The study below is a perfect follow-up to the study I just posted about. Namely, in the immediately preceding blog post I listed a study, which found that one of the most widely-prescribe “antidepressants” of the SSRI class actually worsens depression. Of course, like most pharma drugs, the SSRI class has a number of severe side effects including suicidal and homicidal ideations and attempt, dementia, heart valve disease, diabetes, neurological conditions, etc. In contrast, the B group of vitamins is virtually devoid of serious side effects, even in pharmacological doses, but so far have been lacking evidence of effectiveness for health conditions when used as a monotherapy (i.e. by itself, with no other active drug/substance administered). The study below changes that, and is the first double-blind, randomized, placebo-controlled trial with vitamin B6 and B12 as treatments for depression and anxiety. While both vitamins were found to be ineffective for anxiety, vitamin B6 at daily doses of 88mg-100mg for just a month, produced “large improvements” in depression symptoms. Based on other studies utilizing the same checklists for diagnosing and quantifying depression symptoms, it looks like vitamin B6 was more effective than many of the most widely-prescribe antidepressant drugs, while having no serious side effects. While ~100mg vitamin B6 daily is certainly high, multiple studies have demonstrated that taking the “active” form of B6 known as P5P achieve similar effects at doses 5-10 times lower than pyridoxine Hcl (the cheap and widely available B6 form the study used). In other words, 10mg-20mg P5P daily may be able to replicate the study findings while also further reducing the risk of side effects of high-dose B6 (e.g. neuropathy). As far as mechanism of action – I agree with all of the ones proposed by the study (GABA, dopamine, glutamate, etc), but I will also add to that list the virtually unknown role of B6 as the main endogenous non-steroidal antagonist to cortisol, with the latter being a known cause of depression.
https://onlinelibrary.wiley.com/doi/full/10.1155/da/8926512/
“….Given existing evidence that high-dose vitamin B6 influences neurotransmitter levels and that this has behavioural and psychological effects in animals and humans, we explored its effect on three common negative emotional states—depression, anxiety and stress, in an opportunity sample drawn from the general population. Compared to either placebo or high-dose vitamin B12 tablets, we found that vitamin B6 produced a large improvement in depression symptoms but had no significant effect on anxiety or stress. The largest improvement was evident in participants whose baseline depression scores were classified as indicating mild or more severe depression, but individuals whose baseline depression scores fell just below that cutoff also improved substantially. These effects were confirmed when we adjusted the analysis for baseline differences. This is the first randomised double-blind study to demonstrate the potential of vitamin B6 as a standalone or adjunctive treatment for depression; it builds on a large body of epidemiological evidence indicating a relationship between vitamin B6 status and depression risk, as well as the previous trials showing benefits of vitamin B6 for the mood/depression symptoms experienced in premenstrual syndrome, and the animal work revealing the potential antidepressant mechanism via increasing serotonin and GABA, and reducing glutamate, in the brain.”
https://www.technologynetworks.com/tn/news/could-vitamin-b6-reduce-symptoms-of-depression-415900
“…A daily high-dose Vitamin B6 supplement could significantly reduce symptoms of depression in people who already experience them, new research from the University of Reading has found. The double-blind randomised trial, published this month in the journal Depression and Anxiety, asked participants to take a 100mg Vitamin B6 tablet every day for a month. Those who reported mild or more severe depression at the start showed a reduction in symptoms compared to those given a placebo or Vitamin B12. The findings are the first from a randomised controlled trial to demonstrate the potential of Vitamin B6 as a treatment for depression, and build on a substantial body of epidemiological evidence linking Vitamin B6 status with depression risk.”
