In this study, we compared the acute metabolic and hemodynamic effects of HFCS and sucrose in 40 healthy subjects. We found treatment differences in fructose, glucose, SUA, and SBP. The following metabolic parameters were higher from the HFCS-sweetened beverages than from the sucrose-sweetened beverages: fructose AUC and Cmax, dose normalized glucose AUC and Cmax, relative bioavailability of glucose, changes in postprandial concentrations of SUA, and observed maximum of SBP. There were no differences in relative fructose bioavailability, FE_fructose, FEUA, DBP, HR, Tg, insulin, and lactate. To our knowledge this is the first study to show HFCS is more likely to cause acute adverse effects than sucrose.
We hypothesized that the formulation of HFCS would result in greater systemic fructose exposure than from sucrose. First, HFCS contains more fructose than sucrose. Second, HFCS consists of free fructose and glucose, thus, allowing for the immediate transport of these simple sugars in the intestine. Meanwhile, sucrose must first be metabolized by sucrase before fructose and glucose are available for uptake. Studies have shown that the expression of sucrase can be negatively affected by genetic polymorphisms [26
]. Its activity has also been shown to be inhibited by glucose [28
]. Thus, we hypothesize that sucrase may potentially be a bottleneck, preventing complete metabolism of sucrose in the gut. Therefore, less fructose would be available for transport. In our study, we found that fructose AUC was about 20% greater and Cmax was about 15% greater from the HFCS-sweetened beverages than from sucrose-sweetened beverages. However, the relative bioavailability was not different. Thus, the difference in fructose plasma concentrations between the sweeteners is most likely due to the higher fructose dose from HFCS, which was about 13% greater than from sucrose. Interestingly, we also detected a significant difference in dose normalized glucose AUC and Cmax. This was surprising since the glucose dose from sucrose was 6 g or about 21% higher than from HFCS. This finding suggests that glucose is more efficiently absorbed into the body from HFCS than from sucrose. The mechanism for this enhanced bioavailability of glucose needs to be further elucidated.
Our study found a significant increase in SBP, about 3 mmHg, from HFCS compared to sucrose. However, the increase was very acute. The impact of chronic exposure of higher fructose bioavailability on affecting sustained elevated blood pressure needs to be investigated. Nevertheless, our finding potentially supports the postulated link between high fructose intake and increased SBP. Jalal et al recently reported an association between high fructose intake from added sugars and increased risk of elevated SBP in the National Health and Nutrition Examination Survey [8
]. In a randomized study consisting of 74 men, Perez-Pozo showed that the ingestion of fructose was associated with an increase in BP [37
]. Others have also found a relationship of sugar-sweetened soft drink intake with BP [38
], although this was not observed in a study in which much of the fructose intake originated from fruits [40
Several mechanisms have been proposed for fructose-induced high blood pressure, including fructose-induced hyperuricemia [38
]. This is an appealing mechanism since previous studies have shown that fructose can increase uric acid levels [16
]. Fructose increases uric acid both by acute effects related to ATP consumption and purine degradation, but also via chronic effects to stimulate uric acid synthesis [16
]. Importantly, Feig et al showed that by lowering uric acid levels there was a decrease in BP in hypertensive adolescents with newly diagnosed hypertension [43
]. Futhermore, Perez-Pozo et al showed that by lowering uric acid with allopurinol, the effect of fructose (200 g/d for two weeks) on elevated BP was prevented in healthy adults [37
]. Finally, an epidemiological study has linked uric acid with soft drink ingestion and hypertension in adolescents [44
]. In our study, we detected a treatment difference in SUA levels, which was higher from HFCS than sucrose. Although the difference was small, about 0.2 mg/dL, our findings highlight that SUA levels can increase when fructose levels increase in the body. Thus, our data potentially support the link between higher fructose levels, elevated uric acid levels, and higher SBP levels, although other mechanisms by which fructose could raise blood pressure remains possible [45
Because of the similarity in composition between HFCS and sucrose, it has been speculated that the metabolic effects of these sweeteners are also similar. Studies directly comparing the effects of HFCS versus sucrose are limited. Nevertheless, Melanson et al, Akhaven et al, Soenen et al, and Stanhope et al conducted short-term studies comparing the two sweeteners. These studies found no significant differences on glucose, ghrelin, leptin, insulin, Tg, uric acid, glucagon-like peptide 1, appetite, and food intake [14
]. While their findings seemingly conflict with our results, these studies did not assess fructose bioavailability and did not account for fructose levels. If fructose is an important factor driving the development of various adverse metabolic effects, we hypothesizes that higher fructose exposure would lead to greater effects. If in these studies, there were no differences in exposure to fructose between their study groups, it would not be surprising that HFCS and sucrose resulted in similar effects. Importantly, fructose bioavailability can vary greatly due to various factors, such as individual differences in fructose absorption and metabolism, the effects of glucose on impacting fructose uptake, and liquid versus solid versus mixed sources of fructose-containing sweeteners [49
]. In our study, we were able to detect a higher exposure to fructose from HFCS than from sucrose. Thus, this may explain why we were able to detect a difference in metabolic and hemodynamic effects between the two sweeteners whereas other studies have not.
Our study has several limitations. First, it was determined from the sugar profile analyses that the sucrose in the soft drinks was being hydrolyzed. At the start of the study, about 60% of the sucrose had already been hydrolyzed and by the end of the study, all of the sucrose had been broken down. As a result, the potential important role of sucrase was marginalized and may have reduced our ability to detect a difference in fructose relative bioavailability between HFCS and sucrose, which may have resulted in greater differences in fructose AUC and Cmax. However, the external validity of the study is high since soft drinks are a major source of sucrose and HFCS. For future studies, a more controlled environment can be obtained by having the sugar mixtures made immediately prior to the study visits. Second, the study population consisted of young and healthy individuals. Their responses may have been less dramatic than older individuals who are metabolically at risk, such as those with abdominal obesity or those with metabolic syndrome.
In conclusion, our findings suggest there are differences on various acute metabolic and hemodynamic responses between HFCS and sucrose. A major strength of our study was the fructose measurements. This allowed us to determine that the consumption of HFCS resulted in higher systemic fructose exposure, which may have driven the significant treatment differences detected on glucose, SUA, and, SBP. Although the treatment effects on acute metabolic responses were small, the effects may increase with continued chronic exposure to these sweeteners. Furthermore, it still needs to be determined if there are differences in fructose exposure and metabolic effects from HFCS and sucrose if the sweeteners were consumed over a longer period of time versus the acute bolus that was given in our study. Importantly, further studies are needed to evaluate the impact of variable fructose absorption and/or metabolism on higher fructose exposure and how that may affect long-term metabolic responses and disease risks. Although we did find differences between HFCS and sucrose, both sweeteners are currently consumed in excessive amounts, which may play an important role in driving the prevalence of cardio-renal diseases.