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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.
The Background:
Myopia is a growing global health concern linked to conditions like macular degeneration, glaucoma, and retinal detachment. Its prevalence has surged in recent decades; by 2050, an estimated 5 billion people will have myopia. The increase is especially marked in Asia – a survey in Taiwan reports that 84% of students aged 15 to 18 are myopic, with 24% severely affected.
Dopamine is an important neurotransmitter in the retina, involved in eye development, visual signaling, and refractive changes. The dopamine hypothesis, suggesting that retinal dopamine release helps prevent myopia, has emerged as a leading theory of myopia control.
Most studies show ADHD is highly heritable, often involving dopamine system genes. ADHD is strongly associated with dopaminergic abnormalities, especially in dopamine transporter function and release dynamics.
Medications for ADHD, like methylphenidate, atomoxetine, and clonidine, help regulate dopamine to reduce symptoms.
The Study:
Given dopamine’s critical involvement in both ADHD and myopia, a Taiwanese research team hypothesized that medications for ADHD that influence dopaminergic pathways may have a significant effect on myopia risk.
To evaluate this hypothesis, the team conducted a nationwide cohort study using data from Taiwan’s National Health Insurance (NHI) program, which covers 99% of the nation’s 23 million residents and provides access to comprehensive eye care and screenings. Taiwan requires visual acuity screenings beginning at age four, with annual examinations for school-aged children to promote the early detection of visual anomalies such as myopia.
Furthermore, ADHD medication and diagnosis are tracked through compulsory diagnostic codes. This permits an accurate assessment of the effects of dopaminergic medications on myopia risk.
Propensity score allocation using a multivariable logistic regression model was applied to reduce bias from confounding influences, pairing cohorts based on similar scores.
The Results:
Comparing 133,945 individuals with ADHD with an equal number without ADHD, untreated ADHD was associated with a 22% greater risk of myopia.
However, after adjusting for covariates (gender, age, insured premium, comorbidities, location, and urbanization level), the ADHD cohort receiving medication treatment showed a 39% decreased risk of myopia relative to the untreated ADHD cohort.
Narrowing this further to the ADHD cohort receiving dopaminergic medications reduced the risk of myopia by more than half (52%) relative to the untreated ADHD cohort.
Treatment with two dopaminergic medications reduced the risk by well over two-thirds (72%) relative to the untreated ADHD cohort.
There were no significant differences between methylphenidate, atomoxetine, and clonidine. Each reduced risk by about 50%.
The team did not directly compare the ADHD cohort receiving dopaminergic medications with the non-ADHD cohort. But if there were 122 cases of myopia in the ADHD cohort for every 100 cases in the non-ADHD cohort, and dopaminergic medications halved the cases in the ADHD cohort to about 60, that would represent a roughly 40% reduction in myopia risk relative to the non-ADHD cohort.
The team concluded, “our research indicates that pharmacologically treated ADHD children have a reduced risk of myopia. Conversely, untreated ADHD children are at a heightened risk relative to those without ADHD. Moreover, the cumulative effects of ADHD medications were found to notably decrease myopia incidence, emphasizing the protective influence of dopaminergic modulation in these interventions.”
The Take-Away:
Children with untreated ADHD are more likely to develop myopia, but those receiving dopaminergic medications had a substantially lower risk. The findings suggest that ADHD medications may help protect against myopia by boosting dopamine signaling. More research is needed before firmly drawing this conclusion, but this research could open the door to new approaches for preventing myopia in at-risk children.
Background:
ADHD treatment includes medication, behavioral therapy, dietary changes, and special education. Stimulants are usually the first choice but may cause side effects like appetite loss and stomach discomfort, leading some to stop using them. Cognitive behavioral therapy (CBT) is effective but not always sufficient on its own. Research is increasingly exploring non-drug options, such as transcranial direct current stimulation (tDCS), which may boost medication effectiveness and improve results.
What is tDCS?
tDCS delivers a weak electric current (1.0–2.0 mA) via scalp electrodes to modulate brain activity, with current flowing from anode to cathode. Anodal stimulation increases neuronal activity, while cathodal stimulation generally inhibits it, though effects vary by region and neural circuitry. The impact of tDCS depends on factors such as current intensity, duration, and electrode shape. It targets cortical areas, often stimulating the dorsolateral prefrontal cortex for ADHD due to its role in cognitive control. Stimulation of the inferior frontal gyrus has also been shown to improve response inhibition, making it another target for ADHD therapy.
There is an ongoing debate about how effective tDCS is for individuals with ADHD. One study found that applying tDCS to the left dorsolateral prefrontal cortex can help reduce impulsivity symptoms in ADHD, whereas another study reported that several sessions of anodic tDCS did not lead to improvements in ADHD symptoms or cognitive abilities.
New Research:
Two recent meta-analyses have searched for a resolution to these conflicting findings. Both included only randomized controlled trials (RCTs) using either sham stimulation or a waitlist for controls.
Each team included seven studies in their respective meta-analyses, three of which appeared in both.
Both Wang et al. (three RCTs totaling 97 participants) and Wen et al. (three RCTs combining 121 participants) reported very large effect size reductions in inattention symptoms from tDCS versus controls. There was only one RCT overlap between them. Wang et al. had moderate to high variation (heterogeneity) in individual study outcomes, whereas Wen et al. had virtually none. There was no indication of publication bias.
Whereas Wen et al.’s same three RCTs found no significant reduction in hyperactivity/impulsivity symptoms, Wang et al. combined five RCTs with 221 total participants and reported a medium effect size reduction in impulsivity symptoms. This time, there was an overlap of two RCTs between the studies. Wen et al. had no heterogeneity, while Wang et al. had moderate heterogeneity. Neither showed signs of publication bias.
Turning to performance-based tasks, Wang et al. reported a medium effect size improvement in attentional performance from tDCS over controls (three RCTs totaling 136 participants), but no improvement in inhibitory control (five RCTs combining 234 persons).
Wang et al. found no significant difference in adverse events (four RCTs combining 161 participants) between tDCS and controls, with no heterogeneity. Wen et al. found no significant difference in dropout rates (4 RCTs totaling 143 individuals), again with no heterogeneity.
Wang et al. concluded, “tDCS may improve impulsive symptoms and inattentive symptoms among ADHD patients without increasing adverse effects, which is critical for clinical practice, especially when considering noninvasive brain stimulation, where patient safety is a key concern.”
Wen et al. further concluded, “Our study supported the use of tDCS for improving the self-reported symptoms of inattention and objective attentional performance in adults diagnosed with ADHD. However, the limited number of available trials hindered a robust investigation into the parameters required for establishing a standard protocol, such as the optimal location of electrode placement and treatment frequency in this setting. Further large-scale double-blind sham-controlled clinical trials that include assessments of self-reported symptoms and performance-based tasks both immediately after interventions and during follow-up periods, as well as comparisons of the efficacy of tDCS targeting different brain locations, are warranted to address these issues.”
The Take-Away:
Previous studies have shown mixed results on the benefits of this therapy on ADHD. These new findings suggest that tDCS may hold some real promise for adults with ADHD. While the technique didn’t meaningfully shift hyperactivity or impulsivity, it was well-tolerated and showed benefit, especially in self-reported symptoms. However, with only a handful of trials to draw from, it would be a mistake to suggest tDCS as a standard treatment protocol. Larger, well-designed studies are the next essential step to clarify where, how, and how often tDCS works best.
Background:
The development of ADHD is strongly associated with functional impairments in the prefrontal cortex, particularly the dorsolateral prefrontal cortex, which plays a key role in maintaining attention and controlling impulses. Moreover, imbalances in neurotransmitters like dopamine and norepinephrine are widely regarded as major neurobiological factors contributing to ADHD.
Executive functions are a group of higher-order cognitive skills that guide thoughts and actions toward goals. “Executive function” refers to three main components: inhibitory control, working memory, and cognitive flexibility. Inhibitory control helps curb impulsive actions to stay on track. Working memory allows temporary storage and manipulation of information for complex tasks. Cognitive flexibility enables switching attention and strategies in varied or demanding situations.
Research shows that about 89% of children with ADHD have specific executive function impairments. These difficulties in attention, self-control, and working memory often result in academic and social issues. Without timely intervention, these issues can lead to emotional disorders like depression, anxiety, and irritability, further affecting both physical health and social development.
Currently, primary treatments for executive function deficits in school-aged children with ADHD include medication and behavioral or psychological therapies, such as Cognitive Behavioral Therapy (CBT). While stimulant medications do improve executive function, not all patients are able to tolerate these medications. Behavioral interventions like neurofeedback provide customized care but show variable effectiveness and require specialized resources, making them hard to sustain. Safer, more practical, and long-lasting treatment options are urgently needed.
Exercise interventions are increasingly recognized as a safe, effective way to improve executive function in children with ADHD. However, systematic studies on school-aged children remain limited.
Moreover, there are two main scoring methods for assessing executive function: positive scoring (higher values mean better performance, such as accuracy) and reverse scoring (lower values mean better performance, such as reaction time). These different methods can affect how results are interpreted and compared across studies. This meta-analysis explored how different measurement and scoring methods might influence results, addressing important gaps in the research.
The Study:
Only randomized controlled trials (RCTs) involving school-aged children (6–13 years old) diagnosed with ADHD by DSM-IV, DSM-5, ICD-10, ICD-11, or the SNAP-IV scale were included. Studies were excluded if the experimental group received non-exercise interventions or exercise combined with other interventions.
Cognitive Flexibility
Using positive scoring, exercise interventions were associated with a narrowly non-significant small effect size improvement relative to controls (eight RCTs, 268 children). Using reverse scoring, however, they were associated with a medium effect size improvement (eleven RCTs, 452 children). Variation (heterogeneity) in individual RCT outcomes was moderate, with no sign of publication bias in both instances.
Inhibitory Control
Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (ten RCTs, 421 children). Using reverse scoring, there was an association with a medium effect size improvement (eight RCTs, 265 children). Heterogeneity was moderate with no sign of publication bias in either case.
Working Memory
Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (six RCTs, 321 children). Using reverse scoring, the exercise was associated with a medium effect size improvement (five RCTs, 143 children). Heterogeneity was low with no indication of publication bias in both instances.
Conclusion:
The team concluded, “Exercise interventions can effectively improve inhibitory control and working memory in school-aged children with ADHD, regardless of whether positive or reverse scoring methods are applied. However, the effects of exercise on cognitive flexibility appear to be limited, with significant improvements observed only under reverse scoring. Moreover, the effects of exercise interventions on inhibitory control, working memory, and cognitive flexibility vary across different measurement paradigms and scoring methods, indicating the importance of considering these methodological differences when interpreting results.”
Although this work is intriguing, it does not show that exercise significantly improves the symptoms of ADHD in children. This means that exercise, although beneficial for many reasons, should not be viewed as a replacement for evidence-based treatments for the disorder.
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