Very low-carbohydrate ketogenic diet in treatment-naïve women with endometrial cancer and overweight: a randomized feasibility study
This multicenter, prospective, randomized controlled trial (NCT03285152) evaluates the primary endpoint of feasibility of a very-low carbohydrate diet (VLCD) in 19 women with obesity/overweight and endometrial cancer, who are randomized 2:1 to either a VLCD or a standard diet for 21–28 days. Fifteen participants complete the study, with 91 ± 4% of VLCD meals consumed, 5.5 ± 0.8% weight lost, and no grade 3/4 adverse events. Secondary endpoints include assessments of tumor biology and circulating metabolic biomarkers. Fasting glucose and insulin fall 22 ± 5.9% and 60 ± 3.8%, while total cholesterol and low-density lipoprotein (LDL) rise 6 ± 2.7% and 17.8 ± 8.9%. In a pre-specified exploratory outcome, RNA-Seq shows enrichment of CD8 + T-cells (q < 0.034; NES > 1.75), confirmed by immunohistochemistry (IHC) showing CD8 + T-cells infiltration of the tumor margins (q = 0.034; NES = 1.75). We conclude that VLCD is feasible and well-tolerated. Dietary interventions have been proposed as potential therapeutic strategies in cancer. Here, the authors report a feasibility randomized clinical trial comparing standard diet with a very lowcarbohydrate ketogenic diet (VLCD) in treatment-naive women with endometrial cancer and obesity or overweight.
Authors
- Nadeem R. Abu‐Rustum (ORCID: https://orcid.org/0000-0001-9689-1298)
- Vania Hom (ORCID: https://orcid.org/0000-0001-9872-1153)
- Francis N. Villamater
- Kathryn Gorski
- Michael Sigouros (ORCID: https://orcid.org/0000-0002-0328-8359)
- Katie C. Hootman (ORCID: https://orcid.org/0000-0003-0476-3454)
- Ginger J. Gardner (ORCID: https://orcid.org/0000-0003-3955-3238)
- Andrew J. Plodkowski (ORCID: https://orcid.org/0000-0002-3772-370X)
- Gabrielle Bennetti
- Lewis C. Cantley (ORCID: https://orcid.org/0000-0002-1298-7653)
- Olivier Elemento (ORCID: https://orcid.org/0000-0002-8061-9617)
- Brandon M. Cuevas (ORCID: https://orcid.org/0000-0002-8275-8258)
- Bhavani Ramesh
- Maurice A. Hurd
- Karen Carthew
- Vicky Makker (ORCID: https://orcid.org/0000-0001-9793-7614)
- Oliver Zivanovic (ORCID: https://orcid.org/0000-0003-1305-4991)
- Yukio Sonoda
- Marissa Mezzancello
- Kaity Chang
- Morgan Tomberlin
- Yuan‐Shan Zhu (ORCID: https://orcid.org/0000-0002-7215-8275)
- Alex McPherson
- Jeshua Kim
- Kari Hacker
- Marcus D. Goncalves (ORCID: https://orcid.org/0000-0002-0784-9248)
- Jenna Moyer
- Vance Broach
- Carol Aghajanian
- Krysten Soldan
- Gissell Botero Rodriguez
- Ezequiel Dantas
- John Nguyen (ORCID: https://orcid.org/0009-0007-0560-6684)
- Benjamin D. Hopkins (ORCID: https://orcid.org/0000-0002-7970-6430)
- Jennifer J. Mueller
- Anastasia Tsomides
- Mario M. Leitao
- Britta Weigelt (ORCID: https://orcid.org/0000-0001-9927-1270)
- Katherine Curran
- Alexia Iasonos
- Rema Rao Chaari (ORCID: https://orcid.org/0000-0003-2462-0004)
- Erica Nagase
- Hannah Price (ORCID: https://orcid.org/0009-0001-7909-1712)
- M. Laura Martin
- Lora H. Ellenson
Institutions
- Cleveland Clinic (US)
- Memorial Sloan Kettering Cancer Center (US)
- Harvard University (US)
- Cornell University (US)
- NYU Langone Health (US)
- Dana-Farber Cancer Institute (US)
- Weill Cornell Medicine (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-27
- DOI
- https://doi.org/10.1038/s41467-026-73519-w
- Primary Topic
- Diet and metabolism studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health