Some Questions About Vitamin B6 (P5P)

faxmulder

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Jan 21, 2020
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151
Hi folks,

I’d like to supplement P-5-P (the active form of vitamin B6), since I’ve read it could help with brain fog, focus, overall energy and motivation, by boosting dopamine production.
I've seen also an interesting theory (TBH can't remember where) according to which P5P could also help with premature ejaculation, by reducing prolactin - do you have any experience with this?

I know that B6 (therefore I think also P5P) overdose is a real risk and it can cause neuropathy.

I managed to find only supplements with 50mg, not less.
Is it a too high dose to take everyday? I’m going to take it with magnesium malate.

Is it necessary to take other B vitamins as well? Recently I’ve bought also sulbutiamine so I was planning to take both.

Thanks!
 
M

metabolizm

Guest
Good questions, and I hope someone can give you (and me) some answers. I'm also considering it as a supplement for similar reasons. What I do know, however, is that most will consider 50mg too high a daily dose. I think 10-25mg is a safer range.
 
OP
F

faxmulder

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Jan 21, 2020
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151
Good questions, and I hope someone can give you (and me) some answers. I'm also considering it as a supplement for similar reasons. What I do know, however, is that most will consider 50mg too high a daily dose. I think 10-25mg is a safer range.
thanks man. Yeah is what I'm suspecting too - let's hope somebody will chime in.
 

redsun

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Dec 17, 2018
Messages
3,013
Hi folks,

I’d like to supplement P-5-P (the active form of vitamin B6), since I’ve read it could help with brain fog, focus, overall energy and motivation, by boosting dopamine production.
I've seen also an interesting theory (TBH can't remember where) according to which P5P could also help with premature ejaculation, by reducing prolactin - do you have any experience with this?

I know that B6 (therefore I think also P5P) overdose is a real risk and it can cause neuropathy.

I managed to find only supplements with 50mg, not less.
Is it a too high dose to take everyday? I’m going to take it with magnesium malate.

Is it necessary to take other B vitamins as well? Recently I’ve bought also sulbutiamine so I was planning to take both.

Thanks!

PE is high base noradrenaline levels so lowering it will help PE.

The risk of overdose is due to the pyridoxine versions. Pyridoxine is plant B6, and can actually worsen B6 metabolism by taking it. Pyridoxal is animal B6 (the one we can use) and is not going to give issues like pyridoxine. 10-25mg is perfectly good dose. The B6 you are taking is pyridoxal 5 phosphate and is not going to cause problems.

Of course dont take very high doses, 25mg is more than enough. And if for some reason you do feel bad by all means stop taking. I have taken P5P so many times and zero peripheral neuropathy from it while pyridoxine HCL has given me neuropathy in the past pretty quickly.
 

Shman Frontal

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Feb 23, 2020
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Its important to measure Riboflavin as FAD before you take any B6. Moreover, Brainfog is often a result of lacking Magnesium, therefore you should measure magnesium in the whole blood (not only serum) and manganese as control indicator
 

Amazoniac

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- Disorders affecting vitamin B6 metabolism

"PLP is the only B6 vitamer that acts as a cofactor for enzymes, a role that is enabled by its reactive aldehyde group. It undergoes a condensation reaction with the amino group of amino acids to produce a Schiff base which forms the basis of most of the enzyme catalyzed reactions for which PLP is required.[4] However, because of the reactivity of its aldehyde group PLP can be involved in other, unwanted reactions with macromolecules within the cell (a form of aldehyde or carbonyl stress) analogous to the unwanted reactions of reactive oxygen species. Reactions of PLP with amino groups of proteins can alter their structure[5] and at concentrations of 10 to 100 μM inhibit enzyme activity[6] and aldehydes can damage DNA leading to mutagenesis.[7] PLP can also react with small molecules[8,9] including sulphydryl compounds such as cysteine resulting in the formation of thiazoliodines[10] and with sulfite producing a sulphonate. The aldehyde group of PLP can also react, via Knoevenagel condensation, with Δ1-pyrroline 5-carboxylate and Δ1-piperideine 6-carboxylate. This is the mechanism of PLP deficiency in ALDH7A1 (antiquitin) deficiency and hyperprolinaemia type II, respectively.[11,12] Hence, the cell maintains intracellular levels of free PLP at approximately 1 μM to avoid any unwanted reactions occuring.[13] Consideration of the reactivity of the aldehyde group of PLP is important when treating patients with certain drugs. Drugs that can inactivate PLP include hydrazines (eg, isoniazid and hydralazine), sulphydryl compounds (eg, penicillamine), and substituted hydroxylamines (eg, cycloserine)."

"Besides the role of PLP as a cofactor B6 vitamers may also play other roles within the cell, for example, as antioxidants, quenching singlet oxygen at rates comparable to vitamins C and E.[17] PLP can also modify expression and action of steroid hormone receptors[18] and may have an effect on immune function.[19] Finally, of interest because of its antiepileptic activity,[20,21] PLP is an antagonist of ATP at P2 purinoceptor7 (P2X7).[22] It has been suggested that when neuroinflammation triggers cellular ATP release this can lead to epilepsy by activation of P2X7 receptors;[23] PLP has the potential to block this activation. This could explain the action of PLP on drug-resistant epilepsies besides those genetic disorders discussed in detail below.[24,25]"

"The intestine only absorbs nonphosphorylated B6 vitamers (Figure 2). The phosphorylated forms of B6 and the glucoside of pyridoxine are therefore first hydrolyzed by intestinal phosphatases and an intestinal glycosidase, respectively.[26,27] Once within cells of the intestine, pyridoxine and pyridoxamine can either be converted prior to transport to the liver[28] or once within the liver to pyridoxal phosphate. In the liver (or intestine) pyridoxamine, pyridoxine and pyridoxal, are first rephosphorylated by pyridoxal kinase (EC 2.7.1.35). The flavin mononucleotide (FMN)-dependent enzyme, pyridox(am)ine phosphate oxidase (PNPO; EC 1.4.3.5) converts the phosphates of pyridoxamine and pyridoxine to PLP. Although this occurs mainly in the liver, PNPO is expressed in all cell types. PLP is exported from the liver bound to the lysine 190 residue of albumin.[29]"

"When B6 vitamer intake exceeds requirements, pyridoxal phosphate is dephosphorylated (mainly in the liver) and the pyridoxal is oxidized to pyridoxic acid prior to excretion in urine. Early reports suggested that in humans an aldehyde dehydrogenase (EC 1.2.1.4) or aldehyde oxidase (AOX; EC 1.2.3.1)[30] is responsible for this reaction. However, while in Drosophila pyridoxal has been shown to be a substrate of AOX1[31] it is not metabolized by mouse AOXs.[32]"

"For PLP to enter the brain, it must dissociate from albumin and be dephosphorylated to pyridoxal at the blood-brain barrier (BBB). Dephosphorylation is accomplished by tissue nonspecific alkaline phosphatase (E.C. 3.1.3.1), an ectoenzyme tethered to cell membranes at the BBB by a glycophosphatidylinositol (GPI) anchor."

"Intracellular-free PLP concentrations are maintained at approximately 1 μM[13] to prevent inappropriate reactions (“aldehyde stress” or “carbonyl stress”). Several mechanisms are involved in maintaining low concentrations. Proteins that bind PLP and help maintain low-free PLP concentrations include glycogen phosphorylase in muscle,[36] hemoglobin in erythrocytes,[37] and albumin in plasma.[29]"

"PLP, when in solution, may be rapidly degraded by light and/or oxygen with the formation of dimers or pyridoxic acid 5'-phosphate and other products, respectively.[61] Hence, when a liquid formulation is required each PLP dose should be prepared from a tablet or capsule and given without delay."

"Some children taking high doses of PLP have developed persistently raised transaminases with progression to cirrhosis[62] and hepatocellular carcinoma (unpublished observation). The cause remains uncertain; possibilities included aldehyde stress from PLP and pyridoxal, or toxicity of PLP photodegradation products."​

They discuss 'causes and consequences of PLP deficiency' in various conditions, it's worth checking out.
 

Frankdee20

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I’d take 50-100 MG of P5P with no problem
 

equipoise

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Quite possibly the greatest supplement in doses of 10mg at a time, P5P

Nukes cortisol, shrinks nipples, gives focus
 
K

Kaur Singh

Guest
B6 supplementation can be tricky for some -
at even the low doses of 1 mg of either pyrodoxine Hcl or pyrodoxal 5'-phosphate [P5P / PLP]
it can cause problems either right away or after some time.

Some even have high levels of PLP in blood tests without supplementation

You will find this all across the different support groups for weird diseases.

It's important to listen to this, the lived experiences, in my opinion

I have been reading up on this for a while, and how I am conceptualizing it is:
Very much integral to the stress response, PLP moves out of the cell together with ATP.

How one reacts to supplementation seems to be dependent on which state your cells are in.
Getting out of the stress response would seem a good step to take.

How to know if B6 will affect you negatively?
- You could get tested for blood PLP levels.
Phlebotomist needs to block the vial from being exposed to light *before* blood is drawn,
otherwise your results will be falsely lowered.
Not many labs seem to do this...
- Low and slow. Start really low with B6, and see how your body responds.
Nerve activity buzzing/zapping/etc and sleep disruption are the common effects in those that it is not indicated for.

It seems that most that have the B6 problem have joint hypermobility / other connective tissue issues.

Low and slow.
 
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Dr. B

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Dr. Peat has recommended 10mg per day of P5P.
Peat has talked about giving 10mg of the pyridoxine form in the past. it seems like he approves of that one... he said his friends newborn kid had lethal diarrhea or something and his friend used 10mg pyridoxine to fix it...
but he doesnt recommend using these supplements constantly as nutrients, only for specific problems.

PE is high base noradrenaline levels so lowering it will help PE.

The risk of overdose is due to the pyridoxine versions. Pyridoxine is plant B6, and can actually worsen B6 metabolism by taking it. Pyridoxal is animal B6 (the one we can use) and is not going to give issues like pyridoxine. 10-25mg is perfectly good dose. The B6 you are taking is pyridoxal 5 phosphate and is not going to cause problems.

Of course dont take very high doses, 25mg is more than enough. And if for some reason you do feel bad by all means stop taking. I have taken P5P so many times and zero peripheral neuropathy from it while pyridoxine HCL has given me neuropathy in the past pretty quickly.

whered you find pyrixodine is plant and p5p is animal?
does orange juice contain pyridoxine whereas milk contains p5p form?
i wonder if this is something similar to the issue with vitamin c. remember Peat said nutrition labels dont show the meat/milk vitamin C because its intracellular and they cant test for it?
maybe same things going on with milk and animal foods? meat and milk have very little amounts of b6 whereas banannas and orange juice have good amounts of b6... maybe were just not able to measure the animal forms of these vitamins properly?
 

serling78

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Apr 17, 2019
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Nukes cortisol, shrinks nipples, gives focus

Sounds to me like symptoms of aromatase inhibition. Which I think is great for some or most, but I'm one of those guys who's body doesn't do well on AI's. I just started b6 p5p 3 days ago and by day 2 the AI effects hit me like a sledgehammer.

Are there any others b vitamins to take specifically with b6? Like b12 and then maybe also folate?
 

Birdie

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Opinion is catching up with Ray Peat who recommended keeping any B6 dose down to about 10mg. I thought he recommended the simple form of B6 over the P5P form. I remember discarding all my P5P form after hearing Ray's thoughts. But maybe he revised that unbeknownst to me.

"The new scientific opinion (EFSA) revised in Europe the Tolerable Upper Intake Level (UL) for vitamin B6 of 12.5 mg/day for adults (including pregnant and lactating women), down from the previous UL of 30 mg/day set in 2000. For infants and children the ULs are: 2.2-2.5 mg/day (4-11 months), 3.2-4.5 mg/day (1-6 years), 6.1-10.7 mg/day (7-17 years). Excessive intakes are associated with peripheral neuropathy, a type of damage to nerves in the body’s extremities. Based on available intake data, EU populations are unlikely to exceed the ULs, except for regular users of food supplements containing high doses of vitamin B6."



efsa.europa.eu/en/efsajourn...
 

David PS

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Opinion is catching up with Ray Peat who recommended keeping any B6 dose down to about 10mg. I thought he recommended the simple form of B6 over the P5P form. I remember discarding all my P5P form after hearing Ray's thoughts. But maybe he revised that unbeknownst to me.

"The new scientific opinion (EFSA) revised in Europe the Tolerable Upper Intake Level (UL) for vitamin B6 of 12.5 mg/day for adults (including pregnant and lactating women), down from the previous UL of 30 mg/day set in 2000. For infants and children the ULs are: 2.2-2.5 mg/day (4-11 months), 3.2-4.5 mg/day (1-6 years), 6.1-10.7 mg/day (7-17 years). Excessive intakes are associated with peripheral neuropathy, a type of damage to nerves in the body’s extremities. Based on available intake data, EU populations are unlikely to exceed the ULs, except for regular users of food supplements containing high doses of vitamin B6."



efsa.europa.eu/en/efsajourn...
:rightagain2
 

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