Overview

Zinc is a cofactor in neurotransmitter synthesis and signaling and supports normal brain function. It is naturally abundant in oysters and other shellfish, red meat, poultry, dairy, beans, nuts, and seeds; its absorption is reduced by phytates in whole grains and legumes. In humans, zinc supports hundreds of enzymes and is vital for DNA/RNA synthesis, immune function, wound healing, and neural signaling. Deficiency is associated with changes in cognitive and psychological function; maintaining adequate zinc status is part of the foundation for attention and memory. (We dose within typical dietary-supplement ranges and below upper limits. Typical recommended dietary allowances are ~11 mg/day for adult men and ~8 mg/day for adult women; the U.S. adult tolerable upper intake level (UL) is 40 mg/day (total from food + supplements)).

It regulates dopamine synthesis and receptor activity, and plays a role in LTP–the process underlying memory formation. Cognitive boosts (d≈0.1) likely reflect correcting deficiency rather than benefits from supra-normal levels. More is not better–too much zinc can lead to worsened memory (in mice) and copper deficiency.

More in-depth mechanisms of action:

• Synaptic zinc modulation: A vesicular pool of zinc is co-released with glutamate and modulates NMDA and AMPA receptors. This tuning improves signal-to-noise, supports long-term potentiation, and protects against excitotoxic overdrive during sustained cognitive load.
• Dopamine transporter (DAT): Zinc binds an extracellular site on DAT and can inhibit reuptake, functionally raising synaptic dopamine availability relevant to motivation, attention, and executive control.
• Neurotrophic and redox support: Zinc participates in BDNF signaling, myelin and membrane protein maintenance, and serves as a cofactor for Cu/Zn-SOD, helping temper oxidative stress that impairs cognitive performance.

Clinical studies supporting use (focus-relevant populations)

A) Healthy or mixed adults
• ZENITH trial (Maylor et al., 2006): 387 adults aged 55–87 randomized to 0, 15, or 30 mg/day zinc (gluconate) for 6 months. Broad cognitive battery showed no consistent between-group advantages vs placebo in generally well-nourished participants.

B) Older adults with memory complaints
• Warthon-Medina et al., 2015 systematic review/meta-analysis: Across RCTs and observational studies in adults and children, associations between zinc status/intake and cognition were mixed; baseline deficiency and study heterogeneity likely explain variable findings. Adult RCT evidence remains limited, with suggestive benefit mainly when repleting low status.

C) ADHD (youth)
• Bilici et al., 2004: 12-week, double-blind RCT of zinc sulfate monotherapy in children with ADHD. Zinc outperformed placebo on hyperactivity/impulsivity and socialization domains; effect on inattention was smaller.
• Akhondzadeh et al., 2004: 6-week, double-blind RCT adding zinc sulfate to methylphenidate vs methylphenidate alone. Adjunctive zinc produced greater symptom improvement over time; tolerability was good.
• Arnold et al., 2011: Double-blind pilot using zinc glycinate 15 or 30 mg/day with or without d-amphetamine. Symptom outcomes were equivocal, but 30 mg/day zinc reduced the optimal stimulant dose requirement, suggesting adjunctive value for some patients.

Dose-relationships:
• Goldmind:Focus -- 15 mg/day elemental zinc (bisglycinate).
• ADHD RCTs -- ranged from ~15 mg elemental/day as adjunct (Akhondzadeh) to higher salt doses as monotherapy (Bilici; elemental not always reported), and 15–30 mg/day in adjunct trials (Arnold).
• Healthy older adults -- 15 or 30 mg/day showed neutral cognitive results when baseline status was likely adequate (ZENITH).

Safety
• Typical effects: Occasional metallic taste, mild GI upset, or nausea. Taking with food helps.
• Long-term balance: Chronic high zinc can depress copper status and HDL. Respect the adult tolerable upper intake level and include copper in long-term higher-zinc regimens.
• Interactions: Separate from tetracyclines and quinolones by several hours. Large doses of iron taken simultaneously may reduce zinc absorption.

References
• Warthon-Medina M, et al. Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis. Eur J Clin Nutr. 2015;69:649–661.
• Maylor EA, et al. Effects of zinc supplementation on cognitive function in healthy older adults: the ZENITH study. J Gerontol A Biol Sci Med Sci. 2006;61(11):1196–1203.
• Bilici M, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of ADHD. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(1):181–190.
• Akhondzadeh S, Mohammadi MR, Khademi M. Zinc sulfate as adjunct to methylphenidate for ADHD in children: a double-blind randomized trial. BMC Psychiatry. 2004;4:9.
• Arnold LE, et al. Zinc for ADHD: placebo-controlled double-blind pilot trial alone and combined with amphetamine. J Child Adolesc Psychopharmacol. 2011;21(1):1–19.
• Rucklidge JJ, et al. Vitamin–mineral treatment of ADHD in adults: double-blind randomized controlled trial. Br J Psychiatry. 2014;204(4):306–315.
• Representative observational examples on zinc status and cognition in older adults: Kheirkhah F, et al. Shiraz E-Med J. 2017;18(7):e13093. Marchetti MF, et al. Ciênc Saúde Coletiva. 2022;27(7):2805–2816.