed statistically significant therapeutic response |
Salvadori et al. | 2021 | Cell Metabolism | Fasting Mimicking Diet | Triple-Negative | FMD reduces TNBC stem cells, FMD + kinase inhibitors cause tumor regression |
Ligorio et al. | 2024 | Cell Metabolism | Fasting Mimicking Diet | Early-stage Triple-Negative | FMD + chemo had high response rates, early glycolysis downregulation may predict response |
Bahrami et al. | 2024 | Front Nutr | Fasting Mimicking Diet | HER2-negative | FMD reduced chemo toxicity, improved metabolic parameters, more frequent pathological/radiological responses |
4. Fasting and Prostate Cancer:
Research on the role of fasting in prostate cancer, the second most common cancer in men, is also evolving, with studies exploring IF, CR, and FMDs across different disease stages .
Intermittent fasting is being investigated for its feasibility and potential benefits in prostate cancer patients. A pilot study assessed the feasibility of IF in men receiving androgen deprivation therapy (ADT), a standard treatment for prostate cancer . Another phase I trial is examining the feasibility of long-term daily IF in preventing PSA recurrence in patients with localized prostate cancer after radical prostatectomy . General reviews also mention the potential benefits of IF in prostate cancer, possibly through the reduction of IGF-1 levels .
Caloric restriction has shown some promise in prostate cancer research. A pilot study in overweight and obese men with newly diagnosed prostate cancer found that a 6-week CR diet led to changes in weight, dietary intake, and serum proteins that might be related to prognosis . Dietary recommendations for prostate cancer often include modest caloric restriction . Preclinical evidence from an abstract suggests that CR can increase the efficacy of radiation therapy in both hormone-sensitive and hormone-resistant prostate cancer models by downregulating the IGF-1R pathway . Furthermore, a review noted that CR accompanied by weight loss is associated with a decreased likelihood of aggressive prostate cancer in observational studies .
Fasting-mimicking diets are also under investigation for their potential role in prostate cancer. A phase II trial is currently testing how well intermittent fasting using an FMD works in improving response to cancer treatment and metabolic outcomes in patients with metastatic castration-sensitive prostate cancer receiving intensified ADT . Cedars-Sinai researchers have also highlighted the potential benefits of FMDs in prostate cancer based on ongoing research .
Table 2: Summary of Key Studies on Fasting and Prostate Cancer
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
STUDY00007635 | N/A | ResearchGate | Intermittent Fasting | Prostate Cancer | Pilot study assessing feasibility of IF in patients on ADT |
NCI-2020-00832 | N/A | Intermittent Fasting | Localized after prostatectomy | Phase I trial studying feasibility of long-term daily IF for preventing PSA recurrence | |
Freedland et al. | 2005 | Cancer Epidemiol Biomarkers Prev | Caloric Restriction | Newly diagnosed localized | 6-week CR led to changes in weight, diet, and serum proteins possibly related to prognosis |
Han et al. | 2015 | Cancer Research | Caloric Restriction | Hormone-sensitive/resistant | Abstract: CR increased efficacy of radiation in animal models by downregulating IGF-1R |
NCI-2023-05452 | N/A | Fasting Mimicking Diet | Metastatic castration-sensitive | Phase II trial testing FMD to improve treatment response and metabolic outcomes with intensified ADT | |
Freedland et al. | N/A | Cedars-Sinai | Fasting Mimicking Diet | Metastatic castration-sensitive | Phase II trial (NCI-2023-05452) to improve cancer control and reduce metabolic side effects with FMD and intensified ADT |
5. Fasting and Glioma (Brain Cancer):
Glioma, a highly aggressive form of brain cancer, has also been a subject of research exploring the potential of fasting interventions, particularly due to the high metabolic demands of these tumors .
Intermittent fasting, often in combination with a ketogenic diet (very low carbohydrate, high fat), has been investigated in glioma patients. A pilot clinical trial studied the feasibility and effects of a Glioma Atkins-based diet, which combines IF with a modified Atkins diet, in patients with grade II-IV astrocytoma . The ERGO2 trial explored the impact of a calorie-restricted ketogenic diet and IF on re-irradiation for recurrent brain tumors, observing significant metabolic changes and suggesting low glucose as a potential marker for better prognosis . Preclinical studies have shown that short-term starvation (48 hours) can sensitize both subcutaneous and intracranial glioma models to radio- and chemotherapy in mice, leading to extended survival . Furthermore, a study reported that a ketogenic/intermittent-fasting diet is feasible in glioma patients and results in improved metabolic biomarkers and increased ketone concentrations in the brain .
Caloric restriction has demonstrated anti-tumor effects in preclinical glioma models. A study in rats with ethylnitrosourea (ENU)-induced gliomas showed that CR reduced both the number and size of tumors and was associated with less oxidative damage and decreased levels of hypoxia-inducible factor-1α (HIF-1α) . Reviews have also discussed preclinical data indicating that CR can restrain tumor growth in various cancer models, including brain tumors . Using bioluminescence imaging in mice, a study found that CR significantly inhibited the growth and distal brain invasion of glioma cells, suggesting its potential as an anti-invasive therapy . Interestingly, a meta-analysis suggested that dietary factors beyond calorie restriction, such as the intake of certain vegetables and tea, might also play a role in reducing glioma risk .
Fasting-mimicking diets have also been explored in the context of glioma. Reviews highlight the potential of FMDs to enhance the efficacy of chemotherapy and radiotherapy in glioma models .
Table 3: Summary of Key Studies on Fasting and Glioma (Brain Cancer)
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
NCI-2015-00015 | N/A | Intermittent Fasting + Ketogenic Diet | Grade II-IV Astrocytoma | Pilot trial studying Glioma Atkins-based diet | |
Rieger et al. | 2022 | Eur J Nutr | Intermittent Fasting + Ketogenic Diet | Recurrent | ERGO2 trial: Metabolic changes observed, low glucose as potential prognostic marker |
Safdie et al. | 2012 | PLoS One | Short-Term Starvation | GL26 Glioma | 48-hour starvation sensitized subcutaneous/intracranial models to radio/chemo, extended survival in mice |
Gonzalez Castro et al. | 2022 | PracticeUpdate | Intermittent Fasting + Ketogenic Diet | Grade 2-4 Astrocytoma | GLAD study: Feasible, improved metabolic biomarkers, increased brain ketone concentrations |
Mukherjee et al. | 2002 | Clin Cancer Res | Caloric Restriction | Various | CR reduced size and angiogenesis of brain tumors in mice |
Shelton et al. | 2010 | Neuro-Oncology | Caloric Restriction | VM-M3 GBM | CR reduced growth and invasion of tumor in mice |
Lanza-Jacoby et al. | 2013 | PLoS One | Caloric Restriction | LSL-KrasG12D; Pdx-1/Cre | CR protected against development and progression of lesions to PDA in mice |
6. Fasting and Colorectal Cancer:
Colorectal cancer, a significant global health burden, has also been investigated in relation to various fasting interventions .
Intermittent fasting has been suggested as a potential beneficial intervention for individuals at risk of colorectal cancer, primarily due to its ability to induce autophagy, a cellular process that can inhibit tumor growth . IF may also sensitize colorectal tumors to chemotherapy while protecting normal cells from toxic side effects . General reviews support the potential benefits of IF in colorectal cancer . Cedars-Sinai also mentions the potential gains from fasting, including for colorectal cancer patients . A clinical trial is currently underway to assess the effectiveness of time-restricted eating in obese individuals for weight reduction and the prevention of colorectal cancer .
Caloric restriction has shown promise in preclinical studies of colorectal cancer. A review noted that CR can enhance the anti-tumor effect of chemotherapy in colon cancer models . Interestingly, a study suggested that severe energy restriction during childhood and adolescence might lower the risk of developing colorectal cancer later in life, particularly in men . Reviews also highlight CR as a potent dietary regimen for suppressing carcinogenesis, including in colon cancer . Furthermore, a study in rats demonstrated that CR reduced colonic cell proliferation, a key biomarker associated with colon cancer risk .
Fasting-mimicking diets have demonstrated potential in modulating the gut microbiota in the context of colorectal cancer progression in mice . Research indicates that FMDs can drive antitumor immunity against colorectal cancer by reducing IgA-producing cells . Additionally, a thesis suggested that FMDs could enhance the effectiveness of vitamin C, an antioxidant with potential anticancer properties, in treating KRAS mutant colorectal cancer . Reviews also mention the anticancer characteristics of FMDs in colorectal cancer models .
Table 4: Summary of Key Studies on Fasting and Colorectal Cancer
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
Potential beneficial effects of... | 2022 | Public Health Toxicol | Intermittent Fasting | Risk/Management | IF may benefit patients at risk by inducing autophagy, sensitizing tumors to chemo |
de Groot et al. | 2020 | JAMA Oncol | Fasting Mimicking Diet | Metastatic | FMD during chemo was feasible and safe |
Lugtenberg et al. | 2021 | BMC Cancer | Fasting Mimicking Diet | Metastatic | Higher compliance with FMD in cycle 1 |
Netherlands Cohort Study | 2010 | Int J Epidemiol | Energy Restriction | Colorectal | Severe energy restriction in childhood/adolescence may lower CRC risk, especially in men |
Weng et al. | 2020 | Nat Commun | Fasting | Colorectal | Fasting inhibits aerobic glycolysis and proliferation in CRC via Fdft1-mediated AKT/mTOR/HIF1alpha suppression |
Fasting-Mimicking Diet Drives Antitumor... | 2023 | Cancer Res | Fasting Mimicking Diet | Colorectal | FMD drives antitumor immunity by reducing IgA-producing cells |
Di Tano et al. | 2020 | Nat Commun | Fasting Mimicking Diet | KRAS mutant | FMD enhances vitamin C toxicity in vitro and in vivo |
Kikomeko et al. | 2023 | Ther Adv Med Oncol | Short-Term Fasting | Metastatic | STF during chemo feasible, reduced side effects |
7. Fasting and Leukemia:
Leukemia, a cancer of the blood and bone marrow, has also been a subject of investigation regarding the effects of fasting interventions .
Intermittent fasting has shown potential in preclinical models of leukemia. Research in mice indicated that IF inhibited the development and progression of acute lymphoblastic leukemia (ALL) but not acute myeloid leukemia (AML), possibly through its effects on leptin levels . A feasibility trial in patients with chronic lymphocytic leukemia (CLL) demonstrated that time-restricted eating led to a decrease or stabilization in malignant lymphocyte counts in some participants and improved their quality of life . Reviews have also highlighted the potential of fasting in enhancing cancer treatment and improving outcomes in CLL .
Caloric restriction has been studied in the context of leukemia, particularly radiation-induced myeloid leukemia. A study in mice showed that CR reduced the incidence of myeloid leukemia induced by radiation and prolonged the lifespan of the animals . A report on a study highlighted the negative impact of obesity on ALL treatment and mentioned a trial suggesting potential benefits of caloric and nutrient restriction in B-cell ALL . Reviews also mention the potential of fasting and CR in enhancing cancer treatment and outcomes in CLL . A clinical trial is currently investigating the effects of caloric restriction and activity on chemoresistance in B-cell ALL in younger patients .
Fasting-mimicking diets have shown promising results in preclinical models of CLL. A study demonstrated that FMD combined with bortezomib and rituximab delayed CLL progression and prolonged survival in mice, suggesting a potential therapeutic strategy by targeting starvation escape pathways . News releases have also highlighted the findings of studies on FMDs and CLL, particularly in combination with proteasome inhibitors . Reviews mention the anticancer characteristics of FMDs in ALL and CLL models . Early evidence suggests that FMD plus bortezomib and rituximab may delay progression in CLL . A clinical trial is actively recruiting patients to investigate the effect of FMD with chemotherapy in acute leukemia .
Table 5: Summary of Key Studies on Fasting and Leukemia
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
Zhang et al. | 2022 | Nature Medicine | Intermittent Fasting | ALL | IF inhibited development/progression in mouse models, not AML |
Stringer et al. | medRxiv | Time-Restricted Eating | CLL | Decreased/stabilized malignant lymphocyte counts in some patients, improved QoL | |
Yoshida et al. | 1997 | PNAS | Caloric Restriction | Myeloid Leukemia | CR reduced incidence of radiation-induced myeloid leukemia in mice, prolonged lifespan |
Orgel et al. | N/A | Blood Advances | Caloric Restriction | B-cell ALL | IDEAL trial: CR via diet/exercise showed benefits in overweight/obese individuals, reduced MRD risk |
Raucci et al. | 2024 | Cancer Research | Fasting Mimicking Diet | CLL | FMD + bortezomib/rituximab delayed progression, prolonged survival in mouse models, mild anti-CLL effects with FMD alone |
Kikomeko et al. | 2023 | Ther Adv Med Oncol | Short-Term Fasting | Acute Leukemia | STF during chemo feasible, reduced side effects |
8. Fasting and Lung Cancer:
Lung cancer, the leading cause of cancer-related deaths worldwide, has also been explored in the context of fasting interventions, although human studies remain somewhat limited .
Intermittent fasting has been suggested to hold promise in treating lung cancer, particularly when aligned with circadian rhythms . General reviews also mention the potential benefits of IF in lung cancer . However, experts emphasize the need for more definitive research in humans .
Caloric restriction has shown some promise in preclinical lung cancer models. A study in mice indicated that starvation improved the efficacy of chemotherapy in fibrosarcoma (relevant as a sarcoma) via T cells and autophagy . Another study in mice found that CR inhibited tumor growth across various cell lines, potentially by suppressing mTOR and AKT pathways and reducing glycolysis . An abstract reported that a calorie-restricted ketogenic diet enhanced radiotherapy responses in lung cancer xenografts in mice . Reviews also mention preclinical evidence for CR hindering cancer growth and enhancing therapy efficacy, including in lung cancer models . One review listed a study using significant CR in mice with Lewis lung carcinoma, showing reduced metastatic burden .
Fasting-mimicking diets are being actively investigated in clinical trials for lung cancer. A phase II trial is studying whether an FMD can increase the effectiveness of chemo-immunotherapy in patients with metastatic non-small cell lung cancer . Reviews also mention the anticancer characteristics of FMDs in lung carcinoma xenografts . Cedars-Sinai highlights the potential benefits of FMDs in various cancers, including lung cancer .
Table 6: Summary of Key Studies on Fasting and Lung Cancer
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
Kikomeko et al. | 2023 | Ther Adv Med Oncol | Short-Term Fasting | Metastatic NSCLC | STF during chemo feasible, reduced side effects |
Lu et al. | 2024 | J Oncol | Caloric Restriction (TRE) | Mice (various cell lines) | CR inhibited tumor growth by suppressing mTOR/AKT, reducing glycolysis, accelerating apoptosis |
Simone et al. | N/A | J Clin Oncol | Caloric Restriction + Ketogenic Diet | Lewis Lung Carcinoma (mice) | Abstract: KR diet enhanced radiotherapy responses in xenografts |
NCI-2019-00699 | N/A | Fasting Mimicking Diet | Metastatic NSCLC | Pilot phase II trial studying FMD to increase effectiveness of chemo-immunotherapy |
9. Fasting and Ovarian Cancer:
Ovarian cancer, a leading cause of gynecological cancer deaths, has also been investigated in relation to fasting interventions .
Intermittent fasting is being explored as a potential strategy in ovarian cancer. A clinical trial is evaluating the effect of IF during chemotherapy in patients with stage III or IV ovarian cancer . Reviews suggest that IF may lower cancer risk in patients with polycystic ovary syndrome (PCOS), which can be associated with increased ovarian cancer risk . A study in mice demonstrated that IF-induced ketogenesis inhibited epithelial ovarian tumors by promoting an anti-tumor T cell response . General reviews also mention potential benefits of IF in ovarian cancer .
Caloric restriction has shown promise in preclinical ovarian cancer models. A study indicated that CR restricted ovarian cancer growth in mice by activating AMPK and SIRT1 and inhibiting Akt-mTOR, with metformin showing similar effects . Research calculated a transcriptomic signature based on CR in ovarian cancer patients, finding that a "non-fasting" profile correlated with poorer outcomes, suggesting that tumor molecular characteristics might influence response to CR-like states . An abstract showed that CR rewired macrophage metabolism and promoted macrophage-mediated tumor phagocytosis in murine ovarian cancer . Reviews also mention preclinical evidence for CR hindering cancer growth and enhancing therapy efficacy in ovarian cancer models .
Fasting-mimicking diets have also been investigated in ovarian cancer. Reviews mention RCTs in female cancers, including ovarian cancer, showing lower adverse effects during fasting or FMD with chemotherapy . General reviews also highlight the anticancer characteristics of FMDs in ovarian carcinomas . Studies have also highlighted the safety and metabolic effects of FMDs in cancer patients, which could be relevant to ovarian cancer .
Table 7: Summary of Key Studies on Fasting and Ovarian Cancer
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
NCI-2024-04425 | N/A | Intermittent Fasting | Stage III/IV | Clinical trial evaluating effect of IF during chemotherapy | |
Raffaghello et al. | 2008 | PNAS | Short-Term Fasting | Xenograft | STF protected mice from chemotherapy toxicity in various xenograft models, including ovarian |
Intermittent Fasting induced... | 2023 | PMC10028914 | Intermittent Fasting | Epithelial (mice) | IF increased survival by enhancing T-cell antitumor immunity and BHB |
Algire et al. | 2012 | Cell Cycle | Caloric Restriction | ID8 (mice) | CR restricted tumor growth, activated AMPK/SIRT1, inhibited Akt-mTOR |
Singh et al. | 2024 | J Immunol | Caloric Restriction | ID8p53-/- (mice) | Abstract: CR rewired macrophage metabolism, promoted tumor phagocytosis |
Unlocking Prognostic Potential... | 2024 | ResearchGate | Caloric Restriction | Epithelial | Study aimed to calculate transcriptomic signature of CR and its correlation with progression |
10. Fasting and Pancreatic Cancer:
Pancreatic cancer, known for its aggressive nature and poor prognosis, has also been a target for research on fasting interventions .
Intermittent fasting is being explored in the context of pancreatic cancer. While direct human studies are limited, experts note the need for more research . Reviews suggest potential anticancer effects of fasting by altering hormone and metabolite levels relevant to pancreatic cancer . News reports on preclinical research highlight that ketogenic diets, which share metabolic similarities with fasting, can enhance experimental cancer therapies and starve pancreatic tumors in mice . Reviews also mention that fasting can improve the effectiveness of gemcitabine, a common chemotherapy drug for pancreatic cancer, in preclinical models .
Caloric restriction has demonstrated significant effects in preventing pancreatic cancer development in preclinical studies. Research in mice showed that a calorie-restricted diet sharply reduced the development of pancreatic lesions that can lead to cancer, potentially by affecting IGF-1 levels and inflammatory signaling . A study indicated that CR decreased the growth of murine and human pancreatic tumor cells, as well as NF-κB activation and inflammation-related gene expression, in an IGF-1-dependent manner . Furthermore, research in mice showed that CR delayed the progression of lesions to pancreatic cancer . Reviews also mention preclinical evidence for CR hindering cancer growth and enhancing therapy efficacy in pancreatic cancer models .
Fasting-mimicking diets have shown promise in preventing pancreatic carcinogenesis in mice by altering the gut microbiota and its metabolites, particularly by boosting butyrate-producing bacteria . Reviews also mention the anticancer characteristics of FMDs in pancreatic carcinomas .
Table 8: Summary of Key Studies on Fasting and Pancreatic Cancer
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
Lashinger et al. | 2008 | AACR Meeting Abstracts | Caloric Restriction | Preclinical (mice) | CR sharply reduced development of pancreatic lesions leading to cancer |
Harvey et al. | 2014 | PLoS One | Caloric Restriction | Murine/Human Cells | CR decreased tumor cell growth, NF-κB activation, inflammation in IGF-1 dependent manner |
Lanza-Jacoby et al. | 2013 | Pancreas | Caloric Restriction | LSL-KrasG12D; Pdx-1/Cre | CR delayed progression of lesions to pancreatic cancer in mice |
Ruggero et al. | 2024 | Nature | Ketogenic Diet (similar to fasting) | Mice | Ketogenic diet + drug blocking fat metabolism eliminated pancreatic cancer in mice |
Zhou et al. | 2024 | J Agric Food Chem | Fasting Mimicking Diet | KC (mice) | FMD retarded progression of pancreatic carcinogenesis, altered gut microbiota, increased butyric acid |
11. Fasting and Melanoma (Skin Cancer):
Melanoma, a highly aggressive form of skin cancer, has also been investigated regarding the potential role of fasting interventions .
Intermittent fasting has shown promise in melanoma research. Reviews suggest that IF led to a significant delay in melanoma progression in examined studies . A study indicated that nutrient restriction mimicking IF potentiated the effects of sorafenib, a targeted therapy, in inducing cell death in human melanoma cells in vitro and reduced tumor growth in mice in vivo . Research also showed that cycles of IF combined with sorafenib significantly inhibited melanoma tumor growth in mice .
Caloric restriction has been mentioned in reviews as a potential inhibitor of melanoma advancement . Preliminary research in mice suggested that CR might help slow melanoma cancer progression . Reviews also note preclinical evidence for CR hindering cancer growth and enhancing therapy efficacy in melanoma models . However, a study in mice found that while CR slowed down melanoma tumor growth, it also impaired anti-tumor immune responses and the effectiveness of immunotherapy, suggesting that the treatment context is crucial . Time-restricted eating, a form of IF, may also impede carcinogenesis, potentially including melanoma .
Fasting-mimicking diets have also been explored in melanoma research. Reviews mention the anticancer characteristics of FMDs in melanoma models and their potential to increase the effectiveness of chemotherapy . Studies have highlighted the safety and metabolic effects of FMDs in cancer patients, which could be relevant to melanoma . Reviews also note that cycles of starvation were as effective as chemotherapy in delaying progression of melanoma models and increased chemotherapy effectiveness .
Table 9: Summary of Key Studies on Fasting and Melanoma (Skin Cancer)
Authors | Year | Journal | Type of Fasting | Cancer Stage/Type | Key Findings |
Potential beneficial effects of... | 2022 | Public Health Toxicol | Intermittent Fasting | Risk/Management | IF led to major delay in melanoma progression in studies examined |
Vernieri et al. | 2021 | Cell Metabolism | Fasting Mimicking Diet | Various | FMD was safe, feasible, and reshaped metabolism and antitumor immunity in patients with various cancers, including melanoma |
Di Biase et al. | 2016 | Cancer Cell | Fasting Mimicking Diet | Various | FMD reduced HO-1 to promote T cell-mediated tumor cytotoxicity in preclinical models, including melanoma |
Fasting Cycles Retard Growth of Tumors... | 2012 | Sci Transl Med | Fasting | Mice (various cell lines) | Cycles of fasting delayed progression and increased chemo effectiveness against melanoma |
Effective Synergy of Sorafenib... | 2020 | Cells | Intermittent Fasting | Human Cell Lines/Mice | IF potentiated sorafenib-induced cell death in vitro and reduced tumor growth in vivo |
Dung et al. | 2023 | Nutrients | Caloric Restriction | B16-OVA (mice) | CR slowed tumor growth but impaired CD8+ T cell immunity and anti-PD-1 treatment efficacy |
12. Discussion:
The body of published research on fasting interventions and cancer outcomes reveals a complex and evolving landscape. Across various cancer types, including breast, prostate, glioma, colorectal, leukemia, lung, ovarian, pancreatic, and melanoma, studies have explored the effects of intermittent fasting, caloric restriction, and fasting-mimicking diets. A common thread observed across these interventions is their potential to influence fundamental biological processes relevant to cancer, such as metabolic alterations, immune modulation, and autophagy .
Metabolic changes induced by fasting, such as reduced glucose availability, the induction of ketosis, and altered levels of insulin and IGF-1, appear to play a significant role in the observed effects . These metabolic shifts can create an environment less favorable for cancer cell growth and proliferation, as many cancer cells exhibit a high dependence on glucose . Furthermore, the enhancement of cellular processes like autophagy, which helps in clearing damaged cells and organelles, and the promotion of apoptosis in cancer cells are consistently reported as potential mechanisms underlying the benefits of fasting . The ability of fasting to modulate hormonal signals and influence the immune system, potentially boosting anti-tumor responses and affecting the tumor microenvironment, further contributes to its complex interplay with cancer . Emerging evidence also suggests that fasting can impact the gut microbiome, which in turn can influence cancer development and treatment response .
While preclinical studies in animal models and in vitro experiments have frequently demonstrated promising anti-cancer effects of various fasting interventions, the translation of these findings to human clinical outcomes requires careful consideration. The research reviewed includes a growing number of human studies, particularly clinical trials investigating the feasibility, safety, and efficacy of IF and FMDs as adjuncts to conventional cancer therapies . These studies have shown that fasting interventions can often be safely implemented in cancer patients and may lead to improvements in metabolic markers and reductions in chemotherapy-related toxicities . However, the evidence regarding a direct "cure" for cancer through fasting alone is lacking. The term "cure" in oncology typically implies long-term, complete remission of the disease, which requires substantial evidence from large-scale, well-controlled clinical trials.
It is important to acknowledge the limitations of the current research. Many human studies have relatively small sample sizes and exhibit heterogeneity in fasting protocols, cancer types, and outcome measures, making it challenging to draw definitive conclusions . Furthermore, the long-term effects of fasting interventions on cancer progression and patient survival in humans are still under investigation in many ongoing trials . Individual patient factors, such as overall health status, cancer stage, genetic background, and the specific type of cancer and its treatment regimen, are likely to influence the response to fasting interventions, highlighting the need for personalized approaches .
Therefore, while the research reviewed provides a compelling rationale for the potential benefits of fasting interventions in the context of cancer, it does not definitively prove that fasting cures cancer. The evidence suggests that fasting can play a supportive role in cancer prevention, treatment, and management by modulating various biological pathways and potentially enhancing the efficacy of conventional therapies while reducing side effects in some instances. However, any cancer patient considering a fasting intervention should do so under the close supervision of their medical team, including oncologists and registered dietitians, to ensure adequate nutritional intake, maintain a healthy weight, and avoid potential complications .
13. Conclusion:
The scientific literature on fasting interventions and cancer outcomes reveals a promising area of research with the potential to impact cancer care. Studies investigating intermittent fasting, caloric restriction, and fasting-mimicking diets have demonstrated various beneficial effects across a range of cancer types in preclinical models and increasingly in human clinical trials. These benefits include the modulation of key metabolic pathways, enhancement of cellular protective mechanisms, regulation of hormonal signals, and the potential to boost anti-tumor immunity. While preclinical evidence often shows strong anti-cancer effects, human studies are still evolving, focusing on the feasibility, safety, and efficacy of integrating fasting interventions with standard cancer treatments.
It is crucial to emphasize that the current body of evidence does not support the claim that fasting, in any of its forms, is a proven cure for cancer. The complexity of cancer biology and the heterogeneity of patient responses necessitate rigorous scientific validation through large-scale, long-term randomized controlled trials in humans to definitively establish the therapeutic role of fasting in oncology. However, the findings reviewed suggest that fasting interventions, when implemented appropriately and under medical guidance, may serve as valuable adjuncts to conventional cancer therapies, potentially improving treatment outcomes and the overall well-being of patients. Ongoing and future research will be critical in further elucidating the optimal protocols, identifying the patient populations most likely to benefit, and ultimately determining the precise role of fasting in the comprehensive management of cancer.
14. References:
Please see the provided list of research snippets for the corresponding APA format references. The snippet IDs can be used to locate the relevant citation information.
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