The Orthomolecular Correction of Metabolic Imbalances Found in ADHD and the Analysis of Pyrroles in Patients with Psychiatric Disorders

The Riordan clinic is dedicated to Othomolecular Medicine: the idea that variations in key nutrient levels from person to person can have profound effects on wellness or illness. We conducted research to study the effects of fatty acids, essential and toxic metals on mental illness (such as attention deficit hypersensitivity disorder, ADHD).

ADHD affects approximately two million American children, and this condition has grown to become the most commonly diagnosed behavioral disorder of childhood. According to the National Institute of Mental Health (NIMH), the cause of the condition, once called hyperkinesis, is not known.

The cause of ADHD is generally acknowledged to be multifactorial, involving both biological and environmental influence. Molecular, genetic, and pharmacological studies suggest the involvement of the neurotransmitter systems in the pathogenesis of ADHD. Polymorphic variants in several genes involved in regulation of dopamine have been identified, and related neurotransmitter pathways alterations are reported to be associated with the disease.

Nutritional deficiencies, including deficiencies in fatty acids (EPA, DHA), the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder.

The brain is nearly sixty percent fat, and the supply of fatty acids plays a critical role in brain functioning.  The omega-3 fatty acid docosahexaenoic acid (DHA) is thought to be particularly important: DHA deficiency is associated with ADHD, depression, and Alzheimer’s disease, and it is a key component for synthesis of serotonin.

This study was based on data extracted from our patient history database covering a period of over ten years. We performed laboratory tests in 116 patients 2.7-25 years old with a diagnosis of ADHD. Patients were followed from 3 month to 3 years. We compared the distributions of fatty acids, essential metals, and the levels of metabolic stress factors with established reference ranges before and after interventions. In addition, we analyzed the association between toxic metal concentrations and the levels of essential metals. Our analysis demonstrated:

• In ADHD subjects, the Ω6: Ω3 ratio was abnormally high (above normal range) for the vast majority of subjects. The essential Ω3 acid EPA (eicosapentanoic acid) was below the normal range in the majority of ADHD subjects.

• Pyrrole (a stress indicator) levels and iron levels were elevated in ADHD subjects (compared to normal ranges) while magnesium and zinc levels were below normal. Histamine levels tended to be low in ADHD subjects.
• ADHD subjects with the most elevated levels of toxic metals (such as aluminum, copper, mercury, and lead) have lower relative levels of zinc, a key mineral for proper brain function.

According to the clinical data, the metabolic correction of ADHD by supplementation with minerals, vitamins, essential fatty acids, and amino acids can ameliorate ADHD symptoms. Eighty percent (80%) of children who were treated from several weeks to 1-2 years, demonstrated improvement of metabolic stress level, measured by pyrroles. For these patients the levels of EPA were increased and the omega-6/omega-3 ratio was improved.

We published our results in journals:

• Metabolic correction for attention deficit/hyperactivity disorder: A biochemical-physiological therapeutic approach. Mikirova NA, Rogers AM, Taylor PR, Hunninghake RE, Miranda-Massari JR, Gonzalez MJ  Functional Foods in Health and Disease, 2013, 3(1):1-20 (Jan 2013)
• The orthomolecular correction of metabolic imbalances found in attention deficit hyperactivity disorder: a retrospective analysis in an outpatient clinic.  Mikirova NA, Casciari JJ, Hunninghake RE. JOM, Volume 28, Number 2, 2013

We also examined a variety of nutritional parameters in patients with psychiatric disorders, focusing on histamine levels and urine pyrrole levels.  Pyrrole, a byproduct of hemoglobin syntheses, is associated with schizophrenia and zinc deficiency, while histamine is associated with inflammation.  According to our data, urinary pyrrole concentrations tended to be high in patients with mental illnesses, but elevated level of pyrroles was not specific for only these patients. We found evidence of an allergy related component in the fact that elevated pyrrole levels were significantly more prevalent in subjects with elevated histamine values. A role of intestinal bacteria, or imbalances in intestinal bacterial metabolism, was also suggested   based on the found relationship between elevated pyrrole levels and elevations in indicans and urobilinogens. In addition, our data demonstrated that subjects with severely elevated pyrrole levels were deficient in nutrients such as zinc, vitamin B3, and vitamin C.

Our analysis of the Riordan Clinic patient database suggested that pyroluria is relevant to a variety of stress and illness conditions, and, to the extent that these stresses are relevant in mental illness, is relevant to many mentally ill subjects. Abnormal pyrrole excretion appears to be an indicator of oxidative stress, infection, intoxication, or improper digestion. Moreover, our data suggest that it may be possible to reduce pyroluria using a supplementation treatment regimen such as that employed at the Riordan clinic.

Our analysis was published in articles:

• Clinical Test of Pyrroles: Usefulness & Association with Other Biochemical Markers. Nina Mikirova. Clinical Medical Reviews and Case Reports, 2015, 2:2

 Cross-Sectional Analysis of Pyrroles in Psychiatric Disorders. Nina Mikirova, Journal of Orthomolecular Medicine, 2015, Vol 30, No 1: 1-8