ADHD Premium Panel

Homocysteine is a sulphur-containing amino acid formed during methionine metabolism. Its remethylation to methionine requires folate and vitamin B12, and its transsulphuration to cysteine requires vitamin B6. Elevated plasma homocysteine reflects impaired methylation capacity and has been linked to endothelial dysfunction, neuroinflammation, and altered neurotransmitter synthesis.

In the context of attention-deficit/hyperactivity disorder, elevated homocysteine may signal methylation deficits that compromise monoamine synthesis and myelin integrity. Functional practitioners use it as a marker of B-vitamin status and oxidative stress that may contribute to cognitive and behavioural dysregulation.

Methylmalonic acid accumulates when vitamin B12–dependent conversion of methylmalonyl-CoA to succinyl-CoA is impaired. Serum or plasma MMA is the most sensitive marker of cellular B12 deficiency, rising before haematological changes or macrocytosis appear.

Vitamin B12 is required for myelination and neurotransmitter metabolism. Subclinical B12 deficiency, reflected by elevated MMA, may present with cognitive slowing, mood dysregulation, and attention difficulties that overlap with or exacerbate ADHD symptoms.

Folate is the carrier of one-carbon units in methylation reactions, including remethylation of homocysteine to methionine and synthesis of tetrahydrobiopterin, the cofactor for tyrosine and tryptophan hydroxylases that produce dopamine and serotonin.

Folate deficiency impairs dopamine synthesis and methylation, pathways central to ADHD pathophysiology. Serum folate reflects recent intake; red-cell folate (when available) better reflects tissue stores, but serum folate is widely used for screening.

Cobalamin is a cofactor for methionine synthase and methylmalonyl-CoA mutase, linking it to methylation, myelin synthesis, and mitochondrial metabolism. Serum B12 may be low-normal or frankly low in cellular deficiency, so interpretation with MMA is preferred.

B12 deficiency presents with neuropsychiatric symptoms including cognitive slowing, fatigue, and mood disturbance that may mimic or worsen inattentive ADHD. Children and adults with restricted diets or malabsorption are at risk.

The major circulating form of vitamin D, 25(OH)D is hydroxylated in the kidney to the active hormone calcitriol. Vitamin D receptors are widely expressed in the central nervous system, where the hormone modulates neurotransmitter synthesis, neuroplasticity, and inflammation.

Observational studies link low vitamin D to ADHD symptoms and executive dysfunction. Though causality is not established, screening for deficiency is straightforward and supplementation is low-risk, making 25(OH)D a routine component of integrative ADHD assessment.

Ferritin is the principal intracellular iron-storage protein; serum ferritin reflects total-body iron stores except in the presence of inflammation, which raises it as an acute-phase reactant. Iron is a cofactor for tyrosine hydroxylase and is essential for dopamine synthesis and myelin production.

Low ferritin, even without overt anaemia, is associated with restless-leg syndrome and has been linked to increased ADHD symptom severity and reduced response to stimulant medication. Paediatric and adult guidelines recommend screening ferritin in ADHD evaluation.

TSH, released by the anterior pituitary, stimulates thyroid hormone synthesis and secretion. Its concentration reflects negative feedback from circulating free T4 and T3 and is the most sensitive first-line marker of thyroid dysfunction.

Both hypothyroidism and hyperthyroidism present with cognitive and behavioural symptoms — inattention, fatigue, and slowed processing in hypothyroidism; restlessness, anxiety, and impulsivity in hyperthyroidism — that overlap with ADHD. Screening TSH excludes thyroid disease as a contributor or mimicker.

Free T4 is the unbound, biologically active fraction of thyroxine, the principal secretory product of the thyroid. It provides direct assessment of thyroid hormone availability, complementing TSH when subclinical or central thyroid dysfunction is suspected.

Free T4 helps distinguish primary hypothyroidism (low T4, high TSH) from central hypothyroidism and clarifies borderline TSH results. Thyroid hormone is essential for neurodevelopment, myelination, and the regulation of cerebral metabolism.

Red-cell magnesium reflects intracellular stores more reliably than serum magnesium, which is homeostatically regulated and often normal despite tissue depletion. Magnesium is a cofactor for over 300 enzymes, including those governing ATP synthesis, neurotransmitter release, and N-methyl-D-aspartate receptor modulation.

Magnesium deficiency is associated with hyperexcitability, anxiety, sleep disturbance, and impaired attention. Small trials suggest supplementation may reduce ADHD symptoms, particularly hyperactivity. RBC magnesium is preferred over serum for detecting subclinical deficiency.

Zinc is a trace element involved in neurotransmitter synthesis and modulation, synaptic plasticity, and antioxidant defence. Serum zinc is not a perfect marker of body stores — it is influenced by inflammation, albumin, and diurnal variation — but remains the most practical screening test.

Zinc deficiency and low-normal serum zinc have been reported more frequently in children with ADHD, and some trials suggest zinc supplementation (particularly in deficient populations) may modestly reduce hyperactivity and impulsivity. Screening is common in integrative ADHD evaluation.

Copper is essential for dopamine-beta-hydroxylase, the enzyme that converts dopamine to noradrenaline. Serum copper largely reflects caeruloplasmin-bound copper and is raised by oestrogen and inflammation. Free (non-caeruloplasmin) copper is rarely measured in routine practice.

Copper excess, relative copper:zinc imbalance, or (rarely) Wilson disease can present with neuropsychiatric symptoms. In ADHD panels, copper is measured to assess the copper:zinc ratio, which some functional practitioners interpret as a marker of oxidative stress and monoamine balance.

The molar ratio of serum copper to zinc is a derived marker reflecting the balance of two trace elements that antagonise each other and modulate oxidative stress, immune function, and neurotransmitter metabolism.

An elevated copper:zinc ratio has been proposed as a functional marker of oxidative stress and is sometimes associated with anxiety, hyperactivity, and mood dysregulation. Its clinical utility in ADHD is debated and not part of mainstream guidelines.