Vitamin B6 supplement makes me feel great, why? Safe for long-term use?

LucH

Basebolt said:
He states neuropathy can happen with pyridoxine and P5P. That it may get worse for weeks after stopping but usually will resolve.
=> It happens when the liver can’t evacuate the excess of B6 residues: metabolites become toxic when we overtake what the body needs. The brain protects itself. Lack of glycine will soon take place, with a lot of side-effects. This warning gets applied to pyridoxal phosphate (PLP).
Note: P5P = PLP or PMP
3 forms

PNP = Pyridoxine HCL (nor more that 200-250 gr, gradually).
PLP = pyridoxal phosphate (active form).
PMP = pyridoxamine phosphate
When taking high supplement of Vit B6, the type and the way must be taken into account. Otherwise, do not take into account the warning (applied to high dose).
No Pyridoxine high dose (PN / PNP). PN is then toxic. So, no Pyridoxine HCl, with high dose.
PLP is the active form (pyridoxal 5’-phosphate) but too much of a good thing is bad: metabolites in excess from PLP are not well evacuated and are toxic because of aldehydes. The brain will block the passage. Problems will then happen because of a lack of GABA.
Half-life of PLP and PMP (pyridoxamine) must be taken into account. Let’s say 30 days.
-The dose needed can highly vary. With neuro-sensitive persons, 25 mg B6 every day could be too high after one week reload. Adapt yourself with posology, according to the symptoms (level of inflammation and antioxidant required). Make breaks. E.g. take 20 mg 5 days, the weekend off, during 3 weeks. Then stop for one month (half-life).
PMP (pyridoxamine) could be a better choice for avoiding side-effects of high dose (> 25 mg) but I haven’t seen such supplements at a lower dose (12 - 20 mg).
Zn status may be important in the regulation of vitamin B6 metabolism
Zinc will be needed in the process. If deficient, it won't function...
Source and references
B6 leads to decrease of cytokines in neuropathy
Pyridoxine PLP as pain inhibitor in peripheral neuropathy
Efficacy of Vitamin B1, B6, and B12 in Peripheral Neuropathy
https://mirzoune-ciboulette.forumactif.org/t2041-english-corner-b6-leads-to-decrease-of-cytokines-in-pn#29659
Useful link (in French, translator needed):
Effets de la Vitamine B6 sur les Neurotransmetteurs
https://mirzoune-ciboulette.forumactif.org/t2032-effets-de-la-vitamine-b6-sur-les-neurotransmetteurs#29621

LucH

@Mostlylurling says:
Got links to corroborate this statement about thiamine hcl "safe up to 200-250mgs"?
=> The two links given are about reducing cancer cell proliferation or stimulation.
I didn’t find back my source. But after reading my PC sources, I think I interchange the cheapest form of B1 and B6. I made a mistake. It’s B6 pyridoxine (PN) which is a problem on high dose.

An excess of pyridoxine (PN) is deleterious. No pyridoxine supplement advised: PN has an inhibition effect on PLP, the active form. A tight regulation of the PLP concentration is necessary in the cell: The aldehyde derivatives are toxic. A self-regulation and a protective mechanism coexist. Indeed, there is a radical side effect: PLP will no longer passes the encephalic barrier. A withdrawal effect will soon take place, with a bad impact on neurotransmitters (Gaba).
B6 HCl (PN) is safe but Allil Overtone advices to begin slowly with PN and afterwards to add PLP, by adapting the dose to the ground, with staples, to avoid side effects from metabolites when in excess (brain protection).
For other readers:
B1 HCl is safe:
https://www.medscape.com/viewarticle/760242_5?form=fpf
The vitamin B6 paradox
Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.
https://www.orthofyto.com/wp-content-orthofyto/uploads/2018/01/192123-Vitamin-B6-paradoxMisja-Vrolijk2017.pdf
The neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5′-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.

Sippy

Can neuropathy be caused by B6 deficiency or just toxicity?

LucH

@Sippy said in Vitamin B6 supplement makes me feel great, why? Safe for long-term use?:

Sippy
about an hour ago

Can neuropathy be caused by B6 deficiency or just toxicity?

=> Both can cause damage.
If lack of communication (with problem of electrical or chemistry exchanges), it will affect the brain-stomach axis through the vagus nerve. Toxicity can affect enzyme functions.

But I’d rather say that an optimal amount of B6 PLP and thiamine (with other cofactors) are susceptible to optimize homeostasis and to help recovering.

*) Dr. Lonsdale says:
Thiamine Deficiency and Sympathetic – Parasympathetic Regulation
“The hypothalamus is in the center of the brain computer and it presides over the ANS (Autonomic nervous System), as well as the endocrine (hormone) system. The ANS has two channels of communication known as sympathetic (governs action) and parasympathetic (governs the body mechanisms that can be performed when we are in a safe environment: e.g. bowel activity, sleep, etc.).
When the ANS system is damaged, sometimes by genetic influence, but more commonly by poor diet (fuel), our adaptive ability is impaired.”
Source: Thiamine & the Nervous System
How Can Something As Simple as Thiamine Cause So Many Problems?
By Derrick LONSDALE MD, FACN, CNS. 2023
Understanding Thiamine’s Role in Complex Adverse Reactions – The Limbic System
*) B6 relieving neuropathy
Administration of VitB1, B6, and B12 forte relieved symptoms of moderate peripheral neuropathy with improvement of VAS and TSS scores
VAS score: Visual Analogue Scale (VAS) for pain
TSS score: Total Symptom Score.

B6 modulates the activity of GABA
B6 reduces inflammation and modulates neuro-mediators
Additional K2 MK4 could help in case of “Complex regional pain syndrome”
Ref.: Complex regional pain syndrome: A vitamin K dependent entity?
DOI: 10.1016/j.mehy.2010.03.012 2010

LucH

Mind heavy metal toxicity (especially with mercury)

Heavy metals are likely to take the place of ALA in the chain and to block the enzymatic reactions of metabolism.
ALA = alpha-lipoic acid.
ALA has the ability to trap circulating toxic metals, such as arsenic, cadmium (Cd) and Mercury (Hg). If there is mercury, some enzymes are blocked and homeostasis (return to health) will not be able to take place naturally. The SOD enzyme is found at the mitochondria and cytoplasmic level. Its role is to destroy superoxide anions.
SOD cofactors are trace elements Mn-Zn and Cu.
SOD = Superoxide Dismutase. Its role is to neutralize hyperoxidant free radicals (superpowing reducing role)

Heavy metals such as Cd and Hg move these trace elements away and inhibit the activity of superoxide dismutase.

We repeat: if there is mercury, there will be blocking certain enzymes and homeostasis cannot be set up in this case.
*) Appreciable elements to improve the ground:
Selenium
Vitamins C and E and flavonoids
Co-enzymed vitamins complex

Zn and Mg which are often lacking. Take Mn-Zn and Cu, after chelation (8/1 intake for the Zn and the Cu). 15 to 30 mg of Zn. (=> Contribution necessary for metalo-enzymes).
NB: You must follow a strict protocol in case of detoxification with heavy metals, with recovery breaks.

Formes d'ALA : Acide lipoïque, acide R-alpha-lipoïque, et sodium R-lipoate
Pour les autres pathologies, la forme R-ALA est mieux métabolisée par l'organisme car c'est la forme naturelle de l'acide lipoïque. On parle alors de biodisponibilité améliorée.
Une étude a démontré que la stabilité et la biodisponibilité étaient encore améliorées en convertissant l'acide R-alpha-lipoïque en son sel de sodium, le NaRALA (sodium R-lipoate).
Le sodium R-lipoate atteint des niveaux plasmatiques plus élevés plus rapidement que l'acide R-alpha-lipoïque pur. Il peut permettre d'obtenir une concentration plasmatique dix à trente fois plus élevée que l'acide R-alpha-lipoïque pur8.

Zhang W.J. et al., Dietary alpha-lipoic acid supplementation inhibits atherosclerosis lesion development in apolipoprotein E-deficient mide, Circulation, Jan 22 2008,

MasterPeatler

You probably have high lactate. Try adding in mucuna pruriens or anything which boosts dopamine.

@MasterPeatler said in Vitamin B6 supplement makes me feel great, why? Safe for long-term use?:

You probably have high lactate. Try adding in mucuna pruriens or anything which boosts dopamine.

Thiamine is known to reduce lactate: Severe lactic acidosis reversed by thiamine within 24 hours

MasterPeatler

@mostlylurking I salute you good sir

@MasterPeatler you're welcome. BTW, I'm female, age 74.

Mauritio

Watch out for a possible vitamin B2 deficiency.

@Mauritio
If high dosing thiamine, also watch out for magnesium issues, potassium (I rely on OJ), zinc, riboflavin (yes!).