Case Reports

What We Have Learned About Combining a Ketogenic Diet and Chemoimmunotherapy: A Case Report and Review of Literature

Author and Disclosure Information

Background: A high-fat, moderate-protein, low-carbohydrate ketogenic diet has been reported in the literature as a treatment option for patients with cancer.

Case Presentation: A 69-year-old veteran was initially diagnosed with stage III colorectal cancer and progressed to having liver, pancreatic, and omental lymph node involvement despite completing adjuvant FOLFOX (fluorouracil, leucovorin calcium, and oxaliplatin) after surgery. The patient was treated with FOLFIRI (fluorouracil, leucovorin calcium, and irinotecan hydrochloride) and bevacizumab, followed by encorafenib and cetuximab on progression. Subsequently, he received pembrolizumab but continued to progress. The patient was later placed on trifluridine/tipiracil and bevacizumab concurrent with a ketogenic diet. Positron emission tomography and carcinoembryonic antigen levels indicated disease stabilization for 10 months. On progression, the patient was transitioned to ipilumimab and nivolumab and continued to adhere to the ketogenic diet. The patient’s disease has continued to remain stable for the past 1 year. His degree of ketosis was determined using the glucose ketone index. The patient continues to have a good quality of life during concurrent ketogenic diet and therapy.

Conclusions: This case supports the tolerability of the ketogenic diet along with chemotherapy and immunotherapy and should be considered as an adjunct to standard cancer treatment. In this report, we reviewed the latest literature about cellular mechanism of the ketogenic diet and the efficacy and relationship with chemotherapy and immunotherapy. We are about to open a ketogenic diet protocol at the Veterans Affairs Central California Health Care System in Fresno.



Originally developed for the treatment of refractory epilepsy, the ketogenic diet is distinguished by its high-fat, moderate-protein, and low-carbohydrate food program. Preclinical models provide emerging evidence that a ketogenic diet can have therapeutic potential for a broad range of cancers. The Warburg effect is a condition where cancer cells increase the uptake and fermentation of glucose to produce lactate for their metabolism, which is called aerobic glycolysis. Lactate is the key driver of cancer angiogenesis and proliferation.1,2

The ketogenic diet promotes a metabolic shift from glycolysis to mitochondrial metabolism in normal cells while cancer cells have dysfunction in their mitochondria due to damage in cellular respiration. The ketogenic diet creates a metabolic state whereby blood glucose levels are reduced, and blood ketone bodies (D-β-hydroxybutyrate and acetoacetate) are elevated. In normal cells, the ketogenic diet causes a decrease in glucose intake for glycolysis, which makes them unable to produce enough substrate to enter the tricarboxylic acid (TCA) cycle for adenosine triphosphate (ATP) production. Fatty acid oxidation plays a key role in ketone body synthesis as a “super fuel” that enter the TCA cycle as an alternative pathway to generate ATP. On the other hand, cancer cells are unable to use ketone bodies to produce ATP for energy and metabolism due to mitochondrial defects. Lack of energy subsequently leads to the inhibition of proliferation and survival of cancer cells.3,4

figure 1
The ketogenic diet also works via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, which is one of the most important intracellular pathways for tumor cells (Figure 1).

We previously published a safety and feasibility study of the Modified Atkins Diet in metastatic cancer patients after failure of chemotherapy at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System.1 None of the patients were on chemotherapy at the time of enrollment. The Modified Atkins Diet consists of 60% fat, 30% protein, and 10% carbohydrates and is more tolerable than the ketogenic diet due to higher amounts of protein. Six of 11 patients (54%) had stable disease and partial response on positron emission tomography/computed tomography (PET/CT). Our study showed that patients who lost at least 10% of their body weight had improvement in quality of life (QOL) and cancer response.1 Here we present a case of a veteran with extensive metastatic colon cancer on concurrent ketogenic diet and chemotherapy subsequently followed by concurrent ketogenic diet and immunotherapy at Veterans Affairs Central California Health Care Systems (VACCHCS) in Fresno.


A 69-year-old veteran had iron deficiency anemia (hemoglobin, 6.5 g/dL) about 5 years previously. He underwent a colonoscopy that revealed a near circumferential ulcerated mass measuring 7 cm in the transverse colon. Biopsy results showed mucinous adenocarcinoma of the colon with a foci of signet ring cells (Figure 2).

figure 2
He underwent a laparoscopic-assisted extended right hemicolectomy and partial omentectomy 2 months later. His surgical pathology revealed mucinous adenocarcinoma with 22 out of 45 lymph nodes, consistent with stage IIIC colon cancer (pT3pN2bM0).

The patient received adjuvant treatment with FOLFOX (fluorouracil, leucovorin calcium, and oxaliplatin), but within several months he developed pancreatic and worsening omental metastasis seen on PET/CT. He was then started on FOLFIRI (fluorouracil, leucovorin calcium, and irinotecan hydrochloride) plus bevacizumab 16 months after his initial diagnosis. He underwent a pancreatic mastectomy that confirmed adenocarcinoma 9 months later. Afterward, he briefly resumed FOLFIRI and bevacizumab. Next-generation sequencing testing with Foundation One CDx revealed a wild-type (WT) KRAS with a high degree of tumor mutation burden of 37 muts/Mb, BRAF V600E mutation, and high microsatellite instability (MSI-H).

figure 3
Immunohistochemistry staining showed the loss of nuclear expression of MLH1 and PMS2 (Figure 3).

Due to disease progression, the patient’s treatment was changed to encorafenib and cetuximab for 4 months before progressing again with new liver mass and mediastinal lymphadenopathy. He then received pembrolizumab for 4 months until PET/CT showed progression and his carcinoembryonic antigen (CEA) increased from 95 to 1031 ng/mL by January 2021 (Figure 4).

The patient was started on trifluridine/tipiracil, and bevacizumab while concurrently initiating the ketogenic diet in January 2021. Laboratory tests drawn after 1 week of strict dietary ketogenic diet adherence showed low-level ketosis with a glucose ketone index (GKI) of 8.2 (Table 1).

table 1
Repeat PET/CT 6 months later showed cancer stabilization. His CEA continued to decrease to 23 ng/mL despite less strict dietary adherence, which was reflected in a higher GKI of 56. He intentionally decreased his weight from 184 lb to about 160 lb and remained at this level.

A follow-up PET/CT showed disease progression along with a CEA of 94 ng/mL after 10 months of chemotherapy plus the ketogenic diet (Table 2).

table 2
Due to MSI-H, we started him on combination immunotherapy with ipilimumab and nivolumab while continuing the ketogenic diet. Adherence to the ketogenic diet has been less strict on immunotherapy; however, serial PET/CT shows cancer stabilization.

The patient continued to experience excellent QOL based on the QOL Eastern Cooperative Oncology Group (ECOG) core quality of life questionnaire (QLC-C30) forms, which he completed every 3 months. Twenty-two months after starting the ketogenic diet, the patient’s CEA increased to 293 ng/mL although PET/CT continues to show stable disease (Figures 4, 5, and 6).

figures 4-6


Recommended Reading

The surprising occupations with higher-than-expected ovarian cancer rates
Federal Practitioner
A teenage girl refuses more cancer treatment; her father disagrees
Federal Practitioner
Does timing of surgery affect rectal cancer outcomes?
Federal Practitioner
Regional Meeting Focuses on Women’s Cancer Survivorship
Federal Practitioner
Short bursts of activity may cut cancer risk
Federal Practitioner
FDA clears AI-assisted colonoscopy device
Federal Practitioner
Fatalities from breast cancer have ‘improved substantially’
Federal Practitioner
Early-life antibiotic use may raise risk of early-onset CRC
Federal Practitioner
The best CRC screening test is still this one
Federal Practitioner
Sugary drinks may up risk for liver cancer, liver disease death
Federal Practitioner