Vitamin B6 is an important cofactor in hundreds of different enzymatic reactions.
Low levels of B6 are linked to an increased risk of diabetes, cardiovascular disease, neurodegenerative diseases, and cancer.
Vitamin B6 is also important for reducing oxidative stress and inflammation.
Genetic variants in several B6-related genes can increase your need for vitamin B6. Members will see their genotype report below and the solutions in the Lifehacks section. Consider joining today.
Vitamin B6: An Essential Cofactor
Vitamin B6 is an essential micronutrient that is used in hundreds of different reactions in the body. It’s a water-soluble vitamin that isn’t synthesized by the body nor stored long-term, so we need to replenish our supply regularly by eating foods that contain B6.[ref]
Vitamin B6 comes in multiple forms: pyridoxal, pyridoxine, and pyridoxamine, as well as phosphate ester forms.[ref] The active form of B6 most often used in reactions in the body is pyridoxal5′-phosphate, abbreviated as PLP or P5P.
This is where genetics comes into play: Converting the forms of B6 that we get from food into the active P5P form utilizes specific genes.
This article explains how vitamin B6 is used by your cells, how it is absorbed and converted, and why genetic variants impact an individual’s need for different amounts/different forms of B6.
What does vitamin B6 do in the body?
The biologically active form of vitamin B6, pyridoxal 5′-phosphate (P5P), is used as a cofactor for hundreds of cellular reactions.[ref]
Let me hit the highlights here:
Nervous system and neurotransmitters:
P5P is essential in the process of synthesizing serotonin from the amino acid tryptophan. It is also a cofactor in the synthesis of 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 synthesizing glucose from amino acids through the process of gluconeogenesis. This makes vitamin B6 important in brain energy and in regulating blood glucose levels.
Methylation cycle cofactor:
Vitamin B6 is a cofactor in the methylation cycle and is important for balancing homocysteine levels. It acts as a cofactor along with SHMT for the formation of methylfolate.
(Related article: Homocysteine)
Tryptophan metabolism:
Vitamin B6 is an important cofactor in the kynurenine pathway for tryptophan metabolism, resulting in the formation of niacin.
(Related article: Tryptophan, kynurenine, serotonin)
Let’s look at what B6 deficiency or insufficiency can cause, and then we will go more in depth in a couple of the topics above to show how everything interconnects.
Symptoms of vitamin B6 deficiency:
Overview of how B6 deficiency affects the body:
System/Condition
Symptom or Risk
Nervous System
Seizures, neuropathy, depression, Parkinson’s
Immune System
Decreased T/B cells, increased infection risk
Cardiovascular
Higher homocysteine, heart disease risk
Metabolic
Insulin resistance, higher diabetes risk
Inflammatory Diseases
Worsened symptoms in RA, IBD, COPD, etc.
Insufficiency or borderline deficiency:
While a full-blown deficiency is uncommon, having low levels, insufficiency, or borderline deficiency in vitamin B6 can impact your health. Traditionally, an active B6 concentration of 30 nmol/L has been used as the level of sufficiency in adults. However, more recent studies show that there are effects on cellular function, possibly starting with P5P concentrations less than 100 nmol/L, with more significant differences seen at >50 nmol/L.[ref]
Here are several ways that low levels of vitamin B6 can impact your overall health and wellness:
Decreased immune response: 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). Supplementary B6 (50 mg/day) brought immune function back to normal after four days.[ref]
Heart health: Low vitamin B6 is also linked to an increased risk of cardiovascular disease and high homocysteine.[ref] Related articles:Cardiovascular disease risk and Homocysteine
Diabetes, metabolic health, and advanced glycation end products (AGEs): Vitamin B6 supplementation reduces the onset of diabetes and complications from diabetes. It also acts as a scavenger of advanced glycation end products, which may be why it protects against complications of diabetes.[ref] Related article: Advanced glycation end products
Parkinson’s disease: 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 (an antioxidant) in the brain.[ref] Parkinson’s patients on L-DOPA also often have low or deficient B6 levels.[ref] Related article: Parkinson’s disease and genetic susceptibility
Chronic inflammation: Inflammatory conditions, including rheumatoid arthritis, IBD, diabetes, cancer, and deep vein thrombosis, are all associated with low vitamin B6 levels.[ref] While inflammatory conditions are linked to low vitamin B6 levels, it may be (at least partly) because systemic inflammation decreases the body’s P5P levels, and dietary intake isn’t sufficient to meet the increased need.[ref] Related article:Chronic inflammation and personalized solutions
Asthma and COPD: A recent study showed that higher vitamin B6 intake correlates with higher FEV1 levels (lung function test) in COPD. Similarly, vitamin B6 levels are lower in people with asthma than in healthy control groups. One connection is that low vitamin B6 interacts with IL-33, an inflammatory cytokine often involved in asthma or COPD. Another connection is that B6 is involved in the inflammatory signaling pathways in the lungs.[ref][ref][ref] Related article: Asthma, genetic variants, and IL33 inflammation
A severe dietary deficiency of vitamin B6 is uncommon because B6 is found in many foods; most people get enough of it to meet the lowest amount needed not to cause frank deficiency. However, studies show that borderline deficiency or insufficiency is somewhat common, with up to 32% of young women having insufficient B6 levels in one study.[ref]
Decreased absorption:
Diseases that cause decreased absorption of vitamins can cause B6 deficiency.
Alcoholics are at a higher risk of B vitamin deficiencies
Celiac disease, IBD, or other diseases that affect nutrient absorption can cause vitamin B6 insufficiency
Severe deficiency is a cause of epilepsy:
In the 1950s, an unintended experiment showed that when B6 was accidentally left out of infant formula, the babies had seizures. Severe, rare mutations that cause a genetic deficiency of the active form of vitamin B6 also cause epileptic seizures.[ref]
Oral contraceptive use:
It’s been well known since the 1970s that some women taking oral contraceptives end up having a low level or marginal deficiency of vitamin B6. One study found that in young, college-age women with a generally healthy diet, about 10% had insufficient B6 levels (<30 nmol/L) while on oral contraceptives. Another study found that up to 78% of women on oral contraceptives had B6 levels less than 20 nmol/L. It is thought that the link is that the increase in estrogen shifts the tryptophan pathway to synthesize more kynurenine, which uses more B6 as a cofactor.[ref][ref][ref]
Genetics:
Genetic variants in the genes involved in vitamin B6 absorption and conversion can also increase susceptibility to having low vitamin B6 levels, especially if combined with lower intake or intestinal absorption problems.
Chronic Inflammation:
Chronically elevated inflammatory cytokines decrease vitamin B6 levels through increased utilization of B6 in the kynurenine pathway. A study in cardiovascular disease patients showed that higher inflammation levels tracked with low B6 and higher kynurenine metabolites. Supplementing with B6 reduced the kynurenine metabolites, but it didn’t reduce inflammation.[ref]
Quick Recap: Why Vitamin B6 Matters
Essential for neurotransmitter synthesis, hemoglobin production, glucose metabolism, and methylation.
Deficiency or low levels are linked to immune dysfunction, cardiovascular risk, neurological issues, and inflammation.
Genetics can increase your need for B6 or affect how your body uses it.
Converting B6 from food to the active form, P5P:
Vitamin B6 is the generic name for six different compounds, including inactive forms from foods, the type made by bacteria, and the converted forms used in cellular reactions.
The conversion to the active form is where genetic variants are very important, so stick with me here and let’s dig into this in more detail…
Forms found in nature:
We get vitamin B6 from foods in the pyridoxamine (meats) and pyridoxine (fruits, vegetables, grains) forms. These forms of vitamin B6 are absorbed in the jejunum, which is the second part of the small intestine after the duodenum.[ref]
Gut microbiome:
Some bacteria in our gut can synthesize B6, but other gut bacteria depend on getting B6 from the food we eat or from their neighboring B6-producing bacteria. This means that the type of bacteria in the gut can affect our circulating B6 levels independent of dietary intake – either increasing or decreasing it, depending on our microbiome.[ref][ref]
Absorption:
In the small intestine, vitamin B6 is absorbed mainly by transporter proteins (SLC19A2 or SLC19A3, which also transport thiamine). The transporters are dependent on the pH in the intestines. At higher levels of pyridoxine, the transporters are saturated and no longer transport pyridoxine.[ref] This naturally limits the amount of vitamin B6 you can absorb at one time.
Conversion:
The liver then converts these inactive forms of B6 into the active form, P5P (pyridoxal 5′-phosphate). The P5P form is what is used in cellular reactions, and 70-90% of the vitamin B6 circulating in plasma is this active form.[ref]
The first step of the B6 conversion process in the liver involves pyridoxal kinase (PDXK gene).
Then, a second step of conversion utilizes the pyridoxine phosphate (PNPO) oxidase enzyme. [ref]
Here’s an image to show you what is happening:
Conversion of dietary vitamin B6 to active P5P. Adapted from:[ref][ref]The PNPO enzyme is the rate-limiting factor in the conversion to the active form of vitamin B6. It uses flavin mononucleotide (FMN) as a cofactor.
Epilepsy and movement disorders:
A severe deficiency caused by rare mutations in the PNPO enzyme can result in encephalopathy, epilepsy, and movement disorders from infancy. PNPO mutations are treated with high doses of P5P (active form), thus providing the active form of B6 without the need for conversion. In addition, mutations in ALDH7A1 in the lysine degradation pathway can also cause epilepsy that responds to P5P supplementation.[ref]
Regulation of active B6:
The cellular levels of P5P are fairly tightly regulated in the body with feedback loops and mechanisms in place. For example, high levels of P5P can be converted back to pyridoxal.[ref]
The ALPL gene encodes tissue-specific alkaline phosphatase, which plays a role in how P5P (active B6) is transported across membranes, including in the kidneys. Genetic variants in ALPL that increase the clearance of P5P through the kidneys result in lower vitamin B6 levels in the body. Conversely, rare non-functioning mutations in ALPL cause a genetic condition called hypophosphatasia, which, in addition to high levels of pyrophosphate, causes high levels of P5P.[ref]
Peripheral Neuropathy and Vitamin B6: Goldilocks vitamin
Vitamin B6 deficiency is one of the more common causes of peripheral neuropathy.[ref][ref] On the other hand, excess consumption of vitamin B6 supplements for longer periods (months to years) has been shown to cause neuropathy or movement disorders in a few individuals. Some people report that high doses of B6 cause tingling and numbness.
How does vitamin B6 deficiency cause peripheral neuropathy — and high-dose vitamin B6 supplements also cause neuropathy? It may come down to the type of vitamin B6 used as a supplement, along with the individual’s genetic variants.
There are two forms of B6 available as supplements: Pyridoxine HCL and P5P. Pyridoxine HCL is the more common type and is usually found in cheaper supplements. Recent research shows that supplementing with the pyridoxine form of B6 at higher doses can paradoxically inhibit the creation of P5P.[ref]
Researchers think that excess pyridoxine from high-dose supplements leads to the inhibition of PDXK, the enzyme that converts pyridoxine to P5P. This, in turn, leads to a decrease in the active form of B6 and likely affects GABA biosynthesis. GABA is an inhibitory neurotransmitter that relies on vitamin B6 as a cofactor for biosynthesis.[ref]
Genetic mutations in the PDXK gene, which converts pyridoxine from food into the active P5P form, can cause peripheral polyneuropathy.[ref]
Thus, a safer option for someone with peripheral neuropathy may be to supplement with the active P5P form of vitamin B6.
Making Connections: Kynurenine, Parkinson’s, Neuroinflammation, Detoxification, and B6
I wanted to go deeper into one aspect of vitamin B6 that has a lot of new research on it — the link between Parkinson’s disease (PD), kynurenine, inflammation, gut microbiome, pesticides, and B6. This illustrates the interconnectedness of systems in the body and how not enough of a cofactor, B6 in this case, can cause a shift in biological pathways that has downstream effects.
B6 is low in PD: Parkinson’s is a complex neurological condition with a lot of questions still surrounding its root cause. Researchers have known for a while that B6 levels are often low in people with Parkinson’s disease. However, it wasn’t known if the low B6 levels were a cause of Parkinson’s or an effect, perhaps related to medication usage.
Causal role: A 2025 study in the journal Parkinson’s Disease shows that vitamin B6 insufficiency plays a central role in Parkinson’s through shifting the kynurenine pathway towards more quinolinic acid production.[ref]
So what is quinolinic acid and where does it come from? Quinolinic acid, or QA, is produced in the kynurenine pathway when tryptophan gets converted to kynurenine and subsequently quinolinic acid on the way to becoming niacin. It’s an intermediary that is neurotoxic.
Here’s the pathway:
There’s a lot going on in how the body balances the use of tryptophan for serotonin, melatonin, and kynurenine synthesis. In general, about 90% of tryptophan is converted to kynurenine, which can then be converted to kynurenic acid (generally neuroprotective) or 3-HK, which then converts to the quinolinic acid and niacin pathway.
Inflammation (TNF-alpha, interferons) increases IDO1, which is the enzyme that converts tryptophan to kynurenine, thus increasing the substrate pool available for quinolinic acid production.
In the brain, activated microglia convert tryptophan to kynurenine to quinolinic acid. The quinolinic acid then can activate the NMDA receptors on neurons, acting as an excitotoxin and eventually causing too much activation, oxidative stress, and neuronal damage.
Vitamin B6 in the active form, P5P, is a cofactor for several steps in the kynurenine pathway. If B6 is low, less of the neuroprotective kynurenic acid is synthesized, with the pathway shifting to more 3-HK being produced instead. You’ll notice that B6 is also a cofactor for a subsequent step in the synthesis of quinolinic acid. Low B6 means reduced availability, not a complete lack. So the higher 3-HK levels end up being processed through, to some extent, to higher quinolinic acid. Important here is that 3-HK can pass through the blood-brain barrier, so peripheral inflammation can increase 3-HK levels in the brain that then can convert to quinolinic acid.
So we have increased inflammation increasing IDO1, which shifts tryptophan to the kynurenine pathway, combined with lower B6 levels that shift the pathway towards the 3-HK side, which eventually results in more quinolinic acid in the brain. Quinolinic acid binds to the NMDA receptor, causing overexcitation of the neurons and, eventually, damage to the dopaminergic neurons. (Note that B6 is also a cofactor in dopamine production, adding another pathway that could be involved here.)
Gut microbiome connection to tie this all together:
Changes to the gut microbiome have long been observed in PD patients and before the onset of symptoms. Some gut bacteria produce B6, while others use B6. A shift in balance between producers of B6 and users of B6 can alter how much is available for the host (you) to absorb.
Organophosphates are a type of pesticide, and exposure to organophosphates (e.g. in agricultural workers or living near golf courses) has been strongly associated with an increased relative risk of Parkinson’s. A 2024 study directly ties ambient organophosphate exposure to an altered gut microbiome. The kicker is that the shift in the gut microbiome caused a decrease in gut microbial production of vitamin B6. The study was done using fecal samples from people living in a region known for heavy agricultural pesticide use in California, with 61% of the participants having Parkinson’s disease.[ref]
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 daily limit of B6 is set at 100 mg/day for adults.[ref] The RDA is set at the levels to prevent severe nutrient deficiency, so it may not be the optimal amount that you need.
Consider any genetic variants above, as they may impact whether you need more vitamin B6 than average.
Vitamin B6: Two forms found in supplements
Let’s take a look at the two forms of vitamin B6 available as supplements.
The most common supplement form is pyridoxine or pyridoxine hydrochloride (HCL). This form needs to be converted in the body to the active form, P5P. This is the type that is found in fortified foods, such as breakfast cereals.[ref]
The active form of B6 is Pyridoxal-5-Phosphate (abbreviated P5P or PLP). This form is also available in supplements and can be used more directly by the body.[ref]
Genetic connection: If you have the PDXK or PNPO variants that impair enzyme function, you may find that P5P is a better form of vitamin B6 for you since it avoids the need for those enzymes.
Absorption and thiamine supplements:
As I mentioned above, pyridoxine is taken up in the small intestines via the SLC19A2/3 transporters, which are also the main transporters for thiamine.[ref] I’m not finding any studies that indicate that taking B6 and thiamine together causes problems with saturated transporters; however, if you find that you aren’t absorbing vitamin B6, you may want to try taking it separately from thiamine.
Blocking the SLC19A receptors:
Some prescription medications also use the SLC19A transporters for uptake, and the long-term use of the medications can cause thiamine levels to drop. Common medications include metformin, hydroxychloroquine, and fedratinib. A recent study also found that Sertraline hydrochloride, Amitriptyline hydrochloride, Trimethoprim, Amoxapine, Penicillamine ethanolamine salt, Verapamil, Quinidine gluconate, and Quinapril interact with and likely decrease thiamine absorption.[ref] While studies have not been done looking at vitamin B6 deficiency due to interactions with these medications, it is something to consider as a possibility when using these medications in the long term.
Clinical trials involving vitamin B6:
Here are a few of the clinical trials on vitamin B6 to illustrate the effects at different dosages. This isn’t a recommendation to take B6 long-term at these dosages, but rather a starting point for you. Talk with your doctor if you have any questions about what is right for you.
Improved metabolic health: A small placebo-controlled clinical trial showed that pyridoxine HCL may help to reduce BMI. The study participants were overweight or obese women, and they took 80 mg of pyridoxine HCL per week for 8 weeks. The B6 group showed slight weight loss, reduced fat mass, and decreased insulin resistance (all statistically significant compared to placebo). [ref]
Added to metformin: In newly diagnosed type 2 diabetes patients, the combination of metformin plus 300 mg/day vitamin B6 improved blood glucose levels over metformin alone.[ref] Note that this is in excess of the recommended upper limit, so talk with your doctor about it.
Reduces depression: A randomized, double-blind crossover trial showed that 100 mg of vitamin B6 daily for 4 weeks decreased depression scores in young women who use oral contraceptives (which decrease B6).[ref] A 2026 clinical trial showed that B6 supplementation (pyridoxine) reduced depression scale scores only in depressed individuals, with no effect on mood for people who weren’t depressed.[ref]
High homocysteine: Numerous studies show that high homocysteine levels may respond to supplemental vitamin B6 (usually along with folate and B12). Common dosages were around 50 mg/day.[ref][ref]
Interactions and cautions with supplemental vitamin B6:
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 involves vitamin B6.
Supplement interactions:
Artemisinin is a natural supplement sometimes used for parasite infections or as an antiviral. However, side effects are common with artemisinin. A recent study showed that artemisinin inhibits PDXK, and a downstream effect is decreased GABA.[ref]
Leukemia caution:
Talk with your doctor if you have leukemia (AML) before supplementing with vitamin B6, since it may help accelerate the disease.[ref]
Safety and side effects of supplemental vitamin B6:
Neuropathy at high doses: In addition to the cautions above about excess pyridoxine inhibiting PDXK, leading to a decrease in active P5P, which causes peripheral neuropathy, there are other side effects from excess vitamin B6.
Side effects at high doses: 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 1,000 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]
Effect on sleep and dreaming: Anecdotal evidence suggests that vitamin B6 increases vividness and dream recall. However, a study on supplemental vitamin B6 only showed that it increased dream recall and didn’t affect dream vividness, bizarreness, or color.[ref]
Effect on Restless Leg Syndrome:
A randomized placebo-controlled clinical trial showed that vitamin B6 improved sleep quality compared to a placebo.[ref]
In Summary:
Genetic variants can significantly impact your vitamin B6 metabolism and the amount and type you need. Understanding your genetic variants, diet, and health conditions can help you optimize B6 intake and wellness. Keep in mind that future research may reveal even more about personalized nutrition and B6 requirements.
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About the Author: Debbie Moon is a biologist, engineer, author, and the founder of Genetic Lifehacks where she has helped thousands of members understand how to apply genetics to their diet, lifestyle, and health decisions. With more than 10 years of experience translating complex genetic research into practical health strategies, Debbie holds a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. She combines an engineering mindset with a biological systems approach to explain how genetic differences impact your optimal health.
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