Vitamin B6, pyridoxine, is a peculiar vitamin among the B-family. Whilst necessary for over 100 enzymatic reactions in the body, it seems to be the only B-vitamin that we hear warnings about having a toxicity risk, the primary symptom of which is nerve damage involving paresthesia (tingling and burning), although it’s usually reversible upon prompt cessation. I’ve seen anecdotes of people being able to take up to several hundred milligrams daily long-term with no repercussions, and heard of people experiencing paresthesia just from moderate doses, so I suspect it comes down to individual metabolism and baseline nerve function.

The buildup of homocysteine to excessive levels is results in oxidative stress, heart disease, cancer, and mortality. B6 is fundamental in homocysteine metabolism, and thus is a crucial factor in researching and preventing disease. People in the 75th percentile of serum B6 levels have less than half the risk of lung cancer than those in the 25th percentile (Johansson, et al., 2010).

B6 is a cofactor in the glutamate decarboxylase (GAD) enzyme, which is how we convert the excitatory glutamate into the inhibitory GABA. Dysfunction of the GAD enzyme is implicated in epilepsy, diabetes, autism, anxiety, ADHD, schizophrenia, bipolar disorder, Parkinson’s, and neuropathy. B6 supplementation increased GAD activity by 180% from baseline (Huang, et al., 2016).


B6, probably by its role in modulating the inhibitory GABA system, alleviates sensory sensitivity abnormalities such as hyperacusis, the sensitivity to sound (Kamiyama, et al., 2006).

Autistic people are known to inadequately convert B6 into its downstream activated form, P5P (pyridoxal phosphate), which is needed for the vitamin to do its job in the body (Adams, et al., 2006). Supplementation with the activated P5P, bypassing the body’s defective enzymatic reactions, should have a clinically beneficial effect in autism, because even the inefficient decision to use normal B6 on autistic patients has caused significant improvement (Rimland, et al., 1978).

P5P is also a safe glucocorticoid (cortisol) blocker, thus possessing a general anti-stress effect. It prevents the cortisone-induced development of cleft palate in fetal mice, downregulates our own endogenous cortisol release long-term, prevents stress-induced gastric ulcers in rats, and protects against stress-induced immune system suppression (McCarty, 2000).

Dopaminergic substances deplete B6 (Weir, et al., 1991), so those susceptible to malnutrition, digestive disorders, or any disease involving malabsorption should be aware of their possibly increased need to replenish B6 if using stimulants like caffeine, amphetamines, or the eugeroics like modafinil.

The nightmarish side effects of antipsychotic medications include akathisia (extreme physical agitation), tardive dyskinesia (a possibly permanent repetitive movement disorder), and Parkinsonism. These have all been shown to radically improve or cease with administration of vitamin B6, because of B6’s ability to normalize dopaminergic and GABAergic function in presumably deficient patients with mental illness (Sandyk & Pareshi, 1990; Lerner, et al., 2004). In one study on this, the author suspected that B6 raising serotonin also partially explains why it helps, but from what I’ve learned, serotonin is usually involved in causing all of these issues, since akathisia can also be brought on by the serotonin reuptake inhibitors, by inhibiting dopamine whilst flooding the brain with serotonin (Lane, 1998). Additionally, B6 eliminates tremor induced by lithium treatment (Miodownik, et al., 2002).

Vitamin B6 significantly increases dream content and recall, partly by increasing cortical arousal during REM sleep, and possibly also because of its role in tryptophan’s conversion to serotonin (Denholm, et al., 2018; Ebben, et al., 2002).

The supplement brand I’ve always used is The Vitamin Shoppe’s 50mg P5P, although the safest brands with the least or no additives are Lidtke Technologies’ True B6 (P5P) 50mg capsules and NOW’s 100mg Vitamin B6 capules, and BulkSupplements’ Vitamin B6 powder. Lidtke’s 50mg P5P is probably the best option since the dose is cautious and because it’s the active form. Be careful with B6, start low and go slow, and pay attention to any side effects, stopping immediately if you notice sensory neuropathy symptoms.


Works Cited

Adams, James B., et al. “Abnormally High Plasma Levels of Vitamin B6 in Children with Autism Not Taking Supplements Compared to Controls Not Taking Supplements.” The Journal of Alternative and Complementary Medicine, vol. 12, no. 1, 2006, pp. 59–63., doi:10.1089/acm.2006.12.59.

Aspy, Denholm J., et al. “Effects of Vitamin B6 (Pyridoxine) and a B Complex Preparation on Dreaming and Sleep.” Perceptual and Motor Skills, 2018, p. 003151251877032., doi:10.1177/0031512518770326.

Ebben, Matthew. “Effects Of Pyridoxine On Dreaming: A Preliminary Study.” Perceptual and Motor Skills, vol. 94, 2002, p. 135., doi:10.2466/pms.94.1.135-140.

Huang, Yan, et al. “Pyridoxine Supplementation Improves the Activity of Recombinant Glutamate Decarboxylase and the Enzymatic Production of Gama-Aminobutyric Acid.” Plos One, vol. 11, no. 7, 2016, doi:10.1371/journal.pone.0157466.

Johansson, Mattias. “Serum B Vitamin Levels and Risk of Lung Cancer.” Jama, vol. 303, no. 23, 2010, p. 2377., doi:10.1001/jama.2010.808.

Kamiyama M, Kuriyama S, Watanabe M. [A clinical study of pyridoxine treatment for pervasive developmental disorders with hypersensitivity to sound]. No To Hattatsu. 2006;38(4):277-82.

Lane, Roger M. “SSRI-Induced Extrapyramidal Side-Effects and Akathisia: Implications for Treatment.” Journal of Psychopharmacology, vol. 12, no. 2, 1998, pp. 192–214., doi:10.1177/026988119801200212.

Lerner, Vladimir, and Chanoch Miodownik. “Vitamin B6 Treatment for Tardive Dyskinesia.” The Journal of Clinical Psychiatry, vol. 68, no. 11, 2007, pp. 1648–1654., doi:10.4088/jcp.v68n1103.

Lerner, Vladimir, et al. “Vitamin B6 Treatment in Acute Neuroleptic-Induced Akathisia.” The Journal of Clinical Psychiatry, vol. 65, no. 11, 2004, pp. 1550–1554., doi:10.4088/jcp.v65n1118.

Mccarty, M.f. “Prenatal High-Dose Pyridoxine May Prevent Hypertension and Syndrome X in-Utero by Protecting the Fetus from Excess Glucocorticoid Activity.” Medical Hypotheses, vol. 54, no. 5, 2000, pp. 808–813., doi:10.1054/mehy.1999.0956.

Miodownik, Chanoch, et al. “Lithium-Induced Tremor Treated with Vitamin B6: A Preliminary Case Series.” The International Journal of Psychiatry in Medicine, vol. 32, no. 1, 2002, pp. 103–108., doi:10.2190/db1v-85m4-e65t-r3qa.

Sandyk, Reuven, and Ramsing Pardeshi. “Pyridoxine Improves Drug-Induced Parkinsonism and Psychosis in a Schizophrenic Patient.” International Journal of Neuroscience, vol. 52, no. 3-4, 1990, pp. 225–232., doi:10.3109/00207459009000524.

“The Effect of High Doses of Vitamin B6 on Autistic Children: a Double- Blind Crossover Study.” American Journal of Psychiatry, vol. 135, no. 4, 1978, pp. 472–475., doi:10.1176/ajp.135.4.472.

Weir MR, Keniston RC, Enriquez JI, Mcnamee GA. Depression of vitamin B6 levels due to dopamine. Vet Hum Toxicol. 1991;33(2):118-21.

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