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

LucH

SpaceManJim says
1) I actually have a full genetics panel, what genes/mutations should I look for, and at what values, to determine if I have some methylation issues?
=> MTHFR gene mutation and test required
The MTHFR gene mutation inhibits the body's processing of folic acid (B9) and other important B vitamins.

Some of the best multivitamins for MTHFR mutation are methyl folate (B9), methyl cobalamin (B12) and B6 (PLP), vitamin D3, and glutathione.

And choline (to help recycling homocysteine into methionine).
MTHFR gene = The methylenetetrahydrofolate reductase gene contains the DNA code to produce the MTHFR enzyme.
Note: Not simply acid folic or folate but methyl folate. B9 and B12 have to be methylated.
The MTHFR gene codes for an enzyme that helps your body convert homocysteine in excess when eating proteins. People with high homocysteine levels suffer from low-grade inflammation (not perceived); they typically respond well to supplementation with vitamins such as B6, B12, and folate (B9). The form of vitamin and the posology must be taken into account.
Test price for gene test: +/ 150 $. Most insurance companies do not cover this type of MTHFR gene test, and may leave you with an $800-$1,000 bill.
Home test for 677 and 1298 MTHFR Gene Variants (C677T and A1298C).
See customer review here on amazon (I have no personal background) for the manufacturer ‏: “MTHFR Doctors”. It seems OK.
https://www.amazon.com/Comes-Physician-Recommendations-Results-Interpretation/dp/B07DMVV76W
An MTHFR gene test is used to look for the two most common MTHFR changes called C677T and A1298C. It's possible to have one or both of these gene changes without having any health problems. An MTHFR gene test may be done alone or as part of a group of genetic tests.
Personal advice: useful test but not obliged to if you consider you can manage the problem by adapting the treatment, acting as if you were deficient.
Note that a methylation defect has an impact on thyroid and the whole metabolism.
Useful info (in French, translator needed): Méthylation définition
What is methylation? Very few people know it, when it is the keystone of a multitude of vital actions within our organization (metabolism).
https://www.nutriting.com/experts/methylation/

2) And secondly, do you have any further practical recommendations regarding my supplement usage?
=> Get informed on the side effects when taking high dose of a supplement.
Situation: Restore communication between the brain and the thyroid. Get rid of toxic derivatives resulting from a methylation defect. Find out about the why of how when you take pyridoxine (B6) (form and dosage, errors not to be committed).

1st step:

Get rid of excess of homocysteine
help methylation process
=> I can make suggestion on products if desired.
Mind excess oxalates. It interferes with sulfur and at the end with methylation. I take potassium citrates to neutralize oxalates from spinach or when I eat rhubarb or combine several sources like chocolate, coffee or one of the twelve bastards.
Figure: Aliments riches en Oxalates : 12 Salopards

3) Btw, prolactin is probably an issue for sure, I had minor childhood gyno, maybe even still a little bit now as an adult though much less so. I notice that I feel flabby on bloated in the torso region specifically after sexual activity, but reliably I can pop a B6 afterwards and reverse it.
=> I would take B1 to help to get rid of lactic acid and high level of No when having sexual activity. See beneath too.
Need to be anticipated or it will take 2 or 3 days to get rid of excess. Especially if you eat refined carbs. B2 B3 and particularly B1 are required to assimilate sugars.
B6 can help here to relax.
PLP is required for the synthesis of the neurotransmitters serotonin, norepinephrine, epinephrine, and GABA, and as such is involved in both neuronal excitation and inhibition. (1)
Administration of VitB1, B6, and B12 forte relieved symptoms of moderate peripheral neuropathy. (2)
Tips to relax and lower excess lactic acid:
 Breathing in co2 (bag) slightly lowered it, nothing significant.
 Walking around actually lowers it. 30’ low exercise levels.
 Biotin 50 milligrams would lower it.

doi: 10.3945/an.113.005207 2015 (no need to read further).
https://doi.org/10.14710/dimj.v2i1.9549 M. Silviana, D. et al. 2021. “Therapy in Peripheral Neuropathy Patients” (no need to read further).
Note: I’d add some glycine and magnesium bisglycinate after a sexual event.
A shake with:

Orange juice 150 ml
½ scope of bisglycinate of magnesium (a scope = 2.5 gr)
1 scope potassium citrate (2 ml = 1.25 gr)

50-100 m PLP (20-25 mg if brain-sensible, at the beginning). I took 100 mg PLP with TMG (tri-methyl-glycine).
Explanation:

Collagen could help (glycine). 1 tsp with the meal or a snack with dark chocolate (if appreciated).
B6 modulates the activity of GABA.
PLP is used as a cofactor to synthesize and degrade GABA and modulate its activity. In this way pyridoxine administration facilitates GABA turnover.
PLP is the cofactor for the enzyme glutamate decarboxylase, which converts glutamate (the main excitatory neurotransmitter) into GABA (the main inhibitory neurotransmitter).
B6 can help increase progesterone and decrease estrogen, with adapted proportions. Mind this last point (with adapted proportions). Too much of a good thing is bad.
Source: B6 abaisse-t-il le niveau de dopamine?
Does B6 lower the level of dopamine? Pyridoxine has both dopamine improvement properties and dopamine blocking: on the one hand, pyridoxine (as dopamine) depresses the prolactin release of the pituitary gland; on the other hand, in oral doses of 10 to 20 mg, it quickly reverses the therapeutic effect of dopamine.
Source: Pyridoxine
https://www.sciencedirect.com/science/article/pii/B9780444537171013706
In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016
https://www.sciencedirect.com/referencework/9780444537164/meylers-side-effects-of-drugs
Comment: Vitamin B6 is well documented for its role as a modulator of steroid hormones. Pyridoxal phosphate (PLP), the active form of Vitamin B6, may interfere with the action of the estrogen receptor (ER) by blocking the hormone-binding and/or DNA-binding site of the ER.
Source: PLP as Modulator of Steroid Hormones
PLP decreases estrogens and modulates DNA synthesis
Vitamin B6 Decreases Proliferation and DNA Synthesis of Human Mammary Carcinoma Cell Lines in Vitro. By Brandy Ellen Cowing.
*) Additional info 1:
B6 and molybdenum deficiency could both contribute to anxiety or insomnia. B6 lacks if excess sulfites or low-grade inflammation. When more vitamin B6 is consumed, for instance with arthrosis (anti-inflammation effect), this situation could lead to vitamin B6 deficiency. Deficiency of vitamin B6 blocks the metabolic pathway and leads to accumulation of kynurenine pathway intermediates.
See Chris Masterjohn for reference.
Excerpt (from CM):
B6 is needed to make melatonin and GABA, and to maximally suppress quinolinate. Molybdenum is needed to maximally suppress sulfite. Quinolinate stimulates excitatory glutamate receptors, and sulfite drives the generation of S-sulfocysteine, which does the same. Thus, B6 and molybdenum deficiency could both contribute to anxiety or insomnia.
*) Additional info 2:
Thiamine (B1) has also neuro-protective effects: Brain & Digestive System. There is a connection between the brain, the digestive system and the vagus nerve. Dr. Derrick Lonsdale calls this “dysautonomia and adaptation to the stress environment” when fuel is re-loaded.
Full post on this link (my forum), with explanations, figures, studies links and case reports if you want details and see how to manage in practice with high dose thiamin (B1) (How much and which kind of thiamine?).
https://mirzoune-ciboulette.forumactif.org/t2045-english-corner-anti-stress-neuro-protective-effects-of-thiamine-b1#29712
=> Neuroprotective Effects of Thiamine
Thiamine (vitamin B1) is essential for brain function because of the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism.

Thiamine possesses “universal” anti-stress properties: B1 is mobilized in response to cellular stressors.

Mostlylurking has commented, on a previous post (in High-dose thiamine troubleshooting):
https://bioenergetic.forum/post/18941
“I think that the optimized cellular energy level that thiamine facilitates when working as a co-factor for several enzymes in the Krebs cycle restores the body's balance on the cellular level. Getting the body's energy level working on the cellular level as it is intended is neuro-protective. Think of it as restoring the electrical current that connects the body's cells so that they work in harmony.”
Note: There is a strict protocol when using high dose thiamine (B1).
Additional info (David Nazarian, M.D.)
Thiamine and Hormonal Balance: The Vital Connection
https://www.myconciergemd.com/blog/thiamine-and-hormonal-balance-the-vital-connection/
Excerpt: There is evidence that thiamine aids in maintaining normal thyroid function by lowering oxidative stress and enhancing energy metabolism. Additionally, thiamine is vital for maintaining correct nerve and muscle function, which can also aid in supporting healthy thyroid function.
A balanced diet with thiamine and other critical vitamins and minerals supports thyroid function.
Reminder: Do not take high dose thiamine without B2 (not necessarily every day).
*) To lower lactic acid:
Breathing in co2 slightly lowered it, nothing significant.
Walking around actually lowers it. 30’ low exercise levels.
Biotin 50 milligrams would lower it.

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!).