By defining carbohydrate foods as good or bad on the basis of their glycemic index, diabetologists and public-health authorities effectively misdiagnosed the impact of fructose on human health. The key is the influence of glucose or fructose not on blood sugar but on the liver. Glucose goes directly into the bloodstream and is taken up by tissues and organs to use as energy; only 30–40 percent passes through the liver. Fructose passes directly to the liver, where it is metabolized almost exclusively. As a result, fructose “constitutes a metabolic load targeted on the liver,” the Israeli diabetologist Eleazar Shafrir says, and the liver responds by converting it into triglycerides—fat—and then shipping it out on lipoproteins for storage. The more fructose in the diet, the higher the subsequent triglyceride levels in the blood.*58

The research on this fructose-induced lipogenesis, as it is technically known, was carried out primarily by Peter Mayes, a biochemist at King’s College Medical School in London; by Shafrir at Hebrew University–Hadassah Medical School in Jerusalem; and by Sheldon Reiser and his colleagues at the USDA Carbohydrate Nutrition Laboratory in Maryland. They began in the late 1960s and worked on it through the early 1980s. “In the 1980s,” says Judith Hallfrisch, who worked with Reiser at the USDA, “people didn’t even believe that elevated triglycerides were a risk factor for cardiovascular disease. So they didn’t care that much about the increase in triglycerides. Everything was cholesterol.” (Although sugar also seemed to raise cholesterol levels, particularly LDL, as would be expected for any nutrient that increased triglyceride synthesis in the liver. In 1992, John Bantle reported that LDL cholesterol in diabetic patients was elevated more than 10 percent on a high-fructose diet after a month, which is comparable to what can be achieved by saturated fats.)

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.