Colorectal cancer therapy and nutrition: From ultra-processed consumption to metabolic reprogramming

Table 1 Evidence from animal models: Fasting and caloric restriction in colorectal cancer

Ref.	Type of intervention	Main metabolic findings	Effects on tumor/immunity
Bensalem et al[59], 2025 and Teong et al[72], 2023	Intermittent fasting (ADF: 5:2, iTRE)	blood glucose reduction, insulin reduction, ketone bodies increase, autophagy increase	Tumor growth reduction, metabolic environment less favorable to proliferation
Tsuda et al[77], 2020	Prolonged overnight fast	Synchronization of circadian rhythms, insulin sensitivity increase	Systemic inflammation reduction, cellular repair increase
Luo et al[17], 2024; Nan et al[18], 2025; and Zhong et al[83], 2023	Fasting mimicking diet (cycles)	Glucose reduction, insulin reduction, IGF-1 reduction, ketone bodies increase, expression of cellular stress genes increase	Tumor growth reduction, proliferation reduction, angiogenesis reduction, CD8+ infiltration, microbiota remodeling increase
Vidoni et al[88], 2021 and Caprara et al[89], 2025	Caloric restriction (20%-40%)	Glucose reduction, IGF-1 reduction, mTOR reduction, AMPK increase, autophagy increase	Cell proliferation reduction, apoptosis increase, genomic repair increase, inflammation reduction, stress resistance increase

ADF: Alternate-day fasting; iTRE: Intermittent time restricted eating.

Table 2 Clinical evidence: Fasting and caloric restriction in colorectal cancer

Ref	Intervention	Population/Protocol	Metabolic effects	Clinical or therapeutic impact
Bensalem et al[59], 2025 and Teong et al[72], 2023	Intermittent fasting/TRE (iTRE)	Clinical trials in cancer patients	Blood glucose reduction, insulin reduction, ketone bodies increase, autophagy increase	Metabolic environment less favorable to tumor proliferation, with potential response to therapies increase
Tsuda et al[77], 2020; Khodabakhshi et al[78], 2021; and Mindikoglu et al[79], 2020	Prolonged overnight fasting (> 13 hours)	CRC patient cohorts	Insulin sensitivity, systemic inflammation reduction increase	Risk of tumor recurrence reduction
Vernieri et al[19], 2022; Zhong et al[83], 2023; Ligorio et al[84], 2022; and Ligorio et al[85], 2025	Fasting mimicking diet	Clinical trials in CRC	Glucose reduction, insulin reduction, IGF-1 reduction, ketone bodies increase; L-arginine in tumor tissues increase	Favorable safety profile; response to chemotherapy increase; CD8+ infiltration increase; microbiota remodeling; abundance of B. pseudolongum increase; improved patient prognosis
Bustamante-Marin et al[70], 2023 and Vidoni et al[88], 2021	Moderate caloric restriction (20%-40%)	Clinical trials in cancer patients	Glucose reduction, insulin reduction, IGF-1 reduction, insulin sensitivity increase, autophagy increase	Potential for therapeutic response and tumor progression reduction increase

TRE: Time-restricted eating; iTRE: Intermittent time restricted eating; CRC: Colorectal cancer; B. pseudolongum: Bifidobacterium pseudolongum.

Table 3 Characteristics and main findings of a preclinical study on the ketogenic diet in colorectal cancer

Ref.	Model	Dietary intervention	Main metabolic findings
Montroseand Galluzzi[113], 2022	Immunocompetent and immunodeficient mice, MC38 and CT26 strains (sex not specified)	Ketogenic diet	Effective reduction of MC38 tumor growth; increased sensitivity to immune checkpoint inhibitors (PD-1)
Tsenkova et al[114], 2025	C57BL/6 mice (no sex specified)	Ketogenic diet and stearic acid-supplemented diet	Reduction of colonic tumor burden; induction of apoptosis in cancer cells; ketogenic diet altered the composition and function of the microbiota, enriching stearic acid producers and reducing consumers
Sun et al[115], 2022	Male BALB/c mice	Ketogenic diet	Inhibition of tumor growth; increased antitumor immune response; attenuation of immunosuppression; inhibition of angiogenesis
Jiang et al[116], 2024	Male C57BL/6 mice	Ketogenic diet + chemotherapy	Reduced tumor growth; increased apoptosis; increased sensitivity to chemotherapy

Table 4 Characteristics and main clinical findings on the ketogenic diet in colorectal cancer

Ref.	Population/protocol	Dietary intervention	Clinical or therapeutic impact
Klement et al[117], 2021	Recurrent stage IV colon cancer	Chemotherapy combined with a modified ketogenic diet	Response rate of 60%; disease control rate of 70%; complete response rate of 50%; trend toward longer overall survival in the responder group (50 months vs 32.5 months in the control group)
Egashira et al[118], 2023	Rectal cancer	Ketogenic diet based on natural foods and standard diet during radiotherapy	Reduction in body weight and fat mass; preservation of skeletal muscle mass; tendency toward greater pathological tumor response (higher degree of Dworak regression and higher percentage of near-complete responses)