weight—it is often referred to as “fruit sugar” and appears somehow healthier simply by virtue of that association. And, of course, fructose was perceived as healthy because it does not elevate blood sugar and has a low glycemic index.
As a consequence, high-fructose corn syrup could be used as the primary sweetener, and often the primary source of calories, in products that had the outward appearance of being healthy or natural, or were advertised as such, without revealing the products to be little more than sugar, water, and chemical flavoring. This included sports drinks such as Gatorade, the fruit juices and teas such as Snapple that appeared nationwide beginning in the late 1980s, and low-fat yogurts, which also exploded in popularity with the condemnation of fat in the diet.
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.
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.
This research on the health effects of fructose began to coalesce in the mid-1980s, just as nutritionists were disseminating the notion that fructose was particularly harmless because of its low glycemic index. And this official opinion has proven hard to sway.
Take, for example, the British Committee on Medical Aspects of Food Policy (known commonly as COMA), which in 1989 released a report entitled Dietary Sugars and Human Disease, authored by a dozen of the nation’s leading nutritionists, physiologists, and biochemists and chaired by Harry Keen, who is among the most renowned British diabetologists. The COMA report discussed the evidence, including the research of Reiser, Reaven, and others, and then concluded that the health effects of sugar were insignificant. The report did so, however, with a series of contradictory assumptions. First, Keen and his colleagues concluded that the implications of fructose-induced insulin resistance and elevated triglycerides are limited to a “relatively small group of people with metabolic disorders [that] includes people with diabetes and those with certain rare inherited disorders.” And so, with the exception of this small percentage of the population, they noted, yearly sugar consumption at 1986 levels, estimated at roughly a hundred pounds per capita in the United Kingdom, “carries no special metabolic risks.” On the other hand, they then explained, sugar consumption does carry risk for those “members of the population consuming more than about 200 g per day,” which is 160 pounds per year, or only slightly more (.4 ounce per day) than what the average American was eating in the year 2000 (not the top 10–20 percent, but the average). They next suggested that those individuals with high triglycerides, a proportion that remains unspecified but might constitute the great majority of all individuals with coronary-artery disease, should restrict their consumption of added sugars to twenty to forty pounds per year, or equivalent to the amount consumed in the U.K. in the early years of the Victorian era.
All of this was then summed up in the single statement—echoing the sentiments of the FDA Task Force, the National Academy of Sciences Diet and Health report, and The Surgeon General’s Report on Nutrition and Health, which preceded it—that dietary sugar consumption could not be held responsible for causing disease: “The panel concluded that current consumption of sugars, particularly sucrose, played no direct causal role in the development of cardiovascular…disease, of essential hypertension, or of diabetes mellitus….”
Four years later, The American Journal of Clinical Nutrition dedicated an entire issue to the deleterious effects of dietary fructose. A common refrain throughout the issue was the need for research that would establish at what level of sugar consumption the effects discussed—the elevation of blood pressure and triglycerides, increased insulin resistance, and even accelerated formation of advanced glycation end-products— would lead to disease. “Further studies are clearly needed to determine the metabolic alteration that may take place during chronic fructose or sucrose feeding,” as the Swiss physiologists Luc Tappy and Eric Jequier wrote.
In 2002, the Institute of Medicine of the National Academies of Science released its two-volume report on
