Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 13 (11), e0207024
eCollection

Effects of Fructose-Containing Sweeteners on Fructose Intestinal, Hepatic, and Oral Bioavailability in Dual-Catheterized Rats

Affiliations

Effects of Fructose-Containing Sweeteners on Fructose Intestinal, Hepatic, and Oral Bioavailability in Dual-Catheterized Rats

Leah R Villegas et al. PLoS One.

Abstract

Objective: Fructose is commonplace in Western diets and is consumed primarily through added sugars as sucrose or high fructose corn syrup. High consumption of fructose has been linked to the development of metabolic disorders, such as cardiovascular diseases. The majority of the harmful effects of fructose can be traced to its uncontrolled and rapid metabolism, primarily within the liver. It has been speculated that the formulation of fructose-containing sweeteners can have varying impacts on its adverse effects. Unfortunately, there is limited data supporting this hypothesis. The objective of this study was to examine the impact of different fructose-containing sweeteners on the intestinal, hepatic, and oral bioavailability of fructose.

Methods: Portal and femoral vein catheters were surgically implanted in male Wistar rats. Animals were gavaged with a 1 g/kg carbohydrate solution consisting of fructose, 45% glucose/55% fructose, sucrose, glucose, or water. Blood samples were then collected from the portal and systemic circulation. Fructose levels were measured and pharmacokinetic parameters were calculated.

Results: Compared to animals that were gavaged with 45% glucose/55% fructose or sucrose, fructose-gavaged animals had a 40% greater fructose area under the curve and a 15% greater change in maximum fructose concentration in the portal circulation. In the systemic circulation of fructose-gavaged animals, the fructose area under the curve was 17% and 24% higher and the change in the maximum fructose concentration was 15% and 30% higher than the animals that received 45% glucose/55% fructose or sucrose, respectively. After the oral administration of fructose, 45% glucose/55% fructose, and sucrose, the bioavailability of fructose was as follows: intestinal availability was 0.62, 0.53 and 0.57; hepatic availability was 0.33, 0.45 and 0.45; and oral bioavailability was 0.19, 0.23 and 0.24, respectively.

Conclusions: Our studies show that the co-ingestion of glucose did not enhance fructose absorption, rather, it decreased fructose metabolism in the liver. The intestinal, hepatic, and oral bioavailability of fructose was similar between 45% glucose/55% fructose and sucrose.

Conflict of interest statement

CJR and CR are members of Colorado Research Partners LLC which is developing inhibitors of fructose metabolism. MTL is an inventor on the following patent applications that are related to developing inhibitors of ketohexokinase: “Plant-based inhibitors of ketohexokinase for the support of weight management” - US Patent Application #2014/0377386 A1, “Indazole Inhibitors of Fructokinase (KHK) and Methods of Use in Treating KHK-Mediated Disorders or Diseases” - US Provisional Patent Application #62/473,005, and “Botanical-Based Inhibitors, and Methods Using Same to Treat Nonalcoholic Fatty Liver Disease” - US Provisional Patent Application #62/579,372. MTL and LRV are founders of Microtek, Inc., which is a bioengineering company. These commercial entities did not provide any support for the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Fructose intestinal, hepatic, and oral bioavailability.
Fa x Fg = intestinal availability or fructose absorption. Fh = hepatic availability. F = oral bioavailability.
Fig 2
Fig 2. Fructose serum concentration versus time profiles after oral administration of sugar-sweetened solutions.
A) Fructose concentrations in the portal vein over 6-hr. B) Fructose concentrations in the systemic circulation (femoral vein) over 6-hr. Wistar rats were gavaged with 1 mL of the following solutions: (C) Fructose, (D) 45/55 Glucose/Fructose, (E) Sucrose, (F) Glucose, and (G) Water. Portal serum concentrations are shown as closed symbols. Systemic serum concentrations are shown as open symbols. Data represents the mean ± standard deviation.
Fig 3
Fig 3. Effects of sugar-sweetened solutions after oral administration on fructose pharmacokinetic parameters.
(A) Portal fructose area under the curve (AUCpv) (B), systemic fructose area under the curve (AUCsys), (C) normalized portal fructose area under the curve (AUCpv/D), (D) normalized systemic fructose area under the curve (AUCsys/D), (E) adjusted portal fructose maximal concentration (AdjCmax_pv), (F) adjusted systemic fructose maximal concentration (AdjCmax_sys), (G) normalized adjusted portal fructose maximal concentration (AdjCmax_pv/D), (H) normalized adjusted systemic fructose maximal concentration (AdjCmax_sys/D), (I) portal fructose half-life (T1/2_pv), and, (J) systemic fructose half-life (T1/2_sys). 45/55 G/F = 45% glucose/55% fructose. P-value: * < 0.05, ** < 0.01, and *** < 0.001.
Fig 4
Fig 4
Effects of sugar-sweetened solutions after oral administration on (A) intestinal fructose bioavailability (Fa x Fg), (B) hepatic fructose bioavailability (Fh), and (C) systemic fructose bioavailability (F). 45/55 G/F = 45% glucose/55% fructose. P-value: * < 0.05, ** < 0.01, and *** < 0.001.

Similar articles

See all similar articles

References

    1. Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. The American journal of clinical nutrition. 2004;79(4):537–43. 10.1093/ajcn/79.4.537 . - DOI - PubMed
    1. Vos MB, Kimmons JE, Gillespie C, Welsh J, Blanck HM. Dietary fructose consumption among US children and adults: the Third National Health and Nutrition Examination Survey. Medscape J Med. 2008;10(7):160 Epub 2008/09/05. ; PubMed Central PMCID: PMC2525476. - PMC - PubMed
    1. Sluik D, Engelen AI, Feskens EJ. Fructose consumption in the Netherlands: the Dutch National Food Consumption Survey 2007–2010. European journal of clinical nutrition. 2015;69(4):475–81. 10.1038/ejcn.2014.267 . - DOI - PubMed
    1. Lambertz J, Weiskirchen S, Landert S, Weiskirchen R. Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease. Front Immunol. 2017;8:1159 Epub 2017/10/04. 10.3389/fimmu.2017.01159 ; PubMed Central PMCID: PMCPMC5609573. - DOI - PMC - PubMed
    1. Taskinen MR, Soderlund S, Bogl LH, Hakkarainen A, Matikainen N, Pietilainen KH, et al. Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity. Journal of internal medicine. 2017;282(2):187–201. Epub 2017/05/27. 10.1111/joim.12632 . - DOI - PubMed

Publication types

Feedback