Cookie Preferences
By clicking, you agree to store cookies on your device to enhance navigation, analyze usage, and support marketing. More Info
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
X
March 17, 2025
Background:
Noting that “the results of previous investigations into the therapeutic benefits of probiotics in the treatment of ADHD symptoms remain inconsistent,” a Taiwanese study team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis.
The Study:
The team identified seven randomized controlled trials (RCTs) that met criteria for inclusion: focusing on children and adolescents under 18, with ADHD diagnoses, comparing probiotic interventions with placebo, and using standardized behavioral rating scales to assess ADHD symptoms.
Meta-analysis of these seven RCTs with a combined total of 342 participants found no significant improvement in ADHD symptoms. In fact, six of the seven RCTs clustered tightly around zero effect, while the seventh – a small sample (38) outlier – reported a very large effect size improvement.
Meta-analysis of the three RCTs with a combined 154 individuals that used probiotics with single strains of microorganisms showed absolutely no improvement in ADHD symptoms with no between-study variation (heterogeneity).
Meta-analysis of the four RCTs with a total of 188 participants that used multiple strains pointed to a medium – but statistically nonsignificant – effect size improvement, with high heterogeneity. Removing the previously mentioned outlier RCT collapsed the effect size to zero.
Two of the RCTs (with 72 total individuals), including the outlier, offered probiotics in conjunction with methylphenidate treatment. Meta-analysis of the other five RCTs with 270 persons that were structured around pure supplementation yielded absolutely no improvement in ADHD symptoms with no heterogeneity.
Meta-analyses of the four RCTs with a combined total of 238 participants that examined ADHD subtypes reported no effect on either inattention symptoms or hyperactivity/impulsivity symptoms.
Trivially, given the lack of efficacy, probiotic regimens were tolerated as well as placebo.
The Take-Away:
Ultimately, this meta-analysis found no evidence that probiotics improve ADHD symptoms in children and adolescents. Across seven randomized controlled trials, results consistently showed no significant benefit compared to a placebo. While probiotics were well-tolerated, they did not meaningfully impact inattention, hyperactivity, or impulsivity. These findings suggest that probiotics, whether single or multi-strain, are not an effective treatment for ADHD.
Shun-Chin Liang, Cheuk-Kwan Sun, Chih-Hua Chang, Yu-Shian Cheng, Ruu-Fen Tzang, Hsien-Jane Chiu, Ming Yu Wang, Ying-Chih Cheng, and Kuo-Chuan Hung, “Therapeutic efficacy of probiotics for symptoms of attention-deficit hyperactivity disorder in children and adolescents: meta-analysis,” BJPsych Open (2024) 10, e36, 1–8, https://doi.org/10.1192/bjo.2023.645.
Folic acid, also known as folate, is an essential vitamin(B-9). Inadequate dietary folate has been associated with abnormal fetal brain development. That suggests a deficiency could contribute to neurodevelopmental disorders, including ADHD.
If so, could folic acid supplementation for pregnant mothers help avoid ADHD in offspring?
A Chinese study team conducted a systematic search of the peer-reviewed medical journal literature looking for studies exploring neurodevelopmental effects associated with such supplementation.
It identified six studies that specifically looked for associations with offspring ADHD. A meta-analysis of these studies encompassing a total of 29,634 participants found a 14% (one in seven) reduction in the odds of ADHD in the offspring of mothers taking folate supplementation as opposed to children of mothers not doing so.
There was no sign of either publication bias or between-study heterogeneity.
The authors concluded, "Our meta-analysis indicated that appropriate maternal FA supplementation may have positive effects on offspring's neurodevelopmental outcomes, including improved intellectual development and reduced risk of autism traits, ADHD, behavioral, and language problems."
Given that folate is an essential vitamin in the first place, this suggests ensuring that pregnant women supplement their diet with folic acid. The authors further counseled, "However, further high-quality studies on this topic are needed to confirm the optimal dosage and the right time of FA supplementation and to investigate the underlying mechanisms."
Stimulant medications like methylphenidate and amphetamines are well-established treatments for reducing ADHD symptoms, making a notable difference in focus and behavior. Given that caffeine is also a stimulant, researchers have wondered whether it might offer similar benefits for managing ADHD symptoms. A recent meta-analysis conducted by a Brazilian research team sought to explore this question.
The researchers faced an immediate challenge: there is surprisingly little research directly investigating caffeine's effects on ADHD symptoms. After a thorough review of peer-reviewed literature, they identified only four randomized controlled trials (RCTs) suitable for their analysis, encompassing a combined total of just 152 participants.
The limited number of studies—and participants—meant that the meta-analysis was not as robust as the research team might have hoped. However, they proceeded to examine the available data to determine whether caffeine showed any measurable benefit over a placebo.
The results of the meta-analysis showed a slight decrease in ADHD symptoms among those who consumed caffeine compared to those given a placebo. However, this reduction was not statistically significant. The small sample size likely played a role in this outcome, making the study underpowered. Even if future studies with larger groups of participants were to show statistical significance, the observed effect size would likely remain too small to be clinically meaningful.
Interestingly, the four trials included in the meta-analysis showed very little variation in their findings. Each study slightly favored caffeine over placebo, but none came close to achieving statistical significance.
Ultimately, the researchers concluded that “overall, the totality of the evidence suggests no significant benefit of caffeine over placebo in the treatment of children with ADHD.” The findings indicate that while caffeine might produce a slight reduction in symptoms, it is not an effective alternative to established ADHD treatments like methylphenidate or amphetamines.
This study highlights the importance of relying on proven medications for ADHD management rather than seeking alternatives that lack substantial evidence. While caffeine might offer a slight stimulant effect, it falls short of delivering the therapeutic benefits needed for those with ADHD to manage their symptoms effectively. For clinicians, parents, and individuals with ADHD, these results underscore the value of evidence-based treatments in improving quality of life and daily functioning.
Noting that “Oxidative stress disrupts the structure and function of neurons in the prefrontal lobe of the brain,” and “Structural and functional impairments in the prefrontal cortex have been shown to be highly correlated with behavioral and emotional problems of ADHD,” a Chinese team at Dalian University set out to systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with ADHD.
The team’s systematic search of the peer-reviewed medical literature identified a total of 48 randomized controlled trials (RCTs) or prospective studies involving 12 antioxidant agents (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) that met criteria for inclusion:
Treatment efficacy was measured through ADHD symptom scores using Conners’ parent rating scale (CPRS), Conners’ teacher rating scale (CTRS), ADHD rating scale-parent (ADHD RS-Parent), and ADHD rating scale-teacher (ADHD RS-Teacher), as well as secondary outcome indicators such as the Clinical Global Impressions scale (CGI) and Continuous Performance Test (CPT), relative to controls.
None of the antioxidant therapies were significantly better than placebo.
One limitation is that no effort was made to assess publication bias.
These results indicate that antioxidants should not be used for treating ADHD.
Executive function impairment is a key feature of ADHD, with its severity linked to the intensity of ADHD symptoms. Executive function involves managing complex cognitive tasks for organized behavior and includes three main areas: inhibitory control (suppressing impulsive actions), working memory (holding information briefly), and cognitive flexibility (switching between different mental tasks). Improving executive functions is a critical objective in the treatment of ADHD.
Amphetamines and methylphenidate are commonly used to treat ADHD, but can cause side effects like reduced appetite, sleep problems, nausea, and headaches. Long-term use may also lead to stunted growth and cardiovascular issues. This encourages the search for non-invasive methods to enhance executive function in children with ADHD.
Neurological techniques like neurofeedback and transcranial stimulation are increasingly used to treat children with neurodevelopmental disorders. Neurofeedback is the most adopted method; it is noninvasive and aims to improve brain function by providing real-time feedback on brainwave activity so participants can self-regulate targeted brain regions.
The systematic search and meta-analysis examined children and adolescents aged 6–18 with ADHD. It included randomized and non-randomized controlled trials, as well as quasi-experimental studies that reported statistical data such as participant numbers, means, and standard deviations. Studies were required to use validated measures of executive function, including neurocognitive tasks or questionnaires. They also had to have control groups.
A meta-analysis of ten studies (539 participants) found a small-to-medium improvement in inhibitory control after neurofeedback training, with no publication bias and minimal study heterogeneity*. Long-term treatment (over 21 hours) showed benefits, while short-term treatment did not. However, publication bias was present in the long-term treatment studies and was not addressed.
A meta-analysis of seven studies with 370 children and adolescents found a small-to-medium improvement in working memory after neurofeedback, with no publication bias overall but high heterogeneity. A dose-response effect was observed: treatments over 21 hours showed benefits, while shorter ones did not. However, publication bias was present in the long-term treatment studies and was not addressed.
The study team also looked at sustained effects six months to a year after conclusion of training. Meta-analysis of two studies totaling 131 participants found a sustained small-to-medium improvement in inhibitory control, with negligible heterogeneity. Meta-analysis of three studies combining 182 participants found a sustained medium improvement in working memory, with moderate heterogeneity and no sign of publication bias.
The team concluded, “NFT is an effective intervention for improving executive function in children with ADHD, specifically inhibitory control and working memory. This approach demonstrates a more pronounced impact on working memory when extended beyond 1000 min [sic], with inhibitory control following closely behind. Furthermore, the evidence suggests that NFT may have sustained effects on both working memory and inhibitory control. Given the relatively small number of studies assessing long-term effects and the potential for publication bias, further research is necessary to confirm these effects.”
Moreover, because 1) RCTs are the gold standard, and the meta-analyses combined RCTs with non-RCTs, and 2) data from neurocognitive tasks was combined with data from more subjective and less accurate questionnaires, these meta-analysis results should be interpreted with further caution.
*Heterogeneity refers to the rate of variation between individual study outcomes. High heterogeneity means that there was substantial variation in the results. When a meta-anaylysis has high heterogeneity, it suggests that the studies differ significantly in their populations, methods, interventions, or outcomes, making the combined result much less reliable.
Many news outlets have reported an increase – or surge – in attention-deficit/hyperactivity disorder, or ADHD, diagnoses in both children and adults. At the same time, health care providers, teachers and school systems have reported an uptick in requests for ADHD assessments.
These reports have led some experts and parents to wonder whether ADHD is being overdiagnosed and overtreated.
As researchers who have spent our careers studying neurodevelopmental disorders like ADHD, we are concerned that fears about widespread overdiagnosis are misplaced, perhaps based on a fundamental misunderstanding of the condition.
Discussions about overdiagnosis of ADHD imply that you either have it or you don’t.
However, when epidemiologists ask people in the general population about their symptoms of ADHD, some have a few symptoms, some have a moderate level, and a few have lots of symptoms. But there is no clear dividing line between those who are diagnosed with ADHD and those who are not, since ADHD – much like blood pressure – occurs on a spectrum.
Treating mild ADHD is similar to treating mild high blood pressure – it depends on the situation. Care can be helpful when a doctor considers the details of a person’s daily life and how much the symptoms are affecting them.
Not only can ADHD symptoms be very different from person to person, but research shows that ADHD symptoms can change within an individual. For example, symptoms become more severe when the challenges of life increase.
ADHD symptoms fluctuate depending on many factors, including whether the person is at school or home, whether they have had enough sleep, if they are under a great deal of stress or if they are taking medications or other substances. Someone who has mild ADHD may not experience many symptoms while they are on vacation and well rested, for example, but they may have impairing symptoms if they have a demanding job or school schedule and have not gotten enough sleep. These people may need treatment for ADHD in certain situations but may do just fine without treatment in other situations.
This is similar to what is seen in conditions like high blood pressure, which can change from day to day or from month to month, depending on a person’s diet, stress level and many other factors.
ADHD symptoms start in early childhood and typically are at their worst in mid-to late childhood. Thus, the average age of diagnosis is between 9 and 12 years old. This age is also the time when children are transitioning from elementary school to middle school and may also be experiencing changes in their environment that make their symptoms worse.
Classes can be more challenging beginning around fifth grade than in earlier grades. In addition, the transition to middle school typically means that children move from having all their subjects taught by one teacher in a single classroom to having to change classrooms with a different teacher for each class. These changes can exacerbate symptoms that were previously well-controlled. Symptoms can also wax and wane throughout life.
Psychiatric problems that often co-occur with ADHD, such as anxiety or depression, can worsen ADHD symptoms that are already present. These conditions can also mimic ADHD symptoms, making it difficult to know which to treat. High levels of stress leading to poorer sleep, and increased demands at work or school, can also exacerbate or cause ADHD-like symptoms.
Finally, the use of some substances, such as marijuana or sedatives, can worsen, or even cause, ADHD symptoms. In addition to making symptoms worse in someone who already has an ADHD diagnosis, these factors can also push someone who has mild symptoms into full-blown ADHD, at least for a short time.
The reverse is also true: Symptoms of ADHD can be minimized or reversed in people who do not meet full diagnostic criteria once the external cause is removed.
Clinicians diagnose ADHD based on symptoms of inattention, hyperactivity and impulsivity. To make an ADHD diagnosis in children, six or more symptoms in at least one of these three categories must be present. For adults, five or more symptoms are required, but they must begin in childhood. For all ages, the symptoms must cause serious problems in at least two areas of life, such as home, school or work.
Current estimates show that the strict prevalence of ADHD is about 5% in children. In young adults, the figure drops to 3%, and it is less than 1% after age 60. Researchers use the term “strict prevalence” to mean the percentage of people who meet all of the criteria for ADHD based on epidemiological studies. It is an important number because it provides clinicians and scientists with an estimate on how many people are expected to have ADHD in a given group of people.
In contrast, the “diagnosed prevalence” is the percentage of people who have been diagnosed with ADHD based on real-world assessments by health care professionals. The diagnosed prevalence in the U.S. and Canada ranges from 7.5% to 11.1% in children under age 18. These rates are quite a bit higher than the strict prevalence of 5%.
Some researchers claim that the difference between the diagnosed prevalence and the strict prevalence means that ADHD is overdiagnosed.
We disagree. In clinical practice, the diagnostic rules allow a patient to be diagnosed with ADHD if they have most of the symptoms that cause distress, impairment or both, even when they don’t meet the full criteria. And much evidence shows that increases in the diagnostic prevalence can be attributed to diagnosing milder cases that may have been missed previously. The validity of these mild diagnoses is well-documented.
Consider children who have five inattentive symptoms and five hyperactive-impulsive symptoms. These children would not meet strict diagnostic criteria for ADHD even though they clearly have a lot of ADHD symptoms. But in clinical practice, these children would be diagnosed with ADHD if they had marked distress, disability or both because of their symptoms – in other words, if the symptoms were interfering substantially with their everyday lives.
So it makes sense that the diagnosed prevalence of ADHD is substantially higher than the strict prevalence.
People who are concerned about overdiagnosis commonly worry that people are taking medications they don’t need or that they are diverting resources away from those who need it more. Other concerns are that people may experience side effects from the medications, or that they may be stigmatized by a diagnosis.
Those concerns are important. However, there is strong evidence that underdiagnosis and undertreatment of ADHD lead to serious negative outcomes in school, work, mental health and quality of life.
In other words, the risks of not treating ADHD are well-established. In contrast, the potential harms of overdiagnosis remain largely unproven.
It is important to consider how to manage the growing number of milder cases, however. Research suggests that children and adults with less severe ADHD symptoms may benefit less from medication than those with more severe symptoms.
This raises an important question: How much benefit is enough to justify treatment? These are decisions best made in conversations between clinicians, patients and caregivers.
Because ADHD symptoms can shift with age, stress, environment and other life circumstances, treatment needs to be flexible. For some, simple adjustments like classroom seating changes, better sleep or reduced stress may be enough. For others, medication, behavior therapy, or a combination of these interventions may be necessary. The key is a personalized approach that adapts as patients’ needs evolve over time.
Executive function impairment is a key feature of ADHD, with its severity linked to the intensity of ADHD symptoms. Executive function involves managing complex cognitive tasks for organized behavior and includes three main areas: inhibitory control (suppressing impulsive actions), working memory (holding information briefly), and cognitive flexibility (switching between different mental tasks). Improving executive functions is a critical objective in the management of ADHD.
Recent studies show that exercise interventions can enhance executive function in individuals with ADHD. Unlike traditional medications, which are costly and may cause side effects such as headaches, nausea, or growth issues, exercise can be incorporated into daily routines of children and adolescents without negative reactions.
Some studies report that aerobic exercise does not significantly improve executive function. However, most past reviews of aerobic exercise effects on executive function have focused on people without ADHD, with few examining interventions for children or adolescents with ADHD.
The Study:
A Chinese and South Korean study team conducted a systematic search of the peer-reviewed published literature to perform meta-analyses on randomized controlled trials (RCTs) specifically focused on aerobic exercise interventions for children and adolescents with ADHD.
All studies included were randomized controlled trials involving participants aged 6 to 18 years who had been clinically diagnosed with ADHD. The interventions consisted of various forms of aerobic exercise, while the control groups engaged in either non-exercise activities or daily routines. Each study was required to report at least one outcome measure with usable data for calculating the effect size on executive functioning.
The Results:
Meta-analysis of fifteen RCTs combining 653 children and adolescents with ADHD reported a medium to large effect size improvement in inhibitory control. There was no sign of publication bias, but wide heterogeneity (variation) in outcomes among studies.
Six to eight weeks of aerobic exercise produced modest improvements, with much greater gains seen after twelve weeks. Hour-long sessions were as effective as longer ones. Moderate intensity exercise proved more beneficial than vigorous intensity.
Meta-analysis of eight RCTs combining 399 children and adolescents with ADHD produced a medium effect size improvement in working memory. There was no sign of publication bias, and heterogeneity was moderate.
Once again, six to eight weeks of aerobic exercise produced modest improvements, with much greater gains seen after twelve weeks. Hour-long sessions were as effective as longer ones. But in this case moderate-to-vigorous intensity yielded the best results.
Meta-analysis of ten RCTs combining 443 children and adolescents with ADHD was associated with a medium to large effect size improvement in cognitive flexibility. There was no sign of either publication bias or heterogeneity. Neither the length of treatment, session time, or intensity affected the outcome.
The Take-Away:
The team concluded, “Our study indicates that aerobic exercise interventions have a positive impact with a moderate effect size on inhibitory control, working memory, and cognitive flexibility in children and adolescents with ADHD. However, the effectiveness of the intervention is influenced by factors such as the intervention period, frequency, session durations, intensity, and the choice between acute or chronic exercise. Specifically, chronic aerobic exercise interventions lasting 12 weeks or longer, with a frequency of 3 to 5 sessions per week, session durations of 60 min or more, and intensities that are moderate or moderate-to-vigorous, have the greatest overall effect… caution should be exercised when interpreting these findings due to the significant heterogeneity in inhibitory control and working memory.”
_logo%201.svg)
