Pyridoxine (Vitamin B6) and MTHFR

Pyridoxine (Vitamin B6) and MTHFR

People with an MTHFR genetic mutation are usually aware that they need to supplement with folate and vitamin B12 to assist with healthy methylation. However, pyridoxine (vitamin B6) is also crucial in the methylation process.

Pyridoxine works alongside folate and vitaminB12 in one-carbon metabolism, which is necessary for properly converting homocysteine to methionine. Folate, vitamin B12, and B6 are also essential for neuronal function; deficiencies of these nutrients have been linked to increased risk of neurodevelopmental disorders, psychiatric disease, and dementia.

This article will explain what vitamin B6 is and its many roles in the body. We will discuss insufficient or excess B6intake, the recommended dosage for best results, and why B6 is especially important for those with MTHFR genetic mutations.

Vitamin B6 exists in seven different forms. Of these, pyridoxal and pyridoxal 5′-phosphate (PLP) are the major forms obtained from animal protein, such as liver, beef, pork, and poultry. Pyridoxine, pyridoxamine, PNP (pyridoxine 5′-phosphate), and PMP (pyridoxamine 5'-phosphate)  are the main forms obtained from plants, such as cereal grains, bananas, legumes, pistachios, and potatoes.

Pyridoxine is a coenzyme in more than 140enzyme reactions required to metabolize amino acids, glucose, and lipids. It is also the form used in B6 supplements.

Vitamin B6 is absorbed in the gut and metabolized in the liver, which converts it to PLP, the metabolically active form of B6. PLP functions as a cofactor in both steps in the transsulfuration pathway, in which homocysteine is converted to cystathionine and then to cysteine.

Vitamin B6 (B6) has a central role in the metabolism of amino acids, including important interactions via the glutathione peroxidase (GPX) system. B6-dependent enzymes are required throughout the transsulfuration pathway, the metabolic pathway in which the transfer of sulfur from homocysteine to cysteine occurs.

Transsulfuration is a crucial step in homocysteine metabolism and essential for maintaining healthy homocysteine levels in the body. This pathway also generates the sulfur metabolite cysteine, which is then used to produce GSH (glutathione), the reduced form of glutathione and the body’s most important antioxidant.

Sufficient B12, B6, and folate are therefore essential to maintain healthy levels of homocysteine, and deficiency in any of these nutrients is associated with hyperhomocysteinemia, which is associated with increased risk of heart disease, cognitive problems, and mood disorders.

PLP-dependent enzymes also play essential roles in the metabolism of carbohydrates and lipids, including the breakdown and use of glucose in the body.

B6 plays a role in synthesizing sphingoid bases, the lipid molecules required for myelin formation. It is also important for erythropoiesis, as it functions as a cofactor in forming δ-amino levulinic acid(required in heme biosynthesis) and facilitates the incorporation of iron into protoporphyrin.

Vitamin B6 is also necessary for proper cognitive development through the biosynthesis of neurotransmitters, including GABA (γ-Aminobutyric Acid), serotonin, dopamine, noradrenaline, histamine, glycine, and d-serine.

In the immune system, B6 assists in promoting the production of lymphocytes and interleukin-2, which play vital roles in immune system function. 

In adults, vitamin B6 deficiency can cause symptoms such as:

Pyridoxine is readily available in many foods, and dietary deficiency of B6 is rare.

Although supplementation is advised when B6intake is inadequate, over-supplementing can result in toxicity.

The most common symptoms associated with vitamin B6 toxicity include progressive peripheral sensory neuropathy, which is also the case in B6 deficiency. This manifests as numbness in the extremities, beginning with burning pain in the feet which then moves to the legs and hands. Severe cases may lead to difficulty walking.

Neurological symptoms include paresthesia, hyperesthesia (increased sensitivity of the senses), bone pain, muscle weakness, muscle twitching, and loss of tendon reflexes.

Other symptoms of B6 toxicity may include problems with balance and coordination, sensory ataxia (interruption of sensory feedback signals), and loss of deep tendon reflexes. Stomach pain, loss of appetite, and  headaches have also been reported after taking high doses of B6.  

According to the National Institutes of Health, the recommended intake of B6 for adults aged 19–50 years is 1.3 mg. Pregnant individuals are advised to take1.9 mg, and those breastfeeding to take2.0 mg.

Sensory neuropathy is known to develop at extremely high doses (more than 1000 mg per day). There are some case reports of these symptoms developing at doses of less than 500 mg per day after taking B6 for several months. However, there appear to be no known cases of sensory nerve damage occurring at a daily intake of>200 mg per day.