Genetic Variants that Decrease Vitamin B6

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 to get each day.

Vitamin B6: Essential Cofactor

While we talk about vitamin B6 as one vitamin, there are actually several different forms including pyridoxal, pyridoxine, 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 abbreviated as PLP. This is where genetics comes into play – converting the forms of B6 we get in our foods into the active PLP form.

B6 is a vitamin, meaning we have to get it from our diet since our body can’t make it. It is a water-soluble vitamin that isn’t stored long-term. Thus, we need to get 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: PLP 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: PLP is needed as a coenzyme in creating heme, which is part of the hemoglobin molecule the body uses to carry oxygen through the bloodstream.
  • Creating glucose: PLP is a cofactor for creating glucose from amino acids (gluconeogenesis).
  • Methylation cycle: Vitamin B6 is a cofactor for 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. Diseases that cause decreased absorption of vitamins, though, can cause B6 deficiency. Alcoholics are at a higher risk of B-vitamin deficiency in general, and people on dialysis could also be at a higher risk. Celiac disease can also cause decreased absorption of vitamin B6.

Back in the 1950s, an unintended experiment showed that when B6 was accidentally left out of infant formula, the babies ended up having seizures. There are also severe mutations that cause a genetic B6 deficiency, which causes epileptic seizures.[ref]

What about B6 insufficiency, or low levels of B6? 

  • Studies in older adults show that decreased levels of vitamin B6 cause a significant impact on the immune system. Consuming a diet low in vitamin B6 for three weeks decreased T cells and B cells (white blood cells that fight invaders). Adding supplemental B6 (50 mg/day) brought the immune function back to normal after 4 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, all are 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 dose B6 causes tingling and numbness. Recent research shows that supplementing with the pyridoxine form of B6 at higher doses can paradoxically inhibit the creation of PLP.[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 demonstrate links to low vitamin B6 levels, it may be (at least in part) 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, PLP.

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]


Genetic variants associated with B6:

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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 .


Lifehacks:

The US RDA for vitamin B6 is 1.3 to 1.7 mg/day for adults. Adults over 50 need more B6 (1.7mg/day).[ref]  Keep in mind that vitamin B6 isn’t stored long term, and you need to eat foods that contain enough vitamin B6 daily. One way to track your vitamin intake is through an app such as cronometer.com.

Vitamin B6 from foods comes in several different forms. Plant foods contain both pyridoxine-glucoside (partially bioavailable) and pyridoxine (bioavailable). Animal foods contain pyridoxine (bioavailable). Many measurements of B6 levels in plant foods don’t take into account that pyridoxine-glucoside is not as bioavailable, and therefore you may not be getting as much B6 from plant foods as is published.[ref] This doesn’t mean that plant foods are a bad source for vitamin B6, just that you may need to eat more of them than the data states.

Foods that are high in vitamin B6 include[ref][ref]:

  • Salmon, tuna, mackerel
  • chicken, poultry
  • tofu
  • pork chops
  • beef: liver, steak, hamburger
  • avocado
  • sweet potatoes
  • chickpeas
  • bananas
  • fortified, processed foods (e.g. energy drinks, fortified drink powders, cereal)

High homocysteine:

Numerous studies show that high homocysteine levels may respond to supplemental vitamin B6 (along with folate and B12).[ref][ref]

Medication interactions:

  • If you are on medication, such as levodopa, that causes your body to use more B6, talk with your doctor about supplemental B6 options.[ref]
  • Other medications, such as carbidopa, can cause the active form of B6 (P5P) to be permanently deactivated.[ref] Again, talk with your doctor if you are on a medication that messes with B6.

Related Genes and Articles:

Vitamin C: Do you need more?
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.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.