Recently a friend posed the question: “Could a change in carbohydrate source affect protein formation?” The context for this question was a discussion about whether the shift to corn carbohydrate (principally high-fructose corn syrup) over the last 30 years could have somehow produced the apparent rise in autism? [This latter question might just as easily involve any of several other health conditions besides autism that have also shown a steep rise over the past 30 years.] In principle, the answer to both questions is YES, but not in the way you might expect. Both of these questions really center around the effects of high-fructose corn syrup (HFCS) in our diet. Many people have recently become quite concerned about possible adverse effects from fructose consumption. The effects of fructose and glucose consumption are complicated and not completely understood. In the end, however, HFCS is probably more of concern because of its contribution to our overall increased consumption of simple sugars rather than because of any specific fructose effect.

Carbohydrate is an essential part of the human diet. Carbohydrates range from simple sugars (glucose, fructose, galactose) to complex chains of those sugars. The more complex the carbohydrate, the slower its rate of digestion. In fact, some complex carbohydrates are effectively indigestible (fiber). Because carbohydrate is so important, our bodies have highly complicated and regulated mechansims for storage and use of carbohydrate (see e.g. [1, 2]). The best known of these mechanisms is the insulin system that reacts to and controls blood sugar (blood glucose). Depending on circumstances (exercise, stress, etc), several other hormones (glucagon, epinephrine, norepinephrine, and cortisol) also help regulate carbohydrate storage and levels. All these hormones (including insulin) affect and respond to varied sugar/carbohydrate levels and also affect other aspects of physiology, including protein synthesis and fat metabolism. Though metabolized by many of the same pathways, glucose and fructose differ in some key respects. Insulin levels are highly influenced by glucose, but are only very indirectly sensitive to fructose. Fructose can be used in many (but not all) of the same ways as glucose, and fructose is generally considered to be more easily converted to fat than glucose.

Ingestion of straight glucose produces an initial abrupt rise in blood glucose, followed by a rise in insulin. The elevated insulin induces liver and muscle to store glucose in the form of glycogen and stimulates protein synthesis and eventually fat synthesis. As blood glucose levels begin to drop, insulin levels also drop and glucagon levels rise. This inhibits glycogen synthesis, protein synthesis, and fat synthesis, and also stimulates conversion of glycogen back to glucose. In addition there are specific effects of glucagon on certain enzymatic activities. In contrast, ingested straight fructose can be readily converted to fat, can be converted to glucose in the liver (and then used any way glucose is used) or can be directly metabolized for energy (but not stored as glycogen) by most other cells in the body. Differences in gene expression are observed as glucose concentrations change. Nakamura and coworkers [3] have shown that higher than normal fructose proportions gives rise to complex gene expression in the liver. Because of these complicated regulatory differences, a shift from glucose to fructose consumption could in theory cause changes in protein expression that would be relevant to some disease states. (This has not actually been demonstrated.)

In terms of relative fructose/glucose metabolism, however, HFCS makes a poor villain. The overwhelming majority of caloric sweeteners (and even fruit) have a roughly 50:50 glucose/fructose ratio. Sucrose (table sugar) digests quickly to equal parts fructose and glucose. Honey, maple sugar, cane sugar, etc. all contain ratios of fructose to glucose similar to that in sucrose. The HFCS used in the overwhelming majority of foods is 55% fructose and 40-45% glucose. [Higher ratios are achieved during HFCS production but these are only used in the food industry for specialized confections.] This 55:45 ratio is not appreciably different from the ratio found in most caloric sweeteners (see also “High Fructose Corn Syrup Myths”).

Total consumption of caloric sweeteners is a more plausible (though still unproven) explanation for some health ills which have emerged over the last thirty years. During that time, per capita consumption of caloric sweeteners has increased in the USA by forty percent. This increase is mostly a consequence of higher living standard and decreased relative cost of caloric sweeteners. This latter effect IS largely attributable to HFCS. Prior to the 1950’s, sugar and other caloric sweeteners were generally regarded as ‘expensive’. After its introduction, HFCS became widely used in the food industry principally BECAUSE it was significantly less expensive than other sweeteners. This also made it possible for the food industry to cheaply act on their observation that adding sweetener to almost any food made it more desirable. Thus the economics of HFCS (rather than its biochemistry) could be partially responsible for some of our modern health problems.

Humans have been consuming roughly 50:50 glucose and fructose for tens of thousands of years. The advent of high-fructose corn syrup hasn’t changed that. During most of human history, sweeteners were rare and used only in small amounts. What IS new is the amount of glucose/fructose in our food, and high-fructose corn syrup may well be a culprit. Instead of fixating on imaginary changes in the proportion of fructose to glucose in our diet, we need to focus on the overall amount of caloric sweetener we consume.

1. J. M. Berg, J. L. Tymoczko, and L. Stryer, Biochemistry, 6th ed. New York, NY: W. H. Freeman and Company, 2006.
2. A. L. Lehninger, D. L. Nelson, and M. M. Cox, Principles of Biochemistry, 2nd ed. New York, NY: Worth Publishers, 1993.
3. H-Y. Koo, M. A. Wallig, B. H. Chung, T. Y. Nara, B. H. S. Cho, and M. T. Nakamura, “Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver” Biochim. Biophys. Acta, vol. 1782, no. 5, pp. 341-348, May 2008.