respectively, 21% of energy as fructose, 23% of energy as sucrose, and almost all carbohydrate energy as starch with less than 5% of energy derived from fructose and sucrose. All meals were prepared in a metabolic kitchen and provided to subjects. The fructose diet resulted in significantly lower 1- and 2-hour postprandial plasma glucose levels, overall mean plasma glucose, and urinary glucose excretion than did the starch diet. The reductions in mean plasma glucose with the fructose diet were 24% in type-1 diabetic subjects and 7% in type-2 diabetic subjects. Of note, the fructose diet increased postprandial lactate. There were no differences between the sucrose and starch diets in any of the measure of glycemic control in either subject group.
It next seemed important to extend the period of dietary intervention with fructose to see if beneficial effects on glycemia persisted and to look for potential adverse effects. Accordingly, we compared isocaloric high fructose (20% of energy derived from fructose) and high starch diets (less than 3% of energy derived from fructose) in 6 type-1 and 12 type-2 diabetic subjects using a crossover design . Both study diets were composed of common foods. All meals were prepared in a metabolic kitchen and provided to subjects for 28 days. The diets were well received by all subjects. Mean plasma glucose, urine glucose and serum glycosylated albumin were all lower during the fructose diet than during the starch diet. On day 28 of the fructose diet, mean plasma glucose was 13% lower than on day 28 of the starch diet. However, of concern, fasting serum LDL cholesterol on day 28 of the fructose diet was 11% higher than the corresponding value for LDL cholesterol on day 28 of the starch diet.
Thus, a diet in which fructose was substituted for other carbohydrates was pleasant to eat and resulted in reduced glycemia in people with diabetes but appeared to have an adverse effect on serum LDL cholesterol. This raised concern about fructose as a sweetening agent in the diabetic diet. This finding also raised concern about the potential effects of dietary fructose in the general population since, in the United States and many other countries, fructose is a significant source of dietary energy . Several studies did not find adverse effects of dietary fructose on serum lipids in healthy subjects [17-19]. However, these studies either compared fructose to sucrose or were outpatient studies that did not provide meals to subjects. Since sucrose is composed of 50% fructose, it is not an optimal reference. Moreover, rigorous control of nutrient intake requires the provision of meals. Thus, these studies may not be reliable in assessing the effects of dietary fructose on serum lipids.
Two studies which compared a high fructose diet to a diet nearly devoid of fructose and established rigorous control of nutrient intake by providing all food to subjects both reported adverse effects of fructose on serum lipids [20, 21]. Hallfrisch et al.  reported that high fructose diets consumed for 5 weeks increased fasting plasma LDL cholesterol in healthy and hyperinsulinemic men and increased fasting plasma triglycerides in hyperinsulinemic men. Reiser et al.  found that a high fructose diet consumed for 5 weeks increased fasting plasma LDL cholesterol in healthy men and fasting plasma triglycerides in both healthy and hyperinsulinemic men. These two well-done studies suggested that dietary fructose does adversely affect serum lipids, at least in men. Women were not included in either study.
In an effort to gain additional insight into the effects of fructose on plasma lipids, we compared high and low fructose diets in 24 healthy volunteers (12 men and 12 women; 6 of each gender age <40 years and 6 of each gender age >40 years) . All subjects consumed two isocaloric diets for 6 weeks. One diet provided 17% of energy as fructose. The other diet was sweetened with glucose and was nearly devoid of fructose. Diet order was assigned randomly using a balanced, crossover design. Both diets were composed of common foods and contained nearly identical amounts of carbohydrate, protein, fat, fiber, cholesterol and saturated, monounsaturated and polyunsaturated fatty acids. All meals were prepared in the metabolic kitchen of the University of Minnesota General Clinical Research Center. The fructose diet resulted in higher fasting total and LDL plasma cholesterol at day 28 but this effect did not persist at day 42 (table 3). The plasma triglyceride responses to the diets differed by gender. The fructose diet had no significant effect on fasting or postprandial plasma triglycerides in women (table 3, fig. 2). However, in men, the fructose diet produced significantly higher fasting and postprandial plasma triglycerides. This effect persisted through day 42. On day 42 of the fructose diet, daylong plasma triglycerides (estimated by determining the area under the response curves) in men was 32% greater than during the glucose diet. We concluded that diets high in added fructose may be undesirable, particularly for men. Glucose may be a suitable replacement sugar.
Another potential concern about fructose is its association with increased energy intake and obesity. Worldwide trends in per capita consumption of caloric sweeteners (of which high fructose syrups are a major component) demonstrated an increase from 232kcal/day in the year 1962 to 306kcal/day in the year 2000 . In the United States, caloric sweeteners accounted for 16% of energy intake in the year 1996 . About 43% of the caloric sweeteners came from soft drinks and fruit drinks.
Several authors have suggested that dietary fructose may play a role in the worldwide increase in obesity prevalence [23, 24]. Their reasons for implicating fructose are principally two. The first is the association, mentioned above, between increasing consumption of fructose and increasing obesity. The second is the theoretical possibility that dietary fructose increases energy intake. Clearly dietary fructose stimulates insulin secretion less than glucose and glucose-containing carbohydrates. Insulin stimulates leptin release from adipocytes  and circulating insulin and leptin concentrations were thus lower after ingestion of fructose-containing meals than after ingestion of glucose-containing meals in healthy women . However, energy intake by the women was not greater during the fructose-containing meals. Nevertheless, lower circulating insulin and leptin after fructose consumption might inhibit appetite less than consumption of other carbohydrates and lead to an increase in food intake.
Table 3. Effects of the two study diets on mean fasting plasma lipids 
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