Today it is common to refer to sugar and high-fructose corn syrup as "sugary ingredients." Sugar produced from sugar cane or sugar beets is called sucrose, which is a chemical compound in which glucose and fructose -- two different six-carbon, so-called simple sugars -- are chemically bound together.

When one consumes food containing sucrose -- a disaccharide -- for the most part, the sucrose passes through the digestive system unchanged until it reaches the small intestine where it is broken down through glycolysis into glucose and fructose which are then available to enter the blood stream. Until the 1970s sucrose was the primary "sugary ingredient" used to sweeten foods and beverages. Today it has become rare to find sugar listed as an ingredient on food and beverage labels, even on a food such as candy which is typically associated with sugar.

The substitution of high-fructose corn syrup (HFCS) for sugar in foods and beverages began in the 1970s and its use has grown steadily. Today it is the dominant sweetener used in foods and beverages produced in the United States. HFCS is made from corn starch -- a natural polymer of glucose in which glucose molecules are chemically bound together forming large chains. HFCS is a manufactured sweetener -- a liquid mixture produced from starch, which after hydrolysis, is subjected to an enzymatic process whereby some glucose >molecules are transformed at the molecular level into fructose.

HFCS contains no sucrose and is a very different product from common sugar; it is similar in that it provides equivalent sweetening capacity and it comprises an equivalent proportion of glucose and fructose that sugar has after it undergoes glycolysis in the body. When one consumes foods and beverages sweetened with HFCS, glucose and fructose are available as simple sugars to be metabolized as soon as they become present in the mouth. This is a significant change in the diet. Prior to the introduction of HFCS neither "free" glucose nor "free" fructose were significant constituents of the diet, e.g., an exception is fructose that is present in honey and some fruits.

Tests using radioactive glucose solution are often used to determine the extent of cancer present in cancer patients. The glucose is rapidly taken up by tumors that may be present in the body. Research has shown that both glucose and fructose "feed" or promote the growth of cancers in the body. However, prior to the development and substitution of HFCS for common sugar, both glucose and fructose were not available until sugar reached the small intestine where it had the potential to be broken down into glucose and fructose and then enter the blood stream. Fructose is then metabolized in the liver.

Researchers at UCLA found that following ingestion of a liquid solution of glucose and fructose by healthy volunteers, the fructose level in the blood remained elevated for two or more hours, having the potential to be transported throughout the circulatory system. In contrast, blood glucose levels quickly returned to fasting levels as a result of the body's regulatory system.

Thus, it appears the metabolism of "free" fructose present in HFCS as an ingredient in foods and beverages may possibly travel different pathways from fructose derived from the glycolysis of sucrose in the small intestine.
The contribution of fructose to nucleic acid synthesis was found to be considerably greater than for glucose in pancreatic cancer research directed by Dr. Anthony Heaney at UCLA and reported by Liu et al. in Cancer Research, 70(15) 6368-6376 2010 AACR (American Association of Cancer Research). The researchers found that fructose was preferentially metabolized at 250% higher rates than glucose in the synthesis of nucleic acids, RNA and DNA, contributing to increased capacity for tumor proliferation and possibly metastasis.

The increased availability of free fructose and glucose particularly from HFCS in a liquid form as in soft drinks appears to pose a large risk to consumers who may have cancer or may develop cancer, e.g., in the mouth or the lining of the esophagus or stomach.

Increased consumption of HFCS may have a significant impact on both the increasing incidence and the earlier onset of cancer in the U.S. In view of the UCLA research, it appears that it would be wise for the National Institutes of Health (NIH) to fund research efforts to provide further elucidation of the mechanism for the metabolism of "free" fructose and glucose in the digestive system, e.g., in the mouth, the throat, the esophagus, the stomach, the breasts, etc.

In Johnson &∓ Johnson's 2011 Annual Report, Dr. Bill Hait, Global Head, Janssen Research & Development, states, "The tumor is no longer viewed as a tumor cell living in isolation. A tumor cell is very close to its environment, and it's using its environment to grow better."

In the U.S. prior to the 1970s breast cancer was primarily a disease of post-menopausal women. It is reported that this is still so in Japan where typical Japanese beverages are not sweetened with HFCS. In the U.S. it has become common for women in their 30's, 40's and 50's to develop breast cancer. In a Singapore Chinese study comparing consumption of typical Chinese-style fruit-based beverages and American-style soft drinks, e.g., colas, etc., a significant difference was reported for increased incidence of pancreatic cancer for American-style colas, etc. which typically contain HFCS.

In a 14-year study, consumers of two or more soft drinks per week had a statistically significant risk of pancreatic cancer at the 95% level compared to participants who did not consume soft drinks (Cancer Epidemiology, Biomarkers and Prevention; 19(2): 447-55,2010, AACR). In this study it appears that HFCS may have been a significant factor since, if sweetened, it is likely the Chinese-style fruit-based beverages were sweetened with sugar. In a similar Swedish study of persons who consumed two or more soft drinks per week with those consuming no soft drinks, a 93% significantly greater risk of pancreatic cancer was reported.

Since HFCS is so pervasive in the diet of U.S. consumers and this change is becoming similar in many other countries, it is increasingly difficult to include HFCS as a variable in epidemiological biomarker studies such as those that NIH is currently funding. It also appears that the difference between sugar and HFCS might be a factor influencing the  increasing incidence of diabetes and obesity. Could the fact that the UCLA researchers found that fructose tends to circulate in the blood stream for an extended period of time after ingestion, thereby providing the potential to travel to the brain, be a factor in the increasing incidence of Alzheimer's disease, Parkinson's disease and related diseases.

When I addressed some of these ideas in a "Provocative Question" submitted to the NIH website at 6:12 PM, Saturday, October 22, 2011, I received an email the following Monday morning at 9:36 AM from Maureen Johnson (NIH/NCI) stating, "At this time we are no longer accepting questions to the Provocative Initiatives website. In the future we may open it up again." A second email received October 25 stated "Thank you Sandra for your question but we have closed the website to new questions at the current time."

After receiving the emails, I searched the AACR website and studied recent research on HFCS and fructose.

There are many unanswered questions relating to the role of HFCS and fructose in the diet. The research, reported by Lui, et al., supports the need for additional research and indicates free fructose most likely has a significant impact on cancer development. This information should be made available to cancer researchers and food/beverage producers so they have a better understanding of the significant difference between HFCS and sugar.
Based on the results of recent research on fructose, differences in the consumption of HFCS by cancer patients who take part in clinical trials of proposed new drugs could conceivably influence the results of these studies.

The possibility that HFCS may contribute to cancer development should also be made available to consumers so that they can decide whether they want to continue to purchase foods and beverages that contain HFCS -- the "sugary ingredient" that is used in most sweetened foods and beverages marketed to consumers in the United States.

By Sandra Leith McGowan, MD, St. Michaels

Reprinted from Science Codex