# Fasting and fasting-mimicking diets around chemotherapy

Source: https://onco.cc/technologies/fasting-mimicking-diet/  
OnCo record `fasting-mimicking-diet` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: phase-2
- Last checked: 2026-09-08
- 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

## Sources

- DIRECT trial (Nat Commun 2020): https://doi.org/10.1038/s41467-020-16138-3

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Diet, Exercise & Lifestyle](https://onco.cc/fronts/nutrition-lifestyle/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Metabolic therapy: starving the tumour of a nutrient](https://onco.cc/technologies/metabolic-therapy/), [What actually works after treatment](https://onco.cc/technologies/rejuv-frontier-what-works/)
- pathways: [Nutrient competition & metabolic immunosuppression](https://onco.cc/pathways/nutrient-competition-tme/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- terms: [Energy balance](https://onco.cc/terms/energy-balance/), [Warburg-effect diet claims ('sugar feeds cancer')](https://onco.cc/terms/warburg-effect-diet-claims/)
- bottlenecks: [Funding follows fashion, not burden](https://onco.cc/bottlenecks/b-funding-allocation/), [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/)
- key papers: [Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial](https://onco.cc/key-papers/paper-de-groot-nat-commun/)
- roadmaps: [Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment](https://onco.cc/roadmaps/nutrition-lifestyle-roadmap/)

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