Fasting and Fasting-Mimicking Diets Around Chemotherapy: What the Trials Found

The idea that a short fast around each chemotherapy dose could shield healthy cells and leave cancer cells exposed came from yeast, cell cultures and mice. Human studies since 2009 are small, mostly in women with breast or gynecological cancer, and mostly in people who were well nourished at the start. They report that short fasts can be carried out with mainly mild side effects. Whether fasting lowers chemotherapy side effects is reported both ways, and DIRECT, the largest randomized trial described here, did not show fewer severe side effects, its main goal. No randomized trial on this page reports a survival benefit.

Table of Contents

  1. The Kinds of Fast Being Tested
  2. Mouse and Cell Studies Behind the Idea
  3. First Human Reports and Small Short-Fast Trials
  4. The DIRECT Trial
  5. Other Fasting-Mimicking Diet Studies
  6. What the Pooled Analyses Reported
  7. Weight Loss, Low Blood Sugar and Adherence
  8. Who the Trials Left Out
  9. What Guidelines State
  10. Limits of the Evidence
  11. Key Research Papers
  12. Connections
  13. Featured Videos

The Kinds of Fast Being Tested

The word "fasting" covers very different regimens in these studies, and results from one do not automatically carry over to another.

The body's general response to fasts of these lengths is covered on the Extended Fasts page. This page deals only with fasting timed around cancer drugs.

Mouse and Cell Studies Behind the Idea

The starting theory is called differential stress resistance. It holds that starved normal cells shift into a protective, low-growth state, while cancer cells, driven by growth signals that stay switched on, cannot make that shift. Everything in this section comes from yeast, cultured cells or mice, not patients.

A 2021 review of this literature concluded that with limited human trials, the findings from animal and cell studies cannot be generalized to patients (Sadeghian 2021).

A mouse finding that points the other way

Not every animal result favors fasting. Earlier mouse work had suggested that alternate-day fasting might lessen the heart damage caused by doxorubicin. A 2023 study reported the reverse: in mice treated with doxorubicin, sustained alternate-day fasting increased deaths and impaired heart function. The authors traced this to a pathway involving a protein called transcription factor EB, and also found increased levels of that protein in the cell nuclei of heart tissue from patients with doxorubicin-induced heart failure (Ozcan 2023).

This was a mouse experiment using a sustained every-other-day pattern, which differs from the short fasts timed to each dose in the human trials below. It does not show what happens in patients. Doxorubicin was among the drugs given in several of those human trials, including DIRECT and the 2015 Dutch pilot. The human reports on this page did not list heart outcomes among their main results.

First Human Reports and Small Short-Fast Trials

The 2009 case series. Ten patients with various cancers fasted on their own initiative, for 48 to 140 hours before and/or 5 to 56 hours after chemotherapy. They reported no significant side effects from the fasting other than hunger and lightheadedness. The six who had cycles both with and without fasting reported less fatigue, weakness and digestive side effects while fasting. The authors stated that these cases were not meant to set practice guidelines (Safdie 2009).

The 2016 dose-escalation study. Twenty people on platinum-based chemotherapy, median age 61, 85% women, fasted for 24, 48 or 72 hours, with a target of no more than 200 kilocalories per 24 hours. There was no comparison group without fasting. Fasting-related side effects stayed at grade 2 or below, most often fatigue, headache and dizziness. Less grade 3 or 4 neutropenia (low infection-fighting white cells) in the longer-fasting groups was a trend that did not reach significance (P = 0.17), and reduced DNA damage in white blood cells also fell short (P = 0.08) (Dorff 2016).

The 2015 Dutch pilot. Thirteen women with stage II or III breast cancer negative for human epidermal growth factor receptor 2 were randomized, seven of them to fast for 24 hours before and 24 hours after the start of chemotherapy. Red blood cell and platelet counts seven days after chemotherapy were higher in the fasting group. Side effects other than blood counts did not differ between groups (de Groot 2015).

The 2018 Berlin crossover trial. Thirty-four women with breast or ovarian cancer fasted 60 hours (36 before and 24 after the dose) during half of their chemotherapy cycles and ate normally during the other half. Each woman served as her own comparison. Chemotherapy-related decline in a fatigue and well-being score was 10.4 points in fasted cycles against 27.0 in non-fasted cycles in one group, and 11.0 against 14.1 in the other. No serious adverse effects were reported (Bauersfeld 2018).

The 2020 German crossover trial. Gynecological cancer patients took 25% of their calorie needs for 96 hours during half of their cycles. Thirty completed the study. During fasting cycles, scores for mouth sores, headaches and weakness were lower, the total side-effect score was lower (by 10.36 points, P = 0.023), and chemotherapy was postponed less often (P = 0.034). A ketogenic diet in the days before each fast neither reduced fasting discomfort nor improved adherence (Zorn 2020).

The 2020 water-only trial. Women with gynecological cancer, mostly stage 3 or 4, were randomized to a 48-hour water-only fast around each dose or to no fast. The analysis covered 120 chemotherapy cycles in 20 women. Weight loss and unplanned hospital stays were similar between the groups, and there were fewer dose reductions or delays in the fasting group. Mean quality-of-life scores did not differ significantly, although scores in the fasting group improved over the course of treatment (Riedinger 2020).

The 2022 Egyptian study. Forty-eight women newly diagnosed with breast cancer of that same receptor type were divided into a group fasting 18 hours a day for three days around each of four cycles and a group eating as usual. Digestive side effects were lower with fasting, and blood counts did not differ after cycle 4 (Omar 2022).

The 2026 English feasibility trial (SWiFT). This trial tested a 36-hour water-only fast before capecitabine and oxaliplatin chemotherapy in stage 2 or 3 colorectal cancer. Of 79 people screened, 44 were eligible and only 12 agreed to take part, six in each group. Five of the six in the fasting group adhered to the fast. Interviews found fasting achievable but sometimes felt as an extra burden during chemotherapy (Herbert 2026).

The DIRECT Trial

DIRECT is a randomized phase 2 trial run at 11 Dutch centers with the Dutch Breast Cancer Research Group. It randomized 131 women with stage II or III breast cancer of the same receptor type to a fasting-mimicking diet or their regular diet, for 3 days before and on the day of each chemotherapy cycle given before surgery. After one withdrawal and one ineligible patient, 129 remained: 65 on the diet and 64 on regular food (de Groot 2020).

Side effects

Fewer severe side effects was the stated main goal of this phase of the trial, and that did not happen. Grade 3 or 4 side effects occurred in 75.4% of the diet group and 65.6% of the regular-diet group, not a significant difference. Stopping chemotherapy early was also similar, at 27.7% and 23.8%. One detail complicates the comparison: the diet group did not receive the steroid dexamethasone before the doxorubicin or epirubicin cycles, while the regular-diet group did, because the investigators thought dexamethasone might counteract the diet's metabolic effects. The authors read the similar side-effect rates as suggesting the diet might replace dexamethasone in those cycles (de Groot 2020).

Tumor response

By chance, the share of women with triple-negative tumors in the diet group was double that in the control group. The authors reported that the positive effects persisted after adjusting for receptor status.

Quality of life

Overall quality of life and distress fell during treatment in both groups and returned to baseline 6 months after surgery. In per-protocol analyses, women who kept to the diet scored better on physical, emotional, role, cognitive and social functioning and lower on fatigue, nausea and insomnia than non-adherent women and those on regular food. Women on the diet were also less concerned about, and said they better understood, the possible side effects of their treatment (Lugtenberg 2021).

Why a phase 3 trial did not follow

The trial's data safety monitoring board advised against going on to the planned phase 3 stage, for two reported reasons: the overall complete response rate of 11.7% was significantly lower than anticipated, and adherence was worse than expected. Survival data were to be reported after 5 years of follow-up. A Europe PMC search made for this page did not turn up that survival report.

Other Fasting-Mimicking Diet Studies

The 2024 Iranian randomized trial. Forty-four women with breast cancer of the same receptor type received a modified diet with 2 grams of omega-3, or their regular diet, for 3 days before and during each of 8 cycles of chemotherapy given before surgery. Grade 3 vomiting and neutropenia were more common in the control group (P < 0.001 and P = 0.04). Loss of 90 to 100% of tumor cells and complete or partial response on scans were more frequent in the diet group (P = 0.01) (Bahrami 2024).

The Milan trial (2022). One hundred and one patients with various cancers followed a 5-day diet of up to 600 kilocalories on day 1 and up to 300 on days 2 to 5, repeated with standard treatments that included but were not limited to chemotherapy. Its main goal was safety, measured against a 20% threshold for severe diet-related side effects. The rate was 12.9%. Median blood glucose fell 18.6%, insulin 50.7% and insulin-like growth factor 1 30.3%. Blood and tumor samples showed immune changes the authors linked to better outcomes in other studies. There was no comparison group, so the trial does not show a treatment benefit, and the authors called for phase 2 and 3 trials to test that (Vernieri 2022).

Two sub-analyses of the Milan trial. Five of the 101 patients, all with advanced disease that usually has a poor outlook, had complete and long-lasting tumor responses (Ligorio 2022). In a separate analysis, 14 women with advanced triple-negative breast cancer on carboplatin and gemcitabine plus the diet had a median survival of 30.3 months, against 17.2 months in 76 consecutive patients at the same hospital on carboplatin-based chemotherapy alone (hazard ratio 0.40) (Ligorio 2024). Neither comparison was randomized. The authors of the second analysis wrote that it paves the way for phase 2 trials.

The Genoa trial (2021). Ninety patients at low nutritional risk, in active treatment, in a single-arm trial, received a milder diet with an average of 6.3 cycles per patient, along with dietary and muscle-training instructions between cycles. Side effects related to the diet were grade 1 or 2 only, most often headache (29%) and fatigue (26%). Weight and hand-grip strength stayed stable, fat-free mass rose and fat mass fell (Valdemarin 2021).

The 2025 Chinese pilot. Thirty people with breast cancer ate recipe-based meals giving 34 to 54% of normal calories for four days before and on the day of each of 3 chemotherapy cycles, and 27 completed all three. Grade 3 or worse diet-related side effects occurred at a rate of 5.95% (5 of 84). Weight fell by 2.04 kilograms after a 21-day washout, nearly all of it fat, with muscle mass stable. There was no comparison group (Xue 2025).

The 2026 lung cancer pilot. Ten people with metastatic non-small cell lung cancer, 80% on oral targeted therapy rather than chemotherapy, tried a single 4-day cycle. Nine completed it, none had grade 3 or 4 side effects, and 70% met the calorie requirements (Ghaddar 2026).

What the Pooled Analyses Reported

Reviews that combine these small studies reach different conclusions, partly because they pool different regimens and cancers.

Weight Loss, Low Blood Sugar and Adherence

Weight

Weight loss during treatment is the main concern raised about fasting in cancer patients. The reports vary by regimen:

The 2022 review reported that weight loss appeared in every study it covered, was generally mild, and sometimes required nutritional intervention between cycles (Bozzetti 2022). The Milan authors named the risk of progressive weight loss, through release of amino acids from muscle and fatty acids from fat tissue, as a major issue with this approach, and credited their patient selection and strict stopping rules for limiting it. A 2023 review wrote that in clinical trials "it will remain essential to avoid inducing or aggravating malnutrition" (Arends 2023).

Low blood sugar and other reactions

The most detailed safety data come from the Milan trial, where severe (grade 3 or 4) diet-related events included low blood sugar (hypoglycemia) in 5% of patients, fatigue in 4%, and fainting, nausea, dizziness and a raised liver enzyme in 1% each. One case of hypoglycemia reached grade 4, the only grade 4 event. Serious adverse events occurred in 4 patients, and 2 of those, fainting and severe fatigue, were attributed to the diet. Fatigue of any grade occurred in 90.2% of patients (Vernieri 2022). The milder Genoa diet had one case of symptomatic hypoglycemia among 90 patients and no grade 3 or worse events (Valdemarin 2021).

Adherence

Adherence ranges widely and depends partly on how adherence is defined.

Who the Trials Left Out

All of these safety results apply to the selected people the trials accepted. The Berlin authors wrote directly that the safety of fasting "can only be extrapolated to the selected population of oncology patients," because those with recent weight loss or a low body mass index were excluded (Bauersfeld 2018). Groups excluded by one or more trials:

The people most likely to lose weight on cancer treatment, including those with wasting from advanced cancer, are therefore largely unstudied. The 2022 review found that all seven papers it covered involved seemingly well-nourished patients (Bozzetti 2022). Men are few: most of the studies were limited to women with breast or gynecological cancers, or enrolled mostly women.

What Guidelines State

The guideline text located for this page comes from the European Society for Clinical Nutrition and Metabolism. Its 2017 cancer guideline makes a strong recommendation, on a low level of evidence, "to not use dietary provisions that restrict energy intake in patients with or at risk of malnutrition." On fasting specifically, it states that small studies reported good tolerability but that "because of the risks of malnutrition and because patients might be tempted to prolong fasting episodes, without firm evidence of a benefit fasting during chemotherapy cannot be recommended." It lists the effects of fasting and fasting-mimicking diets on anticancer drugs as a question for research (Arends 2017).

The society's 2021 practical guideline repeats the recommendation and states that "without evidence of a benefit of fasting during chemotherapy, we do not recommend the use of this approach before, during or after the application of anticancer agents" (Muscaritoli 2021). Its commentary on fasting cites the 2009 case series and the 2015 Dutch pilot. It does not discuss DIRECT or the later trials described on this page, so these statements do not weigh that newer evidence.

These are statements by a guideline panel, reported here as such. A wider account of nutrition guidelines during cancer treatment is on the Nutrition in Cancer Care page.

Limits of the Evidence

Key Research Papers

  1. Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(24):8215-20. PubMed PMID: 18378900
  2. Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Science translational medicine. 2012;4(124):124ra27. PubMed PMID: 22323820
  3. Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell stem cell. 2014;14(6):810-23. PubMed PMID: 24905167
  4. Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, et al. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer cell. 2016;30(1):136-146. PubMed PMID: 27411588
  5. Di Biase S, Shim HS, Kim KH, Vinciguerra M, Rappa F, Wei M, et al. Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy. PLoS biology. 2017;15(3):e2001951. PubMed PMID: 28358805
  6. Ozcan M, Guo Z, Valenzuela Ripoll C, Diab A, Picataggi A, Rawnsley D, et al. Sustained alternate-day fasting potentiates doxorubicin cardiotoxicity. Cell metabolism. 2023;35(6):928-942.e4. PubMed PMID: 36868222
  7. Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, et al. Fasting and cancer treatment in humans: A case series report. Aging. 2009;1(12):988-1007. PubMed PMID: 20157582
  8. Dorff TB, Groshen S, Garcia A, Shah M, Tsao-Wei D, Pham H, et al. Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC cancer. 2016;16:360. PubMed PMID: 27282289
  9. de Groot S, Vreeswijk MP, Welters MJ, Gravesteijn G, Boei JJ, Jochems A, et al. The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. BMC cancer. 2015;15:652. PubMed PMID: 26438237
  10. Bauersfeld SP, Kessler CS, Wischnewsky M, Jaensch A, Steckhan N, Stange R, et al. The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study. BMC cancer. 2018;18(1):476. PubMed PMID: 29699509
  11. Zorn S, Ehret J, Schäuble R, Rautenberg B, Ihorst G, Bertz H, et al. Impact of modified short-term fasting and its combination with a fasting supportive diet during chemotherapy on the incidence and severity of chemotherapy-induced toxicities in cancer patients - a controlled cross-over pilot study. BMC cancer. 2020;20(1):578. PubMed PMID: 32571329
  12. Riedinger CJ, Kimball KJ, Kilgore LC, Bell CW, Heidel RE, Boone JD. Water only fasting and its effect on chemotherapy administration in gynecologic malignancies. Gynecologic oncology. 2020;159(3):799-803. PubMed PMID: 32958269
  13. Omar EM, Omran GA, Mustafa MF, El-Khodary NM. Intermittent fasting during adjuvant chemotherapy may promote differential stress resistance in breast cancer patients. Journal of the Egyptian National Cancer Institute. 2022;34(1):38. PubMed PMID: 36089614
  14. Herbert G, England C, Shingler E, Barker RM, Perks CM, Searle A, et al. A feasibility randomised controlled trial of water-only fasting prior to CAPOX chemotherapy for stage 2/3 colorectal cancer. Pilot and feasibility studies. 2026;12(1):10.1186/s40814-026-01848-0. PubMed PMID: 42237427
  15. de Groot S, Lugtenberg RT, Cohen D, Welters MJP, Ehsan I, Vreeswijk MPG, et al. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nature communications. 2020;11(1):3083. PubMed PMID: 32576828
  16. Lugtenberg RT, de Groot S, Kaptein AA, Fischer MJ, Kranenbarg EM, Carpentier MD, et al. Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial. Breast cancer research and treatment. 2021;185(3):741-758. PubMed PMID: 33179154
  17. Bahrami A, Haghighi S, Moghani MM, Khodakarim N, Hejazi E. Fasting mimicking diet during neo-adjuvant chemotherapy in breast cancer patients: a randomized controlled trial study. Frontiers in nutrition. 2024;11:1483707. PubMed PMID: 39703333
  18. Vernieri C, Fucà G, Ligorio F, Huber V, Vingiani A, Iannelli F, et al. Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer. Cancer discovery. 2022;12(1):90-107. PubMed PMID: 34789537
  19. Valdemarin F, Caffa I, Persia A, Cremonini AL, Ferrando L, Tagliafico L, et al. Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment. Cancers. 2021;13(16):10.3390/cancers13164013. PubMed PMID: 34439167
  20. Ligorio F, Fucà G, Provenzano L, Lobefaro R, Zanenga L, Vingiani A, et al. Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial. European journal of cancer (Oxford, England : 1990). 2022;172:300-310. PubMed PMID: 35810555
  21. Ligorio F, Lobefaro R, Fucà G, Provenzano L, Zanenga L, Nasca V, et al. Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial. International journal of cancer. 2024;154(1):114-123. PubMed PMID: 37615485
  22. Xue M, Zhang N, Dong X, Tian Q, Shen K, Wu B. The feasibility and safety of fasting-mimicking diet in breast cancer patients with chemotherapy in China. Breast cancer research and treatment. 2025;213(3):313-323. PubMed PMID: 40711668
  23. Ghaddar F, Ahmed S, Kirsch B, Jennewein L, Uhrich MM, Althouse SK, et al. Brief Report: A Pilot Study Evaluating the Feasibility, Safety, and Compliance With a Fasting-Mimicking Diet in Patients With Metastatic Non-Small Cell Lung Cancer. Clinical lung cancer. 2026;27(4):24-28. PubMed PMID: 42060951
  24. Ferro Y, Maurotti S, Tarsitano MG, Lodari O, Pujia R, Mazza E, et al. Therapeutic Fasting in Reducing Chemotherapy Side Effects in Cancer Patients: A Systematic Review and Meta-Analysis. Nutrients. 2023;15(12):10.3390/nu15122666. PubMed PMID: 37375570
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