As Peter Mayes has explained it, our bodies will gradually adapt to long-term consumption of high-fructose diets, and so the “pattern of fructose metabolism” will change over time. This is why, the more fructose in the diet and the longer the period of consumption, the greater the secretion of triglycerides by the liver. Moreover, fructose apparently blocks both the metabolism of glucose in the liver and the synthesis of glucose into glycogen, the form in which the liver stores glucose locally for later use. As a result, the pancreas secretes more insulin to overcome this glucose traffic-jam at the liver, and this in turn induces the muscles to compensate by becoming more insulin resistant. The research on this fructose-induced insulin resistance was done on laboratory animals, but it confirmed what Reiser at the USDA had observed in humans and published in 1981: given sufficient time, high-fructose diets can induce high insulin levels, high blood sugar, and insulin resistance, even though in the short term fructose has little effect on either blood sugar or insulin and so a very low glycemic index. It has also been known since the 1960s that fructose elevates blood pressure more than an equivalent amount of glucose does, a phenomenon called fructose-induced hypertension.

Because sucrose and high-fructose corn syrup (HFCS-55) are both effectively half glucose and half fructose, they offer the worst of both sugars. The fructose will stimulate the liver to produce triglycerides, while the glucose will stimulate insulin secretion. And the glucose-induced insulin response in turn will prompt the liver to secrete even more triglycerides than it would from the fructose alone, while the insulin will also elevate blood pressure apart from the effect of fructose. “This is really the harmful effect of sucrose,” says Mayes, “over and above fructose alone.”

The effect of fructose on the formation of advanced glycation end-products—AGEs, the haphazard glomming together of proteins in cells and tissues—is worrisome as well. Most of the research on AGE accumulation in humans has focused on the influence of glucose, because it is the dominant sugar in the blood. Glucose, however, is the least reactive of all sugars, the one least likely to attach itself without an enzyme to a nearby protein, which is the first step in the formation of AGEs. As it turns out, however, fructose is significantly more reactive in the bloodstream than glucose, and perhaps ten times more effective than glucose at inducing the cross-linking of proteins that leads to the cellular junk of advanced glycation end-products. Fructose also leads to the formation of AGEs and cross-linked proteins that seem more resistant to the body’s disposal mechanisms than those created by glucose. It also increases markedly the oxidation of LDL particles, which appears to be a necessary step in atherosclerosis.