{"entity":{"id":"fasting-mimicking-diet","kind":"technology","name":"Fasting and fasting-mimicking diets around chemotherapy","aka":[],"tldr":"Fasting-mimicking diets cut food intake for three days around each chemotherapy dose to lower glucose, insulin and IGF-1, which may shield normal cells and sensitise the tumour. The DIRECT trial in early breast cancer improved radiological response but fewer than 20% of patients kept to the diet, and it is unsafe in cachexia or without a dietitian.","summary":"Short-term fasting lowers glucose, insulin and IGF-1 and shifts normal cells into a protective, low-proliferation state ('differential stress resistance') while cancer cells, unable to slow down, may become more chemosensitive. Mouse data are strong. In humans, the DIRECT trial (Netherlands, 131 patients with HER2-negative early breast cancer, Nature Communications 2020) randomised a plant-based fasting-mimicking diet for three days before and on the day of each neoadjuvant chemotherapy cycle: radiological response was better (OR 3.2) and a 90-100% tumour cell loss more frequent in the diet arm, but adherence collapsed (fewer than 20% completed all cycles) and pathological complete response did not differ. Phase 2 trials in breast, colorectal and lung cancer are running; none has a survival endpoint yet. Weight loss and sarcopenia are real risks, and fasting is contraindicated in cachexia.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"DIRECT trial (Nat Commun 2020)","url":"https://doi.org/10.1038/s41467-020-16138-3"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc","colorectal"],"sections":["nutrition-lifestyle","chemotherapy"],"technologies":["cytotoxic-chemotherapy","metabolic-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":["energy-balance","warburg-effect-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-funding-allocation"],"keyPapers":["paper-de-groot-nat-commun"],"journals":[],"dependsOn":[],"notes":[],"principle":"Nutrient deprivation lowers systemic growth signalling (insulin, IGF-1) and induces protective stress responses in normal tissue, potentially widening the therapeutic window of cytotoxics.","strengths":["Strong preclinical rationale","Randomised signal on radiological response in DIRECT","Very cheap"],"limitations":["Adherence is poor","No survival or pCR benefit shown","Risk of muscle loss; unsuitable for malnourished patients"]},"route":"/technologies/fasting-mimicking-diet/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"nutrition-lifestyle","kind":"section","name":"Diet, Exercise & Lifestyle","route":"/fronts/nutrition-lifestyle/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"metabolic-therapy","kind":"technology","name":"Metabolic therapy: starving the tumour of a nutrient","route":"/technologies/metabolic-therapy/"},{"id":"rejuv-frontier-what-works","kind":"technology","name":"What actually works after treatment","route":"/technologies/rejuv-frontier-what-works/"}],"pathway":[{"id":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"term":[{"id":"energy-balance","kind":"term","name":"Energy balance","route":"/terms/energy-balance/"},{"id":"warburg-effect-diet-claims","kind":"term","name":"Warburg-effect diet claims ('sugar feeds cancer')","route":"/terms/warburg-effect-diet-claims/"}],"bottleneck":[{"id":"b-funding-allocation","kind":"bottleneck","name":"Funding follows fashion, not burden","route":"/bottlenecks/b-funding-allocation/"},{"id":"b-generic-repurposing","kind":"bottleneck","name":"No incentive to repurpose cheap drugs","route":"/bottlenecks/b-generic-repurposing/"}],"paper":[{"id":"paper-de-groot-nat-commun","kind":"paper","name":"Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial","route":"/key-papers/paper-de-groot-nat-commun/"}],"roadmap":[{"id":"nutrition-lifestyle-roadmap","kind":"roadmap","name":"Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment","route":"/roadmaps/nutrition-lifestyle-roadmap/"}]}}