America the Fat: Fast Food and Fructose

Few of us associate fructose with hypertension. However, there is increasing evidence that it may play a significant role in the epidemic of human obesity and the metabolic syndrome, conditions closely associated with elevated blood pressure. Two recently published books, both by journalists, throw new light on the origins of the epidemic. The first is Fat Land(Houghton Mifflin), by Greg Critser. The second is Fast Food Nation(Perennial‐Harper Collins), by Eric Schlosser. Both books place a major emphasis on the growth of the fast‐food industry, although Critser's thesis is that the explanation is simply one of supply and demand. The epidemic really started to take off in the 1970s. At that time Earl Butz, President Nixon's secretary of agriculture, eased restriction on farm products, resulting in a major increase in production, particularly of corn, and in farm income. A parallel development was the invention of high fructose corn syrup (HFCS), which is six times sweeter than cane sugar and protects frozen foods from freezer burn. Not surprisingly, the use of HFCS has risen progressively since the 1970s, as we shall see.

Another trend that began at about the same time was “supersizing”—the introduction of ever larger portion sizes in restaurants. This is attributed to an executive of McDonald's Corporation who started in the movie theater business, where much of the profit is from snacks like popcorn and soda. He had the idea that people consider it greedy to get second helpings of food, while double‐sized (“jumbo”) portions are not a problem. From a business point of view, the introduction of supersized portions makes good sense because the cost of the raw materials is relatively cheap, so the additional charge for the larger portions generates more profit. In 1960, the number of calories in a standard helping of french fries at McDonald's was 200; in the '70s it was 320; in the '90s, 450; and today it is 610. According to the US Department of Agriculture, the production of food has increased from 3300 calories per person per day in 1970 to 3800 calories in 1994. Over the same period the average intake increased from 1876 calories a day to 2043.

Two alarming trends in the school system have contributed to the epidemic of childhood obesity, both originally adopted for economic reasons. The first is the abandonment of the school cafeteria in favor of fast‐food companies like Pizza Hut. The second is the decline of physical education classes. These were triggered by the passage of Proposition 13 in California in 1979, which placed a cap on the increases of property taxes. A particularly insidious development was the awarding of exclusive contracts to corporations like Coca‐Cola, that were enabled to place advertisements for their products throughout schools in exchange for substantial payments that the schools could use as they saw fit. Schlosser describes a deal that Coca‐Cola made with a school district in Colorado Springs, CO, by which the schools would get paid if they sold at least 70,000 cases of Coke a year. When sales fell short, the principal instructed teachers to allow the children to bring sodas into the classrooms and ordered the vending machines to be moved to more prominent places.

A recent analysis of 4746 adolescents in 31 urban secondary schools found a remarkable correlation between the frequency of fast‐food consumption and daily calorie intake. ¹ Those who never ate at fast‐food restaurants had an average daily intake of 1952 calories; those who went once or twice a week (50% of the sample) had a daily intake of 2192 calories; and those who went three times or more (another 20% of the sample) had an intake of 2752 calories. Another study used the data from three large national surveys conducted in 1977,1989, and 1996 to assess people's eating habits. ² For almost every type of food examined, consumption increased. Total energy intake increased from 1791 calories in 1977 to 1985 in 1996, but there was a much greater increase in the proportion of this that came from snacks (203 calories in 1977 vs. 351 in 1996). Portion sizes also increased, by far the biggest change being in soft drinks. For most of the foods surveyed, fast‐food establishments served the largest sizes, and restaurants the smallest, but the increase of portion sizes was also evident in food eaten at home.

This brings us back to fructose. Today, most soft drinks, whether they be sodas like Coca‐Cola or fruit juices like cranberry juice, are sweetened with HFCS. Between 1970 and 1997 the consumption of fructose (almost all of it as HFCS) increased by more than a hundred‐fold, while the use of sucrose fell by about a third. ³ This change parallels the change in the prevalence of obesity in the United States. Association is not the same as causality, but there are actually good reasons why there may be a connection. A key point is that fructose is metabolized differently than glucose (of which sucrose is, of course, the usual source). Both glucose and fructose are metabolized in the liver. ³ The metabolism of glucose is limited by two factors: the capacity of the liver to store glycogen and a negative feedback loop driven by ATP and citrate, which inhibit the enzyme phosphofructokinase, a critical step in the glycolytic pathway. In contrast, fructose bypasses the phosphofructokinase step, and it can be metabolized, unchecked, to acetyl CoA and glycerol 3‐phosphate, the building blocks for lipid production by the liver. Human studies have shown that fructose ingestion results in an increase of lipogenesis, whereas consuming the same amount of sucrose does not. ³

Another important difference is that, in contrast to glucose, fructose does not stimulate the secretion of either insulin or leptin, both of which regulate body weight. ⁴ , ⁵ One of the widely quoted misconceptions of diets such as The Atkins Diet and The Zone is that insulin is the villain because of its well‐known property of stimulating lipid synthesis. However, insulin also has opposite effects that are mediated via the central nervous system: when insulin is administered directly into the CNS of animals, food intake is reduced, and knocking out the CNS insulin receptors in mice results in hyperphagia and obesity. ⁶ Leptin also inhibits food intake, and in fact, insulin and leptin may share a common pathway in the brain. ⁷

It may seem paradoxical that if fructose does not increase insulin secretion over the short term, feeding high fructose diets to rats or dogs can induce insulin resistance, a condition characterized by hyperinsulinemia. ⁸ , ⁹ This may be mediated indirectly, perhaps as a result of the increased levels of nonesterified fatty acids or by a reduced production of adiponectin from fat cells. ¹⁰

It is also well established that high fructose diets can induce hypertension in experimental animals, and in fact, fructose‐fed rats are becoming a widely used model for testing new antihypertensive drugs. ³ , ¹¹ When normal Sprague‐Dawley rats are fed a high fructose diet, they develop hypertension that is accompanied by insulin resistance, hyperinsulinemia, and hypertriglyceridemia. ¹² The same thing can be demonstrated in dogs. ⁹ This hypertension is not accompanied by obesity. ⁹ There is some evidence that insulin plays a causal role here, since restoring insulin sensitivity by somatostatin ¹³ or by exercise training ¹⁴ decreases the blood pressure. The mechanisms underlying the hypertension are not well understood, but the sympathetic nervous system appears to be involved because sympathectomized rats do not develop either hypertension or hyperinsulinemia when fed fructose. ¹⁵ Salt sensitivity also plays a role, since in some strains of rats, fructose induces hypertension only when combined with a high salt intake. ¹⁶ Whether fructose contributes to human hypertension has not been studied yet, but the analogies between the animal models of fructose‐induced hypertension and the metabolic syndrome in man are striking. It surely behooves us to find out.