July 21, 2025

What Metabolites Tell Us About ADHD — And What This Means for Diet and Treatment

New research has uncovered important links between certain blood metabolites and ADHD by using a genetic method called Mendelian randomization. This approach leverages natural genetic differences to help identify which metabolites might actually cause changes in ADHD risk, offering stronger clues than traditional observational studies.

Key Metabolic Pathways Involved:

The study found 42 plasma metabolites with a causal relationship to ADHD. Most fall into two major groups:

  • Amino acid metabolites from protein metabolism, including those related to tyrosine, methionine, cysteine, and taurine.

  • Fatty acids, especially long-chain polyunsaturated fatty acids (PUFAs) like DHA and EPA, important for brain function.

What Does This Mean for Diet and ADHD?

Since many metabolites come from dietary sources like proteins and fats this supports the idea that diet could influence metabolic pathways involved in ADHD. However, because the study focused on genetic influences on metabolite levels, it doesn’t directly prove that dietary changes will have the same effects.

Notable Metabolites:

  • 3-Methoxytyramine sulfate (MTS): linked to dopamine metabolism, higher genetic levels of MTS were associated with a lower risk of ADHD. Dopamine plays a crucial role in attention and behavior.

  • DHA and EPA: Omega-3 fatty acids abundant in the brain; higher levels were linked to reduced ADHD risk, supporting existing research on omega-3 supplements.

  • N-acetylneuraminate: Involved in brain development and immune function, with higher levels linked to increased ADHD risk, though more research is needed to understand this.

Five metabolites showed bidirectional links with ADHD, meaning genetic risk for ADHD also affects their levels which suggests a complex interaction between brain function and metabolism.

Twelve ADHD-related metabolites are targets of existing drugs or supplements, including:

  • Acetylcysteine: an antioxidant used in various treatments.

  • DHA supplements: widely used to support brain and heart health.

What This Study Doesn’t Show

While these findings highlight biological pathways, they don’t prove that changing diet will directly alter ADHD symptoms. Metabolite levels are shaped by genetics plus environment, lifestyle, and health factors, which require further study.

Conclusion: 

This research provides stronger evidence of metabolic pathways involved in ADHD and points to new possibilities for diagnosis and treatment. Future work could explore how diet or drugs might safely adjust these metabolites to help manage ADHD.

While this study strengthens the link between amino acid and fatty acid metabolism and ADHD risk, suggesting that diet could play a role, ultimately more research is still needed before experts could use this research to give specific nutritional advice.

Shi S, Baranova A, Cao H, Zhang F. Exploring causal associations between plasma metabolites and attention-deficit/hyperactivity disorder. BMC Psychiatry. 2025 May 16;25(1):498. doi: 10.1186/s12888-025-06951-9. PMID: 40380147; PMCID: PMC12084988.

Related posts

ADHD and Eating Disorders

ADHD and Eating Disorders

A relatively new area of ADHD research has been examining the association between ADHD and eating disorders (i.e., anorexia nervosa, bulimia nervosa, and binge-eating disorder). Nazar and colleagues conducted a systematic review and meta-analysis of extant studies.  

They found only twelve studies that assessed the presence of eating disorders among people with ADHD and five that examined the prevalence of ADHD among patients with eating disorders. Although there were few studies, the total number of people studied was large, with 4,013 ADHD cases and 29,404 controls for the first set of studies and 1,044 eating disorder cases and 11,292 controls for the second set of studies.  The meta-analyses of these data found that ADHD people had a 3.8-fold increased risk for an eating disorder compared with non-ADHD controls.  The level of risk was similar for each of the eating disorders.  Consistent with this, their second meta-analysis found that people with eating disorders had a 2.6-fold increased risk for ADHD compared with controls who did not have an eating disorder. The risk for ADHD was highest for those with binge-eating disorder (5.8-fold increased risk compared with controls).  

This bidirectional association between ADHD and eating disorders provides converging evidence that this association is real and, given its magnitude, clinically significant. The results were similar for males and females and pediatric and adult populations.

We cannot tell from these data why ADHD is associated with eating disorders. Nazar et al. note that other work implicates both impulsivity and inattention in promoting bulimic symptoms, whereas inattention and hyperactivity are associated with craving. The association may also be due to the neurocognitive deficits of ADHD, which could lead to a distorted sense of self-awareness and body image.

Given that ADHD is also associated with obesity, some obese ADHD patients may have an underlying eating disorder, such as binge-eating, which has been associated with obesity in prospective studies. Also, lisdexamfetamine is FDA-approved for treating both binge eating and ADHD, which suggests the possibility that the two conditions share an underlying etiology involving the dopamine system. We do not know if treating ADHD would reduce the risk for eating disorders, as that hypothesis has not yet been tested. But such an effect would seem likely if ADHD behaviors mediate the association between the two disorders.

March 22, 2021

Do Some Foods Cause ADHD? Does Dieting Help?

Do Some Foods Cause ADHD? Does Dieting Help?

If we are to read what we believe on the Internet, dieting can cure many of the ills faced by humans. Much of what is written is true. Changes in dieting can be good for heart disease, diabetes, high blood pressure, and kidney stones to name just a few examples. But what about ADHD? Food elimination diets have been extensively studied for their ability to treat ADHD. They are based on the very reasonable idea that allergies or toxic reactions to foods can have effects on the brain and could lead to ADHD symptoms.

Although the idea is reasonable, it is not such an easy task to figure out what foods might cause allergic reactions that could lead to ADHD symptoms. Some proponents of elimination diets have proposed eliminating a single food, others include multiple foods, and some go as far as to allow only a few foods to be eaten to avoid all potential allergies. Most readers will wonder if such restrictive diets, even if they did work, are feasible. That is certainly a concern for very restrictive diets.

Perhaps the most well-known ADHD diet is the Feingold diet(named after its creator). This diet eliminates artificial food colorings and preservatives that have become so common in the western diet. Some have claimed that the increasing use of colorings and preservatives explains why the prevalence of ADHD is greater in Western countries and has been increasing over time. But those people have it wrong. The prevalence of ADHD is similar around the world and has not been increasing over time. That has been well documented but details must wait for another blog.

The Feingold and other elimination diets have been studied by meta-analysis. This means that someone analyzed several well-controlled trials published by other people. Passing the test of meta-analysis is the strongest test of any treatment effect. When this test is applied to the best studies available, there is evidence that the exclusion of fool colorings helps reduce ADHD symptoms. But more restrictive diets are not effective. So removing artificial food colors seems like a good idea that will help reduce ADHD symptoms. But although such diets ‘work’, they do network very well. On a scale of one to 10where 10 is the best effect, drug therapy scores 9 to 10 but eliminating food colorings scores only 3 or 4. Some patients or parents of patients might want this diet change first in the hopes that it will work well for them. That is a possibility, but if that is your choice, you should not delay the more effective drug treatments for too long in the likely event that eliminating food colorings is not sufficient. You can learn more about elimination diets from Nigg, J. T., and K.Holton (2014). "Restriction and elimination diets in ADHD treatment."Child Adolesc Psychiatr Clin N Am 23(4): 937-953.

Keep in mind that the treatment guidelines from professional organizations point to ADHD drugs as the first-line treatment for ADHD. The only exception is for preschool children where medication is only the first-line treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available. You can learn more about non-pharmacologic treatments for ADHD from a book I recently edited: Faraone, S. V. &Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child AdolescPsychiatr Clin N Am 23, xiii-xiv.

March 20, 2021

Large Sibling Study Finds Genetic Link Between ADHD and Other Disorders

Swedish Countrywide Sibling Population Study Finds Co-occurrence of ADHD with Neurological and Psychiatric Disorders is Largely Due to Genetics

A Swedish-Danish-Dutch team used the Swedish Medical Birth Register to identify the almost 1.7 million individuals born in the country between 1980 and 1995. Then, using the Multi-Generation Register, they identified 341,066 pairs of full siblings and 46,142 pairs of maternal half-siblings, totaling 774,416 individuals.

The team used the National Patient Register to identify diagnoses of ADHD, as well as neurodevelopmental disorders (autism spectrum disorder, developmental disorders, intellectual disability, motor disorders), externalizing psychiatric disorders (oppositional defiant and related disorders, alcohol misuse, drug misuse), and internalizing psychiatric disorders (depression, anxiety disorder, phobias, stress disorders, obsessive-compulsive disorder).

The team found that ADHD was strongly correlated with general psychopathology overall (r =0.67), as well as with the neurodevelopmental (r = 0.75), externalizing (r =0.67), and internalizing (r = 0.67) sub factors.

To tease out the effects of heredity, shared environment, and non-shared environment, a multivariate correlation model was used. Genetic variables were estimated by fixing them to correlate between siblings at their expected average gene sharing (0.5for full siblings, 0.25 for half-siblings). Non-genetic environmental components shared by siblings (such as growing up in the same family) were estimated by fixing them to correlate at 1 across full and half-siblings. Finally, non-shared environmental variables were estimated by fixing them to correlate at zero across all siblings.

This model estimated the heritability of the general psychopathology factor at 49%, with the contribution of the shared environment at 7 percent and the non-shared environment at 44%. After adjusting for the general psychopathology factor, ADHD showed a significant and moderately strong phenotypic correlation with the neurodevelopmental-specific factor (r = 0.43), and a significantly smaller correlation with the externalizing-specific factor (r = 0.25).

For phenotypic correlation between ADHD and the general psychopathology factor, genetics explained 52% of the total correlation, the non-shared environment 39%, and the shared familial environment only 9%. For the phenotypic correlation between ADHD and the neurodevelopmental-specific factor, genetics explained the entire correlation because the other two factors had competing effects that canceled each other out. For the phenotypic correlation between ADHD and the externalizing-specific factor, genetics explained 23% of the correlation, shared environment 22%, and non-shared environment 55%.

The authors concluded that "ADHD is more phenotypically and genetically linked to neurodevelopmental disorders than to externalizing and internalizing disorders, after accounting for a general psychopathology factor. ... After accounting for the general psychopathology factor, the correlation between ADHD and the neurodevelopmental-specific factor remained moderately strong, and was largely genetic in origin, suggesting substantial unique sharing of biological mechanisms among disorders. In contrast, the correlation between ADHD and the externalizing-specific factor was much smaller and was largely explained by-shared environmental effects. Lastly, the correlation between ADHD and the internalizing subfactor was almost entirely explained by the general psychopathology factor. This finding suggests that the comorbidity of ADHD and internalizing disorders are largely due to shared genetic effects and non-shared environmental influences that have effects on general psychopathology."

March 16, 2024

Population Study Finds Strong Association Between Assisted Reproductive Technologies and Offspring ADHD

Taiwanese Nationwide Population Study Finds Strong Association Between Assisted Reproductive Technologies and Offspring ADHD

Background: 

Since the first in vitro fertilization (IVF) in 1978, assisted reproductive technology (ART) has led to over 10 million births worldwide.  

There are four types of embryo transfers, depending on whether they are fresh or frozen, and on their developmental stage. 

Fresh cleavage stage embryos are transferred on day 2 or 3 following fertilization and typically contain four to eight relatively large, undifferentiated cells. Fresh blastocyst embryos are transferred on day 5 or 6 after fertilization. At this point, they have developed over a hundred cells and have differentiated into two types: the inner cell mass, which develops into the fetus, and the outer cell layer, which forms the placenta. 

Globally, more children are now born through assisted reproductive technology using frozen-thawed embryo transfer than fresh embryo transfer.  

Research suggests that ART-conceived offspring may face increased risks of cardiovascular, musculoskeletal, chromosomal, urogenital diseases, and cancers. Might they also be at increased risk for ADHD? 

Study:

Taiwan’s single-payer health insurance covers over 99% of people and records all their healthcare activity. Since 1998, it has kept an ART database for all couples registered for IVF treatment. 

A Taiwanese research team reviewed all records for the five-year period from 2013 through 2017, ultimately analyzing 3,125 live singleton births from fresh cleavage stages, 1,332 from fresh blastocysts, 1,465 from frozen cleavage stages, and 4,708 from frozen blastocysts, alongside 878,643 naturally conceived singleton births. 

The team controlled for the following potential confounders: pregnancy-induced hypertension, chronic hypertension, diabetes mellitus, gestational diabetes mellitus, unhealthy lifestyle, placenta previa, placenta abruption, preterm premature rupture of membrane, and postpartum hemorrhage. 

Results:

With these adjustments, cleavage stage embryo transfers, whether fresh or frozen, were associated with a seven-fold higher rate of ADHD diagnosis in offspring than natural conception. 

Frozen blastocyst embryo transfers were likewise linked to a seven-fold increase in ADHD diagnoses in offspring compared to natural conception. Notably, fresh blastocyst transfers showed a 19-fold increase, likely due to the smaller number of cases in this category. 

The team concluded, “Compared to natural conception, ART is associated with higher risks, particularly for preterm birth, ADHD, and developmental delay.” 

Conclusion: 

This large national cohort suggests that ART-conceived singletons face higher rates of several adverse outcomes, including preterm birth, ADHD, and developmental delay. Clinicians and prospective parents should therefore weigh these potential associations when counseling and planning care, prioritize optimized ART protocols and perinatal management, and ensure early developmental surveillance for ART-conceived children so concerns can be identified and addressed promptly.

It is important to note that the findings also point to the likely contribution of underlying parental infertility in these developmental outcomes. Future research should aim to disentangle parental- versus procedure-related risks to clarify absolute risk magnitudes. As always, associations of this time should not be interpreted as causal due to the inability of observational studies to rule out all possible confounding factors.

October 1, 2025

Why Do So Many Young People Miss an ADHD Diagnosis? Insights from a New Study

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental conditions, yet many young people, especially girls, receive a diagnosis late or not at all. This matters, because a delayed diagnosis often means missed opportunities for support, treatment, and improved long-term outcomes. A recent study by Barclay and colleagues (2024) sheds new light on why ADHD recognition is inconsistent, and what we can do about it.

The Study:

Researchers analyzed data from nearly 10,000 children in the UK Millennium Cohort Study. They compared children whose ADHD was recognized early (ages 5–7), later (ages 11–14), or not recognized at all, despite evidence of symptoms. The team also looked at differences between boys and girls to better understand why diagnosis patterns vary by sex.

Key Findings:
  1. Severity Drives Earlier Recognition
    Children who were diagnosed at a younger age often had more visible difficulties: emotional outbursts, peer conflict, conduct issues, and lower cognitive scores. In other words, the “louder” and more disruptive the symptoms, the more likely ADHD was flagged early.

  2. “Quieter” ADHD May Be Overlooked
    Children with stronger prosocial skills or higher cognitive ability were less likely to be recognized, even if they had clear ADHD symptoms. These children may be able to “mask” their difficulties, or adults may misinterpret their struggles as personality quirks rather than signs of ADHD.

  3. Emotional Dysregulation Matters
    Emotional dysregulation—big swings in mood, difficulty calming down, intense frustration—was strongly linked to recognized ADHD in boys, but not in girls. This suggests that clinicians may pay closer attention to these behaviors in boys, while overlooking them in girls.

  4. Co-occurring Conditions Can Influence Diagnosis
    Children with autism were more likely to have their ADHD identified. On the flip side, those who engaged in more physical activity were slightly less likely to be recognized, though the reasons for this are not yet clear.

What This Means for Clinicians:

The study highlights the importance of looking beyond the “classic” hyperactive child stereotype when considering ADHD. Clinicians should:

  • Pay attention to symptoms of emotional dysregulation, even if they are not part of standard diagnostic checklists.

  • Consider ADHD in children with good grades or strong social skills if other symptoms are present.

  • Be mindful of gender differences, since girls may be more likely to internalize symptoms or present with inattentiveness rather than hyperactivity.

What This Means for Parents and Patients:

If you’re a parent, it’s important to trust your observations. If your child struggles with focus, organization, or emotional regulation—even if they are doing well academically or socially—these could still be signs of ADHD. Advocating for an evaluation can make a big difference.

Moving Forward

This study makes clear that ADHD is not one-size-fits-all. Recognition often depends on how symptoms show up, how disruptive they appear, and even the child’s gender. By broadening our awareness and refining our screening practices, we can ensure that fewer children slip through the cracks and more receive the support they need early in life.

September 30, 2025

ADHD Medication and Academic Achievement: What Do We Really Know?

Parents and teachers often ask: Does ADHD medication actually improve grades and school performance? The answer is: yes, but with important limitations. Medications are very effective at reducing inattention, hyperactivity, and impulsivity but their impact on long-term academic outcomes like grades and test scores is not as consistent.

In the Classroom

The medications for ADHD consistently: Improve attention, reduce classroom disruptions, increase time spent on-task and help children complete more schoolwork and homework. Medication can help children with ADHD access learning by improving the conditions for paying attention and persisting with work.

Does Medication Improve Test Scores and Grades?

This is where the picture gets more complicated.  Medications have  stronger effect on how much work is completed but a weaker effect on accuracy. Many studies show that children on medication attempt more problems in reading, math, and spelling, but the number of correct answers doesn’t always improve as much. Some studies find small but significant improvements in national exam scores and higher education entrance tests during periods when children with ADHD are medicated.

Grades improve, as well, but modestly. Large registry studies in Sweden show that students who consistently take medication earn higher grades than those who don’t. However, these gains usually do not close the achievement gap with peers who do not have ADHD.

Keep in mind that small improvements for a group as a whole mean that some children are benefiting greatly from medication and others not at all.  We have no way of predicting which children will improve and which do not. 

Medication Alone Isn’t Enough

Academic success depends on more than just reducing inattention, hyperactivity and impulsivity. Skills like organization, planning, studying, and managing long-term projects are also critical.  Medication cannot teach these skills.

So, in addition to medication, the patient's treatment program should include educational support (tutoring, structured study skills programs), behavioral interventions (parent training, classroom management strategies), and accommodations at school (extra time, reduced distractions, organizational aids) Parents should discuss with their prescriber which of these methods would be appropriate.

Conclusions 

ADHD medication is a powerful tool for reducing symptoms and supporting learning. It improves test scores and grades for some children, especially when taken consistently. But it is not a magic bullet for academic success. The best results come when medication is combined with educational and behavioral supports that help children build the skills they need to thrive in school and beyond.

September 17, 2025