ajnast4r, on 3-Feb 2009, 01:59 AM, said:
does anyone have any info on p5p bioavailability? i was under the impression it would much higher serum levels of p5p than other forms of b6 but this suggests otherwise:
As only dephosphorylated vitamers can be transported into the cells (Coburn et al., 2003) the bioavailability of intact pyridoxal 5’-phosphate upon oral intake would be low. Bioavailability of vitamin B6 from pyridoxal 5’-phosphate requires hydrolysis of the phosphate group before absorption through the intestinal layer may occur.
Almost all authorities agree on this point generally. But note, first that they say that "only dephosphorylated vitamers can be transported into the cells
", which is not the same as having it absorbed into serum; and remember that when they say that "Bioavailability of vitamin B6 from pyridoxal 5’-phosphate requires hydrolysis of the phosphate group before absorption through the intestinal layer may occur", and that such hydrolysis results in pyridoxal, not simple B6 (pyridoxine). Additionally, some preliminary evidence that while most P5P is indeed dephosphorylated before absorption, some remains intact and is absorbed, either by passive diffusion across the ECF, or perhaps active transport (1-3). Any of these mechanisms could lead to very different pharmacodynamics between B6 and P5P, irrespective of how many molecules of the core pyridoxine structure gets out of the intestinal lumen and into the serum (simple bioavailabiltiy).
IAC, the key point for me is not the ultimate answer to this particular issue, but the outcome on actual health parameters. (4) is an in vivo study showing that P5P lowers AGE/ALE even more than pyridoxamine, and leads to better health outcomes; ther is no equivalent data for pyridoxine, and until someone does a comparative study with a B6 arm showing that it performs as well or better, the take-home message is to take P5P.
That said, I'm continuing to take most of my total B6 as pyridoxamine rather than P5P, because it has actual human clinical trial data on safety and (very limited) efficacy in AGE-related health outcomes,(5) and we don't have such result for P5P for AGE levels or AGE-related health outcomes in any organism, & can even say that it isn't effective in lowering cardiovascular morbidity and mortality after CABG, as animal studies had suggested (6).
Moreover, high-dose B6 has been reported to cause a reversible neuropathy, which has not been reported (as I would assume that it would be) for quite high dose P5P in the pharma trials ((6) and its Phase II precursor), which may also somehow involve the pharmacokinetics or pharmacodynamics; I'd say IAC it's wise to constrain one's total
intake of all of forms of B6, and especially of B6 proper.
It's also worth noting that peak and total AUC bioavailability of P5P is higher from conventional rather than enteric-coated dose forms in humans (7), and when taken 15 mins after a meal rather than on an empty stomach or at the beginnning (8).
NB: there there is again an issue of possible vestigal CoI here, for which I again urge all readers to see my discl0sure
, tho' I swear up and down that my comments are made in good faith and public interest, not out of any anticipation of personal gain.
1. Intestinal absorption of pyridoxal 5'-phosphate at physiological levels in rats.
Morita E, Shirakami Y, Mizuno N.
J Nutr Sci Vitaminol (Tokyo). 1988 Dec;34(6):553-65.
PMID: 3244043 [PubMed - indexed for MEDLINE]
2: Intestinal absorption of pyridoxal-5'-phosphate: disappearance from perfused segments of rat jejunum in vivo
Middleton HM 3rd.
J Nutr. 1979 Jun;109(6):975-81.
PMID: 448455 [PubMed - indexed for MEDLINE]
3: Characterization of pyridoxal 5'-phosphate disappearance from in vivo perfused segments of rat jejunum
Middleton HM 3rd.
J Nutr. 1982 Feb;112(2):269-75.
PMID: 7057264 [PubMed - indexed for MEDLINE]
4. Nakamura S, Li H, Adijiang A, Pischetsrieder M, Niwa T.
Pyridoxal phosphate prevents progression of diabetic nephropathy
Nephrol Dial Transplant. 2007 Aug;22(8):2165-74. Epub 2007 Apr 20.
PMID: 17449494 [PubMed - indexed for MEDLINE]
5. Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB.
Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy
Am J Nephrol. 2007;27(6):605-14. Epub 2007 Sep 6.
PMID: 17823506 [PubMed - indexed for MEDLINE]
6. Efficacy and safety of pyridoxal 5'-phosphate (MCx1) in high-risk patients undergoing coronary artery bypass graft surgery: the MEND-CABG II randomized clinical trial
MEND-CABG II Investigators, Alexander JH, Emery RW Jr, Carrier M, Ellis SJ, Mehta RH, Hasselblad V, Menasche P, Khalil A, Cote R, Bennett-Guerrero E, Mack MJ, Schuler G, Harrington RA, Tardif JC.
JAMA. 2008 Apr 16;299(15):1777-87. Epub 2008 Apr 1.
PMID: 18381567 [PubMed - indexed for MEDLINE]
7. Bioavailability of pyridoxal phosphate from enteric-coated tablets. I. Apparent critical dissolution pH and bioavailability of commercial products in humans.
Kaniwa N, Ogata H, Aoyagi N, Koibuchi M, Shibazaki T, Ejima A, Takanashi S, Kamiyama H, Suzuki H, Hinohara Y, et al.
Chem Pharm Bull (Tokyo). 1985 Sep;33(9):4045-9. No abstract available.
PMID: 4092300 [PubMed - indexed for MEDLINE]
8. Variability in absorption lag time of pyridoxal phosphate under fasting and pre- and post-meal conditions.
Takahashi H, Ogata H, Nagai N, Sugito K, Shimamura H.
Biopharm Drug Dispos. 1994 Aug;15(6):505-17.
PMID: 7993988 [PubMed - indexed for MEDLINE]
Edited by Michael, 03 February 2009 - 07:39 PM.