Fasting and FMD

Also called: fasting-mimicking diet, intermittent fasting, FMD.

Last reviewed 2026-09-16. How this works.

Alongside chemotherapy Grade C

Human evidence exists and does not settle it.

Fasting around chemotherapy did not do what its trial set out to show, though two smaller findings held up.

The declared endpoints were missed. Two secondary findings survived.

The claim

The claim is that a short period of fasting around chemotherapy protects normal cells while leaving cancer cells exposed, so the treatment works better and feels less punishing.

What it does

The laboratory work behind this is genuinely strong, and the book says so. Starvation conditions sensitised fifteen of seventeen cancer cell lines to chemotherapy, fasting cycles alone delayed tumour progression in mice about as well as the drugs did, and in neuroblastoma models fasting plus chemotherapy, but neither alone, produced long-term cancer-free survival.1

That is yeast, cell lines and mice. It is the beginning of a question rather than the answer to one, and the rest of this entry is what happened when the question was put to people.1

The evidence

The DIRECT trial randomised 131 women with breast cancer to a fasting-mimicking approach or a regular diet alongside chemotherapy before surgery. A published commentary characterises the overall result as negative: it did not reduce chemotherapy side effects and did not improve the rate of complete pathological response.23

Two findings survived that. Radiological response was more frequent in the fasting group, and in the analysis restricted to those who followed the diet, near-complete tumour-cell loss was more likely.2

The two that matter most are easy to miss. Side effects were no worse in the fasting group even though the steroid normally given alongside chemotherapy was left out, and chemotherapy-induced DNA damage in circulating immune cells was reduced.23

A phase 3 trial, DIRECT2, is running to test this properly. Its primary endpoints are pathological and radiological response. It has not reported.4

The studies this rests on

  • DIRECT, fasting-mimicking diet with chemotherapy before surgery in breast cancer2

    A randomised trial, open label, phase 2, measured a clinical outcome, 131 participants.

    the declared endpoints were not met; radiological response was more frequent with the diet and DNA damage in circulating immune cells was reduced.

    odds ratio 3.168. radiological complete or partial response, P=0.039

  • DIRECT2, phase 3 fasting-mimicking diet with chemotherapy in breast cancer4

    A randomised trial, open label, phase 3, measured a clinical outcome, 240 participants.

    running, not yet reported. Nothing has been reported from it.

  • BREAKFAST 2, fasting-like approach with chemoimmunotherapy in triple-negative breast cancer (NCT05763992)5

    A trial with no comparison group, open label, phase 2, measured a clinical outcome.

    running, not yet reported. A registered trial is a question, not an answer.

What is absent

No trial in this record measured whether fasting alongside chemotherapy helps anyone live longer. The endpoints were tumour response, side effects and markers in the blood.

Scope: any tumour type.

Established by trial scope, checked 2026-09-16. Result: the declared endpoints of every trial recorded here are response, toxicity or laboratory markers.24

What to ask

Is there a fasting trial running that I could be considered for, rather than trying this on my own?

The dish-to-person gap

This is a way of eating rather than a compound that reaches a concentration in the blood, so the dish-to-person comparison does not apply to it.

When to call your team — no warning signs are recorded

If you have changed how you eat because of something you have read, or are thinking about it, the people treating you can only weigh that if they know about it. That is true when nothing has been written down here, and it is most true then.

The register records no warning signs for this entry. Anyone losing weight during treatment should tell their team, whatever the reason.

Interactions

Fasting around treatment is not checked against treatment classes here. It is, however, exactly the kind of thing worth telling an oncology team about, because it changes the conditions under which a drug is given.

The whole interaction list, and how to turn it into a pharmacy review request.

Find a trial instead

Trials are running, including a phase 3. This is one of the few entries in the book where the honest answer to "should I try it" is that a trial exists to try it inside.

Search ClinicalTrials.gov for recruiting studies of fasting mimicking diet OR fasting

A trial is the same decision with monitoring, a known preparation and a doctor who knows what else you are taking.

References

  1. Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Science Translational Medicine 2012;4(124):124ra27.

    doi:10.1126/scitranslmed.3003293 · PubMed 22323820

    How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 8 note 1.

  2. de Groot S, Lugtenberg RT, Cohen D, 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;11:3083.

    doi:10.1038/s41467-020-16138-3

    How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 8 note 5. The author string is abbreviated in the source that was read and has not been expanded.

  3. Vernieri C, Ligorio F, Zattarin E, Rivoltini L, de Braud F. Fasting-mimicking diet plus chemotherapy in breast cancer treatment. Nature Communications 2020;11:4274.

    doi:10.1038/s41467-020-18194-1

    How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 8 note 2.

  4. DIRECT2: a randomized phase III trial with a fasting mimicking diet program to improve chemotherapy in patients with hormone receptor positive, HER2-negative breast cancer. Dutch Breast Cancer Research Group. Trial-in-progress abstract, Journal of Clinical Oncology 2023;41(16 suppl):TPS630.

    No persistent identifier recorded.

    How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 8 note 3.

  5. Caffa I, et al. Fasting-mimicking diet and hormone therapy induce breast cancer regression. Nature 2020;583:620-624.

    NCT05763992

    How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 8 note 4. The author string is abbreviated in the source that was read and has not been expanded.