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.

Side Effects of Vitamin B6 at very high doses:

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. From the NIH: “Pyridoxine toxicity typically manifests as neurologic symptoms, including paresthesias in the extremities and, in severe cases, difficulty with ambulation. This sensory neuropathy usually develops at doses of pyridoxine above 1000 mg per day. There are some case reports of sensory neuropathies at doses of less than 500 mg per day in patients taking supplements for months. However, none of the studies had sensory nerve damage at a daily intake below 200 mg of pyridoxine per day”.[ref]

Lifehacks:

The US RDA for vitamin B6 is 1.3 to 1.7 mg/day for adults. Adults over 50 may need more B6 (1.7mg/day).[ref] The upper limit of B6 is set at 100 mg/day for adults.

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 (free for the web version, the phone app costs a few $).

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 consider 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 of 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 and supplemental vitamin B6:

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