July 28, 2025

Updates on ADHD and Vitamin D

The Background on ADHD and Vitamin D

In a blog published in the early days of The ADHD Evidence Project, we discussed an Iranian study examining the association between Vitamin D levels and ADHD in children. The meta-analysis combined 13 studies for a total of 10,344 participants. The researchers found that youth with ADHD had "modest but significant" lower serum concentrations of 25-hydroxyvitamin D compared to those without ADHD.

They also identified four prospective studies that compared maternal vitamin D levels with the subsequent development of ADHD symptoms in their children. Two of these used maternal serum levels, and two used umbilical cord serum levels. Together, these studies found that low maternal vitamin D levels were associated with a 40% higher risk of ADHD in their children. 

Ultimately, the researchers noted that this result "should be considered with caution" because it was heavily dependent on one of the prospective studies included in the analysis. We concluded our blog by pointing out that further research, including more longitudinal studies, is needed before clinicians should start recommending vitamin D supplementation to ADHD patients. 

Further Research: 

Since publishing that initial blog, several more studies have been published about this association. 

The World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international task force involving 31 leading academics and clinicians from 15 countries between 2019 and 2021. Their goal was to provide a definitive, evidence-based report to assist clinicians in making decisions around the recommendation of nutraceuticals and phytoceuticals for major psychiatric disorders.

For ADHD, the guidelines found only weak support for micronutrients and vitamin D in treatment. Overall, the task force concluded that nutraceuticals and phytoceuticals currently offer very limited evidence‑based benefit for ADHD management.

Another study published in 2023 systematically assessed the results of previously published studies to examine the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and later offspring psychiatric outcomes. This study found a clear association between maternal vitamin D deficiency and subsequent offspring ADHD. They concluded, “Future studies with larger sample sizes, longer follow-up periods, and prenatal vitamin D assessed at multiple time points are needed.”  To that, I will add that studies of this issue should use genetically informed designs to avoid confounding.

Conclusion:

Taking into account the updated research on the topic, there does seem to be an association between low prenatal vitamin D levels and the risk of subsequent offspring ADHD, but it is too soon to say it is a causal relationship due to the possibility of confounding. There is no high-quality evidence, however, that supplementing with vitamin D will significantly reduce symptoms in current ADHD patients. 

YadollahKhoshbakht, Reza Bidaki, and Amin Salehi-Abargouei, "Vitamin D Status and Attention Deficit Hyperactivity Disorder: A systematic review and Meta-Analysis of Observational Studies," Advances in Nutrition, vol. 9, issue 1, p. 9-20(2018).

Sarris J, Ravindran A, Yatham LN, Marx W, Rucklidge JJ, McIntyre RS, Akhondzadeh S, Benedetti F, Caneo C, Cramer H, Cribb L, de Manincor M, Dean O, Deslandes AC, Freeman MP, Gangadhar B, Harvey BH, Kasper S, Lake J, Lopresti A, Lu L, Metri NJ, Mischoulon D, Ng CH, Nishi D, Rahimi R, Seedat S, Sinclair J, Su KP, Zhang ZJ, Berk M. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World J Biol Psychiatry. 2022 Jul;23(6):424-455. doi: 10.1080/15622975.2021.2013041. Epub 2022 Mar 21. PMID: 35311615.

Upadhyaya, S., Ståhlberg, T., Silwal, S., Arrhenius, B., & Sourander, A. (2023). Maternal Vitamin D Levels during Pregnancy and Offspring Psychiatric Outcomes: A Systematic Review. International Journal of Molecular Sciences, 24(1), 63. https://doi.org/10.3390/ijms24010063

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South Korean Nationwide Population Study: Prenatal Exposure to Acid-suppressive Medications Not Linked to Subsequent ADHD

Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, are often prescribed during pregnancy to treat heartburn and gastroesophageal reflux disease. 

Research shows changes in the gut microbiome can negatively affect neurodevelopment. Since acid-suppressive medications alter gut microbiota, maternal use during pregnancy may impact offspring’s neurodevelopment. Because PPIs and H2 receptor antagonists readily cross the placental barrier, they could potentially influence fetal neurodevelopment.  

The link between prenatal exposure to acid-suppressive medications and major neuropsychiatric disorders is not well understood. With the use of these medications during pregnancy rising, it is important to assess their impact on children's long-term neurodevelopment. This study examined whether maternal use of acid-suppressive drugs is associated with increased risk of neuropsychiatric disorders in children, using a large, nationwide birth cohort from South Korea. 

South Korea operates a single-payer health insurance system, providing coverage for over 97% of its citizens. The National Health Insurance Service (NHIS) maintains a comprehensive database with sociodemographic details, medical diagnoses, procedures, prescriptions, health examinations, and vital statistics for all insured individuals. 

A Korean research team analyzed data from over three million mother-child pairs (2010–2017) to assess the risks of prenatal exposure to acid-suppressing medications. They applied propensity scoring to adjust for maternal age, number of children, medical history, and outpatient visits before pregnancy, to minimize confounding factors. That narrowed the cohort to just over 800,000 pairs, with half in the exposed group. 

With these adjustments, prenatal exposure to acid-suppressing medications was associated with 14% greater likelihood of being subsequently diagnosed with ADHD. 

Yet, when 151,737 exposed births were compared to the same number of sibling controls, no association was found between prenatal exposure and subsequent ADHD, which suggests unaccounted familial and genetic factors influenced the preceding results. 

The Take-Away:

Evidence of these medications negatively affecting pregnancies is mixed, mostly observational, and generally reassuring when these medications are used appropriately. Untreated GERD and gastritis, however, have known risks and associations with the development of various cancers. With no evidence of an association with ADHD (or for that matter any other neuropsychiatric disorder), there is no current evidence-based reason for expectant mothers to discontinue use of acid-suppressing medications.  

February 6, 2026

The 'Medication Tolerance' Myth in ADHD: What the Evidence Actually Says

For years, a persistent concern has shadowed the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): Does the medication eventually stop working? Patients often report that their symptoms seem to return despite consistent use, leading to "dose escalation" or "medication holidays." A new systematic review from Sam Cortese’s team  published in CNS Drugs finally puts these concerns to the test by synthesizing decades of empirical research.

Before diving into the findings, you must understand two often-confused phenomena:

  • Tachyphylaxis (Acute Tolerance): A rapid decrease in response to a drug, often occurring within a single day (24 hours).
  • Tolerance: A gradual reduction in responsiveness over long-term exposure, requiring higher doses to achieve the original effect.

The review analyzed 17 studies covering over 10,000 individuals, and the results provide a much-needed reality check for the clinical community.

The researchers found preliminary evidence that acute tolerance (tachyphylaxis) can occur within a 24-hour window.

  • Subjective Effects: Studies showed that "drug liking" or feelings of euphoria from stimulants often peak and fade faster than the actual drug concentration in the blood.
  • Clinical Impact: This phenomenon is why some older, flat-release formulations were less effective than modern "ascending" delivery systems (like OROS-methylphenidate), which are designed to overcome this daily dip in efficacy.

The most important finding is that tolerance does not commonly develop to the therapeutic effects of ADHD medication in the long term. In one landmark study following children for up to 10 years, only 2.7% of participants lost their response to methylphenidate without a clear external explanation.  Doses, when adjusted for natural body growth, remained remarkably stable over years of treatment.

Consistent with the lack of therapeutic tolerance, the body does not become tolerant to the physical side effects of stimulants.  Increases in heart rate and blood pressure typically persist for as long as the medication is taken.  This underscores why clinicians must continue monitoring cardiovascular health throughout the entire duration of treatment.

If it’s Not Tolerance, What Is It?

If "tolerance" isn't real, why do some patients feel their medication is failing? The review suggests clinicians look at these alternative explanations:

  1. Natural Symptom Fluctuations: ADHD is not a static condition; symptoms naturally wax and wane over time regardless of treatment.
  2. Limited Compliance: Missed doses or inconsistent timing are often the real culprits behind "failing" efficacy.
  3. Life Events & Transitions: New jobs, academic pressures, or stressful life changes can increase the "functional demand" on a patient, making their current dose feel insufficient.
  4. Co-occurring Conditions: The emergence of anxiety, depression, or substance use disorders can mask or mimic a return of ADHD symptoms.

Why This Matters

These results provide clinicians the confidence to tell patients that their medication is unlikely to "wear out" permanently. Rather than immediately increasing a dose when symptoms flare, the first step should be a "clinical deep dive" into the patient's lifestyle, stress levels, and adherence.

For researchers, the review highlights a major gap: most existing studies are small, dated, or of low quality. There is a dire need for robust, longitudinal studies that track both the brain's response and the patient's environment over several years.

For people with ADHD, while your body might get "used to" the initial "buzz" of a stimulant within hours, its ability to help you focus and manage your life remains remarkably durable over the years.

Population Study Finds Association Between Extended Methylphenidate Use By Children and Subsequent Obesity

South Korean Nationwide Population Study Finds Association Between Extended Methylphenidate Use By Children and Subsequent Obesity–Little to No Effect on Adult Height

South Korean Nationwide Population Study Finds Association Between Extended Methylphenidate Use By Children and Subsequent Obesity–Little to No Effect on Adult Height

The Background:

Concerns remain about how ADHD and methylphenidate (MPH) use might affect children's health and growth, and especially how it may affect their adult height. While some studies suggest disrupted growth and a possible biological mechanism, the impact of ADHD prevalence and MPH use is still unclear. Children with ADHD may develop unhealthy habits – irregular eating, low physical activity, and poor sleep – that can contribute to obesity and reduced height. MPH’s appetite-suppressing effect can lead to skipped meals or overeating. Since growth hormone is mainly released during deep sleep, chronic sleep deprivation could plausibly slow growth and impair height development; however, a clear link between ADHD, MPH use, overweight, and shorter stature has never been firmly established. 

The Study:

South Korea has a single payer health insurance system that covers more than 97% of its population. A Korean research team used the National Health Insurance Service database to perform a nationwide population study to explore this topic further. 

The study involved 34,850 children, of whom 12,866 were diagnosed with ADHD. Of these children, 6,816 (53%) had received methylphenidate treatment, while 6,050 (47%) had not. Each patient with ADHD was precisely matched 1:1 by age, sex, and income level to a control participant without ADHD. The sex ratio was comparable in all groups.The team used Body Mass Index (BMI) as an indicator of overweight and obesity. 

The Results: 

The researchers found that being diagnosed with ADHD was associated with 50% greater odds of being overweight or obese as young adults, and over 70% greater odds of severe obesity (BMI > 30) compared to matched non-ADHD controls, regardless of whether or not they were medicated.

Those diagnosed with ADHD, but not on methylphenidate, had 40% greater odds of being overweight or obese, and over 55% greater odds of becoming severely obese, relative to matched non-ADHD controls. 

Methylphenidate users had 60% greater odds of being overweight or obese, and over 85% greater odds of becoming severely obese, relative to matched non-ADHD controls. 

There were signs of a dose-response effect. Less than a year’s exposure to methylphenidate was associated with roughly 75% greater odds of becoming severely obese, whereas exposure over a year or more raised the odds 2.3-fold, relative to matched non-ADHD controls. Using MPH increased the prevalence of overweight from 43.2% to 46.5%, with a greater prevalence among those using MPH for more than one year (50.5%).

It is important to note that most of this effect was from ADHD itself, with methylphenidate only assuming a predominant role in severe obesity among those with longer-term exposure to the medicine. 

As for height, children with ADHD were no more likely to be short of stature than matched non-ADHD controls. Being prescribed methylphenidate was associated with slightly greater odds (7%) of being short of stature, but there was no dose-response relationship. 

Conclusion: 

The team concluded, “patients with ADHD, particularly those treated with MPH, had a higher BMI and shorter height at adulthood than individuals without ADHD. Although the observed height difference was clinically small in both sexes and age groups, the findings suggest that long-term MPH exposure may be associated with growth and body composition, highlighting the need for regular monitoring of growth.” They also point out that “Despite these findings, the clinical relevance should be interpreted with caution. In our cohort, the mean difference in height was less than 1 cm (eg, maximum −0.6 cm in females) below commonly accepted thresholds for clinical significance.”  Likewise, increases in overweight/BMI were small. 

One problem with interpreting the BMI/obesity results is that some of the genetic variants that cause ADHD also cause obesity.  If that genetic load increases with severity of ADHD than the results from this study are confounded because those with more severe ADHD are more likely to be treated than those with less severe ADHD.

Due to these small effects along with the many study limitations noted by the authors, these results should be considered alongside the well-established benefits of methylphenidate treatment.

February 2, 2026