Ingested mannose is rapidly absorbed, becomes widely distributed throughout body fluids, and is extensively incorporated into plasma and tissue glycoproteins within one hour after ingestion. In a study in rats, oral mannose was rapidly absorbed from the intestine and cleared from the blood with a half-time of 30 minutes. After a 30-minute lag following dosing, mannose was incorporated into plasma glycoproteins, and then into glycoproteins of all organs (mainly the liver) during the first hour; glycoprotein incorporation in organs increased 2- to 6-fold at 1-8 hours.2 ,3 In a pharmacokinetic study in humans, blood mannose levels increased in a dose-dependent fashion with increasing oral doses of mannose (0.07-0.21 gram mannose/kg body weight—equivalent to approximately 5-15 grams in a 150-lb human). Peak blood mannose concentrations occurred at 1-2 hours following ingestion, and the clearance half-time was approximately 4 hours. Doses of 0.1 gram mannose/kg body weight (equivalent to 7 grams in a 150-lb human) given at 3-hour intervals maintained blood mannose concentrations at levels 3- to 5-fold higher than the basal level. Results of this study also indicate that mannose can be incorporated directly into glycoproteins in addition to being synthesized from glucose.
There do not appear to be any published studies in animals or humans to indicate that dietary intake of mannose results in adverse biological effects. For example, in an animal study mice were given mannose (1 mg/mL) in their drinking water for a period of 60-70 days, and no toxicity was observed. In fact, growth of experimentally-induced tumors was found to decrease markedly in mannose-treated mice and survivability increased to 67% after mannose treatment compared to 0% in untreated control mice.6 The estimated dose of mannose in this study, based on 15 grams body weight of the mice and daily water consumption of at least 5 mL/mouse, was 333 mg/kg (1mg/mL x 5 mL/day / 0.015 kg); an equivalent dose for a 150-lb human would be approximately 23 grams.
In two other animal studies, chickens were given mannose (25 mg/mL) in their drinking water for 10 days, and the extent of Salmonella typhimurium colonization after inoculation on day 3 of mannose treatment was determined. Based on the average body weight of 134 grams for the mannose-treated chickens and an estimated water consumption of at least 10 mL/day, the estimated dose of mannose was at least 1,865 mg/kg (25 mg/mL x 10 mL/day / 0.134 kg); an equivalent dose for a 150-lb human would be approximately 130 grams. At this extremely high dose, S. typhimurium colonization of the cecal contents was reduced by as much as 99% and no toxicity was apparent.
In humans, no adverse effects have been noted at oral doses of approximately 15 grams.4 Even at oral doses as extreme as 53 grams/day given over an 11-month period, no adverse side effects were observed in patients with carbohydrate-deficient glycoprotein syndrome type 1b.9 Moreover, even when huge amounts (35 grams/hour) of mannose were injected intravenously continuously for 10 hours, human subjects experienced no more serious effects than fatigue, anorexia, malaise, and massive uric acid crystalluria.10 Of course, these intravenous data should be applied with caution to situations of oral exposure, since metabolic differences are common by the two routes of exposure.