Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A 31P MRS study

Bawden, Stephen; Stephenson, Mary C.; Ciampi, Elisabetta; Hunter, Karl J.; Marciani, Luca; Macdonald, I. A.; Aithal, Guruprasad P.; Morris, Peter G.; Gowland, Penny

doi:10.1016/j.clnu.2015.04.001

Cited by 42 publications

(33 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fructose also stimulates the synthesis of uric acid from amino acid precursors (75, 76). The ability of fructose to induce ATP depletion was shown in humans with both intravenous (49, 70, 77, 78) and orally (79) administered fructose. Likewise, an acute rise in uric acid also occurs following fructose ingestion (80–82).…”

Section: Differences In Fructose and Glucose Metabolismmentioning

confidence: 99%

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Jensen

Abdelmalek

Sullivan

et al. 2018

Journal of Hepatology

689

490

View full text Add to dashboard Cite

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, nonalcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked with metabolism of fructose by fructokinase C, resulting in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations in gut permeability, microbiome, and associated endotoxemia contributes to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

show abstract

Section: Differences In Fructose and Glucose Metabolismmentioning

confidence: 99%

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Jensen

Abdelmalek

Sullivan

et al. 2018

Journal of Hepatology

689

490

View full text Add to dashboard Cite

show abstract

“…People with type 2 diabetes with NAFLD with high fructose intake also have lower hepatic adenosine triphosphate (ATP) levels, which is consistent with enhanced fructose metabolism as well . A recent study using 31 P magnetic resonance spectroscopy documented that hepatic ATP concentrations were lowest in participants with higher BMI following OFTT . These studies suggest that fructose metabolism is likely enhanced in people with obesity, diabetes, and/or NAFLD.…”

Section: Discussionmentioning

confidence: 79%

“…29 A recent study using 31 P magnetic resonance spectroscopy documented that hepatic ATP concentrations were lowest in participants with higher BMI following OFTT. 30 These studies suggest that fructose metabolism is likely enhanced in people with obesity, diabetes, and/or NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Fructose tolerance test in obese people with and without type 2 diabetes

Al‐Ozairi

Rivard

Sánchez-Lozada

et al. 2019

Journal of Diabetes

View full text Add to dashboard Cite

Background Fructose is distinct among common sugars in its ability to raise serum uric acid, and some studies suggest fructose‐induced uric acid production may have a role in the ability of this sugar to induce metabolic syndrome. A fructose tolerance test has been previously developed to evaluate the relative ability of fructose to raise uric acid in individuals. However, the effect of fructose to raise uric acid in people with diabetes has not been studied. Methods People with type 2 diabetes (n = 143) and without diabetes controls (n = 132) with similar body mass index (BMI) underwent an oral fructose tolerance test. As a comparison, participants also had their uric acid levels measured after an oral glucose tolerance test on a different day. Results Serum uric acid was lower in people with type 2 diabetes compared to controls with a similar BMI, especially those with poor glucose control (glycosylated hemoglobin [HbA1c] ≥ 8%). Fructose administration raised serum uric acid in both groups, with a lower absolute rise in people with diabetes. People with diabetes with a blunted rise in serum uric acid had higher baseline serum uric acid concentrations and a higher BMI. People without diabetes with a higher BMI also showed a blunted serum uric acid response. Oral glucose administration lowered serum uric acid in both participants, with a greater fall in those with diabetes. Conclusion Both the presence of diabetes and obesity blunt the serum uric acid response to fructose ingestion. These data demonstrate altered fructose‐dependent urate metabolism in type 2 diabetes.

show abstract

“…Interestingly, the ingestion of very large boluses of fructose (50–75 g) by healthy volunteers confirmed these results (Dagnelie and Leij‐Halfwerk, ; Bawden et al . ), but whether similar effects would be observed with lower fructose doses remains debated (Wang et al . ).…”

Section: Introductionmentioning

confidence: 97%

Health outcomes of a high fructose intake: the importance of physical activity

Tappy

Rosset

2019

The Journal of Physiology

View full text Add to dashboard Cite

Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular triose phosphates proportionate to fructose intake. Triose phosphates are then processed into lactate, glucose and fatty acids to serve as metabolic substrates in other cells of the body. With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion, however, escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways. In sedentary subjects, consumption of a fructose‐rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglyceride concentrations, and impairs insulin effects on hepatic glucose production. All these effects can be prevented when high fructose intake is associated with increased levels of physical activity. There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production. Glucose and lactate formed from fructose can also contribute to the re‐synthesis of muscle glycogen after exercise. We therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole‐body energy output related to a low physical activity on the other hand.

show abstract

Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A 31P MRS study

Cited by 42 publications

References 21 publications

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Fructose tolerance test in obese people with and without type 2 diabetes

Health outcomes of a high fructose intake: the importance of physical activity

Contact Info

Product

Resources

About