Wednesday, February 4, 2009

Absorption of Vitamin B12 by Passive Diffusion

This [Berlin et al., 1968: (http://www.ncbi.nlm.nih.gov/pubmed/5751528?dopt=Abstract)] is the original article, as far as I know, showing that about 1.22 percent (the authors also refer to a figure of 1.5 percent, from earlier research) of a dose of oral cyanocobalamin (a form of vitamin B12) is absorbed, apparently by passive diffusion, in an intrinsic-factor-independent manner. This 1.22 percent absorption occurs across a dosage range from 100 ug (0.1 mg) to 100,000 ug (100 mg), and the authors looked at the 24-hour urinary excretion of radiolabeled cyanocobalamin. I obviously don't think that taking doses that high would be wise, and I also don't think that taking high doses of cyanocobalamin is a good idea [because of the added cyanide burden from the cyanide that's liberated from part of a dose of cyanocobalamin, upon its intracellular metabolism (assuming it's not excreted in the urine first)]. In my opinion, cyanocobalamin is an inferior form of vitamin B12, and there's considerable evidence that its transport and retention and bioavailability are inferior to the transport, retention, and bioavailabilities of methylcobalamin or hydroxocobalamin (http://hardcorephysiologyfun.blogspot.com/2009/01/km-values-for-adocbl-binding-to-mmm-and.html).

Assuming the 1.22 percent absorption figure is valid, an oral dose of 17,564 ug/d (17.5 mg/d) of methylcobalamin would be required to very loosely mimic the effect of three-times-weekly, intramuscular injections of 500 ug methylcobalamin (used in a lot of studies) (1,500 ug/7 days = 214.3 ug/d; 214.3/0.122 = 17564). I doubt that one can really compare those two dosage forms, though, because presumably the bioavailability of intramuscular or parenteral methylcobalamin would be higher than the bioavailability from oral methylcobalamin. That seems like an excessively-high dose to me, and I don't know what doses are best. The main concern I would personally have would be with the high levels of free cobalamins that exist in the kidneys, evidently in endosomes or lysosomes. But the reabsorption is evidently saturable, and I've never seen any reports of nephrotoxicity (and many of the articles using the highest doses of i.m. methylcobalamin have administered the methylcobalamin to people with renal failure). A lot of articles have shown nephrotoxicity from methylmalonic acid, though, and vitamin B12 decreases methylmalonic acid levels. Anyway, one would obviously want to check with his or her doctor before taking any supplement.

Also, I was going to mention that the sublingual dosage form is, in my opinion (and the opinion of various authors in the literature), unnecessary. I don't think methylcobalamin is sold in anything other than sublingual (lozenge) dosage forms, however. I think, if I'm remembering correctly, that the transcobalamin I protein (I think it's just called haptocorrin) is present in saliva, and the idea is that methylcobalamin will bind to that and somehow be absorbed to a greater extent or something. But, in my opinion, this doesn't make sense, given that the absorption of dosages in excess of 2.2 ug occurs by passive diffusion and is not dependent on protein binding. One could argue that the binding of methylcobalamin to salivary haptocorrin(s) could in some way prevent its inactivation by sulfite or nitrites in the intestinal luminal fluid (?), but I've never heard anyone suggest that that could occur. I remember an exchange in the literature, in which the authors were trying to explain the reason (in their opinions) the sublingual dosage form wasn't necessary, and the people who were making a counter-response just...didn't understand. They were saying things such as: "there's no reason to think the people swallowed the vitamin B12 immediately," or something like that. I'm not quoting anyone, but, in my opinion, it's not necessary.

No comments:

Post a Comment