Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

Abstract

Objective: To investigate the link between dietary sugar consumption and two separate pathogenetic mechanisms associated with metabolic syndrome: de novo lipogenesis (DNL) and non-enzymatic glycation. Design and participants: We assessed changes in serum D-lactate (the detoxification endproduct of methylglyoxal) concentration in response to nine days of isocaloric fructose restriction in 20 children with obesity and metabolic syndrome, and examined correlations with changes in DNL, liver fat, insulin sensitivity and other metrics of hepatic metabolism. Interventions: Nine days of dietary sugar restriction, with substitution of equal amounts of refined starch. Main Outcome Measures: On day 0 and 10, children had lab evaluation of D-lactate levels and other analytes, and underwent oral glucose tolerance testing, magnetic resonance spectroscopy to quantify fat depots, and 13 C-acetate incorporation into triglyceride to measure DNL. Results: D-lactate was associated with baseline liver fat fraction (p<0.001) and visceral adipose tissue (p<0.001), but not with subcutaneous adipose tissue. At baseline, D-lactate was positively correlated with DNL-AUC (p=0.003), liver fat fraction (p=0.02), triglyceride (p=0.004) and triglyceride to HDL ratio (p=0.002). After nine days of isocaloric fructose restriction, serum Dlactate levels reduced by 50% (p<0.0001), and changes in D-lactate correlated with both changes in DNL-AUC, and measures of insulin sensitivity. Conclusion: Baseline correlation of D-lactate with DNL and measures of insulin sensitivity; and reduction in D-lactate following nine days of isocaloric fructose restriction suggest that DNL and non-enzymatic glycation are functionally linked via intermediary glycolysis in the pathogenesis

Dietary Fructose and the Metabolic Syndrome

“…The authors also elucidated the impact of the diet intervention on the methylglyoxal (MG) pathway [15,63,89,90,91], and surprisingly found that fructose restriction associated with marked reduction of D-lactate, a biomarker of MG metabolism. This change of D-lactate correlated with reduction of liver fat content and DNL [88]. These observations open a new perspective of the adverse metabolic effects of excess fructose intake.…”

“…The key metabolic and mechanistic issues of fructose consumption has been studied during a nine days isocaloric feeding study (fructose restriction to less than 4% of calories) in obese children ( n = 40) with MetS and a high habitual sugar consumption (>50 g/day) [61,87,88]. The metabolic assessment was extensive utilizing magnetic resonance imaging and stable isotope technology for DNL in addition to extensive biomarker platform.…”

A Sweet Connection? Fructose’s Role in Hepatocellular Carcinoma

“…Other short-term investigations in obese children have shown that restricting fructose consumption reduces liver fat, DNL, and improves insulin sensitivity [88,89]. In contrast, studies involving fructose consumption in overweight/obese patients show that long-term or short-term consumption of excess fructose or glucose made no difference in parameters of metabolic-related conditions, such as inflammation, liver triglycerides levels, serum triglycerides, or insulin levels [90][91][92].…”

Fructose contributes to the Warburg effect for cancer growth

“…It was found that hepatic fat accumulation was significantly improved by low sugar diet compared to normal diet [ 26 ]. Other studies have also shown a benefit from isocaloric restriction of fructose on various features including fatty liver, hypertriglyceridemia, and insulin resistance [ 25 , 27 , 28 ].…”