Food is not only essential for our bodily functions, but also for our brain functioning and associated behavioural performance. Some studies have shown that eating more of a certain nutritional compound can enhance your performance. But is it really that simple? Can food supplements support our performance? While performing studies on the micronutrient tyrosine, I found out that it is not that simple, and I will tell you why.

Your food contains a range of nutrients that your body uses amongst others as energy sources and as building blocks for cells. For example, protein-rich food such as dairy, grains and seeds are made up of compounds called amino acids. Amino acids are used for different purposes in your body. Muscles use amino acids from your diet to grow. Some people take advantage of this process to increase muscle growth by eating extra protein in combination with exercise.

But amino acids also have a very important role for brain functioning; specific amino acids such as tryptophan, phenylalanine and tyrosine are precursors for neurotransmitters. Specifically tyrosine is a precursor for the neurotransmitter dopamine, which is crucially involved in cognitive processes such as short-term memory, briefly memorizing a phone number or grocery list. Ingested tyrosine from a bowl of yoghurt or a supplement is digested in your intestines, taken up into the bloodstream and then passes through the barrier between the blood stream and the brain (the blood-brain-barrier). In neurons in the brain, tyrosine is further processed and converted into dopamine. Here, dopamine influences the strength and pattern of neuronal activity and hereby contributes to cognitive performance such as short-term memory.

Short-term memory functions optimally most of the time, but can also be challenged. For example during stressful events like an exam or when faced with many tasks on a busy day, many people experience trouble remembering items. Another example is advancing age; elderly people often experience a decrease in their short-term memory capacity. These decrements in short-term memory have been shown to be caused by suboptimal levels of brain dopamine.

The intriguing idea arises to preserve or restore optimal levels of dopamine in the brain with a pharmacological tweak, or even better, using a freely available nutritional compound. Could it be that simple? Yes and no. Yes, if you eat high amounts of tyrosine, there will be more dopamine precursors going to your brain. But the effects on short-term memory vary between individuals and experiments.

Various experiments have been conducted using tyrosine supplementation to see if cognitive performance can be preserved, with mixed success.

In groups of military personnel, negative effects of stress or sleep deprivation on short-term memory were successfully countered. Subjects were asked to take an ice-cold water bath, known to induce stress, and to perform a short-term memory task [1]. In other experiments subjects remained awake during the night or performed challenging tasks on a computer in a noisy room, mimicking a cockpit [2,3].

The group that took tyrosine before or during these stressful interventions showed less decline in their short-term memory than the group that ingested a placebo compound. Tyrosine supplementation also benefitted performance on a cognitive challenge without a physical stressor, compared with performing a simpler task. Other experiments, without a physical or cognitive stressor didn’t show any differences in performance compared with a control group.

These results show that tyrosine supplementation can benefit performance on cognitive processes, such as short-term memory, but only during challenging or stressful situations that induce a shortage of brain dopamine (for review see 4,5).

However, results have also been shown to vary with age. Experiments in elderly people showed that tyrosine also influences the most challenging task compared with simple processes, but contrary to observations in younger adults, in many older adults tyrosine decreased rather than improved performance [6,7]! It seems that the effects seen in young(er) adults no longer hold in healthy aging adults. This can be due to changes in the dopamine system in the brain with aging, as well as changes in other bodily functions, such as the processing of protein and insulin. This doesn’t mean that tyrosine supplementation should be avoided all together for older adults. The results so far suggest that dosages should be adjusted downwards for the elderly body. Further testing is needed to conclude on the potential of tyrosine to support short-term memory in the elderly.

We can conclude that nutrients affect behavior, but importantly, these effects vary between individuals. So, unfortunately, one size does not fit all. To assure benefits from nutrient supplementation or diet rather than wasteful use or unintended effects, dosages should be carefully checked and circumstances of use should be considered.

REFERENCES
O’Brien, C., Mahoney, C., Tharion, W. J., Sils, I. V., & Castellani, J. W. (2007). Dietary tyrosine benefits cognitive and psychomotor performance during body cooling. Physiology and Behavior, 90(2–3), 301–307

Magill, R., Waters, W., Bray, G., Volaufova, J., Smith, S., Lieberman, H. R., … Ryan, D. (2003). Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation. Nutritional Neuroscience, 6(4), 237–246.

Deijen, J. B., & Orlebeke, J. F. (1994). Effect of tyrosine on cognitive function and blood pressure under stress. Brain Research Bulletin, 33(3), 319–323.

van de Rest, O., van der Zwaluw, N. L., & de Groot, L. C. P. G. M. (2013). Literature review on the role of dietary protein and amino acids in cognitive functioning and cognitive decline. Amino Acids, 45(5), 1035–1045.

Jongkees, B. J., Hommel, B., Kuhn, S., & Colzato, L. S. (2015). Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands-A review. Journal of Psychiatric Research, 70, 50–57.

Bloemendaal, M., Froböse, M. I., Wegman, J., Zandbelt, B. B., van de Rest, O., Cools, R., & Aarts, E. (2018). Neuro-cognitive effects of acute tyrosine administration on reactive and proactive response inhibition in healthy older adults. ENeuro, 5(2).

van de Rest, O.& Bloemendaal, M., De Heus, R., & Aarts, E. (2017). Dose-dependent effects of oral tyrosine administration on plasma tyrosine levels and cognition in aging. Nutrients, 9(12).

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Is there any evidence for using micronutrients for the treatment of mental illness?

The notion that good nutrition is good for the brain is not a new idea. What is relatively new is that, until recently, there were very few well conducted studies examining whether a broad spectrum approach using doses of nutrients higher than what you could get out of a daily diet, could treat a mental disorder.

At my lab at the University of Canterbury, we have been studying the impact of micronutrients (vitamins and minerals) on mental health for the last decade. With more and more people suffering from a mental illness and not enough people getting better with conventional treatments, we need to investigate new ideas. We appear to have reached an impasse improving outcomes for mental health, despite improvements in other areas of medicine.

Mental illness and micronutrientsFor the past several decades, this idea that nutrients might treat mental illness was received with great scepticism and even ridiculed. Some continue to believe that vitamins kill us, despite evidence(1) to the contrary.

And why would this approach even work? Many readers might consider the idea is too simple to be taken seriously. But the general premise is that our brains need nutrients to function and chemicals that are essential for good mental health, like dopamine and serotonin, require micronutrients, like vitamins and minerals. Agricultural practices have changed dramatically over the last 50 years such that our food is just not as nourishing as it was for our ancestors. Perhaps some people are genetically prone to need more nutrients than what they can get out of their food. Maybe giving nutrients in higher doses than what is present in the diet can correct metabolic errors that some people may have inherited. It isn’t that farfetched an idea; don’t forget, a million sailors died from scurvy in the 18th century, before Vitamin C was introduced as a treatment.

Scientific advancements in knowledge of micronutrients

Over the last decade the field has grown substantially. No single study should be interpreted in isolation. There are now over 30 double blind randomised controlled trials (RCT) using a variety of combinations of nutrients and doses across a variety of mental health conditions showing that we can induce a substantial and clinically meaningful change in symptoms just by using nutrients.

It takes two RCTs to put a drug on the market. There are enough RCTs completed internationally that this approach should already be mainstream for the treatment of stress, anxiety, low mood and aggression in prisoners. Sadly, good nutrition and additional nutrients are not on the menu in prisons and if you present to your GP with stress or low mood, chances are pretty good that you will be put on a medication. Most data across the world consistently show that about 10% of the populations are taking an anti-depressant. In some countries, this number is even higher.

There is a long way to go to improve the effectiveness of this approach. More research is required to determine if we can enhance outcomes with a more tailored approach. We are in the infancy of figuring out the mechanism of action. Can we use genetic and nutrient testing to determine the optimal dose and nutrients that someone may require to get better, based on their individual profile? Can we use microbiome analyses to determine what microbial strains are required to best heal the gut to optimise absorption of nutrients? Current and future technologies should allow us to greatly expand the number of people who benefit from a nutritional approach. Eat2BeNice plans to investigate all these mechanism of action.

It is encouraging that some people can have better mental health and more fulfilling lives simply by ensuring their brains receive adequate nutrients and that they will not have to experience the side effects associated with so many medications. Perhaps mental illness will be viewed as being at least partially caused by improper nutrition. Could such a shift influence the stigma associated with mental illness?

We could continue to ignore the data. Or we can embrace the idea, properly fund it, and see how far it can take us in curbing the national trends. Valuing the role of nutrition as part of addressing our mental health statistics must become part of our future. Thanks to the European Commission, this might just happen.

(1) Helen Macpherson, Andrew Pipingas, Matthew P Pase; Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials, The American Journal of Clinical Nutrition, Volume 97, Issue 2, 1 February 2013, Pages 437–444, https://doi.org/10.3945/ajcn.112.049304

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