Pyridoxine (Vitamin B6) and MTHFR banner

Pyridoxine (Vitamin B6) and MTHFR

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Nare Simonyan - PhD Pharmaceutical Science

Medical Reviewer:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

February 10, 2025

Table of Contents

    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 protein2, 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 140 enzyme 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 cofactor3 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.4 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 metabolism5 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.6


    B6 plays a role in synthesizing sphingoid bases7, 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 neurotransmitters8, 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-29, which play vital roles in immune system function.

    Pyridoxine Deficiencies and Toxicity

    In adults, vitamin B6 deficiency10 can cause symptoms such as:


    • Dermatitis (inflammation of the skin)
    • A red, scaly, and greasy rash
    • Numbness and/or prickling in hands and feet
    • Glossitis (sore and red tongue)
    • Chapped lips and/or cracks in the corners of the mouth
    • Confusion, irritability
    • Frequent infections due to reduced immune function
    • Fatigue due to anemia
    • Elevated homocysteine
    • Depression
    • Seizures


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

    Although supplementation is advised when B6 intake is inadequate, over-supplementing can result in toxicity.


    The most common symptoms associated with vitamin B6 toxicity include progressive peripheral sensory neuropathy11, 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 symptoms12 include paresthesia, hyperesthesia (increased sensitivity of the senses), bone pain, muscle weakness, muscle twitching, and loss of tendon reflexes.


    Other symptoms of B6 toxicity 13 may include problems with balance and coordination 14, sensory ataxia15 (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 take 1.9 mg, and those breastfeeding to take 2.0 mg.


    Sensory neuropathy is known to develop at extremely high doses (more than 1000 mg per day16). 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.17

    Can MTHFR Mutations Lead to B6 Deficiencies?

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


    Folate, B12, and B6 are all required for homocysteine metabolism either through folate-mediated one-carbon metabolism or the transsulfuration pathway.


    B6 plays an important role in the methylation process by acting as a cofactor for serine methyl hydroxy transferase (SHMT), the enzyme required for the conversion18 of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate (CH2THF). The MTHFR enzyme then converts CH2THF to folate19, and methionine is converted to S-adenosylmethionine (SAMe), an essential methyl donor.


    Vitamin B6 deficiency is associated with impaired transsulfuration20 and several downstream health concerns, including elevated homocysteine. Animal studies show that B6 deficiency compromises homocysteine remethylation21 and the transsulfuration pathways, indicating that both SHMT and CBS are sensitive to B6 levels.

    Those with high homocysteine levels and/or MTHFR mutations are advised to check their folate, B12, and B6 levels and supplement when necessary. Research shows that supplementation with these vitamins may reduce homocysteine levels22 in people with elevated 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 cells23 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.

    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 function1; 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.

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    References

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      https://pubmed.ncbi.nlm.nih.gov/25173634/

    2. D.A. Bender; "VITAMIN B6";Encyclopedia of Human Nutrition (Second Edition); 2005

      https://www.sciencedirect.com/topics/medicine-and-dentistry/pyridoxamine-phosphate

    3. Juan I Sbodio, Solomon H Snyder, Bindu D Paul; "Regulators of the transsulfuration pathway"; British Journal of Pharmacology: 2018 Aug

      https://pmc.ncbi.nlm.nih.gov/articles/PMC6346075/

    4. Danyel Bueno Dalto, Jean-Jacques Matte; "Pyridoxine (Vitamin B6) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation"; Nutrients; 2017 Feb

      https://pmc.ncbi.nlm.nih.gov/articles/PMC5372852/

    5. Zorislava Bajic, Tanja Sobot, Ranko Skrbic, Milos P Stojiljkovic, Nenad Ponorac, Amela Matavulj, Dragan M Djuric; "Homocysteine, Vitamins B6 and Folic Acid in Experimental Models of Myocardial Infarction and Heart Failure-How Strong Is That Link?"; Biomolecules; 2022 Apr

      https://pubmed.ncbi.nlm.nih.gov/35454125/

    6. Jenny U. Tran, Breann L. Brown; "Structural Basis for Allostery in PLP-dependent Enzymes"; Frontiers in Molecular Biosciences, Vol. 9; 2022

      https://www.frontiersin.org/articles/10.3389/fmolb.2022.884281/full

    7. Ryuichi Mashima, Torayuki Okuyama, Mari Ohira; "Biosynthesis of Long Chain Base in Sphingolipids in animals, Plants and Fungi"; Future Science OA, Vol. 6 Iss. 1; 2019 Nov

      https://www.future-science.com/doi/10.2144/fsoa-2019-0094

    8. Kohji Sato; "Why is vitamin B6 effective in alleviating the symptoms of autism?"; Medical Hypotheses Vol.115 Pg. 103-106; 2018 Jun

      https://www.sciencedirect.com/science/article/abs/pii/S0306987718303141?via%3Dihub

    9. Ho-Kyung Kwak, Christine M Hansen, James E Leklem, Karin Hardin, Terry D Shultz; "Improved vitamin B-6 status is positively related to lymphocyte proliferation in young women consuming a controlled diet"; The Journal of Nutrition; 2002 Nov

      https://pubmed.ncbi.nlm.nih.gov/12421844/

    10. Mary J. Brown, Muhammad Atif Ameer, Sharon F. Daley, Kevin Beier; "Vitamin B6 Deficiency"; StatPearls [Internet]; 2023 Aug

      https://www.ncbi.nlm.nih.gov/books/NBK470579/

    11. Felix Hadtstein, Misha Vrolijk; "Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity"; Advances in Nutrition; 2021 Apr

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483950/

    12. Advances in Nutrition, An International Review Journal

      https://academic.oup.com/advances/article/12/5/1911/6257780

    13. Nancy Hammond, Yunxia Wang, Mazen M. Dimachkie, Richard J. Barohn; "Nutritional Neuropathies"; Neurologic Clinics Vol. 31, Iss. 2, Pg. 477-489; 2013 May

      https://www.sciencedirect.com/science/article/abs/pii/S0733861913000121?via%3Dihub

    14. Felix Hadtstein, Misha Vrolijk; "Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity"; Advances in Nutrition; 2021 Apr

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483950/

    15. Nancy Hammond, Yunxia Wang, Mazen M. Dimachkie, Richard J. Barohn; "Nutritional Neuropathies"; Neurologic Clinics Vol. 31, Iss. 2, Pg. 477-489; 2013 May

      https://www.sciencedirect.com/science/article/abs/pii/S0733861913000121?via%3Dihub

    16. Adam Hemminger, Brandon K. Wills; "Vitamin B6 Toxicity"; StatPearls [Internet].; 2023 Feb

      https://www.ncbi.nlm.nih.gov/books/NBK554500/

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      https://pubmed.ncbi.nlm.nih.gov/10341670/

    18. SHMT1 serine hydroxymethyltransferase 1 [Homo sapiens (human)] Gene ID: 6470; 4 Jan 2025

      https://www.ncbi.nlm.nih.gov/gene/6470

    19. A. Msheik, R. Mahfouz; "Genetics of myocardial infarction: The role of thrombosis-associated genes. A review article"; Meta Gene; 2017

      https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/5-10-methylenetetrahydrofolate

    20. J B Ubbink, A van der Merwe, R Delport, R H Allen, S P Stabler, R Riezler, W J Vermaak; "The effect of a subnormal vitamin B-6 status on homocysteine metabolism."; The Journal of Clinical Investigation; 1996 Jul

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507414/

    21. Cheryll Perry, Sun Yu, Jaclyn Chen, Kabir S Matharu, Patrick J Stover; "Effect of Vitamin B6 Availability on Serine Hydroxymethyltransferase in MCF-7 Cells"; Archives of biochemistry and biophysics; 2007 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976282/

    22. Gloria Olaso-Gonzalez, Marco Inzitari, Giuseppe Bellelli, Alessandro Morandi, Núria Barcons, José Viña; "Impact of supplementation with vitamins B6 , B12 , and/or folic acid on the reduction of homocysteine levels in patients with mild cognitive impairment: A systematic review"; IUBMB life; 2022 Jan

      https://pubmed.ncbi.nlm.nih.gov/34058062/

    23. James W Whittaker; "Intracellular Trafficking of the Pyridoxal Cofactor. Implications for Health and Metabolic Disease"; Archives of biochemistry and biophysics; 2017 Feb

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753123/

    24. Banner Image Designed by Freepik

      https://www.freepik.com/

    Katie Stone - Naturopath

    About the Author

    Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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