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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.
EBI-ADHD:
If you live with ADHD, treat ADHD, or write about ADHD, you’ve probably run into the same problem: there’s a ton of research on treatments, but it’s scattered across hundreds of papers that don’t talk to each other. The EBI-ADHD website fixes that.
EBI-ADHD (Evidence-Based Interventions for ADHD) is a free, interactive platform that pulls together the best available research on how ADHD treatments work and how safe they are. It’s built for clinicians, people with ADHD and their families, and guideline developers who need clear, comparable information rather than a pile of PDFs. EBI-ADHD Database The site is powered by 200+ meta-analyses covering 50,000+ participants and more than 30 different interventions. These include medications, psychological therapies, brain-stimulation approaches, and lifestyle or “complementary” options.
The heart of the site is an interactive dashboard. You can:
The dashboard then shows an evidence matrix: a table where each cell is a specific treatment–outcome–time-point combination. Each cell tells you two things at a glance:
Clicking a cell opens more detail: effect sizes, the underlying meta-analysis, and how the certainty rating was decided.
EBI-ADHD is not just a curated list of papers. It’s built on a formal umbrella review of ADHD interventions, published in The BMJ in 2025. That review re-analyzed 221 meta-analyses using a standardized statistical pipeline and rating system.
The platform was co-created with 100+ clinicians and 100+ people with lived ADHD experience from around 30 countries and follows the broader U-REACH framework for turning complex evidence into accessible digital tools.
Why it Matters
ADHD is one of the most studied conditions in mental health, yet decisions in everyday practice are still often driven by habit, marketing, or selective reading of the literature. EBI-ADHD offers something different: a transparent, continuously updated map of what we actually know about ADHD treatments and how sure we are about it.
In short, it’s a tool to move conversations about ADHD care from “I heard this works” to “Here’s what the best current evidence shows, and let’s decide together what matters most for you.”
The Background:
Meta-analyses have previously suggested a link between maternal thyroid dysfunction and neurodevelopmental disorders (NDDs) in children, though some studies report no significant difference. Overweight and obesity are more common in children and adolescents with NDDs. Hypothyroidism is often associated with obesity, which may result from reduced energy expenditure or disrupted hormone signaling affecting growth and appetite. These hormone-related parameters could potentially serve as biomarkers for NDDs; however, research findings on these indicators vary.
The Study:
A Chinese research group recently released a meta-analysis examining the relationship between neurodevelopmental disorders (NDDs) and hormone levels – including thyroid, growth, and appetite hormones – in children and adolescents.
The analysis included peer-reviewed studies that compared hormone levels – such as thyroid hormones (FT3, FT4, TT3, TT4, TSH, TPO-Ab, or TG-Ab), growth hormones (IGF-1 or IGFBP-3), and appetite-related hormones (leptin, ghrelin, or adiponectin) – in children and adolescents with NDDs like ADHD, against matched healthy controls. To be included, NDD cases had to be first-diagnosis and medication-free, or have stopped medication before testing. Hormone measurements needed to come from blood, urine, or cerebrospinal fluid samples, and all studies were required to provide both means and standard deviations for these measurements.
Meta-analysis of nine studies encompassing over 5,700 participants reported a medium effect size increase in free triiodothyronine (FT3) in children and adolescents with ADHD relative to healthy controls. There was no indication of publication bias, but variation between individual study outcomes (heterogeneity) was very high. Further analysis showed FT3 was only significantly elevated in the predominantly inattentive form of ADHD (three studies), again with medium effect size, but not in the hyperactive/impulsive and combined forms.
Meta-analysis of two studies combining more than 4,800 participants found a small effect size increase in thyroid peroxidase antibody (TPO-Ab) in children and adolescents with ADHD relative to healthy controls. In this case, the two studies had consistent results. Because only two studies were involved, there was no way to evaluate publication bias.
The remaining thyroid hormone meta-analyses, involving 6 to 18 studies and over 5,000 participants in each instance, found no significant differences in levels between children and adolescents with ADHD and healthy controls.
Meta-analyses of six studies with 317 participants and two studies with 192 participants found no significant differences in growth hormone levels between children and adolescents with ADHD and healthy controls.
Finally, meta-analyses of nine studies with 333 participants, five studies with 311 participants, and three studies with 143 participants found no significant differences in appetite-related hormone levels between children and adolescents with ADHD and healthy controls.
The Conclusion:
The team concluded that FT3 and TPO-Ab might be useful biomarkers for predicting ADHD in youth. However, since FT3 was only linked to inattentive ADHD, and TPO-Ab’s evidence came from just two studies with small effects, this conclusion may overstate the meta-analysis results.
Our Take-Away:
Overall, this meta-analysis found only limited evidence that hormone differences are linked to ADHD. One thyroid hormone (FT3) was higher in children with ADHD—mainly in the inattentive presentation—but the findings varied widely across studies. Another marker, TPO-Ab, showed a small increase, but this came from only two studies, making the result less certain. For all other thyroid, growth, and appetite-related hormones, the researchers found no meaningful differences between children with ADHD and those without. While FT3 and TPO-Ab may be worth exploring in future research, the current evidence is not strong enough to consider them reliable biomarkers.
Background:
Recent progress in reproductive medicine has increased the number of children conceived via assisted reproductive techniques (ART). These include:
Although ART helps with infertility, there are concerns about its long-term effects on offspring, especially regarding neurodevelopment. Factors such as hormonal treatments, gamete manipulation, altered embryonic environments, as well as parental age and infertility, may influence brain development and raise the risk of neurodevelopmental and mental health disorders.
With previous studies finding conflicting results on a possible association between ART and increased risk of mental health disorders, an Indian research team has just published a new meta-analysis exploring this topic.
The Study:
Studies were eligible if they were observational (cohort, case-control, or cross-sectional), reported confounder-adjusted effect sizes for ADHD, and were published in English in peer-reviewed journals.
A meta-analysis of eight studies encompassing nearly twelve million individuals indicated a 7% higher prevalence of ADHD in offspring conceived via IVF/ICSI compared to those conceived naturally. The heterogeneity among studies was minimal, and no evidence of publication bias was observed.
The study’s 95% confidence interval ranged from 4% to 10%. Further analysis of five studies comprising almost nine million participants that distinguished outcomes by sex revealed that the increase in ADHD risk among female offspring was not statistically significant. In contrast, the elevated risk in male offspring persisted, though it was marginally significant, with the lower bound of the confidence limit at only 1%.
Results:
A meta-analysis of three studies (1.4 million participants) found a 13% higher rate of ADHD in children conceived via ovulation induction/intrauterine insemination (OI/IUI) compared to natural conception. The effect size, though doubled, remains small. Minimal heterogeneity and no publication bias were observed.
The team concluded, “The review found a small but statistically significant moderate certainty evidence of an increased risk of ADHD in those conceived through ART, compared to spontaneous conception. The magnitude of observed risk is small and is reassuring for parents and clinicians.”
Our Take-Away:
Overall, the meta-analysis points to a small, but measurable increase in ADHD diagnoses among children conceived through ART, but the effect sizes are modest and supported by moderate-certainty evidence. And we must always keep in mind that the researchers who wrote the original articles could not correct for all possible confounds. These findings suggest that while reproductive technologies may introduce slight variation in neurodevelopmental outcomes, the effects are small and uncertain. For families and clinicians, the results are generally reassuring: ART remains a safe and effective avenue to parenthood, and the results of this study should not be viewed as a prohibitive concern. Thoughtful developmental monitoring and open, evidence-based counseling can help ensure that ART-conceived children receive support that caters to their individual needs.
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