High-dose supplementation of Vitamin B6 decreases anxiety

By Tarun Sai LomteJul 25 2022Reviewed by Aimee Molineux

In a recent study published in Human Psychopharmacology: Clinical and Experimental, researchers reported that vitamin B6 supplementation reduced anxiety.

B vitamins play vital roles in the cellular metabolic processes, essential for brain function and the nervous system, including those that help maintain a balance between neural excitation and inhibition. An equilibrium towards excitation has been implicated in multiple neuropsychiatric disorders, including depression and anxiety. As such, it has been suggested that supplementing with high-dose vitamin B might effectively augment behaviorally noticeable effects of inhibition.

In one study, subjects were supplemented with Marmite, rich in vitamin B, and the steady-state visual evoked potentials (SSVEPs) were measured. They observed reduced SSVEP amplitudes after supplementation, which implied an increase in neural inhibition or decrease in excitation. The study mentioned the established role of vitamin B6 in synthesizing gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. However, other mechanisms of action could not be ruled out, given that Marmite is rich in B12 and other B vitamins.

About the study

In the present study, researchers investigated the effects of high-dose supplementation of vitamin B6 or B12 on anxiety and depression. The findings presented here are collective results of double-blind placebo-controlled trials conducted over five years. Participants were a general adult population (chiefly students) recruited in exchange for course credit by advertorials, social media, and word of mouth.

Participants were randomized to receive vitamin B6/B12 or lactose placebo tablets. Individuals were excluded if diabetic, lactose-intolerant, epileptic, or using medications interfering with the absorption of vitamin B. The vitamin B6 tables contained 100 mg of B6 as pyridoxine hydrochloride, and B12 tablets had 1000 μg of B12 as methylcobalamin; the doses far exceeded the recommended daily allowance (RDA). Participants were asked to take one tablet with food daily for 30 to 35 days.

The outcome measures were 1) screen for adult anxiety-related disorders (SCAARED) [for anxiety], 2) mood and feelings questionnaire (MFQ) - long version [depression], 3) visual contrast sensitivity and surround suppression [the ability to detect low-contrast visual targets in the presence/absence of a suppressive background pattern], 4) binocular rivalry reversal rate, and 5) tactile battery test [tactile sensory processing battery].

Findings

The study comprised 478 participants, primarily females (381), aged 18 to 58. Analysis of variance (ANOVA) of the SCAARED data of B6 and placebo cohorts revealed a significant decrease in anxiety post-test, mainly driven by the reduced anxiety among B6 group subjects. The minor reduction in anxiety in the placebo group was insignificant. The ANOVA of B12 and placebo groups revealed a significant decline in anxiety post-test, chiefly driven by a decrease in anxiety among B12 group participants.

The B6 group also had significantly lower post-test scores on the generalized anxiety disorder (GAD) and social anxiety (SA) subscales of SCAARED. The B12 cohort had a significant post-test reduction on the separation anxiety (SEP) subscale. In contrast, no significant changes were noted in the placebo group.

ANOVA comparing B6 and placebo group data of MFQ showed no uniform direction of change in depression post-test. In lieu, depression scores were more likely to decrease post-test in the B6 group but increase in the placebo group; moreover, this approached statistical significance. Nevertheless, t-tests comparing baseline and post-test scores revealed no such significant changes. ANOVA of B12 and placebo cohort data showed no significant changes, and the t-test of baseline and post-test scores of the B12 group was insignificant.

A stronger surround suppression effect was observed in the B6 cohort, reflecting a significant interaction between treatment and the absence/presence of the suppressive surround. Follow-up t-tests revealed a significant difference in the minimum detectable level of contrast between the two cohorts when surround suppression was present and not when it was absent. 

In contrast, the contrast thresholds were higher in the B12 group than in the placebo cohort regardless of surround suppression. However, the effect was marginally larger when surround was present. In the binocular rivalry reversal rate, there were no significant differences between either vitamin group and the placebo cohort. Similarly, the two vitamin groups were not significantly different from the placebo group on any measure from the tactile battery test.

Conclusions

The findings suggested that vitamin B6 supplementation influenced the balance between neural inhibition and excitation. B6 supplementation amplified visual contrast thresholds only in the presence of suppressive surround. Specifically, this indicated an increased neural inhibition by higher GABA levels, given that the effect of surround suppression on contrast thresholds is caused partly by inhibitory GABAergic interneurons.

B6 supplementation also reduced self-reported symptoms of anxiety. The elevated levels of GABA might explain the observed decrease in anxiety. In contrast, B6 supplementation had no apparent effect on other outcome measures (depression, binocular rivalry, and tactile battery tests). Conversely, the team found no apparent effects of B12 supplementation on the outcome measures, albeit the trends suggested lower anxiety and higher visual contrast thresholds.

In conclusion, the study demonstrated that the high-dose vitamin B6 supplementation could influence anxiety and observed that the vitamin also increased surrounding suppression of visual contrast detection. Furthermore, measuring the effects of other micronutrients on these outcome measures might help identify the micronutrients that could be combined and tested as a treatment for anxiety and depression.