Table of Contents
Vitamin B6 (Pyridoxine, Pyridoxal, Pyridoxamine) is one of 8 B-vitamins. B6 is water-soluble and found in every single cell in your body.
Vitamin B6 a required coenzyme for the synthesis of dopamine, epinephrine, GABA, melatonin, norepinephrine, and serotonin.[i]
As a nootropic, Vitamin B6 is crucial for the synthesis of these neurotransmitters. Even mild deficiency results in down-regulation of GABA and serotonin synthesis. Leading to poor sleep, behavior, cardiovascular function, and the loss of hypothalamus-pituitary control of hormone secretion.[ii]
Vitamin B6 was first isolated in the 1930’s. The “6” in Vitamin B6 refers to six common forms, namely pyridoxal, pyridoxine (pyridoxal), pyridoxamine, and their phosphorylated forms.
Pyridoxal phosphate (pyridoxal 5′-phosphate, P-5-P, PLP), the active form of Vitamin B6 is said to be the most versatile organic cofactor in biology. More than 140 distinct enzyme activities in your body and brain depend on PLP.[iii]
The biochemical reactions in your body by PLP-dependent enzymes include the making of hemoglobin, amino acid synthesis and fatty acid metabolism.
PLP also functions as a coenzyme that catalyzes the release of glucose from stored glycogen. Turning it into the type of energy your brain cells can use for fuel.
Vitamin B6 (Pyridoxine) helps:
- Cerebral Circulation: Vitamin B6 is needed to regulate homocysteine. High homocysteine levels are linked to inflammation that can lead to blood vessel damage. And possible plaque buildup leading to heart attack or stroke.
- Neurotransmitters: Vitamin B6 is a cofactor in the synthesis of neurotransmitters dopamine, epinephrine, GABA, norepinephrine, and serotonin. Affecting alertness, cognition, learning and memory and mood.
- Mood: Vitamin B6 helps increase brain serotonin and dopamine levels. Decreasing anxiety, depression, fatigue and pain.
Overview
Vitamin B6 (Pyridoxine, Pyridoxal, Pyridoxamine) is one of 8 water-soluble B-vitamins that are absolutely vital to the highly optimized brain. And is essential to all forms of life.
Vitamin B6 is found in every cell in your body and brain. Vitamin B6 is a necessary cofactor in the folate cycle. And contributes to the synthesis of neurotransmitters dopamine, GABA, melatonin, norepinephrine, and serotonin.
Vitamin B6 has a direct effect on your immune system, gene transcription and expression. And is involved in glucose regulation.
Vitamin B6 protects your blood-brain barrier by regulating homocysteine levels. Excess homocysteine can damage blood vessel linings and neurons, resulting in cognitive decline. B6 also helps form myelin, the fatty sheath that surrounds and protects neurons.
Pyridoxal phosphate (pyridoxal 5′-phosphate, P-5-P, PLP), the active form of Vitamin B6 helps control inflammation in your brain. Low levels of PLP are associated with severe inflammation in the brain.[iv] Leading to neurodegenerative diseases like Alzheimer’s and Parkinson’s. And contributes to heart disease, arthritis, inflammatory bowel disease and diabetes.
Foods rich in Vitamin B6 include bananas, beef, chickpeas, pistachios, pork, potatoes, and turkey.
Even mild Vitamin B6 deficiency can deplete neurotransmitters which leads to cognitive decline. Resulting in brain fog, anxiety, depression and overall poor mental performance.
How does Vitamin B6 (Pyridoxine) work in the Brain?
Vitamin B6 (Pyridoxine) boosts brain health and function in several ways. But two in particular stand out.
- Vitamin B6 is a cofactor in neurotransmitter synthesis. Vitamin B6 and its role in amino acid metabolism makes it a critical component for the synthesis of all major neurotransmitters including dopamine, GABA, melatonin, norepinephrine and serotonin.
The synthesis of these neurotransmitters is entirely dependent on B6 levels in your brain. Even mild deficiency results in less GABA and serotonin synthesis. Resulting in poor sleep patterns, irritability, anxiety, depression, panic attacks and stress.
Low dopamine and norepinephrine levels due to lack of Vitamin B6 leads to depression and loss of memory.
B-Vitamins play a crucial role in optimized cognition. And should be part of every nootropic stack. Unfortunately, there is very little talk in nootropic circles of these vitamins.
A review of vitamin intakes in Germany, the UK, the Netherlands and the USA was conducted to compare vitamin intake to national recommendations. And the study found intake was below recommendations of even the most critical of vitamins. Including B-Vitamins.
The authors of the study noted that this gap exists in vitamin intake and national recommendations for a significant portion of the population. Even though diverse foods were available.[v]
- Vitamin B6 helps reduce inflammation. B6 along with Vitamin B12 and folate help control homocysteine. High levels of homocysteine have been implicated in inflammation leading to damage of blood vessels. Causing heart and neurodegenerative disease.
But homocysteine is not the bad guy when it’s in balance. We need this amino acid for the synthesis of cysteine which is a precursor to the master antioxidant glutathione.
It’s when homocysteine gets out of control that causes problems in our brain and our cardiovascular system. One of the issues with aging is brain shrinkage. Gray matter shrinkage in key areas of the brain have been identified in Alzheimer’s Disease.
Professor David Smith at Oxford University in England conducted a study with 156 elderly patients (age 70+) who were suffering mild memory loss and higher than average levels of homocysteine. High levels of homocysteine are typically the result of deficiencies in Vitamins B6, B12 and folic acid.
For 2 years, the elderly patients received 20 mg of Vitamin B6, 0.5 mg of Vitamin B12 and 0.8 mg of folic acid (folate). The findings of this study were dramatic. Those who took only placebo experienced brain atrophy of 5.6% over those 2 years. Brain shrinkage in those who took the B-Vitamins had only 0.6% brain shrinkage.
This study showed a 7-fold difference in gray matter shrinkage in just 2 years. Vitamin B6 along with B12 and folic acid helped protect brain density. And specifically in the areas of the brain vulnerable to Alzheimer’s.[vi]
How things go bad
Vitamin B6 deficiency is a lot more common than you’d expect in our modern society. B6 from diet alone, especially for vegetarians and the aged is not adequate to supply what our body and brain needs.
↓ Concentration, memory, learning, and recall decline
↑ Anxiety, confusion, irritability, and depression increase
↑ Homocysteine and inflammation increases
↓ Energy levels decline
Vitamin B6 is critical for nerve function. And a deficiency can result in psychiatric disorders, seizures, migraines, chronic pain and mood disorders like depression.
Vitamin B6 (Pyridoxine) benefits
Vitamin B6 is involved in the regulation of cognition function and mood. B6 is a cofactor in the neurotransmitters directly related to alertness, anxiety, attention, concentration, memory and mood.[vii]
When you add Phenylalanine to your stack to boost the neurotransmitters dopamine, epinephrine, norepinephrine and melatonin, it will not work without Vitamin B6. B6 is a critical cofactor in the synthesis of these neurotransmitters.
The same holds true for any nootropic you use with the intention of boosting any of the major neurotransmitters in your brain. Vitamin B6 is absolutely required if you want them to do their job.
You need Vitamin B6 to help control inflammation in your brain. B6 suppresses the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).[viii]
Vitamin B6 is essential for controlling elevated homocysteine levels which can damage blood vessels crucial for optimal cerebral circulation.
A 2008 review of research in the previous 10 years covering a total of 77 studies and 34,000 subjects demonstrated the relationship between cognitive deficits and dementia and the status of folate, or vitamins B12, or B6 and homocysteine levels.[ix]
Vitamin B6 is a coenzyme involved in the synthesis of Heme, an iron-containing component of hemoglobin. Hemoglobin is found in red blood cells and is critical to their ability to transport oxygen throughout your body and brain.
Vitamin B6 concentrations in your brain are about 100-times higher than levels in your blood. B6 is critical to the highly optimized brain.
How does Vitamin B6 (Pyridoxine) feel?
Vitamin B6 is water-soluble, and has been shown to improve energy and mood. Both men and women report a boost in libido when supplementing with B6.
Women report that Vitamin B6 helps control mood swings resulting from PMS.
Neurohackers report that Vitamin B6 helps sleep and creates vivid dreams. Many prefer it over melatonin for sleep.
Those suffering with carpal tunnel syndrome have consistently found relief in symptoms by using Vitamin B6. Many find B6 useful for tendonitis and other joint pain.
Some report that supplementing with Vitamin B6 helps prevent sunburn. And a few have found relief from tinnitus by using B6.
Those dealing with ADHD have found that using Vitamin B6 has helped reduce the reliance on ADHD meds. Likely because B6 is a cofactor in the synthesis of dopamine and norepinephrine.
Vitamin B6 Clinical Research
Vitamin B6 (Pyridoxine) promotes vivid dreams
Read the reviews of those supplementing with Vitamin B6 and you’ll come across several reports of improved sleep and vivid dreams. And we have science to back this up.
12 college students participated in a double-blind, placebo-controlled trial to examine the various claims that Vitamin B6 increase dream vividness, and the ability to recall dreams.
The students were given 100 or 250 mg of Vitamin B6 or a placebo prior to bedtime for 5 consecutive days. Morning reports indicated a significant difference in ‘dream-salience scores’. This is a composite score measuring dream vividness, bizarreness, emotionality and color.
The study suggests that Vitamin B6 may act by increasing arousal during rapid eye movement (REM) sleep. The researchers hypothesized it had something to do with the conversion of tryptophan to serotonin.[x]
Vitamin B6 (Pyridoxine) may prevent Parkinson’s Disease
A study out of the Netherlands suggests that Vitamin B6 could cut the risk of Parkinson’s Disease in half.
Researchers in Rotterdam recruited 5,289 people over the age of 55 and assessed their dietary intake using food questionnaires. This study looked into reports that increased levels of the amino acid homocysteine might promote Parkinson’s Disease.
Numerous studies have reported that higher intakes of folate, Vitamin B12 and Vitamin B6 decrease blood homocysteine levels and could offer protection from Parkinson’s.
It has also been proposed that Vitamin B6 could provide antioxidant effects. And could reduce the risk factor for Parkinson’s by a mechanism that is not related to homocysteine.
After 9.7 years of follow-up, 72 new cases of Parkinson’s Disease had been diagnosed. The average Vitamin B6 intake was 1.63 mg per day, average B12 intake was 5.3 mcg per day, and average folate intake was 218.7 mcg per day.
No significant reductions in the risk of Parkinson’s were found for folate or Vitamin B12. But when the researchers limited their calculations to the 66% of participants who were smokers, they found that the protective effects of high Vitamin B6 intake appeared limited to this group.
The researchers noted that several studies indicate the protective effects of nicotine on brain cells, and reduced the risk of Parkinson’s. Which suggests that Vitamin B6 plus nicotine provides mutually reinforcing beneficial effects.
Since folate and Vitamin B12 showed no relationship to reduced Parkinson’s, the researchers concluded it was not homocysteine that was behind the newly diagnosed patients.
The study authors said that the apparent benefits of B6, “may point towards an alternative mechanism… because several lines of evidence suggest neuroprotective properties of Vitamin B6 through antioxidant capacities”.
Oxidative stress has been shown to be prominent in Parkinson’s Disease, and higher Vitamin B6 intake may reduce Parkinson’s risk through its antioxidant effects.[xi]
Vitamin B6 (Pyridoxine) to beat Panic Attacks
Reduced serotonin levels are known as one of the causes of panic attacks and hyperventilation attacks. Serotonin is synthesized from tryptophan. And for the synthesis of serotonin, you need Vitamin B6 and iron.
The clarify how this works, researchers at Atago Hospital in Japan checked the blood levels (vitamins B2, B6, and B12 and iron) of patients who came into the ER with a panic attack or hyperventilation attack.
The team measured parameters in 21 patients compared to 20 healthy volunteers. The study found that both Vitamin B6 and iron levels were significantly lower in the panic and hyperventilation attack people than in the healthy volunteers.
There was no significant difference in Vitamin B2 or B12. The study concluded that low blood concentrations of Vitamin B6 and iron are involved in panic and hyperventilation attacks.[xii]
Vitamin B6 recommended dosage
Recommended dosage of pyridoxal 5′-phosphate (P-5-P) form of Vitamin B6 is up to 100 mg per day. P-5-P is the only ‘active’ form of B6 available and preferred for nootropic usage. (see “Side Effects” for toxicity with Vitamin B6).
The enzyme L-dopa decarboxylase depends on P-5-P to convert L-DOPA into dopamine. And is involved in the final stages of serotonin synthesis.[xiii]
An analysis of data collected in the USA in 2003-2004 indicated that Vitamin B6 intake from food averaged about 1.9 mg per day.[xiv] The problem is some forms of Vitamin B6 from plants (pyridoxine glucoside) are not very bioavailable.
In most cases, and certainly that of neurohackers using nootropics to boost neurotransmitters or improve mood, Vitamin B6 from diet alone is not enough.
The study mentioned above shows that even those supplementing with 2 mg per day of Vitamin B6 or less had blood levels of B6 much too low.
Vitamin B6 is water-soluble and you excrete it in urine, so supplementation daily is critical.
Women taking birth control pills, or who are menstruating are usually low in Vitamin B6. Those following a strict vegetarian diet are also typically deficient in B6.
Drugs like L-DOPA, anti-tuberculosis medications, metal chelators, methylxanthines to treat respiratory conditions, and long-term use of NSAIDs, anti-convulsants, and phenobarbital all inhibit Vitamin B6 metabolism. If you are using any of these drugs you are likely low in B6.
You can safely dose up to 100 mg per day of Vitamin B6 with no toxic effects.
Vitamin B6 Side Effects
Vitamin B6 (Pyridoxine) is non-toxic at recommended doses. So is considered well-tolerated and safe.
Side effects are rare but very high single doses can include stomach upset, nausea or diarrhea.
Pyridoxine neuropathy is a form of nerve damage caused by high doses of Vitamin B6 when taken for extended periods. Symptoms are loss of coordination, extreme skin sensitivity, bone pain, muscle weakness, and numbness.
Pyridoxine neuropathy has been reported in doses of Vitamin B6 of 200 mg to 5 grams per day for extended periods. When dosing was stopped, symptoms usually disappeared.[xv] [xvi]
This nerve damage has been identified as the destruction of axons and neurons which is reversible at lower levels of toxicity. And irreversible at higher levels of Vitamin B6 toxicity.[xvii] [xviii]
Type of Vitamin B6 to buy
Vitamin B6 from food and supplements comes in the form of Pyridoxine, Pyridoxal, and Pyridoxamine.
These forms of B6 are considered ‘inactive’, but are converted in your liver and intestines into the active form of Vitamin B6 called pyridoxal 5′-phosphate (P-5-P).
For nootropic use, look for a P-5-P supplement or a B-Complex formula that uses P-5-P.
Most multivitamins also include some form of Vitamin B6 in their formula. But many of these multis don’t contain enough for optimum health. And many have an inactive version of this nutrient.
The Performance Lab® NutriGenesis Multi offers a nature-identical form of Vitamin B6 and is now my favorite daily multivitamin/mineral supplement.
I prefer the Performance Lab® multi because it’s more potent, it’s biologically active and I’ve found to be a far more effective multi compared to every other multivitamin supplement I’ve ever used.
Performance Lab® uses their own priority NutriGenesis® vitamins and minerals which are grown on probiotic, plant and yeast cultures in a state-of-the-art lab.
Nootropics Expert Recommendation
Vitamin B6 as pyridoxal 5′-phosphate (P-5-P) up to 100 mg per day
I recommend using Vitamin B6 as a nootropic supplement.
Your body does not make Vitamin B6 on its own. So to get its benefits you must get it from food, or take it as a supplement.
Vitamin B6 is especially helpful for those suffering from low energy levels, anxiety, depression, and chronic pain.
Experience shows Vitamin B6 helps stop and reverse the symptoms associated with high homocysteine levels. B6 in combination with folic acid and Vitamin B12 will lower high homocysteine implicated in heart disease and Alzheimer’s.
Vitamin B6 is also particularly helpful to students and executives who want to boost cognition, learning, memory and mood. Because it raises dopamine, GABA, norepinephrine, epinephrine and serotonin levels in your brain.
Vitamin B6 can help those dealing with ADHD because it helps synthesize dopamine and serotonin in your brain. ADHD symptoms should decline and you may be able to cut back on your ADHD meds.
Vitamin B6 is a must have addition for any nootropic stack. If you are using any nootropics to raise dopamine, GABA or serotonin levels, you absolutely need extra Vitamin B6.
At the very minimum every neurohacker should be using a multivitamin every day that includes Vitamin B6. The best multi I’ve found and use every day is the Performance Lab® NutriGenesis Multi for men or women.
Join The Discussion - 115 comments
Dan
February 20, 2023
Hello David
pyridoxal-5-phosphate coenzyme monohydrate is it the same shape as the regular p-5-p?
Since 50 mg contains 33 mg p-5-p
Or another version of pyridoxal-5′-phosphate [Coenzymated] 100mg contains 60mg p-5-p, do you think these are good forms and how is it different from the usual one?
Thank you very much in advance.
David Tomen
February 21, 2023
Dan, the enzyme cofactor Pyridoxal-5-phosphate monohydrate is a vitamin B6 metabolite that can modify lysyl and valyl residues in proteins. It acts as a coenzyme in transamination reactions by forming a Schiff-base linkage with lysine groups on aminotransferase. It also serves as a coenzyme in some decarboxylation and deamination reactions. It has the ability to inhibit purinergic receptors and intracellular influx of Ca2+. Pyridoxal-5-phosphate monohydrate can modify peptides and suppress their precursor ionization efficiency.
Pyridoxal-5′-phosphate [Coenzymated] is the coenzyme form of Vitamin B6. In other words it is the natural form of Vitamin B6 used by our body and brain.
Dan
March 17, 2023
So which form do you think is better? And also what is better in the form of capsules or tablets, since I read that they should be coated with an enteric coating. And I also noticed that in the ingredients they often list p-5-p, such as 50 mg of p-5-p, and then on top they write that they only contain 33 mg.
I only have the ability to buy on Iherb, and want to choose what’s best for price/quality, and the p-5-p monohydrate from NOW Foods seems good, but I’m not sure.
Thanks so much in advance for the answer!
Mel
December 25, 2022
So my son takes 200mg twice a day of Vitamin B6 HCL with magnesium (prescribed by naturopathy). I am confused about the fact it raises dopamine. He has OCD and VDR Taq +/+ and COMT V158M +/+ genes. I read that those two being homozygous, tend to have high dopamine. OCD can also have high dopamine. He was found recently to have a deficiency of B6. So should he continue it? Or does it make matters worse?
David Tomen
December 26, 2022
Mel, Vitamin B6 a required coenzyme for the synthesis of dopamine. You cannot make dopamine if you do not have adequate levels of Vitamin B6, B9, & B12 in your system.
Cionn
December 23, 2022
Hi David.
First, I’d like to thank you for creating such an incredible resource. I discovered your website last week & haven’t stopped reading since.
You mentioned that Vitamins B6, B9 & B12 need to be balanced. Can you elaborate a little on this please. For a Nootropic beginner like me trying to determine my ideal dosages of each, what do you recommend as a starting ratio of each?
Many thanks.
CM
David Tomen
December 26, 2022
CM, the easiest way to keep them in balance is by using a BioActive B-Complex like this one: https://nootropicsexpert.com/go/life-extension-bioactive-b-complex/
salem
December 17, 2022
hi david
i have high prolactin level, i knew that b6 can lower it
i found b6, 250mg as pyridoxine HCI , from life extension
can i take it , one per day ?
salem
December 17, 2022
i also have P-5-P 100mg from another brand
can i take it, 2 times per day or 3 times?
thanks david
David Tomen
December 21, 2022
Salem, Pyridoxine neuropathy has been reported in doses of Vitamin B6 of 200 mg to 5 grams per day used for extended periods. When dosing was stopped, symptoms usually disappeared. But that is not the case while using natural P-5-P.
Jain rahil
August 12, 2022
Hello david, is it safe to take pyridoxine hcl upto 100mg daily ?
Unable to get p5p in location
David Tomen
August 14, 2022
Yes
Joe
August 3, 2022
When should you take b6
Am or pm?
David Tomen
August 4, 2022
Joe, it doesn’t matter when you take Vitamin B6. You will maintain a steady level of B6 if it is used daily.
Sandra
August 2, 2022
Hi David!
For ADHD should I take more B6 P5P?
Right now my B complex in the morning contain about 23mg of P5P.
So should I buy separate P5P and use next dose before sleep for example? I’ve seen nearly 100mg of B6 in your daily Bioactive B complex from life extension which you recommended me a while ago. There must be a reason for that right?
Thank you ^^
David Tomen
August 2, 2022
Sandra, 100 mg of P-5-P seems to be the maximum but ideal amount that most people need. Each of us is different and you may need less that someone next to you. But it is water soluble and as long as you are using a therapeutic dose you’ll know your system is getting what it needs.
But the B-Vitamins work in synergy. I’m not a big fan of maxing out the dose of one B-Vitamin and not getting enough of the others. Balance is key.
You may want to finish the B-Complex you have then get a better one when you’re finished with what you have.
Chris
July 31, 2022
Very interesting. Thank you for this great info! I have pyroluria, which is characterized by low B6 and zinc, among other things. This helps me understand why P5P is so important, and why a deficit of it creates the symptoms that it does.
I had been taking P5P for quite some time, but a practitioner advised me to stop it and my methyl B vitamins for a while, which was weird and surprising, but I did it. In the meantime, I’ve watched as I’ve lost the last bits of interest I had for anything in life; all of the things I used to love and enjoy are just boring and irritating to me now. I’ve taken DLPA, DPA, tyrosine, all of the things that are supposed to help boost low dopamine mood and focus and felt practically no difference from any of it. I added my B6 back in yesterday after reading this and will hope to see some results.
David Tomen
August 2, 2022
Chris, he probably advised stopping it for a while. Because the thing with problems with methylation can be very complex. And it takes some experimenting until you figure out exactly what you need. To balance things out.