Chronic Fructose Consumption Ups NFALD in Obese, Diabetics

DURHAM, N.C.Obese and diabetic individuals who consume increased amounts of dietary fructose have a higher risk of severe forms of nonalcoholic fatty liver disease (NFALD), according to a study published in the journal Hepatology.

Researchers at Duke University Medical Center discovered chronic fructose consumption in a diet puts people at risk for depleting their store of critically important molecules called ATP that provide liver cells energy for important cellular processes, including metabolism. The ability of the cells to optimally make ATP may already be impaired in diabetics and obese individuals.

"The stores of liver ATP are decreased in obese and/or diabetic individuals who chronically consume increased amounts of fructose-containing beverages," said lead author Manal Abdelmalek, M.D., MPH, Associate Professor of Gastroenterology and Hepatology at Duke.

Unlike other simple sugars, fructose requires ATP for its metabolism. The inability to optimally generate cellular energy as well and the continued consumption of ATP from chronic fructose ingestion can result in the liver's depletion of energy. ATP depletion may increase risk for inflammation and scarring in the liver.

The state of being insulin resistant impairs the ability of a vital enzyme, AMP kinase, to make new ATP molecules," she said. "Increased fructose consumption, and excess utilization of ATP favors the increase in molecules that lead to increased fatty acid synthesis as well as increased uric acid."

The researchers also noted that more uric acid is produced in the body when excess fructose is consumed. Too much uric acid is associated with conditions that include gout, high blood pressure, cardiovascular disease, type 2 diabetes, metabolic syndrome and uric acid stones, a form of kidney stones.

The current study evaluated adults enrolled in the NIH-sponsored Look Ahead Fatty Liver Disease Ancillary Study at Johns Hopkins University. The researchers analyzed dietary questionnaires collected in patients who underwent a magnetic resonance imaging to measure liver fat as well as an intravenous fructose challenge to evaluate the liver's ATP stores and response to ATP depletion. Study participants had been counseled on lower dietary sugar consumption for the management of diabetes. Despite the overall lower levels of fructose use in this study population, the researchers found evidence of liver ATP depletion in those who consumed more fructose.

"The fact we found a difference in liver ATP stores at lower levels of dietary fructose intake does suggest that higher fructose consumption (as would occur with the consumption of processed food and sweetened beverages) could deplete the liver of energy and thus risk causing worse metabolic problems and potentially even liver injury," she said.