Dave Asprey says the pyridoxine form of b6 added to food and supplements blocks the vitamin activity of active b6 for nearly 3 years
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That study is not proof it is "problematic," but that EXCESS of it is. This is not news.
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@bio3nergetic Right. I'd would rather post Asprey's argument with his research but I don't see it. Happy for someone to post it
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@bio3nergetic said in Dave Asprey says the pyridoxine form of b6 added to food and supplements blocks the vitamin activity of active b6 for nearly 3 years:
That study is not proof it is "problematic," but that EXCESS of it is.
Well said.
Excess B6 PNP is said to be neurotoxic above 240 mg.
(PN= pyridoxine phosphate).
PLP is the active form but there is a threshold that must not be exceeded.
There are mainly 3 basic forms of vitamers B6, as you probably know:- PNP = pyridoxine 5’-phosphate
- PLP = Pyridoxal 5’-Phosphate (active form)
- PMP = Pyridoxamine 5’-Phosphate
A tight regulation of the PLP concentration is necessary in the cell: The aldehydes are toxic. A self -regulation and a protective mechanism coexist. But there is a radical side effect: PLP will no longer passes the encephalic barrier. A withdrawal effect will soon take place, with an impact on neurotransmitters. An effect similar to an absence of GABA.
Mind the side-effect then by making staples: I take 100 mg B6 PLP 5 days a week, for 3 weeks, then stop for a week. Repeat once. Every 3 months thereafter.
And twice a week a multi B-50.
Thus, we’ve got a dual role whenever too short or too high supplemented.
Here is a link if interested for details: an excess of Pyridoxal will lead to the inhibition of the enzyme PLK (Pyridoxal Kinase):
English Corner – Vit B6: How much is too much?
https://mirzoune-ciboulette.forumactif.org/t2033-english-corner-vit-b6-how-much-is-too-much#29628
Note:
I take B1 HCl, B2, B3 niacinamide, B6 PLP and 2 x 500 mg TMG as a cure when I want to reduce wrist pain (B6 pumped in case of pain). B6 PLP works well (48 hours delay) against algoneurodystrophy. -
@LucH good info... another approach, is what i call dusting. I have a small container of B6 powder. Almost anytime I need it i.e. sleep disturbance, lack of dreaming/recall, I use my pinky and dip into the powder getting a dusting of it. I have one container for active and one for the pyridoxine form. It truly works this way, and I am ensuring I don't get too much. It is good to make note of how these things make you feel as an individual and what benefits, if any, it gives. I had an older relative do the same and it brought their homocysteine down. Generally their sleep improved.
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Inter-individual differences in pharmacokinetics of vitamin B6: A possible
explanation of different sensitivity to its neuropathic effects
PharmaNutrition. Volume 12, June 2020, 100188Disorders affecting vitamin B6 metabolism
J Inherit Metab Dis. 2019 Jul;42(4):629-646.The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.
Toxicol In Vitro. 2017 Oct:44:206-212.PN raises serum PN and free PL, which are problematic.
Also Pyridoxamine (PM), which is also a metabolite of estrogens and of incomplete enzymatic conversion in the PLP-cofactor-dependent tryptophan/kynurenine pathway, competitively blocks the PLP-cofactor-dependent enzyme functions as it binds with the same pockets of e.g. kynureninase, kynurenine hydroxylase and hydroxyanthranilateoxidase.
Which, btw, is also why estrogen therapy would lead to impaired glucose tolerance due to functional B6-deficiency (Benninck & Schreurs, 1975; Adams et al. 1976; Spellacy et al. 1977).Neurotrophin-3 (info on availability, anyone?) may act as an antidote to vitamin B6 (pyridoxine) toxicosis.
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@CrumblingCookie said in Dave Asprey says the pyridoxine form of b6 added to food and supplements blocks the vitamin activity of active b6 for nearly 3 years:
Inter-individual differences in pharmacokinetics of vitamin B6: A possible
explanation of different sensitivity to its neuropathic effects
PharmaNutrition. Volume 12, June 2020, 100188Disorders affecting vitamin B6 metabolism
J Inherit Metab Dis. 2019 Jul;42(4):629-646.The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.
Toxicol In Vitro. 2017 Oct:44:206-212.PN raises serum PN and free PL, which are problematic.
Also Pyridoxamine (PM), which is also a metabolite of estrogens and of incomplete enzymatic conversion in the PLP-cofactor-dependent tryptophan/kynurenine pathway, competitively blocks the PLP-cofactor-dependent enzyme functions as it binds with the same pockets of e.g. kynureninase, kynurenine hydroxylase and hydroxyanthranilateoxidase.
Which, btw, is also why estrogen therapy would lead to impaired glucose tolerance due to functional B6-deficiency (Benninck & Schreurs, 1975; Adams et al. 1976; Spellacy et al. 1977).Neurotrophin-3 (info on availability, anyone?) may act as an antidote to vitamin B6 (pyridoxine) toxicosis.
Very interesting about pyridoxamine being a metabolite of estrogens.
I should mention that Asprey's claim that pyridoxine is synthetic misleading. All these forms seem to occur naturally and I doubt the p5p he takes or sells is extracted from food so calling that one form "synthetic" doesn't really make sense.
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I like Chris master John’s explanation for b6 toxicity.
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@Jakeandpace why not provide the link or reference for us? If you don't mind
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It's behind a paywall on his substack but I will share a short quote on it and hopefully I don't get banned from it for sharing.
"This is consistent with my hypothesis that B6 neuropathy is due to increasing transamination, with bottlenecks in CoA-requiring pathways leading to CoA sequestration, which can be aggravated by increasing the substrates that enter the bottlenecked pathway, relieved by cofactors that lead to the release of CoA, and relieved by adding B5 to help make new CoA."
That's his claim. He says in his own self experimentation he used P5P and this caused tingling extremities but also better dreams which he liked. He included zinc and this made things worse (but also better as his dreams were better) and concluded it was a bottleneck in energy metabolism. He included b5 and at varying doses and it solved his problem by the sounds of it.
"I have stayed on 75 mg of B6 and 500 milligrams of B5 for months because it is helping my sleep."
of course if you read the full article he provides in depth explanation for this. I really like his ideas on the bottlenecks in energy metabolism as I experienced similar things to him taking biotin in excess.
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@Jakeandpace
Thanks for this bit of info.
Essentially, that's marking out the importance of feeding sufficient nutrients and cofactors to the otherwise starving nerve cells, which are particularly strongly energy-dependent, as they become more active and craving for substrates when boosted by PLP.So it offers an explanation for adverse effects of PLP, pointing specifically to CoA and therefore vitamin B5. Which is useful.
However, what remains completely untouched by this are all those adverse effects from supplementing pyridoxine which are not mediated through PLP but caused through PN, PM, PL, i.e. the adverse effects which distinguish supplementation of PLP from supplementation of PN.
