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Metabolic Fate of Fructose Ingested with and without Glucose in a Mixed Meal

Abstract: Ingestion of pure fructose stimulates de novo lipogenesis and gluconeogenesis. This may however not be relevant to typical nutritional situations, where fructose is invariably ingested with glucose. We therefore assessed the metabolic fate of fructose incorporated in a mixed meal without or with glucose in eight healthy volunteers. Each participant was studied over six hours after the ingestion of liquid meals containing either13C-labelled fructose, unlabeled glucose, lipids and protein (Fr + G) or 13C-labelled fructose, lipids and protein, but without glucose (Fr), or protein and lipids alone (ProLip). After Fr + G, plasma 13C-glucose production accounted for 19.0% ± 1.5% and 13CO2 production for 32.2% ± 1.3% of 13C-fructose carbons. After Fr, 13C-glucose production (26.5% ± 1.4%) and 13CO2 production (36.6% ± 1.9%) were higher (p < 0.05) than with Fr + G.13C-lactate concentration and very low density lipoprotein VLDL 13C-palmitate concentrations increased to the same extent with Fr + G and Fr, while chylomicron 13C-palmitate tended to increase more with Fr + G. These data indicate that gluconeogenesis, lactic acid production and both intestinal and hepatic de novo lipogenesis contributed to the disposal of fructose carbons ingested together with a mixed meal. Co-ingestion of glucose decreased fructose oxidation and gluconeogenesis and tended to increase 13C-pamitate concentration in gut-derived chylomicrons, but not in hepatic-borne VLDL-triacylglycerol (TG).

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Alex’s Notes: Put bluntly, fructose is never consumed in isolation. Even in soda and juice there is glucose present in roughly similar amounts. In fact, just last week we learned that the most popular soda and juice beverages were only 60% fructose if they used high-fructose corn syrup, and less if they did not. Then, just earlier this week we learned that in 18 year olds, the addition of a 50g fructose beverage didn’t alter the metabolic health parameters after consumption for two weeks. So it begs the question, what happens to the fructose? The aim of the study at hand was to assess the metabolic fate of fructose and its interaction with other nutrients of a mixed meal.

The subjects were eight healthy 26 year-olds with an average BMI of 22, and were non-smokers, sedentary, were and not currently on any medications. All subjects completed three trials in a randomized cross-over design: Fructose + Glucose (FrG) meal, fructose only meal (Fr), and a protein and fat control meal (ProLip), with each test being separated by a 3-10 week washout period. All the test meals were identical for protein (20g whey) and fat (20g from cream), while the Fr added 30g of fructose, and the FrG added 30 of fructose and 30g of glucose. All the tests were preceded by 3 days of a standardized 55% carbohydrate, 15% protein, and 30% fat diet.

Unsurprisingly, the sugar meals caused a rapid rise in glucose and insulin, peaking after 150 minutes, but this overall rise was markedly blunted in the Fr compared to the FrG. This is understandable, since fructose must be processed by the gut and liver before even reaching the bloodstream. That said, increases in lactate were identical between conditions, with fructose contributing about 15% of total lactate production. Moreover, about 1/3 the FrG fructose was oxidized into CO2 while it elevated to 37% in the Fr condition. There were no differences in the blood lipid responses between the sugar groups, and total diet-induced thermogenesis was similar across all three trials.

Given these results, about 70% of the ingested fructose load was stored in bodily tissues, either as glycogen or as fat (in both the liver and elsewhere). Roughly 15% of the fructose was converted into lactate, and 20% was converted into glucose. Unfortunately, the amount of fructose that was converted into fat could not be calculated based on the experiments performed, but there was definitely some conversion that likely happened within the gut.

Unfortunately, the test meals were unbalanced in terms of total calories, and this could have affected the results. Similarly, the overall macronutrient ratios were different. Also, the meals were liquid and devoid of starch and fiber. It may very well be that an actual whole-food meal would differ in fructose metabolism, especially if that fructose came from an actual food (7 apples anyone?). Regardless, this study is great in that the absolute amounts of the sugars (30g) is not unrealistic, especially in those who consume sweetened beverages and foods, and this study clearly demonstrates that about 2/3 of fructose is stored in one way or for at least the initial six hours after you eat it.

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