title: A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation.
abstract: Since cancer cells depend on glucose more than normal cells, we compared the effects of low carbohydrate (CHO) diets to a Western diet on the growth rate of tumors in mice. To avoid caloric restriction-induced effects, we designed the low CHO diets isocaloric with the Western diet by increasing protein rather than fat levels because of the reported tumor-promoting effects of high fat and the immune-stimulating effects of high protein. We found that both murine and human carcinomas grew slower in mice on diets containing low amylose CHO and high protein compared with a Western diet characterized by relatively high CHO and low protein. There was no weight difference between the tumor-bearing mice on the low CHO or Western diets. Additionally, the low CHO-fed mice exhibited lower blood glucose, insulin, and lactate levels. Additive antitumor effects with the low CHO diets were observed with the mTOR inhibitor CCI-779 and especially with the COX-2 inhibitor Celebrex, a potent anti-inflammatory drug. Strikingly, in a genetically engineered mouse model of HER-2/neu-induced mammary cancer, tumor penetrance in mice on a Western diet was nearly 50% by the age of 1 year whereas no tumors were detected in mice on the low CHO diet. This difference was associated with weight gains in mice on the Western diet not observed in mice on the low CHO diet. Moreover, whereas only 1 mouse on the Western diet achieved a normal life span, due to cancer-associated deaths, more than 50% of the mice on the low CHO diet reached or exceeded the normal life span. Taken together, our findings offer a compelling preclinical illustration of the ability of a low CHO diet in not only restricting weight gain but also cancer development and progression.
authors.affiliation: The Terry Fox Laboratory, BC Cancer Research Centre, BC Cancer Agency, Department of Pediatrics, Division of Gastroenterology, BC Children's Hospital & University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Ho
authors.forename: Kelvin
authors.initials: K
authors.lastname: Leung
authors.forename: Anderson
authors.initials: A
authors.lastname: Hsu
authors.forename: Beryl
authors.initials: B
authors.lastname: Luk
authors.forename: June
authors.initials: J
authors.lastname: Lai
authors.forename: Sung Yuan
authors.initials: SY
authors.lastname: Shen
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Minchinton
authors.forename: Dawn
authors.initials: D
authors.lastname: Waterhouse
authors.forename: Marcel B
authors.initials: MB
authors.lastname: Bally
authors.forename: Wendy
authors.initials: W
authors.lastname: Lin
authors.forename: Brad H
authors.initials: BH
authors.lastname: Nelson
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sly
authors.forename: Gerald
authors.initials: G
authors.lastname: Krystal
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000517:prevention & control*; D048708:Cell Growth Processes / Q000502:physiology; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D007328:Insulin; D019344:Lactic Acid