Vitamin B6 is found in plant and animal sources. Plants contain mostly pyridoxine and animals contain mostly pyridoxal. These two forms need to be converted to its active form, pyridoxal 5 phosphate (PLP), by the enzyme, pyridoxal kinase, for it to perform its many important functions. The recommended intake for B6 is 1.7mg daily. However in most people, the enzyme pyridoxal kinase, isn’t functioning properly, and the conversion of B6 to its active form is 1:5-10 and sometimes close to zero. As seen here, there was only a 33% increase in PLP, with those who have liver damage. Plus urinary excretion of pyridoxic acid increased significantly. The less conversion you are able to do, the more wasting takes place. (2) The enzyme also requires vitamin B2 as a cofactor. So one can actually have a B6 (PLP) deficiency, even while eating enough B6 through foods. To skip all these issues, you can just supplement with PLP from the start. More on supplements at the bottom.
Here are a few of PLPs’ functions:
PLP 1) cures dematitis (including when induced by “essential fatty acid deficiency”), 2) functions as an enzyme cofactor and/or regulator for >140 enzyme-catalyzed reactions, 3) is essential in amino acid (transsulfuration, polyamine biosynthesis (requires for muscle growth)), glucose (glycolysis, gluconeogenesis, glycogenolysis) and lipid (synthesis of sphingoid bases (required for myelin formation)) metabolism, 4) heme synthesis (a coenzyme for δ-aminolevulinate synthase), 5) B3 synthesis from tryptophan and 6) increases glutathione. (3)
In the brain, PLP is required for the synthesis of the neurotransmitters serotonin, norepinephrine, epinephrine, γ-aminobutyrate (GABA) and histamine. (1) B6 won’t give you a histamine reaction if that’s what you’re thinking, as a dose of 200mg HCL lowers histamine. (4)
A PLP deficiency leads to reduced absorption and storage of vitamin B12, and in increased excretion of vitamin C. Furthermore, B6 acts synergistically with vitamin E to control the metabolism of unsaturated fats (prevent lipid peroxidation and oxidative stress) and with vitamin C in dopamine synthesis through tyrosine metabolism. (5) A deficiency in B6 increases lipid peroxidation, possible due to reduced vitamin C, which is able to recycle oxidized vitamin E back to its oxidant quenching state.
Vitamin B6 for Energy production & methylation
A B6 deficiency results in a lowered concentration of CoA in blood. CoA is used in the Kreb cycle to produce energy.
B6 are involved in the release of glucose from glycogen stores, via the enzyme glycogen phosphorylase, and also during the production of glucose, via gluconeogenesis. (6
PLP increases carnitine (needed to transport long chain fatty acids into the mitochondria) and beta-oxidation (breaks down fatty acids into acetyl-CoA). (7
B6 is essential in methylation, where homocysteine is converted back to methionine (aids in the conversion of THF (tetrahydrofolate) to 5,10-methylene-THF in the folate cycle) or to cysteine (cystathionine synthase and cystathionase enzymes are PLP dependent). A B6 deficiency is associated with elevated homocysteine.
With improved methylation, the SAM/SAH ratio is increased, and SAM is the universal methyl donor. A reduced SAM/SAH ratio may lead to inhibition of transmethylation reaction of DNA, RNA and protein, the synthesis and function of thymic lymphocyte and result in damage to tissues. (8
When energy production is required, cysteine is converted to alpha-ketoglutarate, which is a Kreb cycle intermediate, instead of to taurine/sulfate/glutathione.
Vitamin B6 greatly reduce estrogen levels and receptors
An increased SAM/SAH ratio increases catechol-O-methyltransferase (COMT). COMT increases the breakdown and detoxification of estrogen.
Secondly, PLP inhibits acetyl-CoA carboxylase (ACC-1 and ACC-2), (9
) which is part of the fatty acid synthase (FAS) complex, which synthesizes fatty acids. FAS increases estrogen receptors and increases tissue responsiveness to estrogen. (10
FAS are elevated in numerous hormone (estrogen) related cancers. Estrogen decreases B6, so if you suspect you have high estrogen, you might need a higher dose of B6 to replenish B6 stores and to lower elevated estrogen.
Vitamin B6 improves exercise performance
Skeletal muscle contains about 80% of stored B6 and is involved in the metabolism of some amino acids (citrulline, arginine
It’s involved in the conversion of ornithine to proline and a defect of this PLP enzyme can lead to blindness.
B6 supplementation significantly increases carnosine and/or calcium regulator (13
)) in muscle as well as beta-alanine (which is the precursor to carnosine) (15
Carnosine stimulates mitochondrial biogenesis and is an integral part of skeletal muscle contractility and homeostasis, presumably through its role as anti-oxidant, pH-buffering (inhibit lactate formation), anti-glycation (reducing the rate of formation of advanced glycation end-products (AGEs), which are substances that can be a factor in the development or worsening of many degenerative diseases, such as diabetes, atherosclerosis, chronic renal failure, and Alzheimer’s disease)).
B6 also increases many gene expressions and polyamines that are involved in muscle growth and repair. (16
Vitamin B6 restores hypothyroid
B6 (pyridoxine HCL) treatment in rats restored B6 deficient hypothyroid. (17
) Of the many nutrients required for proper thyroid function, B6 is one of them.
It would be best to use a multi-vitamin containing B6, such as the one I linking at the end of the article, as all nutrients work together, and not just one might be the answer.
Vitamin B6 is androgenic
With adequate B6, testosterone synthesis is optimized, steroid clearance is reduced and the recycling of receptors from the nucleus back into the cytosol after initial translocation is increased. (18
B6 decreases the responsiveness of steroids, as it interacts with steroid hormone-receptors, affecting their genes expression (19
), and in a deficient state, steroids are more responsive. (20
) This might be a very big reason to only stick to small doses, such as <10mg PLP daily. So, although sensitivity is reduced, androgen receptors’ translocation is increased, which increase the rate of androgen bindings.
It’s also been found that pyridoxine HCL increases 5-alpha reductase, but pyridoxal HCL doesn’t. (21
) The study mentioned that pyridoxal phosphate showed modified enzymatic activities of 5-ar, but didn’t conclude if it increased or decreased it. However, it was an in vitro study using rat organs. I bet results will be different in vivo and in humans. I’ll just stick to PLP.
Plasma PLP concentrations are inversely related to markers of inflammation such as C-reactive protein (TNFα, IL-6, IFN-γ, COX-2 and iNOS expression). Inflammation, COX-2 and iNOS all are anti-androgenic and pro-cortisol.
Vitamin B6 lowers cortisol
Just like B6 reduce androgen responsiveness, so it also does with cortisol receptors. B6 reduces the transcription of glucocorticoids. It also seems to antagonize the cortisol receptor and therefore lower the mRNA of cytosolic aspartate aminotransferase (cAST) in the liver and improve liver health. Only PLP had this effect. (22
Vitamin B6 is essential for optimal dopamine levels and it lowers prolactin
B6 increases both dopamine and serotonin. The bigger the dose is, the more serotonin will dominate. You could manipulate the response to B6 if you like. Taking B6 in a bright environment (preferably sunlight) will go do dopamine synthesis (especially when combined with phenylalanine or tyrosine), and before bed would go mostly towards serotonin (dark environment).
To confirm this, taking B6 before bed increases melatonin, of which serotonin is a precursor, (23
) and melatonin increases dream vividness, bizarreness, emotionality, and color, possibly due to increased cortical arousal during periods of rapid eye movement (REM) sleep. (24
) This is also due to increased melatonin synthesis.
High doses of B6 for prolonged durations can lead to peripheral neuropathy, which could just be serotonin syndrome (very high serotonin), and is fully reversible, with dopamine agonists/serotonin antagonists.
Vitamin B6 deficiency is also associated with depression, due to inadequate neurotransmitter synthesis, such as dopamine. B6 (PLP) is successfully used alongside with medication to treat schizophrenic. (25
I think it would also be beneficial for Alzheimer, Parkinson and other conditions related to low dopamine and high serotonin.
B6 would be the perfect substance to complement any dopaminergic substance, as it decreases dopamine breakdown and excretion, despite the increase in COMT (which break down catecholamines) as mentioned above (26
) and also lowers adrenaline. As seen here, B6 lower hypertension, by lowering adrenaline in rats. (27
This is good, as some dopamine raising substances also increase adrenaline (dopamine is the precursor to adrenaline), makes B6 a pretty safe and good dopamine boosting substance, which prevents the jittery-ness and anxiety of adrenaline.
Pyridoxine HCL lowered prolactin by 42% in short stature children, without affecting growth hormone. (28
) This could also be due to the TSH lowering effect. (TSH increases prolactin).
a) Increases retention of magnesium
b) PLP is very beneficial for autism as their enzyme, pyridoxal kinase, is significantly decreased, hence they have very elevated pyridoxine & pyridoxal and very low PLP. (29
) This could also explain that dopaminergic substances will be highly beneficial for autism.
c) B6 deficiency with the use of serum cutoff values for PLP <20 nmol/L (30
d) Increases selenium absorption and is involved in selenium metabolism in various proteins.
e) Increases conversion of glutamate (excitatory neurotransmitter) to alpha-ketoglutarate (Krebs cycle intermediate) via glutamate dehydrogenase. (31
) This is very helpful against conditions that are sensitive to excitation, such as epilepsy, anxiety, etc…
g) Helpful against carpal tunnel syndrome at doses up to 200mg daily, equivalent to ∼20mg PLP. Part of its relieve might come from that it’s also mildly analgesic. (33
h) Absorption is about 75% from food and supplements.
i) Plasma PLP is diminished in inflammatory conditions and, in the case of inflammatory bowel disease (IBD). Any gut irritations and inflammation are known to increase serotonin. (34
j) PLP accelerates the metabolic degradation of ethanol and prevents adenosine triphosphate (ATP) inactivation by acetaldehyde.
– Contains 6mg PLP per serving, 30 servings. Also contains 50mg thiamine HCL, 15mg B2 (R5P), 100mg niacinamide, 1mg biotin. 99% purity ingredients. 80-90% absorption on all ingredients when applied topically.
Pyridoxal 5 phosphate
– 50mg per serving, 100 servings. Bite the cap in 5ths so that you only ingest about 10mgs a day.