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.

 

Please share and like us:
error

Meet Tim: he is an 8-year-old boy, living in the Netherlands with his parents and younger sister. A couple of years ago, Tim was diagnosed with Attention Deficit Hyperactivity/Impulsivity Disorder (ADHD). His psychologist recommended to participate in the TRACE study: this study examines the short- and long-term effects of dietary treatments in children with ADHD. In addition, the TRACE-BIOME study examines the underlying mechanisms of a dietary treatment. For this, we collect blood, stool and saliva samples and we perform a fMRI. These measurements might, among other things, shed light on the role of the brain-gut-axis.

But what’s it like to participate in a clinical trial? First of all, Tim was allocated to one of the two TRACE dietary treatments: an elimination diet or a healthy diet. Tim was allocated to the elimination diet. If we want to know if this diet is effective for Tim, we have to do a lot of different assessments (Figure 1).

Figure 1: assessments TRACE study
The TRACE Study, New Brain Nutrition

 

 

 

Before the baseline, 5 week and 1-year assessments, a couple of measurements already take place:

  • Tim wears an Actigraph one week before the assessment, which measures motor activity and sleep-wake rhythm;
  • Parents collect a stool sample from Tim in which his microbiota can be assessed;
  • Parents and teachers fill out different questionnaires about Tim’s behavior, but also about for example parenting styles;
  • Parents keep track of a food diary: what does Tim eat during two weekdays and one weekend day?

Before starting the elimination diet, Tim’s parents have a consult with one of the TRACE dieticians, so that they can prepare changing the diet of Tim. Then, it is time for the baseline assessment. Tim and his mother meet the researcher at the hospital for the blood venipuncture. He also has to chew on a cotton pad to collect a saliva sample. After this, they walk to Karakter which is a center for Child and Adolescent Psychiatry. The researcher measures his weight, length, blood pressure and heart rate. Next, Tim has to perform a task on the laptop which he really likes! This task assesses cognitive functions such as sustained attention, working memory and cognitive flexibility. After the computer task there is time for a break. Next, they start with a behavioral observation. In this task, Tim first plays with his mother and then with the researchers. The different tasks try to elicit ADHD symptoms and emotion (dys)regulation behavior. Finally, the MRI researcher takes Tim and his mother to the fMRI scanner in which he has to do two different tasks. All in all, the assessment takes about 4 hours.

After 5 weeks of the diet, it is time for the second assessment which is the same as the baseline assessment. The researcher has calculated, based on the parent and teacher questionnaires, if there is a significant response to the diet. Tim shows a 40% reduction of ADHD symptoms, which is a significant response! Therefore, they continue the diet. After 4 and 8 months of the diet, his parents receive some online questionnaires. Finally, after one year they are invited for the final assessment, which is again the same as the baseline assessment (without the fMRI).

 

The following YouTube video explains the assessments described above, in Dutch: ADHD en voeding: TRACE-onderzoek testdag

Please share and like us:
error

In my previous blogs, I explained the research questions of my study. This study will be performed in two cohorts which I will elaborate on in this current blog about early life nutrition and studying gut microbiota. The cohorts are called BIBO and BINGO.  

BIBO stands for ‘Basale Invloeden op de Baby’s Ontwikkeling’ (in English: basal influences on  infant’s development). Recruitment of this cohort started in 2006, and a total of 193 mothers and their infants were included. At age 10, 168 mothers and their children still joined the BIBO study; the attrition rate is thus low. The majority of the mothers are highly educated (76%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. A unique aspect of the BIBO study is the number of stool samples collected in early life. Also, detailed information about early life nutrition has been recorded during the first six months of life (e.g. information on daily frequency of breastfeeding, formula feeding, and mixed feeding). Together, these stool samples and nutrition diaries provide important insights in the relations between early life nutrition and gut microbiota development. Data about children within the BIBO cohort will be collected at age 12,5 years and 14 years. At 12,5 years, the participants will be invited to the university for an fMRI scan (more information about the fMRI scan will be given in a future blog). At age 14, children’s impulsive behavior will be assessed by means of behavioral tests and (self- and mother-report) questionnaires.

BINGO stands for ‘Biologische INvloeden op baby’s Gezondheid en Ontwikkeling’ (in English: biological influences on infant’s health and development). When investigating biological influences on infant’s health and development, it is important to start before birth. Therefore, 86 healthy women were recruited during pregnancy. Recruitment took place in 2014 and 2015. One unique property of the BINGO cohort is the fact that not only mothers were recruited, but also their partners. The role of fathers is often neglected in research, and thus an important strength of this BINGO cohort. Another unique property is that samples of mothers’ milk were collected three times during the first three months of life, to investigate breast milk composition. As for many infants their diet early in life primarily consists of breast milk, it is interesting to relate breast milk composition to later gut microbiota composition and development. Currently, 79 mothers and children, and 54 fathers are still joining the BINGO study. The average age of the participants at the time of recruitment was 32 years for mothers and 33 years for the father. Majority of the parents within this cohort are highly educated (77%) and from Dutch origin (89%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. At age 3, children’s impulsive behavior will be assessed by means of behavioral tests and mother-report questionnaires.

Please share and like us:
error

ADHD and Exercise

ADHD is among the most common psychiatric disorders, with ~3% prevalence in adulthood and ~5% in childhood. ADHD has a high risk for comorbid conditions. Comorbid means that one psychiatric disorder often comes together with another psychiatric disorder. For instance mood, anxiety and substance use disorders have high comorbid rates in adults with ADHD.

Adults with ADHD are also at risk for obesity and major depressive disorders and adolescent ADHD predicts adult obesity: 40% of adults with ADHD are also obese. These are worrying numbers. Many adults who have ADHD suffer from these negative consequences that come with their mental illness.

There is a growing body of scientific evidence of the powerful effects of nutrition and lifestyle on mental health. Exercise is one of them.It helps prevent or manage a wide range of health problems and concerns, including stroke, obesity, metabolic syndrome, type 2 diabetes, depression, a number of types of cancer and arthritis. Besides that, regular exercise can help you sleep better, reduce stress, sharpen your mental functioning, and improve your sex life. Nearly all studies revolve around aerobic exercise which includes walking, jogging, swimming, and cycling.

Recent research shows that exercise might also have a positive effect on ADHD symptoms such as improving attention and cognition1,2 Additional research is needed to explore this effect further, but we can take a look at the mechanisms underlying this effect.

One of the parts in our brain that is affected by exercise is the prefrontal cortex. The prefrontal cortex plays an important role in controlling impulsive behavior and attention, and is positively influenced by exercise. Furthermore, dopamine and norepinephrine play an important role in attention regulation. Ritalin, among one of the most well-known medication for ADHD, also increases levels of dopamine.

When you exercise regularly, the basis levels of dopamine and norepinephrine rise, and even new dopamine receptors are created. These dopamine levels are also the reason why exercise therapy can be effective for people suffering from depression: low levels of dopamine are a predictor of depressive symptoms.

Taken together: people with ADHD are at risk for obesity and depression. Exercise has a positive influence on obesity, depression and ADHD. Wouldn’t it be great if we could treat people with ADHD with an exercise therapy?

The PROUD-study is currently studying the prevention of depressive symptoms, obesity and the improvement of general health in adolescents and young-adults with ADHD. PROUD establishes feasibility and effect sizes of two kinds of interventions: an aerobic exercise therapy and the effects of a bright light therapy.

Exercise and ADHDParticipants follow a 10 week exercise intervention in which they train three days a week: one day of only aerobic activities (20-40 min) and in two of these days, muscle-strengthening and aerobic activities (35 – 60 min). An app guides them through the exercises, and the intensity and duration of these exercises increase gradually. During a 24 week course changes in mood, condition, ADHD symptoms and body composition are measured.

I am really looking forward to the results of the effectiveness of this intervention in adolescents and adults with ADHD. It is great that this study tries to alter a lifestyle instead of temporarily symptom-reducing options. A healthy life is a happy life!

For more information about the PROUD-study see www.adhd-beweging-lichttherapie.nl (only in Dutch) or contact the researchers via proud@karakter.com. For more information about a healthy lifestyle and the positive effects on mental health, see our other blogs at https://newbrainnutrition.com/

 

References

  1. Kamp CF, Sperlich B, Holmberg HC (2014). Exercise reduces the symptoms of attention-deficit/hyperactivity disorder and improves social behaviour, motor skills, strength and neuropsychological parameters. Acta Paediatrica, 103, 709-714.

 

  1. Choi JW, Han DH, Kang KD, Jung HY, Renshaw, PF (2015). Aerobic exercise and attention deficit hyperactivity disorder: brain research. Med Sci Sports Exerc, 47, 33-39.
Please share and like us:
error

In every classroom approximately two children are diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). They struggle with attention problems and hyperactive and impulsive behavior. This has negative consequences for these children. For example, they can have difficulties learning, it puts them at risk for other psychiatric problems, and it can cause parent-child relationship problems. Therefore, children with ADHD do need some sort of treatment for optimizing the quality of their lives.

After psycho-education to the child, parents and teacher, medication is often the first choice of treatment because it is evidence-based. However, there is a growing group of parents that do not wish to medicate their child. They are concerned about the side and long-term effects. Thus, these parents seek other treatment. That is where they get stuck: which other effective treatments are available?

In order to develop new treatments, there is a growing field of research focusing on risk factors for ADHD symptoms. One of these risk factors that has been studied increasingly is nutrition. Nutrition plays a role in physical well-being, but could also play a role in psychological well-being and cognitive functioning. Consequently, dietary treatments could be an alternative treatment for children with ADHD. There is a long history of research in nutrition, but there is not enough evidence yet about the (cost-)effectiveness to implement dietary treatments in clinical health care.

Elimination DietSo far, studies examining the effectiveness of a so-called elimination diet showed the strongest effects (1). The aim of an elimination diet is to find out which products trigger ADHD symptoms. However, results of these studies are inconclusive because of several limitations. First, outcome measurements used in these studies were not objective. Second, studies suffered from a sample bias towards highly motivated and educated parents. Third, underlying mechanisms are still unknown. Fourth, long-term effects are unknown. Moreover, it is unknown if an elimination diet is more effective in reducing ADHD symptoms than a healthy diet based on the World Health Organization (WHO) guidelines (2).

We thought: can we take into account these limitations and examine the effectiveness of two dietary treatments? This resulted in the TRACE study: ‘Treatment of ADHD with Care as usual versus an Elimination diet’ (TRACE) study. This is the first study to determine the short- and long-term effectiveness and cost-effectiveness of two dietary treatments as initial addition to care as usual as a treatment trajectory for children with ADHD.

We will substantially improve upon previous studies by implementing the intervention in non-commercial mental health centers, including blinded and objective measurements, and comparing two dietary treatments with care as usual. Also, understanding the biological effects could inform clinicians to potential markers and targets for preventative or individualized treatment. For this reason, we also examine the underlying biological mechanisms (e.g. mechanisms in the gut and brain) of dietary treatments (TRACE-BIOME and TRACE-MRI studies). We collect blood, stool and saliva samples.

The TRACE study is a two arm randomized control trial: participants are randomized to either an elimination diet or a healthy diet. The comparator arm includes children who are being treated with care as usual. Currently, we included in each dietary treatment arm about half of the targeted participants (N=81 in each dietary group). In the care as usual group, we included about one third of the targeted participants (N=60).

We hope to finish inclusion around January 2020.   am really looking forward to the results and hope to share this with you in a couple of years! If you have any questions, feel free to contact us via trace@karakter.com

References:

(1) Nigg, J. T., Lewis, K., Edinger, T., & Falk, M. (2012). Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms,         restriction diet, and synthetic food color additives. Journal of the American Academy of Child & Adolescent Psychiatry, 51(1), 86-97. https://doi.org/10.1016/j.jaac.2011.    10.015 . Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321798/

(2) Izquierdo Pulido, M. L., Ríos Hernández, A., Farran, A., & Alda, J. Á. (2015). The role of  diet and physical activity in children and adolescents with ADHD. Recent Advances in Pharmaceutical Sciences V, 2015, Research Signpost. Chapter 4, p. 51-64.  Link: http://diposit.ub.edu/dspace/bitstream/2445/67543/1/T_1444299316Munozv%204.pdf

Please share and like us:
error


Welcome to New Brain Nutrition. You can enjoy FREE Online Courses when you Log In or Join here.

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.

Partners:
You may log in here to our Intranet website with your authorized user name and password.