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B vitamins on the brain: Do they improve mental health?

Study under review: A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and 'At-Risk' Individuals.

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Quick Takes

  • What question this study addressed: Does B vitamin supplementation impact symptoms of depression, anxiety, stress, and overall mood?

  • Who this study applies to: Healthy people without a clinical mood disorder but who may be at risk for one.

  • What the intervention was: Supplementation with at least three types of B vitamins for at least four weeks.

  • What the main takeaway is: In general, B vitamin supplementation may lead to a small reduction in stress, but has no clear impact on overall mood, depression, or anxiety.

  • Caveats: The studies included in this meta-analysis used a wide range of doses, different B vitamins, and also involved other supplements that could impact mood. This makes it very difficult to ascribe any effects seen here strictly to certain B vitamins and to make appropriate dosing recommendations.

Introduction

Mood disorders represent a category of mental illness that impact a person’s persistent emotional state. They affect nearly 21% of all adults in the U.S. at some point during their lives. The emotional states that mood disorders affect include depression, stress, and anxiety. Over the past several decades, there has been an increasing awareness about the relationship between diet and mental health, including mood disorders.

B vitamins have received extra attention as a dietary component of mood disorders because of their relationship[1] to brain function. B vitamins play a role in brain chemistry, specifically related to mood, as they act as cofactors ultimately necessary for the synthesis of dopamine and serotonin, as shown in Figure 1. These neurotransmitters are both key components in regulating mood. Supplementation with B vitamins has a good safety profile and may have a lower risk of side effects than antidepressants.

There have been several investigations into the effect of B vitamin supplementation on many aspects of mood. For example, randomized controlled trials have shown that B vitamin supplementation improves depression[2], anxiety[3], and work-related stress[4]. However, not all studies[5] have shown benefit. As such, there is a need to examine the literature in a broader scope to understand the effect B vitamins might have on mood disorders. The present study was a systematic review and meta-analysis of randomized controlled trials examining the effect of B vitamins on mood.

B vitamins are critical components in the synthesis of neurotransmitters that regulate mood, such as dopamine and serotonin. Previous studies have yielded mixed results on the effects of vitamin B supplementation on mood disorders. The present study was a systematic review and meta-analysis of randomized controlled trials examining the effect of B vitamins on mood.

What was studied?

The study under review was a systematic review and meta-analysis of randomized controlled trials examining the effect of B vitamins on mood. The study followed PRISMA guidelines, but does not appear to have been preregistered. The study included randomized trials with human participants that reported quantified mood outcomes (i.e. stress, well-being, and fatigue) and that were published during or after the year 2000.

Studies that were included in the analysis had to involve daily supplementation with three or more B group vitamins and be at least four weeks in length. Studies were allowed to include other vitamins and/or minerals in addition to the B vitamins, as well as other types of supplements. Only studies involving non-clinical adult populations (older than 18 years of age) were included. Participants were either healthy or at risk for mood disorders. At-risk was defined as having a nutritional deficiency, elevated levels of a psychological mood measure, subclinical symptomatology, or vulnerability to mood disorders.

Standardized mean differences and 95% confidence intervals were used to report results. Heterogeneity was assessed using the Cochran Q statistic and I2 value. The authors utilized funnel plots to identify potential sources of heterogeneity if an I2 value was at least 75%.

A total of 18 studies were included in the review, but only 12 were deemed eligible to meta-analyze. Of the studies included in the review, vitamin B6 and B12 were included in all studies, while folate (vitamin B9) was included in all but one study. Vitamins B1, B2, B3, and B5 were included in all but two studies, while vitamin B7 was only included in 10 studies (Figure 2). Only two studies included interventions that had only B vitamins, with some studies including interventions that contained more than 50 ingredients. (e.g. vitamin C, vitamin K, magnesium, copper, potassium, probiotics, and other nutraceuticals). For all but one study[6], the doses ranged from 2 to 300 times the recommended daily intake of the Australian National Health and Medical Research Council.

This meta-analysis examined the effects of B vitamins on mood in healthy and at risk populations without clinical mental disorders. There were 12 studies included in the analysis and the doses ranged from 2 to 300 times the recommended daily intake of the Australian National Health and Medical Research Council.

What were the findings?

The effect of B vitamins on overall mood (defined as a measure of mental health or current state of psychological well-being) and subcomponents of mood, including stress, well-being, and fatigue, was reviewed qualitatively by the authors, as enough quantitative data was not available on overall mood for meta-analytic approaches. The qualitative review determined that there were mixed effects of B vitamins on mood, with some studies showing a benefit and others showing no effect.

Depressive symptoms were measured in 11 of the 18 included studies. When all studies were included, there was no significant effect of B vitamins on depression. Several different scales were used to assess depressive symptoms, leading to high levels of heterogeneity (I2= 95%). After removing two studies that were substantial outliers, the heterogeneity was abrogated (I2= 0%), yet vitamin B supplementation still did not show a significant reduction in depressive symptoms.

Stress was measured in 10 of the 18 studies, with seven of the 10 utilizing the Perceived Stress Scale (PSS), which measures the degree to which situations in one's life are appraised as stressful[7]. The meta-analysis revealed that supplementation with B vitamins significantly reduced stress symptoms, with a small effect size (SMD = 0.23). However, there was moderate heterogeneity across studies (I2= 60%).

Anxiety was measured in 10 of the 18 studies. Individual studies did show some benefit, while other studies did not. The meta-analysis found that there was no significant benefit of B vitamin supplementation on anxiety.

The authors also reported some data on blood biomarkers that reflect B vitamin status (e.g. folate, B12, B6, and homocysteine). Four studies reported vitamin B12 levels, three reported B6 levels, and five reported homocysteine levels. Supplementation with B vitamins did increase levels of B vitamins in the blood as well as reduced levels of homocysteine in the blood, compared to placebo.

Supplementation with B vitamins may reduce measures of stress, but probably not depressive symptoms or anxiety in healthy people or people at risk for a vitamin deficiency. Moreover, supplementation with B vitamins does increase blood levels of B vitamins and lowers homocysteine.

The bigger picture

The current systematic review and meta-analysis suggests supplementation with B vitamins does not substantially improve overall mood, but may offer a small benefit for reducing stress. These data also indicate that B vitamin supplementation is likely an effective way to increase circulating levels of B vitamins. However, given the high levels of heterogeneity present, the wide range of doses and types of B vitamins, and the presence of other nutrients in some studies, it is difficult to discern a true effect in the present study.

As depicted in Figure 3, the study under review included randomized controlled trials that included several B vitamins, along with many other ingredients. It is possible that the other ingredients either competed with the B vitamins or masked any effect due to opposite and compensatory effects. It is also possible that the other ingredients were responsible for the positive effects observed on stress. Given the wide range of interventions included in the studies, it is difficult to determine the effects attributed to B vitamins compared to the effects of other ingredients, as well as which B vitamins may have been more effective than others. The dosages were also incredibly varied, from two-fold to 300-fold more than the daily recommended intake.

The one positive finding that was observed in this study was a reduction in stress. However, the reduction in stress observed in the present study may also not be linked to B vitamins per se. Three of the studies (Armborst et al.[8], Carrol et al.[6], Kennedy et al.[9]), that heavily weighted the results toward a significant reduction in stress all utilized ingredients other than B vitamins in their interventions. For example, one study[8] utilized a multi-ingredient intervention that included tyrosine[10] and magnesium[11], which have also been shown to reduce stress. Another one of these studies[9] also included magnesium. So, even the reduction in stress may have been due to confounding by ingredients other than B vitamins. Another consideration is whether or not B vitamins would have any effect in individuals who are not deficient in B vitamins.

The study also used scales to provide a quantification of mental states. This method has shortcomings and does not provide highly quantifiable or accurate measures of mental states. That said, a true gold standard measure of measuring mood in a healthy population or in people at risk for vitamin deficiency does not exist, and this was reflected in the heterogeneity of measures used in the studies included in this review.

The study under review has several strengths. The study followed PRISMA guidelines and included both healthy and at risk populations. Mood was also measured using three different facets of mood (i.e. depressive symptoms, stress, and anxiety). The study also had some key limitations. First, there was a high level of heterogeneity across studies, which is reflective of the varied dosages and interventions used in the individual studies. Second, B vitamins were not isolated variables and were included as components of a larger list of ingredients/interventions used in each study. Third, there is no gold standard measure for mood measurements, making it difficult to reliably and accurately assess the primary outcome of the study. Finally, the study was not preregistered.

B vitamins play known roles in neurotransmitter metabolism, and there is rationale behind their use for mood disorders. The present study found that supplementation with B vitamins did not substantially alter mood, but may have a small benefit for stress. However, there are substantial limitations to the study that make clean interpretations difficult. As such, the study did not provide robust evidence as to whether B vitamins do, or do not, have an effect in humans on mood disorders.

Frequently Asked Questions

Q. Is there an upper limit to how high a dose of B vitamins is safe to take?

There are upper limits as to what is considered safe for B vitamin supplementation. Each B vitamin has a different upper limit, with some resulting in more serious adverse events than others. For example, vitamin B6 can cause neuropathy at doses of about one gram per day or more, which is around 800 times the recommended daily intake. You can find a full resource covering the upper daily limit suggestions at the NIH Office of Dietary Supplements for information on each of the B vitamins.

What should I know?

Mood disorders impact roughly one out of every five people over the course of a lifetime, making them one of today’s bigger mental health issues. There is a growing interest in the role that diet plays in mental health, including mood disorders. As B vitamins play a role in the synthesis and regulation of neurotransmitters, there has been interest in the potential therapeutic benefit vitamin B supplementation might have on mood disorders.

The present study found that supplementation with B vitamins did not substantially alter general measures of mood, nor did it improve depressive symptoms or anxiety. However, there was a small benefit seen for stress. On the other hand, there were substantial limitations involved with the randomized trials that were included in the analysis, such as confounding variables from additional ingredients and highly varied dosages. These limit the ability to draw firm conclusions based on the results. While there may be a benefit from vitamin B supplementation for mood disorders, this study does not provide any conclusive evidence on whether it does or does not have an effect.

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See other articles with similar topics: Vitamin B, Mood, Depression, Anxiety, Stress.

See other articles in Issue #63 (January 2020) of Study Deep Dives.

Other Articles in Issue #63 (January 2020)

References

  1. ^ Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients. (2016)
  2. ^ Syed EU, Wasay M, Awan S. Vitamin B12 supplementation in treating major depressive disorder: a randomized controlled trial. Open Neurol J. (2013)
  3. ^ Lewis JE, et al. The effect of methylated vitamin B complex on depressive and anxiety symptoms and quality of life in adults with depression. ISRN Psychiatry. (2013)
  4. ^ Stough C, et al. The effect of 90 day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. (2011)
  5. ^ Ford AH, et al. Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial. J Clin Psychiatry. (2008)
  6. ^ a b Carroll D, et al. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological well-being in healthy young male volunteers: a double-blind placebo-controlled trial. Psychopharmacology (Berl). (2000)
  7. ^ Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. (1983)
  8. ^ a b Armborst D, et al. Impact of a Specific Amino Acid Composition with Micronutrients on Well-Being in Subjects with Chronic Psychological Stress and Exhaustion Conditions: A Pilot Study. Nutrients. (2018)
  9. ^ a b Kennedy DO, et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl). (2010)
  10. ^ Banderet LE, Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull. (1989)
  11. ^ Boyle NB, Lawton C, Dye L. The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients. (2017)