In this interview, we talk to Dr. David Field about his latest research on anxiety and depression and whether vitamin B6 supplements can help reduce it.
Could you please introduce yourself and tell us what inspired your latest research on anxiety and depression?
I am an Associate Professor at the University of Reading in the UK. Over the years I have researched a wide range of topics, including functional brain imaging, how we visually perceive the world and use information from our senses to perform complex actions like catching a ball, and whether brain function can be affected by what we eat. I now bring the broad scientific perspective I have developed working in these diverse fields to the question of whether dietary interventions can improve mental health and well-being.
As for the inspiration for the present work, about five years ago I acted as a reviewer for a study that looked at the effects of eating Marmite (!) every day for several weeks on visual processing. Remarkably, the results of this study showed that eating Marmite increased the level of the inhibitory neurotransmitter GABA in the visual part of the brain, slightly reducing the level of neuronal activity. But Marmite contains many different B vitamins as well as other ingredients that could potentially explain this result, plus many people don’t like the taste of Marmite!
I wanted to find out which individual ingredients in Marmite were driving the effect, and B6 and B12 were the most likely candidates, so I decided to team up with Innopure, who donated vitamin tablets, and test them individually against a placebo. I added the measures of anxiety and depression, which were not in the marmite study, because I reasoned that if GABA levels were altered, it might improve these disorders, because we know that decreased GABA levels in the brain occur in both of these conditions .
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Although anxiety and depression are common mental health conditions, our knowledge of their mechanisms is limited. Why is that?
My point is that the mechanisms underlying anxiety and depression are relatively poorly understood because many different levels of explanation are needed to understand what causes them, and therefore science is taking longer to understand. Let me explain what I mean: some conditions have an entirely genetic cause, while others can be caused entirely by exposure to a specific environmental factor, such as a chemical. But part of the explanation for anxiety and depression is socioeconomic, part of the explanation is psychological, and part is at the metabolic level.
To illustrate, there is strong evidence that the increased prevalence of anxiety and depression over the past few decades is due to increased wealth inequality and income inequality caused by political choices. For example, we can see that the rise in mental illness is greater in countries with more inequality. Yet, at the same time, it is true that in the brain of any depressed or anxious person there are changes in the levels of neurotransmitters (signaling molecules) that play a causal role at a different level than socioeconomic causes. It is a very difficult scientific problem to establish the relationship between the different levels of explanation that apply, and I don’t know of anyone really trying to do that.
Previous research has been conducted on various vitamins, as well as Marmite, and their effects on anxiety and depression. What makes your training different?
One thing that makes my study different is that I examined the effects of individual vitamins (both vitamin B6 and vitamin B12) compared to a placebo. Previous studies have looked at the effects of cocktails of vitamins, minerals and sometimes other ingredients on anxiety/stress/depression. Looking at the effect of individual vitamins is more useful from a scientific point of view, because in addition to understanding the efficacy, you also get more clues about the mechanism; it’s just really hard to speculate on the mechanism when using a multivitamin or nutritional product.
Another thing that makes my research different is that in addition to measuring anxiety and depression, since I hypothesized that the main mechanism by which B6 might help with these things might be increased GABA, I also included lab tasks in my research , which give you a clue as to whether GABA in the brain has changed; earlier studies simply measured anxiety and depression.
My background in vision science inspired the lab task I used to see if GABA changes: our seamless ability to ignore the background in a visual scene and focus on what matters depends on inhibitory neurons that use the neurotransmitter GABA , and this can be measured in a laboratory as the strength of “visual surround suppression.”
Your study focuses specifically on vitamin B6. In what types of foods can this vitamin be found?
Before answering this question, it is important to clarify that we have given a dose of vitamin B6 that would be very difficult to obtain from dietary sources alone. It is also important to say that many foods contain vitamin B6 and complete deficiency is rare. (But an often overlooked point in official advice based on RDAs and similar metrics is that the question of what is the optimal level of a given vitamin is not the same as the question of the minimum intake to avoid a complete deficiency).
Foods high in B6 include chickpeas, liver, tuna, salmon, chicken, fortified breakfast cereals, bananas, turkey, and yeast-based spreads. But there is much more.
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Your latest research focuses on reducing anxiety and depression through vitamin B6 supplementation. Could you please tell us more about your study and its results?
By randomly assigning participants to three groups, we compared the effects of taking high-dose vitamin B6 with that of placebo or high-dose vitamin B12. We used questionnaires and laboratory tasks to measure the effects of these interventions. We found a decrease in the mean level of anxiety and a trend toward a decrease in depression. Our laboratory tasks showed subtle changes in visual processing. It is worth noting that our sample had a high (moderate) level of anxiety at baseline, while this was not the case for depression. It is plausible to assume that we were able to detect a (moderate) reduction in anxiety due to the high baseline.
Our evidence is most consistent with the following explanation, although I still wouldn’t consider it 100% proven as a causal pathway: In the brain, neural excitation and neural inhibition are constantly competing with each other. Anxiety is associated with decreased levels of inhibition, and in particular with decreased levels of the inhibitory neurotransmitter GABA. You can think of GABA as having a calming effect on the brain. Decreased neural inhibition in anxiety allows excitatory neural activity to increase above normal levels. Some recent theories also directly link depression to reduced GABA; moreover, it is assumed that depression and anxiety are highly related conditions.
Vitamin B6 enters the picture because it is a cofactor for a metabolic pathway in the brain that converts the excitatory neurotransmitter glutamate to the inhibitory (calming) GABA. By increasing the amount of the cofactor, we slightly speed up the rate of this metabolic process, and so you end up with a little more of the neurotransmitter GABA and a little less glutamate. The net effect of this is a slight decrease in activity in the brain.
Although your study is small, it demonstrates the power of nutrition-based interventions. What are some advantages to people trying these interventions first instead of turning to medication?
There is currently no data comparing B6 supplements to other treatments for anxiety and depression, so I can only answer this with plausible speculation that I would like to test by collecting data. I would suggest that the reduction in anxiety achieved by taking high dose B6 is less than would be achieved by a patient taking drugs such as SSRIs.
Furthermore, we do not yet know whether vitamin B6 was effective for most of the participants in our study or only for a subset; this is a general limitation of studies like ours that analyze effects “on average” in a sample. To evaluate vitamin B6 as a treatment for anxiety that a doctor would consider diagnosing, a large clinical trial would first need to be conducted.
One possible advantage of vitamin B6 over things like SSRIs is far fewer side effects.
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What additional research needs to be done before this is a realistic choice for patients?
See above, clinical trial. But also see below because I don’t think taking B6 alone is going to be the most effective strategy. It should be combined with other things.
What are the next steps for you and your research?
We have shown that taking a high dose of vitamin B6 can affect the balance of an important metabolic pathway in the brain, causing a slight reduction in anxiety in our participants. But the most important takeaway can be seen by thinking beyond this to some other micronutrients, which (given our current understanding of metabolism) may also affect other metabolic pathways involved in calming the brain. If these were also rigorously tested, we could move on to assess the combined effect of several such interventions – hopefully the combined effect might be more clinically meaningful for patients than vitamin B6 alone.
But to carry out the necessary program of scientific work and clinical trials to implement the above proposal, substantial financial support is required. Unfortunately, since you cannot patent the effects of taking a high dose of a vitamin, mineral, or plant compound, the pharmaceutical industry cannot profit from funding this research, and so the industry is incentivized to continue pushing for pharmacological solutions. This is a major problem and the government needs to think about what it can do to change this.
Where can readers find more information?
Please provide links to any material that may be relevant to our audience.
They could read:
- Kalueff, AV, & Nutt, DJ (2007). The role of GABA in anxiety and depression. Depression and anxiety, 24(7), 495-517.
Or they could look at the Marmite study that got me thinking about it in the first place:
- Smith, AK, Wade, AR, Penkman, KE, & Baker, DH (2017). Dietary modulation of cortical excitation and inhibition. Journal of Psychopharmacology, 31(5), 632-637.
For Dr. David Field
In addition to the broad research experience I mentioned earlier, I also hold a local leadership role in the UK Research Evaluation Framework and am a local leader for the UK Academics Union, UCU.