Fish is an important component of a healthy diet. Especially fatty fish types such as herring, mackerel, sardines and salmon are often mentioned in relation to brain health. Many people take fish oil capsules aiming to improve their mood or feel more focused, or even in the hopes of preventing dementia. What makes fish, and especially fatty fish, so special?

Fatty Acids
Fatty fish is a rich source of polyunsaturated fatty acids, or PUFA’s (also called omega-3 fatty acids,ω−3 fatty acids, or n−3 fatty acids). PUFA’s come in different kinds, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and α-linolenic acid (ALA). The latter, ALA, is plant-based. It is found in walnuts, chia seed, flaxseed, and vegetable oils. The other two, EPA and DHA, are found in fatty fish. Fish do not produce PUFA’s themselves. Rather, PUFA’s accumulate in fish as they eat
algae or prey fish. In fact, nowadays, to pertain the health benefits of eating fatty fish despite most
consumption fish having lived in captivity, aquaculture feed is artificially enriched with fish oil [1].

Building Block of the Brain
PUFA’s are, quite literally, building blocks of the brain. Especially DHA is highly abundant in the
human brain, where it supports proper functioning of cell membranes. To obtain enough PUFA’s for
optimal functioning, our brains depend largely on what we eat. Mammals, including humans, are
unable to synthesize ALA. This is why ALA is referred to as an essential fatty acid . When ALA is ingested, however, our body can convert it to EPA and/or DHA. Therefore, strictly speaking, DHA and EPA are not essential fatty acids. However, ALA conversion to DHA or EPA is limited: even very high levels of ALA intake cannot fully compensate for the absence of DHA or EPA in a diet [2].

Deficiencies and supplementation
Most dietary advisory bodies recommend a minimum of 200 milligrams of omega-3 fatty acids per day, which equals about one portion of fatty fish per week (see for instance the Eatwell Guide [3]). Especially in countries where fish is not a standard meal component, it can be a challenge to meet this recommendation. For specific groups such as vegetarians or vegans, meeting the recommended intake is virtually impossible. If your diet is deficient in PUFA’s, taking fish oil capsules can be a solution. In fact, gelatin-free capsules are available for vegans and vegetarians, containing PUFA’s from algae rather than from fish.

Fish Oil Capsules to Treat ADHD Symptoms?
Most children in Western countries do not meet the guidelines regarding fatty fish intake [4]. Among youths with attention-deficit hyperactivity disorder (ADHD), even fewer meet the guidelines, resulting in lower PUFA blood-serum levels in children and adolescents with ADHD as compared to their peers without ADHD [5]. This has led researchers to believe that, possibly, low PUFA blood-serum levels may cause attention problems, hyperactivity, and impulsivity. If true, high intake of fatty fish or fish oil supplementation with capsules might reduce ADHD symptoms. To test this promising hypothesis, many researchers have measured symptoms in children and adolescents before and after several weeks of fish oil treatment. Unfortunately, when researchers reviewed all of these studies up until 2012, they concluded that the majority of studies found no beneficial effect of fish oil on ADHD symptoms [6]. Note, however, that this does not preclude the possibility that fish oil supplementation may have a beneficial effect for some children or adolescents with ADHD. Moreover, even if fish oil supplementation does not improve ADHD symptoms, supplementing PUFA deficiencies may provide other health benefits for this group. For instance, it may lower the risk of cardiovascular disease [7].

REFERENCES:
[1] https://www.iffo.net/

[2] Burns-Whitmore B, Froyen E, Heskey C, Parker T, San Pablo G (2019). Alpha-Linolenic and Linoleic Fatty Acids in the Vegan Diet: Do They Require Dietary Reference Intake/Adequate Intake Special Consideration? Nutrients, 11(10):E2365.

[3] https://www.nhs.uk/live-well/eat-well/the-eatwell-guide/

[4] Sichert-Hellert W, Wicher M, Kersting M. (2009). Age and time trends in fish consumption pattern of children and adolescents, and consequences for the intake of long-chain n-3 polyunsaturated fatty acids. Eur J Clin Nutr, 63(9):1071-5

[5] Burgess JR, Stevens L, Zhang W, Peck L (2000). Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr, 71(1 Suppl):27S-30S

[6] Gillies D, Sinn JKH, Lad SS, Leach MJ, Ross MJ (2012). Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database of Systematic Reviews, 7:CD007986

[7] Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, Summerbell CD, Worthington HV, Song F, Hooper L (2020). Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews, 3: CD003177

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Although you might be under lockdown, you are still allowed to go to the supermarket to buy food. The following information might help in terms of making healthier choices on what foods to buy.

When we are under high stress, we can often reach for foods that are “comforting” (like cookies, donuts, cake, pastries, and chocolate bars), but these foods may not be the best choice for feeding your brain under stressful and demanding circumstances. Comfort foods are often calorie-rich but nutrient-poor.

Further, under high stress (and it doesn’t actually matter what has caused the high stress, whether it be a natural disaster like an earthquake or fire, or witnessing something really traumatic or being stressed because of financial and health uncertainty), the reactions our body goes through can be quite similar. We release adrenaline. This is part of our natural alarm response system.

Adrenaline is an essential neurotransmitter that is released as part of the fight-flight response. It enables our body to get us to safety, shut down non-essential functions, and make sure the muscles needed for flight or flight get activated. Cortisol, a hormone, is also essential for the alarm system to function optimally.

Unfortunately, over extended periods of time, the alarm system can go into over-drive, and this is one factor that can lead to re-experiencing memories, flashbacks, hypervigilance, being on edge all the time, feeling anxious and panicky when reminded of the traumatic event, struggling with sleeping and having nightmares.

Making neurotransmitters (like dopamine or serotonin) and hormones (like cortisol) requires micronutrients, which are numerous kinds of vitamins and minerals. This is a well-established scientific fact. Micronutrients like zinc, calcium, magnesium, iron, and niacin are all essential for making neurotransmitter chemicals for the brain and the body. If your body is depleted of these nutrients, then either it won’t have sufficient nutrients to make these essential chemicals, or it will redirect all resources to the fight-flight response (as it is so vital for survival) and there won’t be much left for ensuring optimal brain function to do things like concentrate, regulate moods and sleep.

Consequently, as micronutrients get depleted at a high rate during times of stress, we need to replenish them in greater quantity from our food (and perhaps other sources).

Where can we get these micronutrients from?

Answer: Nutrient-dense foods; real food, not ultra-processed foods.

Compare a banana to a cookie; one obtains far more of these micronutrients (like potassium, magnesium, folate) that are required for brain function from a banana. Eating kale chips over potato chips would also provide more nutrients. Reaching for a carrot stick and dipping it in hummus would be better for your brain than gorging down a commercial meat pie (although meat pies can be healthy if they contain lots of vegetables too). Choosing nuts and seeds over pretzels would also give you better brain food.

Overall, to cope well with stress your goal should be to increase intake of plant food and food high in nutrient density while still getting adequate protein, fats and carbs. Fish is a great source of protein and of essential fatty acids, which are also vital for brain function. In eating these types of foods, you would be shifting your diet from a Western type of diet (ultra-processed, high in sugar) to a Mediterranean-style diet (high in fruits and veggies, fish, nuts, healthy fats and low in processed foods).

Therefore, stop counting calories and start focussing on nutrients, especially nutrients that are good for your brain!

Would this be sufficient to sooth the over activated alarm system in a situation of high and chronic stress? Possibly, although some people might need more nutrients than what they can get out of their diet, even if it is a healthy one. There are many reasons for this, some of which reflect reduced nutrient density in modern foods, some of which are due to our own specific genetic make-up, and some have to do with the health of our microbiome (the millions of helpful bacteria that live inside us, especially in our gut).

If you do need to consume more nutrients than what you can source from your diet, or you are struggling with cooking due to your particular circumstances and the stresses you are experiencing, or you are time poor because of family or work demands, what do you take in terms of a supplement? Research from the Mental Health and Nutrition Lab in Christchurch, NZ found that following the Christchurch earthquakes as well as other research on stressed communities shows that B vitamins in particular can be helpful. A recently published meta-analysis confirmed the positive effect of B vitamins on reducing stress. In addition, some may find reduction of intrusive thoughts require additional minerals as well.

Basic tips

  1. Start with whole foods diet approach including good fats, nuts, seeds, fish, modest amount of meat, vegetables, fruit, whole grains
  2. Shifting towards eating “real” as opposed to processed foods naturally eliminates unnecessary food additives such as artificial colors, flavors, sweeteners and preservatives that do not add nutritional value and may contribute to psychiatric symptoms in some people
  3. Limit sugar intake (sugar is everywhere in processed foods, energy/fizzy drinks – look at labels to spot the hidden sugar)
  4. Watch caffeine and alcohol intake doesn’t creep up
  5. Eat a good solid nutrient-dense breakfast: e.g., omelette with vegetables, muesli (oats, nuts, raisins) with milk, yogurt, fresh fruit
  6. Aim for 80:20. That is mostly real food but still enjoy treats! And when you do, savour them!

Being in lockdown for some might mean having a lot of extra time on your hands. Maybe take the opportunity to try new recipes, learn what to do with chick peas or how to cook beans, make bread, yogurt or cheese, But overall focus on what you can control. And when it all gets a bit too much, focus on your breath. It is amazing what a few deep breaths, slowly inhaling, holding and exhaling, can do to calm the mind.

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Interview with Annett Oehlschläger, author of the book “You can eat stability?!“

After listening to a talk given by Miss Oehlschläger at a conference on bipolar disorder in 2019, and learning how she, as an affected person herself, manages her disorder, I decided to conduct this interview with her to stress the importance of a solid knowledge about one’s disorder, but also about body processes and nutrition. This interview had been conducted in German and translated to English.

Miss Oehlschläger, after living with the diagnosis of a bipolar disorder for many years, you wrote a book named “Stabilität kann man essen?!“ (“You can eat stability?!“) What made you write this book?

Simply speaking: There hasn’t been a book yet which investigated what effect nutrition, exercise, biological rhythm, sleep, and light have on mood and energy fluctuations. During my literature research I was surprised at first that there were so many connections, and I grew angry because I had never heard about this during my psychiatric treatment. It was my wish that other affected people learn about these connections. This was the reason to write this book.

Who is the book written for and what could be reasons to read it?

So first and foremost, it is written for those who are affected by a bipolar disorder, that’s why it is called “Steps for Self-Management”. But it could also be worth reading for people who don’t get along with psychotropic drugs and for people with other psychiatric disorders than those of the bipolar spectrum.

What does “bipolar pilot” exactly mean?

When I created my website, I was looking for a catchy term and while doing this I actually found the term “pilot.” Even though it has nothing to do with the disorder at all at first sight, it is very suitable. A pilot is someone who is helping a non-local to find the right way and that is how I understand my offer. Everybody has to take the journey on his or her own, I can only accompany a part of it. I make an offer and show how to live self-determined and as autonomously as possible with the disorder. With me as an example, I show how to become an expert of my own disorder. I am there for upcoming questions and I offer my experience and my advice.

Would you say that the book is also worth reading for people without a bipolar disorder or for relatives of people with a bipolar disorder or for people with another mental or psychiatric disorder?

Yes, I’d say so. I have been told several times that my explanations are focused on bipolar disorder, but that many connections are shown that basically affect everyone. Everybody has to eat and everybody wants to stay healthy. The things I’m describing don´t only have to do with the bipolar disorder, but also with how to keep the body healthy, and how close body and mind are connected.

In your experience, how do nutrition and psyche relate to each other?

It has always bothered me that the psyche and the body were perceived as something independent and separate from each other. All materials that our body needs, except oxygen, come into our body via food and drinks, and then the body builds it‘s substances from it and produces the necessary energy. Conversely, what I do not ingest and what the body cannot produce itself, or what it cannot process, cannot be built into the cells. My conviction is that the way people eat plays an important role in all chronic diseases, including bipolar disorder. For people with mental disorders the following relation is important: Emotions and thoughts don’t just materialize out of nowhere. They are built in the brain using amino acids and are controlled by messenger substances. This is quite a complex procedure, but it just doesn’t work right without the necessary raw material. Everybody might have already experienced the feeling of well-being after having eaten something sweet, like chocolate. Here, the connection is obvious. To rephrase a saying by Feuerbach: You are not only what you eat, you also feel according to what you have eaten.

Why is the realization that psyche and nutrition are so strongly connected not widespread and an integral part of every therapy or medical consultation?

I often asked myself the same question while I was reading the books. I asked two doctors who helped me with the diet change. One of them is an internist and environmental physician from Rostock, Germany, and he told me that medical students do not learn this. The focus is rather on the treatment of symptoms, mainly using medication. And I have experienced nothing different in psychiatry, symptoms are treated with medication. The vast potential of biochemistry and orthomolecular medicine remains unused. I find this quite regrettable. Additionally, there are guidelines that are set up by professional societies, and each doctor has to treat according to these guidelines. And then, there is also the healthcare system which is growing more and more specialized. This brings certain advantages, no doubt. But especially when it comes to the psyche, in my opinion, you need a holistic approach to sustainably help an affected person.

In your experience, what do exercise and sleep have to do with the psyche in addition to diet?

This has something to do with a human beings’ system, which has evolved over thousands of years. We are adapted to our environment and living conditions that have evolved only very slowly over the thousands of years. The so-called modern progress over the last 200 years brought so many fundamental changes in our living conditions we are not adapted to – yet. Sensitive people react with disturbances in their system. Bipolar disorder is one of them. A basic element of our living condition was regular exercise. The human being is made for walking and not for sitting. The saying “sitting is the new smoking” states that a lack of exercise is similarly unhealthy as smoking is. When we walk, we release endorphins. These are happiness hormones and pain killers, which made it possible for mankind to run long distances. If you move, you brighten up. I find this a very easy way to lift your mood, you just have to get up and do it.

Further, chronobiology has found out that it is important for our well-being to stick to biological rhythms. If you act against these rhythms you risk affecting your health, i.e., sleeping disorders. This is a common symptom of bipolar disorder and other mental conditions. The sleep-wake-cycle is an important pacemaker, such as sunlight. It is not irrelevant when you eat or sleep when you work or regenerate. Regularity stabilizes. Mental stability can be achieved by living according to these rhythms. I do live according to these principles.

And if we are going to be more practically now, what would you say, which food should one eat?

Of course, all of the food I need for a good mood. These foods have to provide all the 47 substances that each body necessarily needs in order to stay healthy: 10 amino acids, omega-3 and omega-6 fatty acids, 13 vitamins and 22 minerals and trace elements.

However, we don’t eat single substances but complex food. So by selecting my food, this is what I do: If I am aware that drive and mood are dependent on amino acids, then the logical conclusion is that I eat food that contains these. Proteins are built from amino acids. Enhancing your protein intake doesn’t necessarily mean eating more meat. Fish, eggs, and legumes contain protein as well.

Further, many processes in my body require enzymes, co-enzymes and co-factors: This is where vitamins, minerals and trace elements come into play. They are needed so that the substances eaten can be absorbed by the body, and also by the brain. If I know that, then I am aware that I have to eat food that provides these substances – these are mainly vegetables, nuts, seeds, and fruit.

Going shopping at the supermarket, I often get the impression that these foods only account for a small proportion of the vast offer. More dominant are sugar-sweetened beverages, alcohol, packed and conserved foods, bread, bakery products, and candy. We are constantly exposed to these temptations. If you want to eat according to what your brain needs, you can stick to these easy advices:

Don’t consume sweetened beverages, which also include fruit juice and smoothies, because they contain large amounts of sugars. These simple sugars are mood killers.

Don’t buy processed food. You will recognize processed food mainly because it is packaged and contains a lot of food additives. If there are many different ingredients on the list, chances are quite high that there are additives in it that nobody really needs. Their true serving is to make the product either more tasty – using salt, sugar, flavor enhancers, emulsifiers, and the like, or to enhance shelf life by preservative agents or antioxidants, or to make the product more appealing by adding colorants.

The issue with these unnecessary additives is that they harm the gut – in some people more, in some people less. This can lead to a reduced ability to absorb the substances needed, on the one hand, and on the other hand it can happen that the gut gets leaky and unwanted substances can enter the body. This can also lead to sickness. Both affects drive and mood.

Simply speaking, for a good mood and drive I need foods that are as natural as possible, regionally produced, seasonally, and preferably organic. A large part of my nutrition comes from these foods. If I stick to these principles, I take care of a good basis for mental stability.

And what about fat?

Fat is an essential substance, too. We could not survive without fat. If you consider that 60% of our brain’s dry matter is composed of fat, that each cell in our body is coated by a double lipid layer, then one can hardly comprehend this fat phobia which has been going on for many years.

However, there is fat that is beneficial for mood and drive, and there is fat that is unfavorable for the psyche. For thinking, we need a properly functioning of signal conduction in the brain. Our feelings are influenced by our thoughts and the other way round, both are a product of our brain. Both affect our behavior – all of which are very complex processes of the brain.

The cells build those fats into their cell walls that the person ingests. For the membranes to be fluid enough they need a certain composition of fatty acids. Here, the synergy between vitamin D and the omega-3 fatty acids EPA and DHA play a crucial role. Vitamin D is needed when neurotransmitters are built, and EPA makes sure that the cell membrane is fluid enough so that the neurotransmitter can be spilled into the synaptic cleft. DHA takes care that the receptor at the post synapse can pick up the signal to be transmitted. This is why I take specific care to take up at least 2 grams of fish oil every day.

Would you say that nutrition ultimately plays a greater role than psychotropic drugs in improving the disease?

From my point of view, in an acute crisis, psychotropic drugs are a blessing. I am convinced that I would not be alive anymore today if I hadn’t received medication.

But what’s bugging me is constant medication. I, too, have been told that I have to take psychotropic medication all my life. I have a different point of view today. To stay stable permanently, I only need medication as long until my body is strong enough to stabilize my psyche.

This is a long-lasting, exhausting, and also pricy process. Not everybody manages that. This is why it might be that somebody still needs to take psychotropic medication.

A diet that provides all the substances my body needs adds considerately to strengthen the overall health and also the immune system. That way, one improves one’s overall quality of life, not only the mental stability. In this sense, nutrition plays a bigger role.

Can an improvement of the disorder solely occur through nutrition?

Bipolar disorder is a serious mental disorder with many causes. Stress plays a pivotal role, my reaction towards it just as well, just as my core beliefs. A sole change in diet can’t change anything about that, it takes psychotherapy and psychoeducation. However, I can influence my vulnerability towards stressors through my diet. For example, a certain level of magnesium is important for being able to relax and to stand above things. Magnesium is also called “salt of inner peace”, and for a reason.

Further, the effect of my diet on my mood is influenced by the origin of my food, and what it contains or doesn’t contain anymore. Take selenium for example. This is very important for the thyroid gland and, by the way, enhances your mood. Through the last ice age, it has been washed out of the ground here in Germany. So if I eat local products, they contain less selenium than food from the US, for example.

If I measure my blood composition and see that I lack a certain substance that I can’t properly ingest via my food, I go for food supplements. I don’t manage to get all the nutrients I need through the food I eat.

But an improvement of the mental disorder depends on many more factors. Nutrition is the most important part, in my opinion, because only through nutrition I get the raw material for the production of neurotransmitters. No drug can achieve that.

To clarify which components are important for a good mood and drive, I like to use the metaphor of a jigsaw puzzle, just as in my book. Only when all the pieces are in place, I get a coherent image – that of mental stability. Which pieces I need are quite specific. But it’s worth it to find that out. My puzzle pieces were psychotropic drugs, psychotherapy and psychoeducation at first. Today I don’t need these components anymore. But other factors play a role now: nutrition, exercise, sleep, stress management, self-care, and a meaningful occupation. And also, regular measurements of blood levels to identify imbalances or low levels of substances at an early stage and being able to react promptly. These are my puzzle pieces for stability, so it’s not nutrition alone.

You have already mentioned the keyword “dietary supplements.” Which dietary supplements should one take, or should you take any at all?

Sometimes I get the impression that when it comes to the topic of food supplements, it is often about opinions and factoids rather than scientific facts. Often it is stated that supplements are unnecessary if you eat healthily because then you get everything you need. Or that supplements have a beneficial effect only for the producers. I have believed such statements for a long time before I started having my blood levels measured. My level of vitamin D had been so low I basically didn’t have any of it in my blood. The level of magnesium had been below the reference value, B vitamins had been at the lower level, not to talk about zinc and selenium, and the overall level of protein had been way too low. And at that stage I had been eating healthily, or I had assumed that my nutrition is healthy and contains everything I need. So there had to be something wrong here, or what was the reason for these results?

Today I know that certain essential substances are not available in our food in adequate amounts – or not anymore. Take selenium for example. It is even more dramatically regarding vitamin D. This can be built by the skin, so technically it is not really a vitamin. Experts, such as Prof. Holick from the US, call it a prohormone, because it is associated with more than a thousand of metabolic processes, and more than 2000 of our 23000 genes depend on vitamin D directly or indirectly. Because of the degree of latitude we live in regarding Germany, between October and April the sun is so low we can’t build vitamin D at all. The angle of the sunbeams is below 45 degrees, and so the UVB part of the sunlight doesn’t reach our skin. However, vitamin D reservoirs are depleted after 4 months, so even after I have built up enough vitamin D during the summer it won’t help me get through the winter. Vitamin D is very important for the mood. Once you experience what a difference it makes if you refill such a lack of a substance you stop believing those depreciative statements, even if they come from a doctor.

My recovery started with heightening my vitamin D level. It was at 7ng/ml and today I make sure it stays around 60-70ng/ml. Since I don’t build it appropriately through sun exposure or food I take supplements. So I supplement what I don’t get otherwise if I see that I’m lacking it.

On the other hand, it’s no use just to take anything just because somebody told me it’s good for me. Everybody has his or her individual metabolism. If two persons eat the same food, blood levels can differ. So supplements are very helpful if they are taken specifically and for a purpose.

People with mood fluctuations or mental issues should know their level of vitamin D, especially if they take psychotropic drugs because these drugs deplete the body’s vitamin D reservoirs. B vitamins are vital because they enable the building of serotonin, the happiness hormone, from tryptophane. B vitamins act as co-factors here; this is why I recommend eating a handful of nuts every day because they are full of B vitamins.

It also needs omega-3 fatty acids, magnesium, iron, zinc, but describing this here would go too far. But I am describing this in my book in detail.

As a last question, which message do you definitely want to transmit to the readers with this interview? Everybody should be worth it him- or herself to stabilize oneself by following a healthy diet. For me, measuring my blood levels is part of it, so really going to the lab to have your status determined and when you add supplements to your diet, to see what happens. And I am convinced that if you fill up such deficiencies, then everyone will experience his or her own miracle, just as I have experienced it. Because nobody believed that one can become psychologically stable by just a change in diet. Even “only” an improvement of the quality of life is an achievement in my opinion. I know enough sufferers who take psychotropic drugs, but still take dietary supplements such as omega-3 fatty acids and vitamin D because they improve their life situation. And that is actually what we want, isn’t it?

Miss Oehlschläger, we that you very much for this interview!

About the author: Annett Oehlschläger has been diagnosed with Bipolar Disorder when she was 47 years old. She has been solely occupied with this disorder for eight years and has been to psychiatric hospitals 24 times during these years. Through psychotropic medication and many hours of psychotherapy, the bipolar phases got shorter and the dose of medication could be reduced – however, Miss Oehlschläger still didn’t really become mentally stable. She set out to search for alternatives. Through a diet and lifestyle change and by tackling her vitamin and mineral deficiencies she has been managing to become stable for six years now. This made her write a book called „Stabilität kann man essen?!“ (“You can eat stability?!” – available in German) which has been sold more than 3000 times so far.

About the interviewer: Anne Siegl, PhD is a psychologist and neuroscientist at Klinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum, Frankfurt am Main, Germany. She is researching effects of nutrition on psychological well-being.

This interview has been conducted and translated together with Laura Müller, B.Sc. Laura Friederike Müller, B.Sc., is a Student of Psychology at the Fresenius University of applied Sciences in Frankfurt am Main. At the time of the interview she has been doing an internship in the Eat2beNice project group at the Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, studying the effects of nutrition and lifestyle on mental health.

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When exposed to UVB-radiation, the human body produces vitamin D out of cholesterol. Vitamin D is therefore also known as the “sunshine vitamin”. Healthy vitamin D levels in people are thought to play a role in preventing several health problems, such as cardiovascular diseases, osteoporosis, mood disorders, diabetes and other autoimmune diseases [1]. In a previous post, Dr. Faraone also outlines the association between vitamin D and ADHD in children and adolescents [2]. In most western countries, the beneficial effects of vitamin D are well-established. Pregnant women are even advised to add vitamin D supplementation to their diet to stimulate the fetal growth [3].

People that live further from the equator, have fewer hours of UVB-radiation and are more prone to vitamin D insufficiency. For example, residents of northern Canada and Norway have very little UVB exposure during November through February. During those months, vitamin D intake is even more important.

Residents of the arctic circle, whose families have lived there for generations after generations, have diets that are traditionally relatively high in vitamin D. The diet contains among other things: liver, trout, Atlantic salmon, seals and whales. As younger generations gradually shift away from the traditional diet, vitamin D insufficiency becomes more common among northern residents [5]. It is yet unclear if the decline in traditional diets will be accompanied by a rise in vitamin D insufficiency-related health problems. However, it is well established that several of these health problems have been uncommon among northern residents in the past [6].

Research shows that in countries further away from the equator, vitamin D levels are steady with regular UVB-exposure: Going outdoors around noon, sun bed use (with caution) and sun seeking holidays. And in the UVB-scarce months, regular vitamin D intake becomes in particular important to prevent from low vitamin D levels and its possible consequences [4].

References

[1] Wessels I, & Rink L (2019) . Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin D. J Nutr Biochem. Oct 30;77:108240. doi:10.1016/j.jnutbio.2019.108240. [Epub ahead of print]

[2] https://newbrainnutrition.com/adhd-and-vitamin-d-deficiency/

[3] Gallo S, McDermid JM, Al-Nimr RI, Hakeem R, Moreschi JM, Pari-Keener M, Stahnke B, Papoutsakis C, Handu D, Cheng FW (2019). Vitamin D Supplementation during Pregnancy: An Evidence Analysis Center Systematic Review and Meta-Analysis. J Acad Nutr Diet. Oct 25. pii: S2212-2672(19)30849-4. doi: 10.1016/j.jand.2019.07.002. [Epub ahead of print]

[4] Brustad M1, Edvardsen K, Wilsgaard T, Engelsen O, Aksnes L, Lund E (2007). Seasonality of UV-radiation and vitamin D status at 69 degrees north. Photochem Photobiol Sci. 2007 Aug;6(8):903-8. Epub 2007 Jun 27.

[5] El Hayek Fares J, & Weiler HA(2016). Implications of the nutrition transition for vitamin D intake and status in Aboriginal groups in the Canadian Arctic. Nutr Rev. 2016 Sep;74(9):571-83. doi: 10.1093/nutrit/nuw020.

[6] Dewailly E Blanchet C Lemieux S et al (2001). n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik . Am J Clin Nutr. 74 : 464 – 473 .[/st_text][/st_column][/st_row]

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I have noticed a growing number of companies offering to measure nutrient levels and then offering a personalized treatment approach to address deficiencies identified. I have also been sent individual blood results from members of the public and asked whether the results can be used to direct the best treatment. Others contact me and tell me their nutrient levels are “normal” so their doctor told them there was no need for additional nutrients.

It is a reasonable question because there are many studies that suggest that people with psychological problems such as ADHD have lower levels of nutrients in their blood relative to the nonclinical population. What we don’t know is whether it is necessary to be deficient in order to benefit from additional nutrients than what you can get out of your diet.

So what does the research say?

Our lab at the University of Canterbury in New Zealand is one of a few that has specifically investigated whether nutrient levels are predictive of response to a broad spectrum micronutrient intervention. It is important to note that not many labs take this approach, that is giving a combination of nutrients together and then assess treatment response. Many researchers make the assumption that one must be deficient to benefit from nutrients, and therefore select people for the deficiency and only treat them. We treat everyone, regardless of identified deficiency, and then assess whether the deficiency predicts who will respond and who won’t.

Overall, our research shows that the effect, if there is one, is weak, and certainly not useful at an individual level as a good predictor of treatment outcome.

Here is what we did: We assessed some key nutrients pre-treatment via serum/plasma. We measured vitamin B12, vitamin D, zinc, copper, folate, ferritin, potassium, sodium, calcium, and homocysteine. We have looked at two data sets – an adult study and a child study, both comparing vitamins/minerals to placebo in the treatment of symptoms associated with ADHD.

Findings from the adult ADHD trial:

Participants improved significantly on all outcome measures after exposure to the micronutrients for 8 weeks; 61% were identified as responders.

But, there was no relationship between baseline functioning and baseline nutrient levels. This was a bit surprising given that studies have identified deficiencies in magnesium, zinc and iron in children with ADHD. Surprisingly, we didn’t find that these nutrient levels were highly correlated with ADHD symptoms.

Very few predictors were identified. We found that greater pre-treatment with ferritin predicted who would be an ADHD responder. We wondered if those with higher ferritin had higher inflammation and therefore responded more rapidly to the treatment as the micronutrients may have improved inflammation.

Lower pre-treatment vitamin D predicted greater change on a measure of mood. This finding is not unexpected as low vitamin D levels have been associated with low mood. Pre-treatment copper gave us a signal, but it was weak and mixed.

Micronutrient supplementsIt is important to note that while there were these small signals, there were still many people with normal levels of these nutrients who benefitted from the nutrient approach, only there were fewer relative to those with vitamin D and copper deficiencies.

No other relationships between baseline nutrient levels and treatment response were identified. In other words, zinc, iron and vitamin B12 pre-treatment did not predict who would benefit and who would not. Further, there were no specific demographic variables (age, socio-economic status, gender, marital status, education) which contraindicated micronutrient treatment for ADHD in adults.

Findings from the child trial:

We identified that 49% of the children responded to the micronutrient intervention. Substantial nutrient deficiencies pre-treatment were observed only for vitamin D (13%) and copper (15%), otherwise most children entered the trial with nutrient levels falling within expected ranges. Lower pre-treatment folate and B12 levels, being female, greater severity of symptoms and co-occurring disorders pre-treatment, more pregnancy complications and fewer birth problems were identified as possible predictors of greater improvement for some but not all outcome measures although predictive values of all of them were weak. Lower IQ and higher BMI predicted greater improvement in aggression.

It is important to note that levels of folate pre-treatment for ADHD responders was within the normal reference range for folate (>8nmol/L). In other words, the blood tests did not identify responders as deficient in folate, just lower relative to non-responders. Note though, that there were many children with higher B12 and folate who did benefit from the nutrient treatment. No other relationships between pre-treatment nutrient levels and treatment response were identified.

It is also important to point out that across two studies, replication did not occur and any findings we did observe were incredibly modest. As such, they could not be used at an individual level to reliably identify who might benefit from this treatment approach. We see this as good news as it means people don’t have to feel they need to get expensive testing done before trying nutrients. The bad news is that the search is still on to figure out why some people respond and some don’t.

Although not reported in these trials, we have also looked at the predictive value of nutrient levels recorded from hair samples and similarly, the levels were also not overly helpful at predicting treatment response.

Do nutrient levels have to change for benefit to occur?

Now this is a tricky question. But we have now published a study looking at this very question, that is, whether change in a nutrient biomarker is correlated with improvement in mental health. Our overall findings were that they were not.

I think this type of question stems from research in medicine such as physicians tracking cholesterol levels in order to determine whether they are associated with the progression of disease (such as incidence of stroke). Change in cholesterol levels are used to estimate risk for future cardiovascular events.

In the mental health world, at best, they are weakly correlated with improvement in symptoms and probably not that helpful. We investigated whether changes in serum nutrient levels mediate clinical response to a micronutrient intervention for ADHD. Data were compiled from two ADHD trials (8-10 weeks), one in adults (n = 53) and one in children (n = 38). Seven outcomes included change in ADHD symptoms, mood, overall functioning (all clinician-rated) as well as response status. Change in serum/plasma nutrient levels (vitamins B12 and D, folate, ferritin, iron, zinc, and copper) were considered putative mediators.

We found that a decrease in ferritin and an increase in copper were weakly associated with greater likelihood of being identified as an ADHD responder; none of the other nutrient biomarkers served as mediators. Perhaps we need to look to see if other tissue (like hair or microbiome samples) might be more useful. Monitoring these biomarkers is unlikely helpful in understanding clinical response to a broad-spectrum micronutrient approach.

Blood levels don’t necessarily tell us what is going on in the brain and what nutrients are being used and what isn’t being used. We didn’t look at ALL nutrients so it may be we missed an important biomarker. It may be ratios are more important. But next time a professional is keen to track nutrient levels as a proxy for response, perhaps be a bit sceptical about whether the data support such testing.

Is the term deficiency accurate?

The term “deficiency”, as is often used in the ADHD literature when discussing nutrient levels, may be problematic. Although research shows that the ADHD group mean nutrient levels are often below control group means, the ADHD means are typically still falling within the normal reference range, potentially challenging the use of the term “nutrient deficiency” when attempting to investigate causes of ADHD and in relation to predicting response to nutrients. Given that reference ranges are generally defined as the set of values that 95 percent of the normal population falls within, this does not necessarily mean that these ranges are best equipped to identify what is required for optimal health for any particular individual.

Had functional ranges (the range used to assess risk for disease before the disease develops) been used in these studies, many more would have been identified with “deficiencies”. An important hypothesis which requires further investigation is that some individuals may have suboptimal nutrition for brain health despite having nutrient levels within the reference range. In other words, they might have a nutrient deficiency relative to their metabolic needs rather than relative to general population levels.

It is exciting that the EAT2BeNice consortium (NewBrainNutrition) will be looking at nutrient levels alongside other biomarkers so we can confirm whether these results are replicable. Hopefully some of the other biomarkers will prove more useful at predicting treatment response. Afterall, it is a valid clinical question to wonder – when a treatment works, who does it work for and why? These types of data inform clinical practice and can help the consumer decide whether you should go for that expensive testing, or not bother. At this stage, I wouldn’t bother.

References

  1. Rucklidge JJ, Johnstone JM, Gorman B, Boggis A, Frampton CM. Moderators of treatment response in adults with ADHD treated with a vitamin-mineral supplement. Prog Neuropsychopharmacol Biol Psychiatry. 2014;50:163-71.
  2. Rucklidge JJ, Eggleston MJF, Darling K, Stevens A, Kennedy M, Frampton CM. Can we predict treatment response in children with ADHD to a vitamin-mineral supplement? An investigation into pre-treatment nutrient serum levels, MTHFR status, clinical correlates and demographic variables. Prog Neuropsychopharmacol Biol Psychiatry. 2018.
  3. Rucklidge JJ, Eggleston MJF, Boggis A, Darling K, et al. Do Changes in Blood Nutrient Levels Mediate Treatment Response in Children and Adults With ADHD Consuming a Vitamin–Mineral Supplement? Journal of Attention Disorders. 2019. 0:1087054719886363.

 

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When we are under high stress, we can often reach for foods that are “comforting” (like cookies, donuts, cake, pastries, and chocolate bars), but these foods may not be the best choice for feeding your brain under stressful and demanding circumstances. Comfort foods are often calorie-rich but nutrient-poor.

Further, under high stress (and it doesn’t actually matter what has caused the high stress, whether it be a natural disaster like an earthquake or fire, or witnessing something really traumatic), the reactions our body goes through can be quite similar. We release adrenaline. This is part of our natural alarm response system.

Adrenaline is an essential neurotransmitter that is released as part of the fight-flight response. It enables our body to get us to safety, shut down non-essential functions, and make sure the muscles needed for fight or flight get activated. Cortisol, a hormone, is also essential for the alarm system to function optimally.

Unfortunately, over extended periods of time, the alarm system can go into over-drive, and this is one factor that can lead to re-experiencing memories, flashbacks, hypervigilance, being on edge all the time, feeling anxious and panicky when reminded of the traumatic event, struggling with sleeping and having nightmares.

Making neurotransmitters and hormones requires micronutrients, which are numerous kinds of vitamins and minerals. This is a well-established scientific fact. Micronutrients like zinc, calcium, magnesium, iron, and niacin are all essential for making neurotransmitter chemicals for the brain and the body. If your body is depleted of these nutrients, then either it won’t have sufficient nutrients to make these essential chemicals, or it will redirect all resources to the fight or flight response (as it is so vital for survival) and there won’t be much left for ensuring optimal brain function to do things like concentrate, regulate moods and sleep.

Consequently, as micronutrients get depleted at a high rate during times of stress, we need to replenish them in greater quantity from our food (and perhaps other sources).

Where can we get these micronutrients from?

Answer: Nutrient-dense foods; real food, not ultra-processed foods.
Compare a banana to a cookie; one obtains far more of these micronutrients (like potassium, magnesium, folate) that are required for brain function from a banana. Eating kale chips over potato chips would also provide more nutrients. Reaching for a carrot stick and dipping it in hummus would be better for your brain than gorging down a commercial meat pie (although meat pies can be healthy if they contain lots of vegetables too). Choosing nuts and seeds over pretzels would also give you better brain food.

Overall, to cope well with stress your goal should be to increase intake of plant food and food high in nutrient density while still getting adequate protein, fats and carbs. Fish is a great source of protein and of essential fatty acids, which are also vital for brain function. In eating these types of foods, you would be shifting your diet from a Western type of diet (ultra-processed, high in sugar) to a Mediterranean-style diet (high in fruits and veggies, fish, nuts, healthy fats and low in processed foods).

Therefore, stop counting calories and start focussing on nutrients, especially nutrients that are good for your brain!

Would this be sufficient to sooth the over-activated alarm system in a situation of high and chronic stress? Possibly, although some people might need more nutrients than what they can get out of their diet, even if it is a healthy one. There are many reasons for this, some of which reflect reduced nutrient density in modern foods, some of which are due to our own specific genetic make-up, and some have to do with the health of our microbiome (the millions of helpful bacteria that live inside us, especially in our gut).

If you do need to consume more nutrients than what you can source from your diet, or you are struggling with cooking due to your particular circumstances and the stresses you are experiencing, or you are time poor because of family or work demands, what do you take in terms of a supplement? Research from the Mental Health and Nutrition Lab in Christchurch, NZ found that following the Christchurch earthquakes as well as other research on stressed communities shows that B vitamins, in particular, can be helpful. A recently published meta-analysis confirmed the positive effect of B vitamins on reducing stress. In addition, some may find a reduction of intrusive thoughts require additional minerals as well.

Nutrition resources for psychologists and mental health professionals working with people struggling with anxiety post-trauma:

When working with people struggling with stress/anxiety, research shows that it is essential that their diet includes foods that are nutrient-dense. This means being aware of foods that are high in vitamins and minerals as well as being a good source of fats, proteins and carbohydrates.

You can ask some simple questions:

  • How many times a week do you eat fast food meals or snacks?
  • How many regular fizzy drinks do you drink each day?
  • Snacks? Favourite Foods? Problem Foods?
  • Any restrictions? Allergies? Aversions?
  • How many servings of fruit do you eat each day?
  • How many servings of vegetables do you eat each day?
  • How often do you eat red meat (good source of iron, folate)?
  • Do you eat fish? (good to know if they are vegan, vegetarian, or gluten-free)

These questions can start the conversation to find out if they are eating nutrient dense foods.

Here are some basic tips:

  1. Start with whole foods diet approach including good fats, nuts, seeds, fish, a modest amount of meat, vegetables, fruit, whole grains
  2. Shifting towards eating “real” as opposed to processed foods naturally eliminates unnecessary food additives such as artificial colours, flavours, sweeteners and preservatives that do not add nutritional value and may contribute to psychiatric symptoms in some people
  3. Limit sugar intake (sugar is everywhere in processed foods, energy/fizzy drinks – encourage clients to look at labels to spot the hidden sugar)
  4. watch caffeine and alcohol intake doesn’t creep up
  5. Eat a good solid nutrient-dense breakfast: e.g., omelette with vegetables, muesli (oats, nuts, raisins) with milk, yogurt, fresh fruit
  6. If your client is struggling with cooking or a change in diet is not working enough to reduce psychological symptoms, you can consider suggesting supplements as there has been a lot of research on them. If suggesting supplements, stick to the data and published research, the best research is on adding additional B vitamins (like Blackmores or Berocca). For more information please email the Mental Health and Nutrition Research Group: mentalhealthnutrition@canterbury.ac.nz

Here are some useful resources:

A recent radio interview about dietary patterns and stress: https://www.radionz.co.nz/national/programmes/nights/audio/2018687489/nutrition-during-times-of-stress-and-trauma

Harvard Medical School has put together lots of resources on healthy eating, including the healthy eating plate: www.health.harvard.edu/staying-healthy/healthy-eating-plate

The Helfimed trial was a successful trial that showed the benefit of assisting people suffering from depression to nudge over to a more Mediterranean-based diet. They have lots of recipes on their website: http://helfimed.org/cgi-sys/suspendedpage.cgi

The Mood and Food Centre in Melbourne often blogs on diet-related topics. Check out their website: http://foodandmoodcentre.com.au/

Dr Drew Ramsey has some excellent resources on eating well on a budget: https://drewramseymd.com/uncategorized/brain-food-budget/

There are lots of great resources at this site: https://www.getselfhelp.co.uk/freedownloads.htm

Books that we have enjoyed reading on nutrition and mental health that do have some scientific basis to their recommendations:

  • Brain Changer – Prof Felice Jacka
  • Finally Focused – Dr James Greenblatt
  • The Mad Diet – Suzanne Lockhart
  • The anti-anxiety food solution –Trudy Scott
  • What the FAT? – Prof Grant Schofield (also includes recipes)

Rachel Kelly has devised a cookbook directly focused on eating foods that will contain nutrients help you feel mentally better:

https://www.rachel-kelly.net/books-apps/

How to eat well on a budget:
From the British Dietetic Association: A healthy diet can be more expensive than a diet made up of more refined foods. Fish, fruit and vegetables can be particularly pricey. However, by cutting down on sugary drinks and snacks, takeaways and alcohol, you can save money to be spent on healthier items. Take care to buy only as much as you know you can use within the next few days to reduce waste. You can also cut your costs by taking advantage of special promotions and by shopping at market stalls which are often cheaper than supermarkets.

If you live alone you could save money by splitting purchases with friends (larger pack sizes are usually cheaper) or by cooking several portions of a dish and freezing some of them. This also saves fuel and saves you the effort of preparing meals every day. Frozen fruit and vegetables are often cheaper than fresh produce and are usually just as good nutritionally (with no wastage). Fresh fruit and vegetables are usually cheapest when they are in season.

Also, research from Australia has shown that a Mediterranean style diet was cheaper than a poor quality diet.

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What is vitamin B1 (thiamine)?

Thiamine, which is also known as vitamin B1, is an essential micronutrient, which is required for metabolism, enzymatic processes and conduction of nerve signals. All living organisms use thiamine, but it can be made only in bacteria, fungi and plants. In humans, gastrointestinal microbiota also produces thiamine, but not enough for the organism functioning. Thus, we, as well as other animals must obtain vitamin B1 from the diet.

Thiamine deficiency

Deficiency of thiamine can affect the cardiovascular, nervous and immune systems. A severe and chronic form is known as beriberi. Wet beriberi affects cardiovascular system resulting in tachycardia, high arterial and venous pressures, leg swelling. Dry beriberi affects nervous system resulting in impairment of sensory, motor and reflex functions and altered mental status. Worldwide thiamine deficiency is most widely reported in populations where primary food source are polished rice and grains. In Western countries, it most commonly affects people suffering from alcoholism or chronic illness. Thiamine deficiency in patients with alcohol use disorder often lead to Kosakoff syndrome, a chronic disease with severe memory loss and learning problems.

Food sources of thiamine

It is very easy to add foods rich with thiamine to the diet. Food sources of thiamine include beef, pork, eggs, liver, nuts, oats, oranges, seeds, legumes and yeast. Such foods as rice, pasta, breads, cereals and flour are often fortified with vitamin B1 as the processing involved in creating these products removes thiamine. Thiamine supplements and medications are available on market to treat or prevent thiamine deficiency. Remarkably, B1 is well tolerated and has almost no side effects.

Bioavailable analogues of Thiamine

Analogues of vitamin B1, such as benfotiamine or dibenzoyl thiamine, have improved bioavailability, due to their higher lipid solubility, which facilitate permeation in cell membranes. As a result, they provide higher levels of thiamine in muscle, brain and liver. This can be the reason of their higher effectiveness.

Thiamine as medication

Thiamine was the first of the water-soluble vitamins to be discovered, and since early 20th century it was extensively studied. Most commonly thiamine supplementation is used to treat syndromes associated with severe thiamine deficiency and during pregnancy and lactating due to increased need for this vitamin. Rapid recovery can occur within hours if thiamine is given intravenously. If concentrated thiamine supplements are not available, diets rich with thiamine will also lead to recovery, though at a slower rate.

New properties of thiamine

Recently, other important roles of thiamine including the regulation of oxidative stress were discovered [1]. As emotional stress is associated with oxidative stress in the brain, it was hypothesized that thiamine can counteract negative effects of the stress. And indeed, in studies on mice thiamine precluded negative changes in mood and emotionality, as well as neuroinflammation and oxidative stress caused by stress [2,3]. It also ameliorated cellular proliferation and neurogenesis in the hippocampus under stress conditions. In agreement with animal studies, vitamin B1 was also able to ameliorate symptoms of major depressive disorder in patients [4] or work stress-related mood swings [5].

Thus, thiamine was shown as a promising treatment for the depressive-like changes and excessive aggression, caused by stress. Hopefully, new studies on thiamine will be conducted in the nearest future to show novel properties of this vitamin.

 

References

[1]      L. Bettendorff, P. Wins, Biological functions of thiamine derivatives: Focus on non-coenzyme roles, OA Biochem. 1 (2013).

[2]      N. Markova, N. Bazhenova, D.C. Anthony, J. Vignisse, A. Svistunov, K.-P. Lesch, L. Bettendorff, T. Strekalova, Thiamine and benfotiamine improve cognition and ameliorate GSK-3β-associated stress-induced behaviours in mice, Prog. Neuro-Psychopharmacology Biol. Psychiatry. 75 (2017) 148–156.

[3]      A. Gorlova, D. Pavlov, D.C. Anthony, E.D. Ponomarev, M. Sambon, A. Proshin, I. Shafarevich, D. Babaevskaya, K.-P. Lesсh, L. Bettendorff, T. Strekalova, Thiamine and benfotiamine counteract ultrasound-induced aggression, normalize AMPA receptor expression and plasticity markers, and reduce oxidative stress in mice, Neuropharmacology. (2019).

[4]      A. Ghaleiha, H. Davari, L. Jahangard, M. Haghighi, M. Ahmadpanah, M.A. Seifrabie, H. Bajoghli, E. Holsboer-Trachsler, S. Brand, Adjuvant thiamine improved standard treatment in patients with major depressive disorder: results from a randomized, double-blind, and placebo-controlled clinical trial, Eur. Arch. Psychiatry Clin. Neurosci. 266 (2016) 695–702.

[5]      C. Stough, A. Scholey, J. Lloyd, J. Spong, S. Myers, L.A. Downey, The effect of 90 day administration of a high dose vitamin B-complex on work stress, Hum. Psychopharmacol. Clin. Exp. 26 (2011) 470–476.

 

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Children with ADHD who keep taking micronutrients over one year are mostly in remission in their symptoms with no side effects

The results from a University of Canterbury (UC) study into the longer term effects of micronutrients on ADHD symptoms in children was recently published in the Journal of Child and Adolescent Psychopharmacology.  

This study was led by Dr Kathryn Darling at the Mental Health and Nutrition Lab in Christchurch (under the supervision of Eat2BeNice Scientist Julia Rucklidge) and looked at the long-term effects of a broad-spectrum micronutrient (vitamins and minerals) in attention-deficit/hyperactivity disorder (ADHD) treatment.

Eighty-four of the 93 children who entered a 10-week randomised controlled trial (micronutrients versus placebo), followed by a 10 week phase of all children taking micronutrients, then completed follow-up assessments after 12 months. This allowed us to gather valuable information about what happens when people choose to stay on or come off the micronutrient treatment.

The study showed that children who benefit in the short term from taking a broad-spectrum vitamin/mineral formula maintain those benefits or continue to improve when they keep taking it longer term, without side effects.

Continued micronutrient treatment was associated with improvements in ADHD symptoms which were similar to, or greater than, those associated with stimulant medication. Unlike stimulant medications, micronutrients were associated with improvements, rather than worsening, in mood and anxiety. This indicates that micronutrients can be a serious treatment option for those who choose not to take medications. Micronutrients may be especially helpful for children with ADHD who also have difficulties with mood or anxiety.

Other key findings from this research:

  • Those who continued to take micronutrients did not have any ongoing side effects.
  • Children who continued to take micronutrients and children who changed to medications (like methylphenidate/Ritalin/Concerta) either stayed well or continued to show improvement in ADHD symptoms at 12-month follow-up assessment, while those who stopped treatment altogether did not.
  • Children who switched from micronutrients to medications like methylphenidate/Ritalin were more likely to have problems with mood or anxiety at the 12-month follow-up assessment, which were worse than at the end of the micronutrient trial. After the end of the trial, mood and anxiety symptoms had generally continued to improve for the children who stayed on micronutrients, and mostly stayed the same for those who stopped treatment.
  • The most common reasons people stopped taking micronutrients were the cost and number of pills to swallow.
  • Based on dominant treatment, more of those who stayed on trial micronutrients (84%) were identified as “Much” or “Very Much” improved overall relative to baseline functioning, compared to 50% of those who switched to psychiatric medications and only 21% of those who discontinued treatment. Fifteen (79%) of those still taking micronutrients, 8 (42%) of those using medications, and 7 (23%) of those who discontinued treatment were considered in remission based on parent-reported ADHD. Those who stayed on micronutrients were more likely to have failed medication treatment in the past.

It is important to note that these findings are reporting on group averages, so the effect of micronutrients or other treatments for any specific child may have been different. People do respond differently to any form of treatment – perhaps they benefited across all areas of functioning or perhaps had no benefit at all.

This study is limited due to its naturalistic observational status but allows us to evaluate effectiveness in the real world. No funds were received from the manufacturer of the micronutrients.

If you want to know more about the micronutrients we studied, email mentalhealthnutrition@canterbury.ac.nz

 

Reference:

Darling, K. A., Eggleston, M. J., Retallick-Brown, H., & Rucklidge, J. J. (2019). Mineral-Vitamin Treatment Associated with Remission in Attention-Deficit/Hyperactivity Disorder Symptoms and Related Problems: 1-Year Naturalistic Outcomes of a 10-Week Randomized Placebo-Controlled Trial. Journal of child and adolescent psychopharmacology.

https://doi.org/10.1089/cap.2019.0036

 

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This week, my lab at the University of Canterbury published the first investigation1 into whether a mineral-vitamin supplement could change the bacteria in the microbiome of children with ADHD. Our preliminary data, based on our sample of 17 kids (half of whom were given micronutrients and half were given placebo for 10 weeks), hints at increased diversity and changes in the types of bacteria contained in the microbiome of the children exposed to the micronutrients. This type of study starts to moves us beyond the efforts to show that micronutrients benefit some people with psychiatric symptoms, and towards figuring out why they might exert their influence. So what does this mean?

First off, what is the microbiome?

The gut microbiome is defined as the trillions of microbes that inhabit the human digestive tract. In additional to playing a crucial role in digesting food, they also play pivotal roles in immune and metabolic functioning, gene expression, as well as playing a role in the expression of psychiatric symptoms through the gut-brain connection.2 We also know that they generate essential vitamins. When our microbiome gets into a state of dysbiosis (microbial imbalance), in addition to the physical symptoms like reflux, poor digestion, pain, constipation and/or diarrhoea, it is thought that dysbiosis can also lead to increased permeability of the gut wall, increased production of endotoxins, increased inflammation and decreased nutrient synthesis.

How do we learn about what bacteria are within and on us?

Research on the human microbiome has grown exponentially in the past decade. However, it was only recently that we could fairly cheaply quantify and describe the bugs contained within us. 16S rRNA sequencing (the technology we used) is a key methodology in identifying bacterial populations and allows scientists to easily and reliably characterize complex bacterial communities.3 This methodology is a simple and effective alternative to microbial culture, and provides detailed information about the various species of bacteria that are contained within our microbiome. The sequencing gives information on bacterial diversity, as well as details about the specific family (e.g., Bifidobacteriaceae), genus (e.g., Bifidobacterium), and species (e.g., Bifidobacterium Longom).

What about the microbiome of kids with ADHD?

What scientists are now wondering is whether people who suffer from specific psychiatric symptoms, like those associated with ADHD, have a different bacterial composition than those who don’t have these symptoms and whether these differences can help us understand the severity of the symptoms. In other words, is it possible that our bugs can make us impulsive? And if so, if we changed the bugs, can we become less impulsive?

There isn’t a huge literature exploring this topic in ADHD. Preliminary studies suggest that antibiotics in the first 6 months of life may increase risk of ADHD symptoms at 11 years of age,4 although this finding hasn’t been replicated.5 Another study found that the Phylum Actinobacteria is overrepresented in ADHD compared with controls.6 Other research suggests that reduced alpha diversity may exist in young patients with ADHD, specifically that boys with ADHD had more Bacteroidaceae relative to controls, with the species Neisseriaceae identified as a particularly promising ADHD-associated candidate.7 Although this finding of reduced alpha diversity was not observed in treatment-naïve children with ADHD, Jiang and colleagues noted that the more an individual had the species Faecalibacterium, the lower their ADHD severity.8

Overall, there are intriguing signals but the signals are not always replicating. Much more research with larger samples is needed to try to determine if there are reliable bacterial biomarkers. We also need to parse out the effect of diet, medications, age, ethnicity and gender on the results that have been reported. Further, we don’t know whether these differences are causal or a result of ADHD or completely irrelevant to the expression of the symptoms.

We still don’t know if changing the relative amount of a bacteria can change psychiatric symptoms. We know that diet manipulation can change levels of bacteria but whether those changes in bacteria are necessary for improvement in psychological states requires much more research.

So what did we find?

Looking at the microbiome over a short period of time with a small sample is challenging. There is such diversity in the bacteria within us and between us that it is a challenge to explore changes and also whether changes are meaningful. But we did observe some intriguing effects:

  1. The observed taxonomic units (OTU), a measure of community richness, significantly increased in treatment group but not in placebo group. We think this is a good thing.
  2. We observed significant greater decrease in abundance of genus Bifidobacterium from phylum Actinobacteria in active versus placebo and that the more it decreased, the more the ADHD symptom scores dropped. If Bifodobacterium is contributing to the symptoms of ADHD, this is a good thing.
  3. We also observed a significant positive correlation between Actinobacterium abundance and Clinician ADHD IV-RS rating scale before the intervention was introduced, which suggests that Actinobacterium may play a role in the expression of ADHD.

What does this mean?

The small sample makes it difficult to generalize from this study. However, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome. Previous research from our lab has shown that micronutrients do exert some positive effects on ADHD and associated symptoms.9 10 These findings suggest that micronutrient treatment may result in a more diverse microbiome which may in turn, have a positive effect on brain health.

What next?

The field of the microbiome is literally exploding with new studies out every day. The focus currently is trying to find ways to manipulate the microbiome for positive response. This has mainly been explored through either adding in bacteria (in the form of probiotics or psychobiotics if targeting psychological symptoms), diet manipulation, or more recently, fecal microbiota transplants. I do worry a bit that this search for the magic-bullet bacteria that causes distress may turn out to be as disappointing as the search was for candidate genes, but it is worth some effort to figure out if this is an important lead.

Eat2BeNice (New Brain Nutrition) plans to explore the role of the microbiome in multiple ways, including determining whether individuals with high impulsivity/compulsivity have a unique microbiome profile, whether targeted probiotics can improve impulsivity/compulsivity symptoms, and also whether improvement in impulsivity/compulsivity symptoms from diet manipulation and via the use of supplements can be explained via changes in the microbiome. Watch this space!

REFERENCES 

  1. Stevens AJ, Purcell RV, Darling KA, et al. Human gut microbiome changes during a 10 week Randomised Control Trial for micronutrient supplementation in children with attention deficit hyperactivity disorder. Sci Rep 2019;9(1):10128.
  2. Frye RE, Slattery J, MacFabe DF, et al. Approaches to studying and manipulating the enteric microbiome to improve autism symptoms. Microb Ecol Health Dis 2015;26:26878-78.
  3. Ames NJ, Ranucci A, Moriyama B, et al. The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science. Nurs Res 2017;66(2):184-97.
  4. Slykerman RF, Coomarasamy C, Wickens K, et al. Exposure to antibiotics in the first 24 months of life and neurocognitive outcomes at 11 years of age. Psychopharmacology (Berl) 2019;236(5):1573-82.
  5. Axelsson PB, Clausen TD, Petersen AH, et al. Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder. J Child Psychol Psychiatry 2019;60(2):151-59.
  6. Aarts E, Ederveen THA, Naaijen J, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One 2017;12(9):e0183509.
  7. Prehn-Kristensen A, Zimmermann A, Tittmann L, et al. Reduced microbiome alpha diversity in young patients with ADHD. PLoS One 2018;13(7):e0200728.
  8. Jiang HY, Zhou YY, Zhou GL, et al. Gut microbiota profiles in treatment-naive children with attention deficit hyperactivity disorder. Behav Brain Res 2018;347:408-13.
  9. Rucklidge JJ, Eggleston MJF, Johnstone JM, et al. Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial. J Child Psychol Psychiatry 2018;59(3):232-46.
  10. Rucklidge JJ, Frampton CM, Gorman B, et al. Vitmain-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised palcebo-controlled trial. The British Journal of Psychiatry 2014;204:306-15.
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A team of Iranian researchers recently published a meta-analysis seeking to determine what, if any, association there may be between low Vitamin D levels and ADHD in children and adolescents.

Combining the results from thirteen studies with 10,334 participants, they found that youth with ADHD had “modest but significant” lower serum concentrations of 25-hydroxyvitamin D than normally developing children. The weighted mean difference was just under 7 nanograms per milliliter. The odds of obtaining such a result by chance would be less than one in a thousand (p < .001). There was little to no sign of publication bias. Between-study heterogeneity, however, was very high (I2 = 94).

Vitamin D and ADHDThese results suggest an association. But are low serum levels of Vitamin D a cause or effect of ADHD? Causation is vastly more difficult to establish than association. To begin to tease this out, the researchers identified four prospective studies that compared maternal Vitamin D levels with the subsequent development of ADHD symptoms in their children. Two of these used maternal serum levels, and two used umbilical cord serum levels. Together, these studies found that low maternal Vitamin D levels were associated with a 40% higher risk of ADHD in their children. Whether maternal serum or umbilical cord serum measurements were used had little or no effect on the outcome. Study heterogeneity was negligible. But the authors noted that this result “should be considered with caution” because it was heavily dependent on one of the prospective studies included in the analysis. All of which suggests a need for further prospective studies.

In the meantime, the authors suggest it would be prudent to increase sun exposure and Vitamin D supplementation given the prevalence of Vitamin D deficiency.

REFERENCES

Yadollah Khoshbakht, Reza Bidaki, and Amin Salehi-Abargouei, “Vitamin D Status and Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Observational Studies,” Advances in Nutrition, vol. 9, issue 1, p. 9-20 (2018).

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