The Multifaceted Role of DHA During Toddlerhood: Supporting Synapse Formation, Early Neural Development, Learning Ability, Memory, and Cognitive Function

Toddlerhood is a critical period of neurodevelopment characterized by rapid maturation of language, memory, attention, executive function, motor coordination, emotional regulation, and social cognition, supported by coordinated processes including neuronal differentiation, dendritic arborization, axonal growth, synaptogenesis, myelination, neurotransmission, and activity-dependent synaptic plasticity. Docosahexaenoic acid (DHA; 22:6 n-3), a long-chain omega-3 polyunsaturated fatty acid highly enriched in neuronal and retinal membranes, plays essential structural, metabolic, and signaling roles in the developing brain. Although brain DHA accumulation is greatest during late gestation and the first two years of life, membrane remodeling and cognitive maturation continue throughout toddlerhood, making adequate DHA intake an ongoing nutritional priority. Brain DHA status depends on dietary intake, lipid transport, genetic factors, developmental stage, and overall nutritional status because endogenous synthesis from alpha-linolenic acid is limited. Mechanistically, DHA enhances neuronal membrane fluidity, receptor function, neurotransmission, neurite extension, dendritic development, synaptic protein expression, and long-term potentiation, while increasing phosphatidylserine-mediated activation of neuronal survival pathways. DHA is also converted into bioactive mediators, including synaptamide, protectins, and resolvins, which promote neurogenesis, synaptogenesis, and regulation of neuroinflammation. Efficient transport across the blood–brain barrier via the MFSD2A transporter further underscores the importance of adequate DHA availability for optimal brain function. Collectively, these mechanisms provide strong biological plausibility for DHA involvement in synapse formation, neural maturation, learning, memory, attention, and cognitive development. However, evidence from human intervention studies remains inconsistent. While some studies have reported associations between higher DHA status and improved vocabulary, reading, learning, or cognitive performance, several randomized controlled trials in toddlers and preschool children have found no significant improvements in standardized developmental outcomes following DHA supplementation, particularly among adequately nourished populations. These discrepancies likely reflect differences in baseline DHA status, dietary quality, dosage, intervention duration, developmental timing, prematurity, genetic variation, socioeconomic factors, and outcome measures. This narrative review synthesizes current evidence regarding the physiological significance, molecular mechanisms, and functional effects of DHA during toddlerhood, highlighting the contrast between robust mechanistic evidence and mixed clinical findings. Overall, ensuring adequate dietary DHA should be considered an important component of balanced toddler nutrition, particularly in populations at risk of insufficient intake or developmental vulnerability, while recognizing that optimal neurodevelopment also depends on adequate energy, protein, iron, iodine, choline, sleep, responsive caregiving, language stimulation, physical activity, and enriched learning environments. Further well-designed toddler-specific trials are needed to identify the populations most likely to benefit and to establish the optimal dose, duration, and cognitive outcomes of DHA supplementation.