A full version of this blog was recently posted on: https://mind-the-gap.live/2020/05/20/why-following-instructions-is-essential-for-treatment-success-and-why-this-is-really-difficult/

Imagine that you are a researcher who wants to know if daily physical activity training can improve mood and mental health in individuals with ADHD. Ideally – from a research perspective – you would keep these individuals at your laboratory for a couple of weeks, monitor everything they do, and ask them repeatedly how they feel. This setting is very controlled, and you are sure that your participants will do the exercise exactly as they are supposed to do. However, spending weeks in a laboratory would be very unpleasant for the research participants, and very unfeasible. The alternative is to make the research intervention (in this case: the physical activity training) part of your participants’ daily life. This is what we call a more ‘naturalistic’ setting. But how do you know if they really do the training? And how do you monitor what else they do, eat, and feel during the research period?

For this, we use activity sensors and smartphone apps. Through such an app researchers can send questions and exercises to participants throughout the day. For instance asking how they feel at that moment, or what they have eaten. We can also track how much they move and exercise. Together, these measurements are called Ambulatory Assessment. Our researchers at Karlsruhe Institute for Technology in Germany are experts on these types of measurements. You can read more about this in the blogs by researchers Clara Hausmann and Elena Koch.

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Are you a morning or an evening person? Your chronotype is linked to your preference of when you go to sleep and when you are most productive during the day. “Larks” are generally 2-3 hours ahead, they feel and function better during the first half of the day and go to bed rather early. “Owls” prefer to work in the evenings and tend to go to bed and wake up later. The third chronotype is the in-between, balanced version of these two.

Your chronotype is linked to your circadian rhythm which is your inner clock that regulates your sleep/wake cycle. In many mental health conditions, this rhythm is disturbed. Persons with ADHD for instance often have an evening chronotype. However, we don’t yet know what is cause and consequence. Does a disturbed circadian rhythm cause symptoms like inattentiveness and impulsivity? Or do the same mechanisms that cause ADHD also de-regulate the sleep/wake cycle?

Dina Sarsembayeva is investigating how chronotypes are linked to mental health problems. In this blog, she explains more about chronotypes and her research.

This blog was written together with Dina Sarsembayeva. Dina is a master student of clinical epidemiology at the University of Groningen, The Netherlands.

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For women who use medication, being pregnant can raise a lot of questions and concerns. “Should I discontinue stimulants when I am pregnant?” “Is it harmful to my developing baby if I take ADHD medications during my pregnancy?” “What are the risks both to me and my baby if my ADHD goes untreated?” “What is the best way to manage my ADHD during pregnancy?”

Researcher Lin Li and her colleagues investigated all currently published evidence about the safety of ADHD medication use while pregnant. Based on that they concluded that using ADHD medication during pregnancy does not seem to have any serious consequences for the mother or her children. However, they also acknowledge that the current evidence on this is still limited and can be biased by confounding results (read this blog) by Lin Li about the problems with ‘confounders’ in research).

The results of this study were recently published in the scientific journal CNS Drugs. Lin Li also wrote a blog about these findings, which you can read here.

Further Reading:
Is it safe to use ADHD medication during pregnancy? – by Lin Li https://mind-the-gap.live/2020/05/12/is-it-safe-to-use-adhd-medications-during-pregnancy/

Is maternal excessive weight or obesity prior to pregnancy a risk factor for ADHD? – by Lin Lin https://newbrainnutrition.com/is-maternal-excess-weight-or-obesity-prior-to-pregnancy-a-risk-factor-for-adhd/

Li, L., Sujan, A.C., Butwicka, A. et al. Associations of Prescribed ADHD Medication in Pregnancy with Pregnancy-Related and Offspring Outcomes: A Systematic Review. CNS Drugs (2020). https://link.springer.com/article/10.1007/s40263-020-00728-2

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Can gut bacteria cause ADHD? While there are some signs that the bacteria in our gut play a role in mental health, it is difficult to establish whether – and how – this relationship is causal. By studying mice, researchers have now found that gut bacteria from individuals with ADHD can change the behaviour and brain functioning of mice after they have been given a poo-transplantation from these individuals. This is a first hint that gut bacteria indeed may play a part in the development of ADHD and other mental health conditions.

There are many factors that influence our mental health, and we still understand very little of them. One aspect that has gained a lot of interest in the past years is whether bacteria and other microbes in our gut can influence the functioning of our brain through what is called the gut-brain axis. Bacteria in the gut play an important part in the digestion of food, interact with our immune system, and provide essential substances that our bodies (including the brain) need for proper functioning.

The tricky part in this research is that there are also many factors that influence the composition of our gut bacteria. Diet is one of these factors, but also the way you are born (i.e. through natural birth or c-section), how much stress you experience, medication that you use, whether you live in a city or in a rural area, and much, much more. This makes research on causal influences between gut bacteria and mental health very complex.

To get some insights into how gut bacteria influence the brain and behaviour, researchers study mice (or other so-called model organisms such as rats and fruit flies). Mice in research experiments are raised in very controlled environments. Specifically for studying the effects of gut bacteria, mice are reared in complete sterile environments. This means that there are no bacteria or other microorganisms in and on these animals, and so also their intestines are completely germ-free. Germ-free mice are not ‘normal’. They generally respond more strongly to stressors, are less fearful and have worse memory compared to mice raised in non-sterile environments [1]. However, these germ-free mice are very useful to test the effects of introducing specific bacteria to their gut.

This is what researchers Anouk Tengeler and Sarita Dam have done [2]. They obtained poo-samples from individuals with ADHD and from children without ADHD, and then transplanted a bit of this poo to the guts of the mice. This way, the bacteria from these samples colonized the guts of the mice. About a month later, the researchers found that the mice that had received the bacteria from the persons with ADHD behaved more anxious compared to the mice that had received bacteria from children without ADHD. They also found differences in the brains of the mice: connections between certain brain regions were less strong in the mice that had received the ADHD-bacteria.

The researchers write in their scientific publication that they do not suggest that ADHD is caused by changes in gut bacteria. What they do conclude is that these bacteria can influence brain functioning and behaviour, at least in mice, and this should therefore be further investigate to understand ADHD and other mental disorders. In the Eat2beNICE research consortium we are studying this for example with the TRACE elimination diet trial. Here, researchers are collecting poo from children with ADHD that participate in the trial so that they can investigate the role of gut bacteria further.

You can watch a video abstract of the scientific article by Tengeler et al. here:



[1] Luczynski et al. (2016). Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior. Int J Neuropsychopharmacol, 19(8). https://academic.oup.com/ijnp/article/19/8/pyw020/2910071

[2] Tengeler et al. (2020). Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice. Microbiome, 8 (44). https://www.ncbi.nlm.nih.gov/pubmed/32238191

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Having Attention Deficit / Hyperactivity Disorder (ADHD) can be quite a burden to someone’s quality of life. People with ADHD generally have problems with regulating their attention and their impulses, resulting in concentration and memory problems as well as reckless behaviour [1]. Luckily, this condition is receiving more attention these days, and an increasing number of people are receiving adequate treatment in the form of medication and/or behavioural therapy. But what is much less known is that many people with ADHD also suffer from other mental and somatic conditions.

The research consortium Comorbid Conditions of ADHD (“CoCA”) investigates the prevalence and the mechanisms of ADHD comorbidity [2]. This research focusses on the four most prevalent comorbidities: depression, anxiety, substance abuse, and obesity. It is important to learn more about these conditions in the context of ADHD, as this can raise awareness among health care professionals. For instance, it can happen that an adult seeks treatment for depression, while this person also has undiagnosed ADHD. What’s more, the ADHD may even be the underlying cause of the depressive symptoms. In this case, it might be better to treat the ADHD symptoms first.

A first step to raise awareness is to map out how often these comorbidities occur together with ADHD. For this, the researchers from the CoCA project have made use of several very large population datasets that contain information of millions of people. From these datasets they can find patterns of ADHD comorbidity. This way they have shown that indeed depression, anxiety, substance use disorder and severe obesity are much more frequent in individuals with an ADHD diagnosis.

Other patterns that emerge from this data is that depression, anxiety and obesity are more frequent in women compared to men in the general population, and this sex-difference is also present amongst individuals with ADHD. This means that when a woman with ADHD seeks treatment, it is especially important to be aware of these other conditions that may increase symptoms and reduce the quality of life.

To learn more about the prevalence of ADHD comorbidities, you can watch this webinar. Here dr. Catharina Hartman and myself explain and discuss the first findings from the CoCA project.



[1] https://newbrainnutrition.com/adhd/

[2] www.coca-project.eu

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Master students, PhD candidates, post-doctoral scientists and other early career researchers are lucky this summer: from 13 – 17 July they can join the first Radboud Summer School on Brain, Bacteria and Behaviour. During this intense week students will learn from various international experts in the field about the gut microbiome – brain axis, get hands-on practice with handling and analysing data and prepare themselves for setting up their own research projects in this exciting new field. The summer school takes place at the Radboud University in Nijmegen, The Netherlands.

The course program includes a wide variety of topics and activities, ranging from state-of-the-art updates on routes of gut-brain communication to hands-on sessions using bioinformatic pipelines for data analysis. For those that still have energy left, the Radboud Summer School organises social events in the evenings, together with students from other summer courses.

Several scientists of the Eat2beNICE consortium are involved in the course, including project coordinator dr. Alejandro Arias Vasquez (who is leading the course), microbiologist dr. Clara Belzer and psychologists dr. Carolina de Weerth and dr. Mirjam Bloemendaal. In addition, experts from other countries will travel to Nijmegen to teach, including dr. Christine Fulling (University College Cork, Ireland), dr. Rochellys Diaz Heijtz (Karolinska Institutet, Sweden) and dr. Leo Lahti (University of Turku, Finland).

More information about the course, fees and registration can be found here: https://www.ru.nl/radboudsummerschool/courses/2020/brain-bacteria-behaviour/

We’re looking forward to an interesting summer!

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Feeling more happy after a run? Or feeling a bit blue during the dark winter days? Regular exercising and regular daylight exposure can influence your mood, behaviour and sleep-wake cycle 1,2,3. But can this also be used in a therapeutical setting, for instance in addition to or instead of the usual treatment with medication?

The PROUD trial aims to investigate the potential of bright light therapy and physical exercise to improve and prevent depression and obesity in adolescents and young adults with ADHD. This clinical trial is part of the CoCA research project, in which comorbid conditions of ADHD are investigated [insert hyperlink: https://coca-project.eu/coca-phase-iia-trial/study/]. In addition, we collect the stool samples of all participants in order to investigate the effects of physical exercise on the gut microbiome and how this is linked to behaviour. That part of the study is part of the Eat2beNICE research project.

Most people with Attention Deficit Hyperactivity Disorder (ADHD) receive medication to reduce their symptoms4. While this medication works well for many people, there is a lot of interest in other types of treatment. One reason for this is that people with ADHD suffer from additional conditions, such as depression5 and obesity6. The risk for developing these comorbid conditions is especially high during adolescence and young adulthood4.

Adolescents and young adults (age 14-45) with ADHD that want to participate are randomly assigned to one of three groups: 10-weeks of daily light therapy (30 minutes), 10-weeks of daily physical exercise (3x per day) or 10-week care as usual (for instance, the normal medication). The random assignment is very important here in order to compare the different interventions. We don’t want to have all people that like sports in the physical exercise group, because then we don’t know if the effects of the physical exercise are due to the intervention, or due to the fact that these people just like sports better.

Another nice feature of the study is that it uses a phone app (called m-Health). This app is used to remind the participants to do their exercise or light therapy, but it also gives feedback and summaries of how the participant is doing. The app is linked to a wrist sensor that measures activity and light.

The clinical trial is currently ongoing in London (England), Nijmegen (Netherlands), Frankfurt (Germany) and Barcelona (Spain). We can’t look at the results until the end of the trial, so for those we will need to wait until 2021. But in the mean time the PROUD-researchers have interviewed four participants. You can read these interviews here:

This blog is based on the blog “10 weeks of physical exercise or light therapy: what’s it like to participate in our clinical trial?” by Jutta Mayer and Adam Pawley, 9 Oct. 2018 on MiND the Gap – https://mind-the-gap.live/2018/10/09/10-weeks-of-physical-exercise-or-light-therapy/


  1. Terman, M. Evolving applications of light therapy. Sleep Medicine Reviews. 2007; 11(6): 497-507.
  2. Stanton, R. & Reaburn, P. Exercise and the treatment of depression: A review of the exercise program variables. Journal of Science and Medicine in Sport. 2014; 17(2):177-182
  3. Youngstedt, S.D. Effects of exercise on sleep. Clinical Sports Medicine. 2005; 24(2):355-365.
  4. Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727-738.
  5. Jacob CP, Romanos J, Dempfle A, Heine M, Windemuth-Kieselbach C, Kruse A, et al. Co-morbidity of adult attention-deficit/hyperactivity disorder with focus on personality traits and related disorders in a tertiary referral center. Eur Arch Psychiatry Clin Neurosci. 2007;257:309–17.
  6. Cortese S, Moreira-Maia CR, St Fleur D, Morcillo-Penalver C, Rohde LA, Faraone SV. Association between ADHD and obesity: a systematic review and meta-analysis. Am J Psychiatry. 2016;173:34–43.
  7. Meinzer MC, Lewinsohn PM, Pettit JW, Seeley JR, Gau JM, Chronis-Tuscano A, et al. Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood. Depress Anxiety. 2013;30:546–53
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Why 12 genetic markers for ADHD are exciting news for New Brain Nutrition

We are finally here: for the first time, genome-wide significant markers are identified that increase the risk for Attention Deficit / Hyperactivity Disorder (ADHD). This research was conducted by an international consortium of more than 200 experts on genetics and ADHD, and includes several researchers that are also involved in our Eat2beNICE project (the scientific basis of this New Brain Nutrition website). The findings were recently published in the prestigious journal “Nature Genetics” and will greatly advance the field of ADHD genetics research.

Why is this finding so important?

The genetics of ADHD are very complex. While ADHD is highly heritable, there are likely to be thousands of genes that contribute to the disorder. Each variant individually increases the risk by only a tiny fraction. To discover these variants, you therefore need incredibly large samples. Only then can you determine which variants are linked to ADHD. The now published study by Ditte Demontis and her team combined data from many different databases and studies, together including more than 55,000 individuals of whom over 22,000 had an ADHD diagnosis.

We can now be certain that the twelve genetic markers contribute to the risk of developing ADHD. Their influence is however very small, so these markers by themselves can’t tell if someone will have ADHD. What’s interesting for the researchers is that none of these markers were identified before in much smaller genetic studies of ADHD. So this provides many new research questions to further investigate the biological mechanisms of ADHD. For instance, several of the markers point to genes that are involved in brain development and neuronal communication.

Why are our researchers excited about this?

A second important finding from the study is that the genetic variants were not specific to ADHD, but overlapped with risk of lower education, higher risk of obesity, increased BMI, and type-2 diabetes. If genetic variants increase both your risk for mental health problems such as ADHD, and for nutrition-related problems such as obesity and type-2 diabetes, then there could be a shared biological mechanism that ties this all together.

We think that this mechanism is located in the communication between the gut and the brain. A complex combination of genetic and environmental factors influence this brain-gut communication, which leads to differences in behaviour, metabolism and (mental) health.genetic markers for adhd

The microorganisms in your gut play an important role in the interaction between your genes and outside environmental influences (such as stress, illness or your diet). Now that we know which genes are important in ADHD, we can investigate how their functioning is influenced by environmental factors. For instance, gut microorganisms can produce certain metabolites that interact with these genes.

The publication by Ditte Demontis and her co-workers is therefore not only relevant for the field of ADHD genetics, but brings us one step closer to understanding the biological factors that influence our mental health and wellbeing.

Further Reading

Demontis et al. (2018) Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics. https://www.nature.com/articles/s41588-018-0269-7

The first author of the paper, Ditte Demontis, also wrote a blog about the publication. You can read it here: https://mind-the-gap.live/2018/12/10/the-first-risk-genes-for-adhd-has-been-identified/

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Mediterranean diet could prevent depression, new study finds” [CNN]; “Mediterranean diet ‘may help prevent depression‘” [BBC]. The publication of Lassale and her colleagues in the prestigious scientific journal Molecular Psychiatry on the association between Mediterranean Diet and depression, received a lot of attention in the media last week.

So, can diet really influence your mental health? The publication of Lassale shows that there are indications that what you eat is related to how you feel. But because this study is an observational study, we can’t conclude anything yet about causation. In other words, we don’t know yet whether eating healthy causes you to feel less depressed, or whether feeling depressed causes you to eat unhealthy.

Causal links between diet and mental health

Diet and mental healthThe researchers of the European consortium Eat2beNICE are investigating exactly this causal link. The way we do this is through clinical trials. In this way, we first let chance decide whether a person receives a particular diet or is part of the control group. Through this randomization we can be sure that the differences that we find between the two groups are really due to the dietary intervention that people received, because all other factors are the same between the two groups.

Specifically for the effects of the Mediterranean diet on behaviour, in the Eat2beNICE project we are using the information and measurements available from the PREDIMED-PLUS trial. In this study, we are looking specifically for the effect of a calorie-restricted Mediterranean diet, combined with physical activity, on several behavioral outcomes related with several psychiatric diseases of adults at high cardiovascular risk.

At the same time, we are conducting three other clinical trials:

  1. In Nijmegen (The Netherlands), we investigate the effects of a very strict, hypo-allergenic diet on behavioural problems in children with ADHD.
  2. We are investigating the effects of vitamin supplements in a clinical trial that will be conducted in Mannheim(Germany) and Groningen(The Netherlands).
  3. Researchers in Barcelona (Spain) and Frankfurt (Germany) are investigating the effects of probiotics (i.e. bacteria that are good for you) on mental health in adults that are highly impulsive and/or aggressive.

Through these studies we hope to be able to identify if these types of food improve mental health and in which circumstances. This can have big implications for psychiatry, where putting someone on a specific, personalised diet may be a way to improve treatment. Also, people who are at a risk for developing mental health problems may benefit from specific diets to reduce this risk. But before this can be put into action, we first need good scientific data on what really works.

How can food drive human behaviour?

A second aim of our large research consortium is to identify the mechanisms between nutrition and the way the brain works. We think that the bacteria that live in your gut play a large role in this, as they interact with other systems in your body, including your brain. So we are collecting poop samples of the people that are participating in our clinical trials to identify which bacteria are more or less common in our participants compared to the control population. We are also measuring our participants’ behaviour and we will scan their brains. We hope that this will help us understanding better why certain types of food can be beneficial for mental health, and why some others increase the risk for mental health problems. This too will help to elucidate, and understand, the causal links between food and behaviour.

In short, we are very thankful for the study of Lassale and her colleagues, for backing up the evidence that what you eat is related to how you feel and behave. Now there’s work for us to do to prove the causal and mechanistic links. We’ll keep you posted here!


Authors Jeanette Mostert and Alejandro Arias-Vasquez work at the department of Genetics at the Radboud University Medical Center in Nijmegen, The Netherlands. Alejandro Arias-Vasquez is the project coordinator of the Eat2beNICE project. Jeanette Mostert is the dissemination manager.


Further reading

Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, Akbaraly T. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry. 2018 Sep 26. doi: 10.1038/s41380-018-0237-8.


Blog by Jordi Salas explaining the Lassale paper and the PREDIMED trial:

Blog by Jolanda van der Meer on hypo-allergenic diet (TRACE study): http://newbrainnutrition.com/adhd-and-food-elimination-diet/

Blog by Julia Rucklidge on trials with vitamin supplements: http://newbrainnutrition.com/micronutrients-and-mental-health/

Blog by Judit Cabana on the Gut-Brain axis: http://newbrainnutrition.com/the-gut-brain-axis-how-the-gut-relates-to-psychiatric-disorders/


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This month, August 2018, I started as dissemination manager at New Brain Nutrition. This means that I will make sure that the information generated in this research project is spread out to society. Together with the dissemination and communication team of New Brain Nutrition, I strive to inform and educate as many people as possible about how nutrition influences our gut, our brain and our mental health.

Now I didn’t study communication or marketing. Rather, I studied Cognitive Neuroscience and did a PhD on brain connectivity in adults with ADHD. But while doing this PhD research, I became very interested in science communication. I organised an open day, started a blog with fellow PhD students, and participated in science battles. And through these experiences I learned that for science communication the most important ingredient is a willingness to convey your story to someone else.

The art of storytelling is thought to be as old as humanity itself. People are better at remembering and comprehending stories [1] and stories attract more attention than what’s called ‘logical-scientific communication’ [2]. However, storytelling is often viewed as unfit for sharing scientific results, because a story provides a subjective interpretation of data [3]. In a good story, only the elements that contribute to the story are told, while the ones that do not match the narrative are left out. That surely is not what we want to do in science communication!

New Brain Nutrition Research through StorytellingHowever, I do think that scientists should use the art of storytelling in their science communication to non-expert audiences. There is just too much and too complex data and information out there. If we want people to hear about our findings, and understand what they mean, we need to help them to read, comprehend and remember this information. Narratives are often the best way to do this. When telling these stories, we need to make careful decisions about the goal of our story (do you want to persuade your audience of something, or is the goal comprehension?), the level of accuracy (can you use a metaphor that is not entirely accurate, in order to accurately describe a certain process in an understandable way?) and whether or not to leave out certain facts of the story [2]. These decisions can be difficult, and we might sometimes make the wrong decisions, but overall I believe that we can all learn the art of telling good, honest stories.

At the same time, science can be much more open and transparent about the data and the findings themselves. I therefore think that open science, including open access publications and data sharing, should go hand-in-hand with storytelling in science communication. Share your story, your interpretation of the data, with the public. Take them along in your reasoning, which you have developed over the years as an expert in your field. And at the same time, share your data and your findings so that those who want to can come up with their own interpretations and conclusions.

So that’s my goal: telling you the stories of our research. As accurately as possible, without hiding information or twisting plots, but in an interesting, engaging and comprehensible way. And I hope that this will be a dialogue rather than a monologue. Tell us what you think, what your questions are, what you find difficult to believe, what you want to know more about. Then together we can build the story of New Brain Nutrition.

This blogpost was inspired by a recent article in The Guardian: https://www.theguardian.com/commentisfree/2018/jul/20/our-job-as-scientists-is-to-find-the-truth-but-we-must-also-be-storytellers



[1] Schank, Roger C. & Abelson, Robert P. (1995) Knowledge and Memory:  The Real Story.  In: Robert S. Wyer, Jr (ed) Knowledge and Memory: The Real Story. Hillsdale, NJ. Lawrence Erlbaum Associates.  1-85. http://cogprints.org/636/1/KnowledgeMemory_SchankAbelson_d.html

[2] Dahlstrom, Michael F. (2014) Using narratives and storytelling to communicate science with nonexpert audiences. PNAS, 201320645. https://doi.org/10.1073/pnas.1320645111

[3] Katz, Yarden (2013) Against storytelling of scientific results. Nature methods, 10 (11). https://doi.org/10.1038/nmeth.2699


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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 728018

New Brain Nutrition is a project and brand of Eat2BeNice, a consortium of 18 European University Hospitals throughout the continent.

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