Supervised Keto Diet/Triplet Chemo Improves Survival in Pancreatic Cancer

A medically supervised ketogenic diet (MSKD) administered alongside a triplet chemotherapy regimen of gemcitabine, nab-paclitaxel, and cisplatin significantly prolonged overall survival (OS) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).^1,2 According to results from a randomized phase 2 trial (NCT04631445) announced by Virta Health and published in Cancer, the metabolic intervention successfully enhanced the efficacy of standard-of-care cytotoxic therapy without compromising safety or patient weight.

How efficacious was adding the keto diet to chemotherapy?

The integration of the MSKD with chemotherapy resulted in a median OS of 13.7 months compared with 10.2 months for patients receiving chemotherapy with a standard diet (HR, 0.58; 95% CI, 0.25-1.37; P = .107). The median progression-free survival (PFS) was 8.5 months compared with 6.2 months (HR, 0.53; 95% CI, 0.21-1.37; P = .096).

Additionally, the disease control rate (DCR) at 9 weeks was 93.8% in the MSKD arm and 87.5% in the non-MSKD arm (P = 1.000). A best overall response of partial response (PR) was observed in 68.8% of the MSKD arm vs 31.2% of the non-MSKD arm (P = .110). Furthermore, the investigators noted that the maximum change in target lesion tumor burden did not differ between the 2 arms significantly (P = .090).

Using daily ketone tracking, nutritional ketosis (0.5-3.0 mM) was achieved by 15 of 16 patients in in the MSKD arm at any point during the study; the mean BHB levels were 0.49 (95% CI, 0.36-0.63), and the median proportion of days in ketosis was 39.4% (range, 0%-95.8%).

The MSKD arm had a significantly higher change in median BHB levels from cycle 1, day 1 to cycle 4, day 1—0.04 (IQR, –0.03 to 0.78) in the MSKD arm and –0.05 (IQR, –0.41 to –0.02)—per laboratory data obtained on the first day of every 3 cycles (P = .021).

“The mechanism of action is not fully understood, but this nutrition approach has shown in preclinical work to improve the effect of anti-cancer therapy, and that was shown in this clinical trial,” stated Erkut Borazanci, MD, director of the Oncology Research Division of HonorHealth Research Institute, and one of the study paper’s lead authors, in the press release.¹

How was the trial designed?

Investigators of the multicenter, randomized phase 2 trial enrolled 32 evaluable patients with metastatic PDAC who were randomly assigned in a 1:1 ratio to receive intravenous nab-paclitaxel, gemcitabine, and cisplatin with or without an MSKD. Patients in the MSKD arm received nutritional therapy through the Virta Health platform. Dietary recommendations were total carbohydrates at less than or equal to 30 grams per day and daily protein intake of 1.5 grams per kilogram of reference body weight; other facets of the diet were prescribed individually to maximize safety, effectiveness, and satisfaction.

Eligibility criteria required patients to be 18 years or older, have histologically or cytologically confirmed metastatic PDAC, and no prior systemic therapy for metastatic disease. Patients were required to have measurable disease per RECIST v1.1 criteria, a Karnofsky score of greater than or equal to 70%, and adequate organ function.

How safe was the MSKD diet for patients with pancreatic cancer?

The addition of the MSKD did not significantly increase the toxicity profile of the triplet chemotherapy regimen. MSKD-related adverse events (AEs) included fatigue (n = 3), constipation (n = 3), weight loss (n = 3), decreased appetite (n = 1), dehydration (n = 1), dizziness (n = 1), nausea (n = 1), and body ache (n = 1), all of which were grade 1 or 2. No patients discontinued MSKD due to AEs.

Chemotherapy-related AEs and treatment-related deaths did not occur on study. With regard to grade 3 or higher chemotherapy-related AEs, there were no significant differences between the treatment arms for anemia, diarrhea, or platelet count decrease (all P >.2).

“Pancreatic cancer is among the deadliest cancers, and improving outcomes by any margin is rare,” stated Adam Wolfberg, MD, MPH, chief medical officer of Virta, in the press release.¹ “Seeing a nutritional intervention—delivered remotely and safely—makes this level of impact extraordinary.”

References

1. Virta Health’s nutrition therapy extends survival by 34% in stage IV pancreatic cancer patinets, new clinical trial shows. News release. Virta Health. March 12, 2026. Accessed March 13, 2026. https://tinyurl.com/yhsj5jxw
2. Jameson GS, Roe DJ, Borazanci E, et al. A randomized phase II trial of gemcitabine, nab-paclitaxel, cisplatin with or without a medically supervised ketogenic diet for patients with metastatic pancreatic cancer. Cancer. 2026;132(6):1124-1135. doi:10.1002/cncr.70343