Unregulated xylitol, sorbitol or fructose metabolism

The monosaccharides are all ultimately metabolised into pyruvate. The addition of lots of monosaccharide results in the delivery of a lot of glycolysis pathway intermediates.

The outcome is an increase in gluconeogenesis, glycogenesis and lipogenesis.   What else are you going to do with all this fuel, if not store it?

xylitol sorbitol and fructose toxicity

The result of increased substrate delivery for the glycolysis-like “fructolysis” pathway is the arrival of huge amounts of pyruvate into the process, because it is the end result for all these pathways.

Weirdly, it seems that in the “fed” state, the delivery of fructose does not result in more pyruvate entering gluconeogenesis or glycolysis – rather, the carbons from the fructose somehow ended up in the rising serum lactate.


Does this really happen in humans?

These days, its hard to find people who become acidotic because they consumed vast quantities of either fructose or sorbitol. However, case reports of accidental “sugar overdose” are available. In one such report, some 15 litres of sorbitol-mannitol urethral irrigation fluid were absorbed by a patient who then went on to develop a lactic acidosis with a lactate up to 6.8mmol/L at one point.

Fructose infusion also seems to have this dose-dependent effect and it has been demonstrated in diabetics as well as healthy volunteers. Thankfully, fructose is not seen any more in clinical use; many decades ago it was thought of as an alternative for glucose infusion in diabetic ketoacidosis, largely because its entry into cells does not rely on insulin.


 Underwood, Ao H., and E. A. Newsholme. "Properties of phosphofructokinase from rat liver and their relation to the control of glycolysis and gluconeogenesis." Biochemical Journal 95.3 (1965): 868.


Mayes, Peter A. "Intermediary metabolism of fructose." The American journal of clinical nutrition 58.5 (1993): 754S-765S.


Trépanier, C. A., et al. "Another feature of TURP syndrome: hyperglycaemia and lactic acidosis caused by massive absorption of sorbitol." British journal of anaesthesia 87.2 (2001): 316-319.


Bergström, Jonas, Eric Hultman, and Aasmund E. Roch‐Norlund. "Lactic acid accumulation in connection with fructose infusion." Acta Medica Scandinavica184.1‐6 (1968): 359-364.


Sahebjami, Hamid, and Raymond Scalettar. "Effects of fructose infusion on lactate and uric acid metabolism." The Lancet 297.7695 (1971): 366-369.