Fructose metabolism in humans - what isotopic tracer studies tell us

Abstract

Fructose consumption and its implications on public health are currently under study. This work reviewed the metabolic fate of dietary fructose based on isotope tracer studies in humans. The mean oxidation rate of dietary fructose was 45.0% ± 10.7 (mean ± SD) in non-exercising subjects within 3-6 hours and 45.8% ± 7.3 in exercising subjects within 2-3 hours. When fructose was ingested together with glucose, the mean oxidation rate of the mixed sugars increased to 66.0% ± 8.2 in exercising subjects. The mean conversion rate from fructose to glucose was 41% ± 10.5 (mean ± SD) in 3-6 hours after ingestion. The conversion amount from fructose to glycogen remains to be further clarified. A small percentage of ingested fructose (<1%) appears to be directly converted to plasma TG. However, hyperlipidemic effects of larger amounts of fructose consumption are observed in studies using infused labeled acetate to quantify longer term de novo lipogenesis. While the mechanisms for the hyperlipidemic effect remain controversial, energy source shifting and lipid sparing may play a role in the effect, in addition to de novo lipogenesis. Finally, approximately a quarter of ingested fructose can be converted into lactate within a few of hours. The reviewed data provides a profile of how dietary fructose is utilized in humans.

Figure 1

Major metabolic pathways and flux of dietary glucose and fructose. P = phosphate. For enzymes numbered in circles: 1 = hexokinase/glucokinase or Glucose-6-phosphatase, 2 = phosphoglucose isomerase, 3 = hexokinase, 4 = fructokinase, 5 = glycogen synthase or phosphorylase, 6 = phosphofructokinase, 7 = aldolase, 8 = triose phosphate isomerase, 9 = triose kinase, 10 = several enzymes including pyruvate kinase, 11 = pyruvate dehydrogenase complex,12 = lactate dehydrogenase,13 = ketothiolase and other 3 enzymes,14 = enzyme group related to citric acid cycle, 15 = acetyl CoA carboxylase,16 = multienzyme complexes, 17 = acyl CoA synthase, 18 = glycerol-phosphate acyl transferase and triacylglycerol synthase complex. The dashed-line and arrow represents minor pathways or will not occur under a healthy condition or ordinary sugar consumption. The compound names in bold would be major metabolic intermediates or end products of glucose or fructose metabolism.

Figure 2

Dietary fructose and glucose oxidation (in normal subjects, mean + SD). On horizontal axis, ‘studies = number’ means that how many studies the bar data averaged from. In the Figure, 3–6 hours and 2–3 hours represent study monitoring period. The noted data variations between studies could be due to the differences of sugar dosages, tracer labeling forms, sugar administration methods, subject characteristics, and/or measurement errors. Also, the produced CO₂ from labeled sugar oxidation can arise directly from sugar molecules themselves, or other compounds converted from the sugars, such as glucose, lactate, or fatty acid from fructose.

Figure 3

Metabolic fate of dietary fructose carbons. The data are obtained within study periods less than or equal to 6 hours. After 50–150 gm fructose ingestion, the peak of fructose concentration in plasma would be between 3–11 mg/dL. The percent data above arrow lines or under box are the estimated amounts of ingested fructose doses via the pathway, and the question mark represents that the data remain to be further confirmed. The dash-line represents presumably minor pathways.