Vitamin B6: Genetics, Absorption, and Deficiency

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: An 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

Members: Log in to see your data below.
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 .

NBPF3 gene: neuroblastoma breakpoint family member 3, mutations in this gene are linked to neurodevelopmental disorders

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 .



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About the Author:
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.

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