Background: Metabolic reprogramming is a hallmark of cancer characterized by the switch from oxidative phosphorylation to aerobic glycolysis. Accumulating evidence suggests that reducing dietary carbohydrate intake may ameliorate metabolic reprogramming and suppress proliferation of tumor cells. However, the clinical benefit of carbohydrate restriction remains unknown.

Objective: To examine the low-carbohydrate diet and macronutrient intake after colorectal cancer diagnosis in relation to mortality among stage I-III patients.

Methods: We evaluated data on 1,303 colorectal cancer patients in the Nurses’ Health Study (1980-2012) and Health Professionals Follow-up Study (1986-2012) who completed a validated food frequency questionnaire at least one year after diagnosis. An overall low-carbohydrate-diet score was created based on the percentage of energy as carbohydrate, fat, and protein (a higher score reflects a higher intake of fat and protein and a lower intake of carbohydrate). We also created an animal- and vegetable-based low-carbohydrate-diet score on the basis of the intake from animal and vegetable food sources, respectively. We prospectively assessed the association of the low-carbohydrate-diet score and macronutrient intake with CRC-specific and overall mortality using Cox proportional hazards regression. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for a variety of potential confounding factors, including age, sex, cancer stage, grade of differentiation, subsite, alcohol use, smoking status, physical activity, body mass index, regular use of aspirin, total calorie, and intake of folate, calcium, fiber, processed red meat, and vitamin D.

Results: We observed 584 deaths, of which 132 were classified as colorectal cancer-specific deaths over a median of 10 years of follow-up. No association was found for overall and animal-based low-carbohydrate-diet score with colorectal cancer-specific mortality, with the HR comparing the highest to the lowest quartiles of 0.92 (95% CI, 0.77-1.09, P for trend=0.33) for the overall score and 0.99 (95% CI, 0.84-1.17, P for trend=0.94) for the animal-based score. In contrast, vegetable-based low-carbohydrate-diet score was associated with lower colorectal cancer-specific mortality (HR, 0.67, 95% CI, 0.53-0.85, P for trend<0.001). Replacement of carbohydrate with fat, particularly vegetable fat, was associated with lower mortality of colorectal cancer (HR per 10%-energy substitution, 0.49, 95% CI, 0.29-0.85, P for trend=0.01). Similar results were found for all-cause mortality.

Conclusion: Among patients with colorectal cancer, replacing carbohydrates with vegetable fat may reduce the risk of all-cause and colorectal cancer-specific mortality.

Citation Format: Mingyang Song, Kana Wu, Jeffrey Meyerhardt, Omer Yilmaz, Shuji Ogino, Charles Fuchs, Edward Giovannucci, Andrew T. Chan. Association of low-carbohydrate diet and macronutrient intake with colorectal cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3270. doi:10.1158/1538-7445.AM2017-3270