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Pyridoxine (Vitamin B6) and MTHFR

Pyridoxine (Vitamin B6) and MTHFR | Methyl-Life

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.

What is Vitamin B6?

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’s B6 Functions in the Body

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. 

Pyridoxine Deficiencies and Toxicity

Pyridoxine Deficiencies and Toxicity

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

  • Dermatitis(inflammation of the skin)

  • A red, scaly, greasyrash

  • Numbness and/orprickling in hands and feet

  • Glossitis (sore andred tongue)

  • Chapped lips and/orcracks in the corners of the mouth

  • Confusion,irritability

  • Frequent infectionsdue to reduced immune function

  • Fatigue due toanemia

  • Elevatedhomocysteine

  • Depression

  • Seizures

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.  

Vitamin B6 Dosages

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.

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Can MTHFR Mutations Lead to B6 Deficiencies?

Can MTHFR Mutations Lead to B6 Deficiencies

Although MTHFR mutations may not directly leadto B6 deficiency, B6 is a vital component of the methylation process.

Folate, B12, and B6 are all required forhomocysteine metabolism either through folate-mediated one-carbon metabolism orthe transsulfuration pathway.

B6 plays an important role in the methylationprocess by acting as a cofactor for serine methylhydroxytransferase (SHMT), theenzyme required for the conversion of serine and tetrahydrofolateto glycine and 5,10-methylene tetrahydrofolate (CH2THF). The MTHFR enzyme then converts CH2THF to folate, and methionine isconverted to S-adenosylmethionine (SAMe), an essential methyl donor.

Vitamin B6 deficiency is associated with impaired transsulfuration and severaldownstream health concerns, including elevated homocysteine. Animal studiesshow that B6 deficiency compromises homocysteine remethylationand the transsulfuration pathways, indicating that both SHMT and CBS aresensitive to B6 levels.

Those with high homocysteine levels and/orMTHFR mutations are advised to check their folate, B12, and B6 levels andsupplement when necessary. Research shows that supplementation with thesevitamins may reduce homocysteine levels in people withelevated homocysteine.

Choosing the Right Supplementation Options

Vitamin B6 is a vital nutrient for numerous biochemical processes in the body. It is especially important to there methylation of homocysteine, and B6 deficiency has been shown to contribute to hyperhomocysteinemia.

Most people obtain sufficient B6 from their diet. However, B6 should be supplemented when a deficiency is detected, provided that safe dosing protocols are observed. Excess B6 can result in serious symptoms, most notably peripheral sensory neuropathy. This should not be confused with B6 deficiency, which can have the same result.

Supplementing with the active form of B6 (pyridoxal 5’ phosphate) is highly recommended as this is the form that can pass directly into cells to function in enzymatic reactions, ensuring proper uptake and utilization of the nutrient.

For those with MTHFR mutations, supplementing with vitamin B6 alongside folate and vitamin B12 is highly recommended for healthy methylation and overall wellbeing. Sufficient B12, B6, and folate reduce homocysteine levels, while deficiency of B vitamins is associated with an increased risk of heart disease, cognitive problems, and mood disorders.

The Methyl-Life® product range is designed specifically for those with MTHFR, and the Chewable Methylated Multivitamin includes both active folate (as methylfolate), active B12 (as hydroxycobalamin), and activeB6 (as pyridoxal 5’ phosphate). This exclusive formula's nutrients can help reduce homocysteine levels, promote glutathione production, and support myelin sheath repair.

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    Written By,
    - Jamie Hope



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