Vitamin B6 is an important co-factor in hundreds of different enzymatic reactions.[ref] Low levels of B6 are linked to an increased risk of diabetes, cardiovascular disease, neurodegenerative diseases, and cancer. B6 is also important for reducing oxidative stress and inflammation.
Genetic variants — along with lifestyle factors — play a role in how much vitamin B6 you need each day. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today.
Vitamin B6: Essential Cofactor
While we talk about vitamin B6 as one vitamin, there are actually several different forms, including pyridoxal, pyridoxine, and pyridoxamine, as well as their phosphate ester forms.[ref] The active form of B6 most often used in reactions in the body is called pyridoxal 5′-phosphate and is abbreviated as PLP or P5P. This is where genetics comes into play – converting the forms of B6 we get in our foods into the active P5P form.
B6 is a vitamin, meaning we can’t synthesize it in the body and must get it from food. It is a water-soluble vitamin that isn’t stored long-term. Thus, we need to get vitamin B6 from our foods each day.[ref]
The function of B6 in the body:
The active form of vitamin B6 (pyridoxal 5′-phosphate) is important for hundreds of different reactions. Let me hit the highlights here:
- Nervous system: P5P is essential in the process of creating serotonin from the amino acid tryptophan. It is also needed for the process of creating dopamine, histamine, glutamate, and GABA.[ref]
- Hemoglobin: P5P is needed as a coenzyme in creating heme, which is part of the body’s hemoglobin molecule to carry oxygen through the bloodstream.
- Creating glucose: P5P is a cofactor for creating glucose from amino acids (gluconeogenesis).
- Methylation cycle: Vitamin B6 is a cofactor in creating methyl folate.
- Tryptophan metabolism: Vitamin B6 is an important cofactor in the kynurenine pathway for tryptophan metabolism, resulting in the formation of niacin.
(Read more about your tryptophan metabolism genes)
Symptoms of vitamin B6 deficiency:
A true deficiency of vitamin B6 is uncommon because B6 is found in many foods.
However, diseases that cause decreased absorption of vitamins can cause B6 deficiency.
- Alcoholics are at a higher risk of B-vitamin deficiencies
- People on dialysis could also be at a higher risk.
- Celiac disease can also cause decreased absorption of vitamin B6.
In the 1950s, an unintended experiment showed that when B6 was accidentally left out of infant formula, the babies had seizures. Severe, rare mutations which cause a genetic B6 deficiency also cause epileptic seizures.[ref]
What about B6 insufficiency or low levels of B6?
Studies in older adults show that decreased levels of vitamin B6 have a significant impact on the immune system. Consuming a diet low in vitamin B6 for three weeks decreased T and B cells (white blood cells that fight invaders). Adding supplemental B6 (50 mg/day) brought the immune function back to normal after four days.[ref]
Low vitamin B6 is also linked to an increased risk of cardiovascular disease.[ref]
A low intake of B6 is linked to a higher risk of Parkinson’s disease.[ref] Not only is B6 important in dopamine production, but it is also important in the creation of glutathione (antioxidant) in the brain.[ref]
Inflammatory conditions, including rheumatoid arthritis, IBD, diabetes, cancer, and deep vein thrombosis, are all linked to low vitamin B6 levels.[ref]
Peripheral Neuropathy and B6:
- Peripheral neuropathy can have many causes, including vitamin B6 deficiency.[ref][ref]
- Caution is warranted, though, in supplementing with vitamin B6 at higher doses. Some people report that high doses of B6 cause tingling and numbness. Recent research shows that supplementing with the pyridoxine form of B6 at higher doses can paradoxically inhibit the creation of P5P.[ref] (There are two forms of B6 available as supplements: Pyridoxine and P5P. Pyridoxine is usually in cheap supplements.)
Inflammation and B6:
While inflammatory conditions are linked to low vitamin B6 levels, it may be (at least partly) because systemic inflammation decreases the body’s PLP levels. When the body is fighting off inflammation.[ref]
Converting B6 from food to P5P:
We get vitamin B6 from foods in the pyridoxamine and pyridoxine (fruits, vegetables, grains) form. The liver then converts this, through a couple of steps, into the active form, P5P.
Dangers associated with too much B6:
Excess consumption of vitamin B6 supplements for long periods of time (months to years) has caused neuropathy or movement disorders in a few individuals. Additional symptoms of excessive consumption may include nausea, heartburn, skin rash, or photosensitivity.[ref]
Vitamin B6 Genotype Report
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the member’s only information in the Lifehacks sections.
ALPL gene: codes for the alkaline phosphatase enzyme. Genetic variants that increase ALPL cause an increased clearance of vitamin B6 and thus lower vitamin B6 levels.[ref]
Check your genetic data for rs1256335 (23andMe v4, v5; AncestryDNA):
- G/G: decreased vitamin B6 levels[ref]
- A/G: decreased B6
- A/A: typical
Members: Your genotype for rs1256335 is —.
Check your genetic data for rs1697421 (23andMe v4, v5; AncestryDNA):
- C/C: typical
- C/T: slightly decreased vitamin B6 levels
- T/T: slightly decreased vitamin B6 levels[ref]
Members: Your genotype for rs1697421 is —.
Check your genetic data for rs1780316 (23andMe v4):
- C/C: typical
- C/T: slightly decreased vitamin B6 levels
- T/T: slightly decreased vitamin B6 levels[ref]
Members: Your genotype for rs1780316 is —.
Check your genetic data for rs4654748 (23andMe v4, v5; AncestryDNA):
- C/C: lower vitamin B6 concentrations[ref][ref]
- C/T: slightly lower vitamin B6 (compared with T/T)
- T/T: typical (or higher) vitamin B6
Members: Your genotype for rs4654748 is —.
ALDH7A1 gene: aldehyde dehydrogenase 7A1, which impacts the lysine catabolic pathway. Mutations in this gene can cause epilepsy, thought to be the result of PLP being used up in a reaction in the lysine pathway. This PLP deficiency then results in reduced GABA synthesis, causing seizures.[ref]
Check your genetic data for rs121912707 Glu427Gln (23andMe v5; AncestryDNA):
- C/C: typical
- C/G: carrier of a mutation linked to vitamin B6 dependent epilepsy[ref]
Members: Your genotype for rs121912707 is —.
Check your genetic data for rs121912708 (23andMe v4; AncestryDNA):
- G/G: typical
- G/A: carrier of a mutation linked to vitamin B6 dependent epilepsy[ref]
Members: Your genotype for rs121912708 is —.
The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.
Related Articles and Topics:
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Like most nutrients, our genes play a role in how vitamin C is absorbed, transported, and used by the body. This can influence your risk for certain diseases, and it can make a difference in the minimum amount of vitamin C you need to consume each day.
Vitamin A: Converting beta-carotene
Genetics plays a huge role in how well you convert the carotenes into retinol. Some people are great at converting beta-carotene in their diet into the retinol form. Others carry genetic variants that significantly impair that conversion.
BHMT: Genetic Variants that Impact Methylation
BHMT is involved in homocysteine methylation and impacts the methylation cycle.
Rheumatoid Arthritis Genes: Root Causes
Rheumatoid arthritis is caused by an immune system attack on the joints, causing thickening and inflammation of the joint capsule. It is caused by a combination of genetic susceptibility and environmental triggers.
Brown, Mary J., et al. “Vitamin B6 Deficiency.” StatPearls, StatPearls Publishing, 2022. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK470579/.
Clayton, Peter T. “B6-Responsive Disorders: A Model of Vitamin Dependency.” Journal of Inherited Metabolic Disease, vol. 29, no. 2–3, June 2006, pp. 317–26. PubMed, https://doi.org/10.1007/s10545-005-0243-2.
Farhad, Khosro, et al. “Causes of Neuropathy in Patients Referred as ‘Idiopathic Neuropathy.’” Muscle & Nerve, vol. 53, no. 6, June 2016, pp. 856–61. PubMed, https://doi.org/10.1002/mus.24969.
Gregory, Jesse F. “Accounting for Differences in the Bioactivity and Bioavailability of Vitamers.” Food & Nutrition Research, vol. 56, Apr. 2012, p. 10.3402/fnr.v56i0.5809. PubMed Central, https://doi.org/10.3402/fnr.v56i0.5809.
Hazra, Aditi, et al. “Genome-Wide Significant Predictors of Metabolites in the One-Carbon Metabolism Pathway.” Human Molecular Genetics, vol. 18, no. 23, Dec. 2009, pp. 4677–87. PubMed Central, https://doi.org/10.1093/hmg/ddp428.
Hinz, Marty, et al. “The Parkinson’s Disease Death Rate: Carbidopa and Vitamin B6.” Clinical Pharmacology: Advances and Applications, vol. 6, 2014, pp. 161–69. PubMed, https://doi.org/10.2147/CPAA.S70707.
Ishihara, Junko, et al. “Intake of Folate, Vitamin B6 and Vitamin B12 and the Risk of CHD: The Japan Public Health Center-Based Prospective Study Cohort I.” Journal of the American College of Nutrition, vol. 27, no. 1, Feb. 2008, pp. 127–36. PubMed, https://doi.org/10.1080/07315724.2008.10719684.
Keene, Keith L., et al. “Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial.” Frontiers in Public Health, vol. 2, Aug. 2014, p. 112. PubMed Central, https://doi.org/10.3389/fpubh.2014.00112.
Laciak, Adrian R., et al. “Structural Analysis of Pathogenic Mutations Targeting Glu427 of ALDH7A1, the Hot Spot Residue of Pyridoxine-Dependent Epilepsy.” Journal of Inherited Metabolic Disease, vol. 43, no. 3, May 2020, pp. 635–44. PubMed, https://doi.org/10.1002/jimd.12184.
Meydani, S. N., et al. “Vitamin B-6 Deficiency Impairs Interleukin 2 Production and Lymphocyte Proliferation in Elderly Adults.” The American Journal of Clinical Nutrition, vol. 53, no. 5, May 1991, pp. 1275–80. PubMed, https://doi.org/10.1093/ajcn/53.5.1275.
Modica, Joseph S., et al. “Pearls and Oy-Sters: Vitamin B6 Deficiency Presenting with New-Onset Epilepsy and Status Epilepticus in a Patient with Parkinson Disease.” Neurology, vol. 94, no. 24, June 2020, pp. e2605–07. n.neurology.org, https://doi.org/10.1212/WNL.0000000000009647.
“Nutrient Ranking Tool.” Myfooddata, https://tools.myfooddata.com/nutrient-ranking-tool. Accessed 29 July 2022.
Office of Dietary Supplements – Vitamin B6. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/. Accessed 29 July 2022.
Olde Loohuis, Loes M., et al. “The Alkaline Phosphatase (ALPL) Locus Is Associated with B6 Vitamer Levels in CSF and Plasma.” Genes, vol. 10, no. 1, Dec. 2018, p. 8. PubMed Central, https://doi.org/10.3390/genes10010008.
Romagnolo, Alberto, et al. “Levodopa-Induced Neuropathy: A Systematic Review.” Movement Disorders Clinical Practice, vol. 6, no. 2, Feb. 2019, pp. 96–103. PubMed, https://doi.org/10.1002/mdc3.12688.
Scott, T. M., et al. “B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary Cognitive Trial.” The Journal of Prevention of Alzheimer’s Disease, vol. 4, no. 3, 2017, pp. 174–82. PubMed, https://doi.org/10.14283/jpad.2017.15.
Shen, Liang. “Associations between B Vitamins and Parkinson’s Disease.” Nutrients, vol. 7, no. 9, Aug. 2015, pp. 7197–208. PubMed, https://doi.org/10.3390/nu7095333.
Tanaka, Toshiko, et al. “Genome-Wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations.” American Journal of Human Genetics, vol. 84, no. 4, Apr. 2009, pp. 477–82. PubMed Central, https://doi.org/10.1016/j.ajhg.2009.02.011.
Ueland, Per Magne, et al. “Direct and Functional Biomarkers of Vitamin B6 Status.” Annual Review of Nutrition, vol. 35, 2015, pp. 33–70. PubMed Central, https://doi.org/10.1146/annurev-nutr-071714-034330.
Ulvik, Arve, et al. “Evidence for Increased Catabolism of Vitamin B-6 during Systemic Inflammation.” The American Journal of Clinical Nutrition, vol. 100, no. 1, July 2014, pp. 250–55. PubMed, https://doi.org/10.3945/ajcn.114.083196.
VCV000017995.22 – ClinVar – NCBI. https://www.ncbi.nlm.nih.gov/clinvar/variation/17995/. Accessed 29 July 2022.
Vrolijk, Misha F., et al. “The Vitamin B6 Paradox: Supplementation with High Concentrations of Pyridoxine Leads to Decreased Vitamin B6 Function.” Toxicology in Vitro: An International Journal Published in Association with BIBRA, vol. 44, Oct. 2017, pp. 206–12. PubMed, https://doi.org/10.1016/j.tiv.2017.07.009.
Wang, Junjuan, et al. “The Effects of a Single Oral Dose of Pyridoxine on Alpha-Aminoadipic Semialdehyde, Piperideine-6-Carboxylate, Pipecolic Acid, and Alpha-Aminoadipic Acid Levels in Pyridoxine-Dependent Epilepsy.” Frontiers in Pediatrics, vol. 7, Aug. 2019, p. 337. PubMed Central, https://doi.org/10.3389/fped.2019.00337.
Wei, Yao, et al. “Pyridoxine Induces Glutathione Synthesis via PKM2-Mediated Nrf2 Transactivation and Confers Neuroprotection.” Nature Communications, vol. 11, no. 1, Feb. 2020, p. 941. PubMed, https://doi.org/10.1038/s41467-020-14788-x.
Zhang, Dong-Mei, et al. “Efficacy of Vitamin B Supplementation on Cognition in Elderly Patients With Cognitive-Related Diseases.” Journal of Geriatric Psychiatry and Neurology, vol. 30, no. 1, Jan. 2017, pp. 50–59. PubMed, https://doi.org/10.1177/0891988716673466.
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.