Reference
Aune D, Chan DSM, Vieira AR, et al. Dietary fructose, carbohydrates, glycemic indices and pancreatic cancer risk: a systemic review and meta-analysis of cohort studies. Ann Oncol. 2012;23(10):2536-2546.
Design
Systemic review and meta analysis of 10 cohort studies (13 publications), one of which was a case cohort study
Participants
1,156,512 participants
Study Parameters Assessed
Glycemic index (GI) or glycemic load (GL) and pancreatic cancer risk
Key Findings
A diet high in fructose was associated with an increase in the risk of pancreatic cancer [summary RR=1.22 (95% CI: 1.08–1.37) per 25 g/day]. However, no statistically significant association was found between intakes of total carbohydrates, sucrose glycemic index, or glycemic load and pancreatic cancer.
Practice Implications
Pancreatic cancer is the 4th leading cause of cancer death in the United States.1 The National Cancer Institute estimates in the year 2012, there will be 43,920 new cases of pancreatic cancer—and 37,390 deaths.2 Currently there are no established methods for screening or early detection; thus primary prevention by altering modifiable risk factors is probably the most effective way of reducing the pancreatic cancer burden. With the exception of tobacco smoking,3 diabetes,4 and obesity,5 relatively few modifiable risk factors have been established.
In the meta-analysis by Aune et al, one modifiable factor becomes clear: the consumption of the monosaccharide fructose.6 Naturally occurring in fruits and vegetables, fructose also occurs in various manufactured forms such as high fructose corn syrup (in soft drinks, processed foods and candy) and agave nectar (marketed as a healthy alternative to high fructose corn syrup). The meta analysis observes a linear dose-response increase in pancreatic cancer risk with each increment of 25 grams/day of fructose.7
The U.S. Department of Agriculture estimates the average American consumes more than 65.6 pounds of high fructose corn syrup per year.8 The third National Health and Nutrition Examination Survey reported that more than 10% of America’s daily calories come from fructose—of which the largest part comes from sweetened beverages.9
Dietary fructose can promote cancer growth by a number of mechanisms, including altered cellular metabolism, increased reactive oxygen species, DNA damage, and inflammation.10 Epidemiological studies have reported positive associations between fructose intake and type 2 diabetes and obesity in humans, both of which are established risk factors for pancreatic cancer.11-13
The metabolism of fructose differs from that of other carbohydrates. Fructose is used preferentially in the synthesis of nucleic acids. The synthesis of nucleic acids and nucleotides is necessary for proliferating tissues, especially cancer cells. The contribution of fructose to nucleic acid synthesis through the pentose phosphate pathway (catalyzed by transketolase) is greater than that of glucose. Suppression of transketolase-like protein decreases cancer cell proliferation; inversely, activation of transketolase stimulates cancer cell proliferation.14 The enhanced protein synthesis caused by fructose appears to promote a more aggressive cancer phenotype.15
Data collected for 14 years from The Singapore Chinese Health Study using a 648,387 person-years cohort found that individuals who consumed 2 or more soft drinks per week were twice as likely to develop pancreatic cancer.16 Similarly, a paper published in the American Journal of Clinical Nutrition, using a cohort of 77,797 people followed for 7 years revealed a 93% increase in the occurrence of pancreatic cancer in those who drank 2 or more soft drinks per day.17
Despite the fact that naturally occurring fructose (in fruits and vegetables) is chemically identical to high fructose corn syrup and agave (in sweets and soft drinks), there is a marked difference in the delivery systems.
However, data regarding the intake of fruits and vegetables indicates a reduced risk of pancreatic cancer.18 Despite the fact that naturally occurring fructose (in fruits and vegetables) is chemically identical to high fructose corn syrup and agave (in sweets and soft drinks), there is a marked difference in the delivery systems. Fruits and vegetables contain quantities of fiber and antioxidants that seem to have an inverse effect on pancreatic cancer risk.19
Addressing the type, variety, and quantity of fructose intake with patients is a simple practice and can potentially save lives.
For more research involving integrative oncology, click here.
