Sugar sweetened beverage consumption has been paralleled with a global epidemic of obesity and with increased rates of colorectal cancer incidence among young and middle aged adults, suggesting a potential link between these types of drinks, obesity, and colorectal cancer development.
Studies indicate excessive sugar sweetened beverage intake causes obesity, and obese men are at increased risk of colorectal cancer; but it is not clear whether SSBs contribute directly to tumor formation. Obesity and metabolic syndrome are important confounders which can indirectly affect tumour development by changing physiologic and endocrine systems in several organs.
Genetically engineered mouse models with adenomatous polyposis coli genes deleted were used to investigate direct links between cancer and HFCS. APC is a gatekeeper in colorectal cancer, deleting the protein leaves the animals predisposed to developing intestinal cancers; without it normal intestinal cells don’t stop growing or die going on to form early stage polyp tumour, and 90% of CRC patients have this type of APC mutation.
APC deficient mouse models and control mice were given free access to water sweetened with 25% HFCS composed of a glucose to fructose ratio of 45:55; both groups became obese within 2 months, and the controls developed metabolic syndrome. Another group of modified animals were syringe fed a daily amount of HFCS water equivalent to a human drinking one can of soda per day; these animals did not become obese or develop metabolic syndrome, however after 2 months they developed larger and high grade tumours than those developing in control mice with unsweetened water. Similar results were yielded in different models developing tumours in the colon rather than in the small intestines.
Researchers suggest “chronic intake of modest amounts of high fructose corn syrup facilitates tumour growth in the setting of APC deficiency independent of obesity and metabolic syndrome. Early stage tumours can occur by chance and without notice, consuming even modest amounts of HFCS can boost tumour growth and progression independently of obesity”. This may explain why increased intake of HFCS during the past three decades is correlating with increased rates of CRC in the age group of 25-50 within the USA.
While investigating the mechanism by which HFCS may promote tumour growth the APC -/- models that were syringe fed moderate amounts of HFCS were found to have had high levels of glucose and fructose in their colons, of which their tumours were effectively utilizing both types via different routes. Fructose appears to be retained by the tumours; amounts reaching the liver and serum was decreased in tumour bearing modified animals, implying fructose was being trapped by the tumour rather than being transported to the liver and blood.
Although metabolized differently fructose and glucose have similar calorific value and structures. Techniques such as radiolabelling were used to trace the fate of each in the modified animals to find fructose was being converted to fructose-1 phosphate in the tumours; the altered tumour cell metabolism and generated fatty acids supported tumour growth. “Findings suggest the role of fructose in tumours is to enhance glucose’s role of directing fatty acids synthesis, resulting abundance can be used by cancer cells to form cellular membranes and signaling molecules to grow of influence inflammation.”
Next the APC deficient mice were modified to lack genes coding for the enzyme KHK involved in fructose metabolism, or FASN which is a key enzyme in fatty acid synthesis. Modified animals deficient in either did not develop larger tumours seen in the original APC deficient mice even when fed the same. “Results reveal that CRC utilize HFCS as fuel to increase rates of tumour growth; and shows a direct molecular mechanism for correlation between consumption of sugar and colorectal cancer.”
It was concluded that “high fructose corn syrup contributes to intestinal tumorigenesis in mice by accelerating glycolysis and de novo lipogenesis, in effects that are independent of obesity and metabolic syndrome. HFCS rapidly increases levels of glucose and fructose in intestinal lumen and serum allowing intestinal tumour to take them up for growth.”
“Fructose is not essential for survival and growth of normal cells, suggesting therapies targeting fructose metabolism are worth exploring. Avoiding sugary beverages such be encouraged as much as possible instead of relying on drugs would reduce the availability of sugar in the colon.” according to the researchers. “Further research is required to determine if findings can be extrapolated to humans. Taken together findings suggest therapeutic targeting of fructose metabolism may be a strategy for slow progression of colorectal cancer.”
