This double blind, randomized, prospective study compared changes in weight and body composition, as well as risk factors for coronary heart disease, type 2 diabetes and the metabolic syndrome in overweight and obese individuals before and after a twelve week, free living intervention during which low fat (1%) milk was prescribed, sweetened by either sucrose or HFCS to deliver 10% or 20% of calories from the sweetener in the context of hypocaloric, mixed nutrient meal plans. This is the first attempt to examine the impact of prescribing either sucrose or HFCS (10% or 20% of calories) at the 25th and 50th percentile fructose population intake levels as a component of mixed nutrient, hypocaloric meal plans in a free living environment. The major finding of this prospective study is that typical population intake levels of added sugars prescribed at the level to deliver the 25th and 50th percentile population levels of fructose consumption  does not prevent weight loss and associated improvements in body composition when prescribed in the context of a well designed and supervised weight loss program (Figure 1).
In the current study, individuals in the four intervention groups who started with normal serum cholesterol achieved reductions in serum cholesterol ranging from 13 to 19 mg/dL which is consistent with the amount of weight loss achieved and is clinically significant.
Initial concern was raised that there might be a unique relationship between obesity and the consumption of HFCS because of the temporal association between increased use of HFCS in the American food supply to the increased prevalence of obesity between 1970 and 2000 . Despite the popularity of this suggestion, there are numerous reasons this hypothesis should be discarded. Firstly, the temporal association between HFCS and obesity ended in 1999, when HFCS use began to diminish . Secondly, numerous countries around the world have a similarly increasing prevalence of overweight and obesity as the United States, but do not use HFCS. Lastly, subsequent research studies have shown there is no difference between HFCS or sucrose in any metabolic parameter measured in human beings including glucose, insulin, leptin, ghrelin, triglycerides, uric acid, appetite or calories consumed at the next meal [31, 32, 37]. Both the American Medical Association  and the American Dietetic Association  have issued statements declaring that there is nothing unique about HFCS that leads to obesity. Both of these statements note that all caloric sweeteners contain calories and should be used in moderation. The present data further support the theory that, when consumed at levels up to the 50th percentile for fructose in the context of a hypocaloric diet, neither HFCS nor sucrose impedes weight loss. These data provide further support to the concept that overall caloric consumption rather than one particular component of the diet is most important for achieving weight loss.
Recent concern has been raised that it may be the fructose moiety of both sucrose and HFCS that could potentially contribute to obesity [5, 6, 29]. This argument is based on research performed showing differences in short term energy regulating hormones when comparing a pure fructose model to a pure glucose model [24–26]. Neither fructose nor glucose alone is available in the ordinary food supply as an isolated or pure substance, and neither is consumed alone in significant amounts. It has also been argued that differences in hepatic metabolism between fructose and glucose may stimulate increased caloric consumption and, therefore, increased risk of weight gain and obesity [40–42].
Some epidemiologic studies have reported an increase in energy intake in various population groups related to increased sugar sweetened beverage consumption [7–9]. However, evidence regarding a potential positive association between sugar sweetened beverage consumption and obesity is inconsistent . Because of the metabolic nature of overweight and obesity and the complexity of the western diet, it is unlikely that a single food or food group is the primary cause. Randomized, clinical feeding trials have shown inconsistent results from testing the effects of added sugar on weight gain. Differences in study instruments and methods, population studied and study design may have contributed to these inconsistent findings.
It should be noted that since the added sugars in this study were delivered in low fat milk, the increased consumption of vitamin D may have contributed to some of the results observed. Indeed, in this study 50% increases in vitamin D occurred as a result of milk consumption. Deficiencies in vitamin D and low serum 25 (OH) D levels have been correlated with impaired glucose tolerance, the metabolic syndrome and diabetes independent of obesity . It should also be noted that vitamin D is essential for the metabolism of insulin and may contribute to reduction in the level of CRP . Furthermore, vitamin D may contribute to LDL reduction. Thus, our reported results on cholesterol parameters must be treated with some caution.
Our data demonstrate that equally hypocaloric diets provoked similar weight changes regardless of type or amount of sugar consumed. This finding is not surprising since our research group and others have previously shown the metabolic equivalency of sucrose and HFCS [31, 32]. Strengths of the current study are that it is a double blind, randomized, prospective study with a relatively large sample size which explores normal population consumed levels of fructose as delivered through normally-consumed sweeteners, sucrose and HFCS. Weaknesses are that subjects were only followed for twelve weeks and that children, adolescents and elderly subjects over the age of 60 were excluded. A further potential weakness in the current study is the 35% dropout rate, although this dropout rate is consistent with other trials of comparable size and duration [46, 47]. The added amount of exercise in this study (45 minutes of walking or comparable exercise three times a week) may have also contributed to the observed weight loss, although most studies report that weight loss from exercise alone is typically modest [48, 49]. It should also be noted that 78% of participants in the intervention groups were female. This may limit the ability of these data to be generalized to the public since some animal data suggests that gender influences response to fructose [50, 51] and young women are more resistant to fructose induced hypertriglyceridemia than males and hyperinsulinemic women are more susceptible [52–54]. Furthermore, plasma leptin exhibits sexual dimorphism with higher concentrations in women as androgens have a suppressive effect on leptin secretion [55, 56]. These are further gender differences which may impact on the ability to generalize from data generated largely in women. Since sucrose and/or HFCS consumptions in the diets could not be measured, the actual differences in intake of these two sugars remain unknown, which should also be taken into consideration in interpreting these data.
Further studies employing larger numbers of subjects from more diverse population groups, and higher doses approaching 90th percentile fructose intakes (approximately 15% of calories as fructose) of either sucrose or HFCS, with longer duration appear warranted.
Common misunderstandings about HFCS  have distorted public perceptions, pressuring food manufacturers to replace HFCS with sucrose and municipal and state legislators to mandate removal of HFCS from school nutrition programs. Our data suggest that such actions are pointless and potentially misleading to consumers, since HFCS and sucrose are nutritionally interchangeable.
In conclusion, similar decreases in weight and indices of adiposity are observed when overweight or obese individuals are subjected to hypocaloric diets with different prescribed levels of sucrose or high fructose corn syrup.