B6 a New Approach for Depression, Anxiety?

Batya Swift Yasgur, MA, LSW

July 26, 2022

High-dose vitamin B6 supplements may reduce feelings of anxiety and depression, new research suggests.

Investigators compared supplementation with a 1-month course of vitamin B6 or B12 to supplementation with placebo in almost 500 adults. Results showed that vitamin B6 supplementation was associated with reductions in self-reported anxiety and a trend toward decreased depressive symptoms.

In addition, the vitamin B6 group showed increased levels of gamma-aminobutyric acid (GABA), as indicated by results on a visual test that was administered at the end of the trial. The test results demonstrated subtle changes in participants' visual performance. The researchers considered this to be consistent with controlled levels of GABA-related brain activity.

However, "before practicing clinicians would recommend taking high doses of vitamin B6, a full-scale clinical trial would have to be carried out to verify the findings, assess any side effects, and find out which types of patients do or don't benefit," study investigator David Field, PhD, associate professor, School of Psychological and Clinical Language Sciences, University of Reading, United Kingdom, told Medscape Medical News.

"My relatively small study can only be considered as an initial proof of concept," Field said.

The findings were published online July 22 in the Journal of Human Psychopharmacology: Clinical and Experimental.

Eat Marmite?

"Recent research has connected mood disorders and some other neuropsychiatric conditions with disturbance in this balance, often in the direction of raised levels of brain activity," Field noted.

Vitamin B6 is a coenzyme in the synthesis of GABA, an inhibitory neurotransmitter, from glutamate. Some previous research has suggested that vitamins B6 and B12 have a role in improving mood-related outcomes.

Field had reviewed a 2017 study of the effects on visual processing of eating Marmite, a type of food spread rich in vitamin B, every day for a few weeks.

"Remarkably, the results of that study suggested that eating Marmite had increased the level of the inhibitory neurotransmitter GABA in the visual part of the brain, damping down the level of neural activity slightly," he said.

However, Marmite contains other B vitamins and other ingredients that might potentially account for this result, "plus, a lot of people don't like the taste of Marmite," Field noted.

Therefore, he wanted to "find out which individual ingredients were driving the effect, and B6 and B12 were the most plausible candidates."

He decided to test these vitamins individually and to compare them to placebo. "I added the measures of anxiety and depression that were not in the Marmite study because I reasoned that if GABA levels were altered, this could improve those disorders, because we know that decreased levels of GABA in the brain occur in both of those conditions," Field added.

Over the course of 5 years, investigators recruited 478 participants aged 18 to 58 years (mean age, 23 years; 381 women). Of these, 265 reported having anxiety, and 146 reported having depression.

The study participants were randomly assigned to receive either vitamin B6 (100 mg pyroxidine hydrochloride), vitamin B12 (1000 mg methylcobalmin), or placebo tablets once daily for a month.

They also completed the Screen for Adult Anxiety Related Disorders (SCAARED) and the Mood and Feelings Questionnaire (MFQ) long version at baseline and following supplementation ("post-test"), and they underwent three sensory tests that acted as assays of inhibitory function at post-test.

In addition, 307 participants completed the Visual Contrast Sensitivity and Surround Suppression, which "measures the minimum percentage contrast between the lighter and darker regions of a striped pattern that can be detected (called the contrast threshold)," the investigators note.

The contrast threshold was measured with and without a suppressive surround mask that increases the threshold ― an effect mediated by GABAergic connections in the visual cortex.

Participants (n = 172) also completed the Binocular Rivalry test and the Tactile Test Battery (n = 180). Both tests are designed to measure responses requiring GABAergic inhibitory activity.

"Subtle Changes"

ANOVA analyses revealed a "highly significant" reduction in anxiety at post-test (F[1,173] = 10.03, p = .002, ηp 2 = .055), driven primarily by reduced anxiety in the B6 group (t[88] = 3.51, P < .001, d = .37). The placebo group also showed some reduction in anxiety, but it was not deemed significant, and the overall interaction itself did not reach significance.

A comparison of the B12 group with the group that received placebo revealed a significant reduction in anxiety at post-test (F[1,175] = 4.08, P = .045, ηp 2 = .023), similarly driven by reduced anxiety in the B12 group (t[89] = 1.84, P= .069, d = .19) ― but the interaction was not significant.

Among the B6 group, there was a highly significant reduction in scores on the generalized anxiety disorder and social anxiety subscales of the SCAARED, and there was a trend toward reductions on the other subscales. Among the B12 group, there was a significant reduction only on scores on the separation anxiety subscale. No significant changes were found in the placebo group.

The ANOVA test analysis of the B6 and placebo group data showed "no uniform direction of change" in depression at post-test. The researchers found a "tendency" for depression scores to decrease between baseline and post-test in the B6 group but to increase in the placebo group ― an interaction that "approached" significance (F[1,96] = 3.08, P = .083, ηp2 = .031), they report.

The ANOVA analysis of the B12 and placebo group data revealed no significant or trending effects, and the t-test comparing baseline and post-test scores in the B12 group was similarly nonsignificant.

B6 supplementation did change visual contrast thresholds, but only when a suppressive surround was present. There were "no clear effects" of B6 supplementation on other outcome measures, including binocular rivalry reversal rate and the tactile test battery, the investigators note.

"We found that supplementation with B6 produced subtle changes in tests of visual processing in a way that suggested an increase in the level of the inhibitory neurotransmitter GABA," Field reported.

Vitamin B6 is a "cofactor for a metabolic pathway in the brain that converts the excitatory neurotransmitter glutamate into the inhibitory/calming GABA," he said.

"By increasing the quantity of the cofactor, we slightly speed up the rate of this metabolic process, and so you end up with a bit more of the GABA neurotransmitter and a bit less glutamate. The net effect of this is to slightly reduce the amount of activity in the brain," Field added.

Most Common Nutrient Deficiency

Commenting for Medscape Medical News, Carol Johnston, PhD, professor and associate dean for faculty success, College of Health Solutions, Arizona State University, Phoenix, said vitamin B6 is "the most common nutrient deficiency in the US"; 16% of men and 32% of women are reportedly B6 deficient.

"Young women on birth control are at higher risk for B6 deficiency due to effects of oral contraceptives on B6 metabolism," whereas vitamin B12 deficiency is more common in older adults, said Johnston, who was not involved with the study.

The current study's population mainly consisted of young women, and the interpretation of the data is "limited" because the researchers did not measure blood status for B6 and B12, Johnston noted. It is possible the sample was low in B6 and that the supplements "improved cognitive measures."

Because the population was young ― no one was older than 60 years ― B12 status was likely "adequate in the sample, and supplementation did not have an impact," she said.

Overall, Johnston cautioned that it is important to "alert clinicians and the general public about the concerns of overdosing B6." For example, supplementation at high amounts can cause potentially irreversible sensory neuropathy, she noted.

"The safe upper limit defined by experts is 100 mg per day ― the dosage used in this trial. Daily supplementation should not exceed this level," Johnston said.

The vitamin tablets used in the study were supplied by Innopure. The investigators and Johnston have reported no relevant financial relationships.

Hum Psychopharmacol. Published online July 19, 2022. Full article

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).

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