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A team of German researchers explored five million member records from a database that tracks more than sixty nationwide statutory health insurance programs. The database closely tracks the characteristics of the overall German population.

This was a longitudinal cohort study, tracking individuals first diagnosed with adult ADHD between 2013 and 2017. Anyone who was not continuously insured during this period was excluded, as were those who died, plus anyone older than 55 to prevent bias from high morbidity in the top age brackets.

The study team used the database to add up direct healthcare costs, including inpatient care, outpatient care, psychotherapy, medical aids and remedies, medication, and sickness benefits. In Germany, sickness benefits kick in after more than six weeks of continuous inability to work.

The study tracked data within a window extending both four years back and four years forward from the initial adult ADHD diagnosis.

The resulting study cohort consisted of 2,380 persons between 18 and 55, initially diagnosed with ADHD at an average age of 35. Sixty percent were male.

One-third were prescribed ADHD medication upon diagnosis. Four years later, only one-eighth were still on medication.

Almost two-thirds received psychotherapy, dropping to under a third in succeeding years.

During the year following diagnosis, average healthcare costs totaled about €4,000 per individual. For those who initiated ADHD medication, the average cost was just over €5,400, and for those who did not it was almost €3,500.

The authors concluded, "An important finding of the present investigation is that in the year of initial diagnosis, less than one-third of individuals received any prescription of ADHD-specific medication, and only a fourth got at least two prescriptions. At the same time, almost two-thirds of individuals received psychotherapy in the year of ADHD[adult ADHD] diagnosis. In about one-third of individuals, psychotherapy had been initiated already before a diagnosis of ADHD, presumably for treatment of comorbid disorders. ... In current German guidelines, ADHD-specific medication is recommended as the first choice ... Apparently, despite the vast body of evidence for the beneficial effects of ADHD-specific medication, at least in the short-term, and in contrast to the recommendations of previous and current guidelines, stimulant medication is only reluctantly prescribed in newly identified adults with ADHD. ... Overall, our findings suggest that significant deficiencies may currently exist concerning the reality of healthcare for ADHD in Germany, and that guideline recommendations are not yet comprehensively implemented in everyday routine care."

Two recent meta-analyses, one by an Asian team, and the other by a European team, have reported encouraging results on the efficacy of physical exercise in treating ADHD among children and adolescents.

One, a Hong Kong-based team (Liang et al. 2021) looked at the effect of exercise on executive functioning.

The team identified fifteen studies with a combined total, of 493 participants that met the criteria for inclusion. As the authors noted, "only a few studies successfully blinded participants and therapists, due to the challenges associated with executing double-blind procedures in non-pharmacological studies."

After adjusting for publication bias, the meta-analysis of the fifteen studies found a large improvement in overall executive functioning.

The studies varied in which aspects of executive functioning were addressed. A meta-analysis of a subset of eleven studies encompassing 406 participants found a large improvement in inhibitory control. A meta-analysis of another subset, of eight studies with a total of 311 participants, found a large improvement in cognitive flexibility. Finally, a meta-analysis of a subset of five studies encompassing 198 participants found a small-to-medium improvement in working memory.

Nine studies involved acute (singular) exercise interventions lasting 5 to 30 minutes, while twelve studies involved chronic (regular) exercise interventions ranging from 6 to 12 weeks, with a total duration of 12 to 75 hours. The chronic exercise was more than twice as effective as acute exercise. The former resulted in large improvements in overall executive functioning, the latter in small-to-medium improvements.

No significant differences were found between aerobic exercises (such as running and swimming) and cognitively engaging exercises(such as table tennis and other ball games, and exergaming ... video games that are also a form of exercise, relying on technology that tracks body movements).

The authors concluded that "Chronic sessions of exercise interventions with moderate intensity should be incorporated as a treatment for children with ADHD to promote executive functions."

Meanwhile, a German study team (Seiffer et al. 2021) looked at the effects of regular, moderate-to-vigorous physical activity on ADHD symptoms in children and adolescents.

They found eleven studies meeting their criteria, with a combined total of 448 participants. A meta-analysis of all eleven studies found a small-to-moderate decline in ADHD symptoms. However, the three studies with blinded outcome assessors found a large and statistically highly significant decline in symptoms, whereas the eight studies with blinded outcome evaluators found only a small decline that was not statistically significant.

When compared with active controls using pharmacotherapy in a subgroup of two studies with 146 participants, pharmacotherapy held a small-to-moderate advantage that fell just short of statistical significance, most likely because of the relatively small sample size.

The authors concluded that moderate to vigorous physical activity (MVPA) "could serve as an alternative treatment for ADHD," but that additional randomized controlled trials "are necessary to increase the understanding of the effect regarding frequency, intensity, type of MVPA interventions, and differential effects on age groups."

Previous population studies have shown that children with ADHD have a much higher risk of traumatic injuries than their normally developing peers, and that such risk can be greatly reduced with methylphenidate treatment.

But what about the parents of children with ADHD? How does their risk compare with that of parents of normally developing children?

Taiwan has a single-payer public health insurance system that maintains comprehensive healthcare records of virtually every resident.

A Taiwanese research team availed itself of the Taiwan Maternal and Child Health Database, which covers 99.8% of all births, to identify 81,401 fathers and 87,549 mothers who had at least one offspring with ADHD and 1,646,100 fathers and 1,730,941 mothers with no offspring with ADHD.

The team determined children's ADHD status based on either an inpatient diagnosis or four or more  diagnoses.

It looked for parental traumatic injuries including burn injury, fracture, and traumatic brain injury.

To address covariates, it adjusted for age, urbanicity, low-income level, and competing risk of death.

Adjusted for those covariates, parents of children with ADHD were 20% more likely to suffer bone fractures, 27% more likely to have traumatic brain injuries, and 30% more likely to have burn injuries requiring medical treatment than parents of normally developing children.

The elevated risks were significant across the board, but roughly twice as much s for mothers as for fathers of children with ADHD - up 30% vs 15% for bone fractures, up 35% vs 23% for burn injuries, and up 45% vs 21% for traumatic brain injuries.

The authors noted that ADHD is highly heritable and that the findings may in part point to undiagnosed adult ADHD.

Another contributing factor, they suggested, is that "studies have revealed that a high proportion of parents having children with ADHD experience depression and anxiety. Stress-related negative emotions (depression and anxiety) were shown to cause loss of concentration, thereby increasing the likelihood of accidental events such as traffic accidents and contributing to the increased risks of traumatic injury among parents of children  ADHD."

The much-higher elevated risk for mothers seems to support this hypothesis, because mothers continue to be the principal caregivers in Taiwan, and are thus more exposed to the behaviors of their children. The authors cited a study indicating that "diagnosis of ADHD for children was reported to be a predictor of increased caregiver burden."

They concluded, "Given that knowledge is fundamental to act, it is essential to educate the parents of children with ADHD on the increased risk of traumatic injuries they may have. ... The need for behavioral and pharmacological intervention in parents of children with ADHD should be evaluated, especially in the parents with undiagnosed ADHD or sub-threshold ADHD symptoms. It deserves further prospective studies with longer follow-up periods to explore whether undiagnosed ADHD, care burden of parents, and children's aggressive behaviors contribute to the increased risks of traumatic injuries in parents of children with ADHD."

Sweden has a national single-payer health insurance system that includes virtually the entire population. It also has a system of national registers that track every resident from birth to death. That makes it possible to conduct nationwide population studies with a very high degree of precision and reliability.

In addition, one of the national registers is the Swedish Twin Register. Tracking all twins in the population enables studies to evaluate the degree to which observed associations may be attributable to genetic influences and to familial confounding. The twin method relies on the different levels of genetic relatedness between monozygotic ("identical") twins, who are genetically identical, and dizygotic ("fraternal") twins, who share on average half of their genetic variation (as do ordinary full siblings).

A Swedish team of researchers identified 42,582 Swedish twins born between 1959 and 1985, and who were, therefore, adults by the time of the study (20-47 years old). Of these, 24,872 (three out of five) completed a web-based survey with 1,300 questions covering lifestyle and mental and physical health. Out of this group, 17,999 provided information on ADHD symptoms and food frequency.

Self-reported ADHD symptoms came from nine inattention components and nine hyperactivity/impulsivity components, covering the 18 DSM- IV symptoms of ADHD.

The food frequency questionnaire included 94 food items, with the following frequency categories: never, 1-3 times/month, 1-2 times/week, 3-4 times/week, 5-6 times/week, 1 time/day, 2 times/day, 3 times/day.

In the raw data, the two subtypes of ADHD exhibited very similar associations. Both had significant associations with unhealthy diets. Both were more likely to be eating foods high in added sugar, and neglecting fruits and vegetables while eating more meat and fats.

After adjusting for the degree of relatedness of twins (whether monozygotic or dizygotic) and controlling for the other ADHD subtype, the associations remained statistically significant for inattention, but diminished to negligible levels or became statistically non-significant for hyperactivity/impulsivity.

Even for persons with inattention symptoms, adjusted correlations were small (never exceeding r = 0.10), with the strongest associations being for overall unhealthy eating habits (r = 0.09), eating foods high in added sugar (r = 0.10) or high in fat (r = 0.05), and neglecting fruits and vegetables (r = 0.06). All other associations became statistically non-significant.

For persons with hyperactivity/impulsivity symptoms, the only associations that remained statistically significant ­- but at tiny effect sizes - were unhealthy dietary patterns (r = 0.04) and consumption of foods high in added sugar (r = 0.03).

The further genetic analysis, therefore, focused on the strongest associations, between ADHD subtypes on the one hand, and unhealthy dietary patterns and eating foods high in added sugar on the other hand. The heritability estimates (the fraction of phenotypic covariance explained by genetic influences) were 44%, 40%, and 37% for inattention and high-sugar food, inattention and unhealthy dietary patterns, and hyperactivity/impulsivity and high-sugar food, respectively.

 When examining only differences between pairs of monozygotic("identical") twins, the correlations became stronger for inattention, rising to r = 0.12 for unhealthy eating habits and r = 0.13 for consumption of foods high in added sugar. For hyperactivity/impulsivity symptoms, the association with unhealthy eating habits was weaker, and the association with consumption of foods high in added sugar became statistically insignificant.

The authors concluded, "we identified positive associations between self-reported trait dimensions of ADHD and intake of seafood, high-fat food, high-sugar food, high-protein food, and an unhealthy dietary pattern, and negative associations with consumption of fruits, vegetables, and a healthy dietary pattern. However, all the associations are small in magnitude. These associations were stronger for inattention compared to hyperactivity/ impulsivity. This pattern of associations was also reflected at the etiological level, where we found a slightly stronger genetic correlation between inattention with dietary habits and hyperactivity/impulsivity with dietary habits. Non-shared environmental influences also contributed to the overlap between ADHD symptom dimensions and consumption of high-sugar food and unhealthy dietary pattern. However, shared environmental influences probably contributed relatively little to the associations between ADHD symptoms and dietary habits. ... significant MZ twin intraplate differences also provided support for a potential causal link between inattention and dietary habits.

While influenza normally only threatens the elderly or those with complicating conditions, the 2009 H1N1 variant struck children particularly hard.

ADHD is known to be associated with inflammatory and immune-related disorders such as asthma, eczema, and allergic rhinitis. These disorders can aggravate respiratory infections such as influenza. Moreover, the cognitive deficits characteristic of ADHD - difficulty following instructions, reduced ability to control impulsive behavior and resulting nail-biting, and poor hand hygiene - can increase the probability of infection in the first place.

A Taiwanese research team explored how drug treatment for ADHD might affect the risk of childhood influenza. Only two drugs are approved in Taiwan for treating ADHD: the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine. Because the latter is only recommended for patients who have unsatisfactory outcomes with MPH, MPH is the drug used in the vast majority of cases.

Taiwan is one of the relatively few countries that track the health care of its entire population in a comprehensive database, thanks to a single-payer health care system launched in1995. From the National Health Insurance Research Database, the Bureau of National Health Insurance in 2005 used random sampling to create a million-person Longitudinal Health Insurance Database (roughly five percent of the population).

From this latter database, the research team identified 9,826 patients newly diagnosed with ADHD. They excluded 1,786 with influenza before their ADHD diagnosis. After further excluding those outside the youth age brackets or who had gotten a flu shot during the year preceding enrollment, they were left with 5,259 patients with ADHD under age 18. Of these, 661 got influenza following diagnosis of ADHD.

In this ADHD cohort, 43 percent had not used any medication. Of the 57% who used medication, 20 percent did so for 90 days or less, and 37 percent for over 90 days.

After controlling for gender, age, level of urbanization, psychiatric or physical illnesses, and other medication use(sedative/hypnotics/anxiolytics), those prescribed MPH over 90 days were 38 percent less likely to get influenza requiring interaction with the health care system. There was a lesser reduction for those taking MPH 90 days or less, but it was not statistically significant.

A significant limitation is the fact that data from in-school vaccination programs are not included in the database used. If children receiving less or no medication were also less likely to be vaccinated, this unexplored covariate could explain the results. Further study is needed.

Celiac disease is an autoimmune disorder triggered by dietary gluten in genetically predisposed individuals. Gluten is a protein found in wheat and related grains such as barley and rye. The disease affects one to two percent of Western populations.

An international team of physicians conducted a nationwide cohort study of the Swedish population to explore the relationship between childhood celiac disease and subsequent psychiatric disorders, including ADHD, as well as suicide attempts and suicide.

With data from all 28 pathology departments in Sweden, they identified all 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016, and no previous history of psychiatric disorder. They then matched them with 94,249 children controls matched for age, sex, county, and calendar year from the Swedish national registers that encompass the entire resident population.

To address shared intrafamilial confounding, including genetic and early environmental factors, the team also compared 13,015 individuals with celiac disease with their 18,024 non-celiac siblings.

Additional Swedish national registers (Patient Register, Cause of Death Register) then made it possible to link the preceding data with data on subsequent psychiatric disorders and suicides for all the children in the study.

Celiac disease diagnosed in childhood was associated with a 19 percent higher risk of any subsequent psychiatric disorder at any time than for controls. The greatest spike in risk - 70 percent higher than for non-celiac controls - was in the first year following diagnosis of celiac disease. Restricting follow-up until the age of 18 years, celiac disease was linked to a 26 percent increased risk of any psychiatric disorder. For adults 18 and over, the increased risk declined to just 11 percent. So an initial sharp spike was followed by a steeply declining curve over time.

For ADHD, the increased risk at any time after the diagnosis of celiac disease was 29 percent. That compares with 47 percent for autism spectrum disorder, 34 percent for eating disorders, 20 percent for mood disorders, and 12 percent for anxiety disorders. There was no increased risk of psychotic disorders, behavioral disorders, personality disorders, psychoactive substance abuse, suicide attempts, or suicide. For adults 18 and over, however, the increased risk of ADHD rose to 39 percent, second only to autism spectrum disorder. For these two psychiatric conditions, there was an upward curve rather than a declining one.

The sibling analyses found a reduced but still significant 12 percent increased risk of psychiatric disorder following a diagnosis of celiac disease, again with the first-year spike of 48 percent increased risk declining to insignificance for the period beginning five years later. For ADHD, the increased risk also descended to 12 percent, but became non-significant, suggesting the increases were primarily attributable to confounding variables.

Among the 2,071 children with celiac disease who had a follow-up biopsy that showed mucosal healing of the small intestine in response to a gluten-free diet, the association with subsequent psychiatric disorders vanished.

The authors speculated that the spike in psychiatric diagnoses in the year following diagnosis of celiac disease could be because "the systemic inflammatory response is mediating this relationship," or could be due to "the psychosocial stress associated with adapting to the gluten-free diet." "However," they cautioned, "this risk is unlikely to be due to the gluten-free diet alone since we also observed an increased risk of psychiatric disorders preceding the diagnosis of celiac disease, possibly related to the systemic inflammatory response described above."  We must also keep in mind that such studies cannot rule out all sources of confounding or the possibility that being diagnosed with celiac disease leads to more exposure to the healthcare system and more opportunities for a diagnosis of ADHD to be recognized.

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Bilirubin is an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile. Elevated levels in blood serum can cause jaundice, a yellowing of the skin, or whites of the eyes.

More than one in twenty Swedish newborns are treated for neonatal jaundice, which is particularly common among preterm babies. It is usually benign.

A team of Swedish researchers used e Swedish Medical Birth Register, which contains information on all children born in the country, to identify all 814,420 single births without birth defects between 1992 and 2000, and followed them until 2009. They then identified instances of neonatal jaundice and of ADHD through linked nationwide medical registers.

The team also identified a sub-sample of full siblings (384,290 children from 181,354 families) in order to control for shared familial traits.

In the unadjusted results, children with any kind of neonatal jaundice were 38% more likely to be diagnosed with ADHD. After adjustment for known confounding variables, two-thirds of the association disappeared, with a residual increased risk of 13%.

There are, however, two types of neonatal jaundice: hemolytic and non-hemolytic. Hemolytic jaundice is typically caused by the mother's immune system mistaking the fetus' red blood cells as a threat, and responding by attacking with antibodies, rupturing and destroying the cells.

The study found no association between hemolytic jaundice and ADHD, either in the raw results or after adjusting for known confounders. Unsurprisingly, there was also no association in the sibling comparison.

That meant that all the association was concentrated among children born with non-hemolytic jaundice, who in the crude results were 43% more likely to subsequently develop ADHD. Adjusting for known confounders again reduced the association by two-thirds, to 14%. But among siblings, that association vanished altogether. Children born with non-hemolytic jaundice were no more likely than their non-jaundiced siblings to develop ADHD.

The authors concluded that "neonatal jaundice is not likely a causal risk factor for ADHD."

The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo in combination with cognitive-behavioral group psychotherapy or (GPT) individual clinical management (CM), the latter two being active controls. This was a year-long trial.

The German study team randomly assigned 433 participants with adult ADHD to each of the four study groups. As this was a 2 x 2 matrix trial, each study group included both one pharmacological intervention (MPH or placebo) and one psychological intervention (GPT or CM).

GPT included mindfulness training, skills for stress management, emotion regulation, and time management as well as behavioral analyses. CM sessions focused on participants' current concerns and medication.

As is usual in such trials, the number of participants decreased throughout the study as some individuals dropped out. At 13 weeks, 337 participants were still taking their study medication.

Both MPH and placebo were started at 10 mg doses, then up-titrated depending on clinical response. After 13 weeks, the mean MPH dose had risen to 50 mg, and the mean dose of placebo to 58 mg.

Safety

Among those taking MPH, 96 percent of participants reported at least one adverse event. Among those on placebo, the equivalent figure was 88 percent.

The principal adverse events occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8 %), dry mouth (15 vs. 4.8 %), palpitations (13 vs. 3.3 %), gastrointestinal infection (11 vs. 4.8 %), agitation (11 vs. 3.3 %), restlessness (10 vs. 2.9 %), excessive sweating, rapid heartbeat, and weight decrease (all 6.3 vs. 1.9 %).

The only adverse event that occurred significantly more frequently in the placebo group was a temporary loss of consciousness caused by a fall in blood pressure (2.4 vs. 0%).

Serious adverse events were infrequent in both groups, affecting 7.3 percent of those in the MPH group and 4.3 percent of those in the placebo group. The difference between groups was not statistically significant. There were no deaths.

While patients on MPH lost an average of 1.2 Kg during the year, those on placebo remained constant (gained 0.3 Kg). Changes in blood pressure were negligible in both groups. Average heart rate rose by 3 beats per minute in the MPH group, versus a 1 beat per minute decline in the placebo group. There were no significant differences in clinically relevant electrocardiogram abnormalities between the two treatment groups.

Turning to psychological interventions, 90 percent of participants in the GPT group and 94 percent in the CM group experienced at least one adverse event. Differences between the two groups were not statistically significant. Serious adverse events occurred in 3.9% of the GPT participants and 7.7 percent of the CN participants, but again the difference between groups was not statistically significant. There were no clinically relevant changes in weight, blood pressure, or heart rates in these groups throughout the study.

The study team found no modulating effects of either form of psychological treatment on the distribution of adverse events under MPH and placebo treatment.

The authors concluded, "adverse events were found more frequently in patients receiving MPH compared to placebo and were mostly attributable to the centrally stimulating and sympathomimetic action of MPH, including agitation, restlessness, dry mouth, decreased appetite, palpitations, tachycardia [rapid heartbeat], and hyperhidrosis [excessive sweating]. About these adverse events, a causal relationship with MPH seems likely, supported by both the pharmacological effects of MPH as well as previous safety data. ... It is important to note that patients receiving MPH in COMPAS significantly profited from the medication about the reduction of ADHD symptom load, thus the risks of adverse events have to be weighed against the clear benefits. ... Premature termination of MPH due to an adverse event as major reason occurred in less than 10 % of patients and was not statistically significantly different from placebo."

Danish health care is universal and free. That means there is very complete data available that covers the entire population. The health registers are linked to other national registers that provide access to socioeconomic information. That offers unusual opportunities to research correlations across an entire national population.

Moreover, the health care system requires a high standard for diagnosis of ADHD - evaluation by specialist doctors or psychiatrists rather than a general practitioner. An exception is when parents seek a diagnosis from a private practicing child psychiatrist, in which case diagnostic registration is not mandatory and data is therefore incomplete.

A trio of Danish researchers used the country' national registers to conduct a nationwide population cohort study to explore the cumulative effects of social disadvantages as risk factors for being diagnosed with ADHD.

They looked at all 632,725 children born in Denmark during the 1990s, of which 23,287 (3.7 percent) either had a registered diagnosis in the Patient Registry or else were undergoing ADHD treatment before age 18. Of these, 12,610 children had a registered ADHD diagnosis and entered medical treatment, 4,049 children had a registered diagnosis with no medical treatment, and 6,628 children entered medical treatment with no registered diagnosis. The latter were presumably diagnosed by private practicing psychiatrists. Adjustments were made for gender, immigrant status, birth characteristics (weight, gestational age), single-parenthood, parent ADHD diagnosis, and the number of children in the household.

The study determined that parental educational attainment had the largest effect on the risk of ADHD. Having parents who completed no more than the minimum compulsory education was associated with a 3.5 percentage point higher risk of getting an ADHD diagnosis. Completing no more than upper secondary education was associated with a 1.3 percent higher risk. But there was a sharp bifurcation in the two alternative components of upper secondary education. Children of parents who completed a vocational track faced a 1.7 percent increase in risk, whereas those whose parents completed a college preparatory track faced a negligible 0.17 percent increase.

Parental unemployment also had a significant effect. Youths whose parents were unemployed most of the year faced a 2.1 percent higher risk of ADHD, whereas those whose parents were unemployed less than half the year faced a 1.3 percent higher risk.

Relative income poverty had a comparable impact. Children of parents in the lowest income quintile faced a 2.3 percent higher risk of ADHD than those of parents in the uppermost income quintile. Those in the second-lowest quintile faced a 1.9 percent higher risk than those in the uppermost quintile; those in the middle quintile a 1.3 percent higher risk, and those in the second-highest quintile a 0.8 percent higher risk.

All three cases showed a dose-response relationship, in which higher gradations of social disadvantage were associated with higher levels of risk.

Since these social disadvantages often overlap, the researchers looked at combinations as well and found them to be roughly additive in effect. Parental unemployment plus relative income poverty was associated with a 1.9 percent higher risk of offspring ADHD. Parental unemployment plus completion of no more than compulsory education was associated with a 3.2 percent higher risk. Parental relative income poverty plus completion of no more than compulsory education produced a 4.2 percent higher risk. Finally, Parental relative income poverty plus completion of no more than compulsory education plus unemployment was associated with a 4.9 percent higher risk.

The authors concluded, "This study shows that specific and well-measured parental social disadvantages in terms of unemployment, relative income poverty, and low educational attainment independently affect the risk of ADHD."

A recently published meta-analysis compared the treatment of ADHD with multi-nutrient supplements versus placebo.

Children received either placebo or Daily Essential Nutrients(Vit A 384 IU, Vit C 40 mg, Vit D 200 IU, Vit E 24 IU, Vit K 8 μg, B1 4 mg, B21.2 mg, B3 6 mg, B6 4.67 mg, B9 50 μg, B12 60 μg, B7 72 μg, B5 2 mg, Ca 88 mg, Fe 0.92 mg, P 56 mg, I 13.6 μg, Mg 40 mg, Zn 3.2 mg, Se 13.6 μg, Cu 0.48 mg, Mn0.64 mg, Cr 41.6 μg, Mo 9.6 μg, P 16 mg. Proprietary blend: Choline bitartrate, Alpha-lipoic acid, Inositol, Acety-l-carnitine (as acetyl-L-carnitine hydrochloride), Grape seed extract, Ginkgo biloba leaf extract, Methionine (asL-methionine hydrochloride), Cysteine (as N-acetyl-L-cysteine), Germanium sesquioxide (as chelate), Boron, Vanadium, Lithium orotate, Nickel. Other ingredients: Cellulose glycine 45 mg, Citric acid 26.814 mg, Magnesium stearate24 mg, Silicon dioxide 20 mg).

Adults received either placebo or EMP+ (Vit A 5760IU, Vit C 600 mg, Vit D 1440 IU, Vit E 360 IU, B1 18 mg, B2 13.5 mg, B3 90 mg,B5 21.6 mg, B6 36 mg, B9 1440 μg, B12 900 μg, Biotin 1080 μg, Pantothenic acid21.6 mg, Ca 1320 mg, Fe 13.74 mg, P 840mg, I 204 μg, Mg 600 mg, Zn 48 mg, Se204 μg, Cu 7.2 mg, Mn 9.6 mg, Cr 624 μg, Mo 144 μg, K 240 mg, Germaniumsesquioxide 20.7 mg, B 2400 μg, V 1194 μg, Ni 29.4 μg, Choline bitartrate 540mg, DL-phenylalanine 360 mg, Citrus bioflavonoids 240 mg, Inositol 180 mg,Glutamine 180 mg, L-methionine 60 mg, Gingko biloba 36 mg, grape seed extract45 mg).

Using the Global Assessment of Functioning (GAF) scale for adults, and the Children's Global Assessment Scale (CGAS) for children, the study team reported moderate improvements in overall functioning from the use of the supplements. GAF and CGAF are used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of an individual.

Yet no significant improvements were found for either clinician-rated or observer-rated ADHD Change Scores.

Moreover, the positive finding was compromised by a series of methodological shortcomings:

·        It was just barely a meta-analysis, involving only two studies.
·        The combined number of participants in the two studies was small, 173, consisting of 93 children in one study and 80 adults in the other.
·        Both studies had the same lead author, Julia J. Rucklidge, who was also a member of the meta-analysis team.

With only two studies, there was no way to evaluate publication bias.