Key insights and research directions on DHA supplementation: mechanisms, implications, and future perspectives
| Topic | Key insights | Mechanisms | Implications | Challenges and considerations | References |
|---|---|---|---|---|---|
| Nonlinear effects of DHA | The relationship between maternal omega-3 LC-PUFA levels and fetal neurodevelopment may follow a nonlinear pattern. | Lower DHA may support fetal brain development while excessive DHA may lead to oxidative stress. | Excessive DHA intake can impair neuronal function by generating ROS. | Animal studies show that high DHA levels result in oxidative damage, affecting cellular function. | [12, 33, 50] |
| Tailored strategies for maternal intake | Tailored DHA intake strategies are critical to optimize maternal and fetal health. | DHA levels need to be adjusted based on baseline maternal DHA and specific needs for preterm infants. | Ensures adequate DHA intake while preventing over-supplementation, avoiding risks associated with excessive intake. | Customizing DHA intake reduces risks, but high-dose supplementation for women with sufficient omega-3 intake could be unnecessary and risky. | [43, 44, 51, 52] |
| Optimizing DHA supplementation: timing, dosage, and population considerations | Understanding the timing, dosage, and population-specific needs of DHA during pregnancy is essential. | Maternal-fetal nutrient exchange varies due to genetic, nutritional, and metabolic factors. | Identifying optimal DHA and EPA concentrations at different gestational stages is key for neurodevelopment. | Variability in needs across populations makes it difficult to recommend one-size-fits-all supplementation. | [33, 53, 54] |
| Safety and tolerability | Omega-3 supplementation up to 5 g/day of EPA and DHA is considered safe for pregnant and lactating women. | Clinical trials show doses up to 2.7 g/day of DHA are well tolerated with minimal adverse effects. | High doses may increase bleeding risks, but these are rare and typically not clinically significant. | Despite potential bleeding risks, higher doses of DHA during pregnancy may have limited clinical significance. | [22, 43, 55, 56] |
| Limited evidence on lactation | Research on DHA supplementation during lactation is limited. Effects on child cognitive outcomes remain inconclusive. | Evidence linking DHA supplementation during lactation to improved neurodevelopmental outcomes is scarce. | The role of DHA supplementation during lactation is unclear and needs more research. | Variability in study design, sample sizes, and outcomes makes it difficult to assess the impact of DHA during lactation. | [18, 57, 58] |
| Population-specific interventions | DHA supplementation benefits vary based on baseline omega-3 status. Populations with low DHA levels may benefit more. | Lower doses of DHA (300–400 mg/day) may be as effective as higher doses (e.g., 1,440 mg/day) in supporting neurodevelopment. | Personalized nutritional strategies based on baseline omega-3 levels could optimize neurodevelopmental outcomes. | Individual responses to DHA supplementation may vary significantly, requiring personalized approaches to intervention. | [40, 59, 60] |
| Cognitive and behavioral outcomes | DHA supplementation may have lasting cognitive and behavioral effects, such as attention regulation and academic performance in childhood. | DHA supports brain development, influencing attention, academic performance, and social behavior. | Long-term studies are necessary to fully understand DHA’s impact on cognitive and behavioral outcomes. | Findings on long-term cognitive effects of DHA supplementation are inconsistent, and further studies are needed to clarify these effects. | [40, 61–63] |
| Neural plasticity and lifelong development | DHA supports neural plasticity, neurogenesis, and synaptic plasticity, suggesting long-term benefits for brain health and cognitive development. | DHA enhances neural circuits, supporting lifelong cognitive and behavioral development. | Supplementation during critical brain development periods may influence cognitive and behavioral trajectories. | The full extent of DHA’s impact on long-term brain development remains understudied, and more research is needed. | [33, 64–66] |
DHA: docosahexaenoic acid; LC-PUFA: long-chain polyunsaturated fatty acids; ROS: reactive oxygen species; EPA: eicosapentaenoic acid
