I was just going to discuss the issue of the addition of mannitol vs. xylitol in some oral ATP disodium preparations. The traditional "dogma" is that oral mannitol is not absorbed to any significant extent, but Pappenheimer (1990) [Pappenheimer, 1990: (http://www.ncbi.nlm.nih.gov/pubmed/2116731?dopt=Abstract)] found that this was not the case, at least in animals. This could conceivably be important, given that the potentially-slow conversion of mannitol into fructose, by sorbitol dehydrogenase or other enzymes (Pappenheimer, 1990), in the liver could mean that its osmotic or "osmoregulatory" effects could become an issue for some susceptible individuals. Vernacchio et al. (2007) [Vernacchio et al., 2007: (http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1780176&blobtype=pdf)(http://www.ncbi.nlm.nih.gov/pubmed/17097152)] noted that unabsorbed xylitol could also potentially cause osmotic effects but that there's rapid adaptation to those effects. In any case, it's unlikely to be an issue, but my sense is that mannitol could potentially be more problematic than xylitol, and either unabsorbed or absorbed mannitol could conceivably be slightly problematic if taken at high dosages. Intravenous mannitol used to be used to treat cerebral edema and may still be used in some cases, but it tends to lead to derangements in osmolytes in the long term. This is not at all likely to happen in this context, but I'm just saying that much milder osmoregulatory changes might require a couple of days of adaptation, conceivably, with the ingestion of a sugar alcohol. Or there may be some maximal amount, particularly of mannitol, that any given individual can ingest without experiencing nausea or something like that. The amounts would probably be too small, though, to cause issues, but it's something to be aware of and to not confuse with the effects of ATP. The research suggests that, as noted by Vernacchio et al. (2007), there would be adaptation to any such effects in a few days. The magnitudes of the effects of xylitol vs. mannitol would also, obviously, depend on the amounts of each sugar alcohol in a given ATP preparation, and, without referring to any specific brands, some xylitol-containing ATP preparations seem to contain xylitol in combination with other sugars and might therefore contain a lower amount of "total sugar alcohols" than some other preparations might. This could potentially cause fewer side effects if a person were using higher dosages in the short term, for example. Researchers have used up to 4,000 or 4,200 mg per day of ATP in humans (actually, there's one study in which researchers used something like 6 grams per day, but it wasn't clear to me that it was actually absorbed or that the tablets actually broke apart). I doubt it would be necessary to use dosages that high (even as high as 4,000 mg/day), but the amounts of phosphate and also mannitol or other sugar alcohols could conceivably become factors that would warrant consideration at higher dosages. I doubt the amount of phosphate would be an issue at any dosage of ATP a person would take, but people who have kidney disease could conceivably want to specifically discuss that type of thing with their doctors. Obviously, one should always discuss these things with one's doctor.
It's interesting that Pappenheimer (1990) found that even glucose was absorbed, to a significant extent, by passive, paracellular diffusion (between the cells, rather than transport into the epithelial cells) and that solvent drag effects contributed to that mode of absorption. There's a general tendency to underestimate the contribution of passive diffusion to the intestinal absorption of compounds. I've seen research that provides evidence of the passive absorption of lots of different compounds, including guanosine, other nucleosides or nucleotides, reduced folates, etc. But the authors of a lot of articles talk about "brush-border transporters" and so on, and I've seen that the assumption of "brush-border" carrier-mediated transport can lead to erroneous pharmacology-related conclusions. In some cases, for example, researchers may argue that the rate of absorption is saturable or that only X amount of a compound can be absorbed at any given time, and those types of conclusions, based on the assumption of absorption by carrier-mediated transport, can tend to be invalid.
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