Efficacy of Docosahexaenoic Acid Supplementation in Patients with Age-related Cognitive Decline, A Systematic Review and Meta-analysis
Musa Masood1, Saad Masood2, Muhammad Hamza Khalid1, Asna Moghis1, Abdul Wasay1, Ayesha Khan1, Muhammad Zubair1, Huzaifa Nawaz3, Hafiz Sohail Ashraf4
1Allama Iqbal Medical College, Lahore, Pakistan, 2Allama Iqbal Medical College, 3Services Institute of Medical Sciences (SIMS), Ghaus-ul-Azam Jail Road, Lahore, Pakistan 54000, 4Carle foundation Hospital Urbana Illinois
Objective:
To assess the efficacy of docosahexaenoic acid (DHA) supplementation versus placebo in patients with age-related mild cognitive impairment (MCI), focusing on cognition and serum biomarkers.
Background:
Age-related MCI, in the absence of overt neurodegenerative disease, is an increasing public health concern due to its effects on function and quality of life. DHA, an omega-3 fatty acid abundant in neuronal membranes, has neuroprotective, anti-inflammatory, and synaptic roles, but evidence for its clinical benefit in MCI remains inconsistent.
Design/Methods:
Following PRISMA guidelines, we performed a systematic review and meta-analysis. Four databases (PubMed, Google Scholar, Cochrane Library, and ClinicalTrials.gov) were searched up to September 2025. Eligible studies assessed MMSE, WAIS-RC subtests (IQ, Digit Span, Information, Arithmetic), serum DHA, amyloid-β 42/40, or geriatric depression scores. Data was pooled using a random-effects model (RevMan 5.4), with subgroup analyses at 3, 6, and 12 months. Heterogeneity was assessed using I² statistics.
Results:
Nine trials including 1,381 participants (692 DHA, 689 placebo) were analyzed. DHA supplementation significantly increased serum DHA (MD 7.68, 95% CI 6.69–8.66; p<0.00001, I²=84%) and reduced amyloid-β 40 (MD −1.20, 95% CI −1.79 to −0.62; p<0.0001, I²=84%) and amyloid-β 42 (MD −3.15, 95% CI −3.50 to −2.79; p<0.00001, I²=71%). Subgroup analyses confirmed benefits at 6 and 12 months. <br bcx0"="">DHA improved overall IQ (MD 3.07, 95% CI 0.27–5.87; p=0.03, I²=96%) and Information subtest scores (MD 0.33, 95% CI 0.01–0.64; p=0.04, I²=97%). MMSE showed short-term benefit at 3 months (p=0.01) but no sustained effect (MD 0.78, p=0.07). Digit Span and Arithmetic showed no benefit, and depression scores were unaffected (p=0.88).
Conclusions:
DHA supplementation in age-related MCI improves serum DHA and lowers amyloid-β, with modest gains in selective cognitive domains. Global cognition, working memory, and mood remain unaffected. Further trials are needed to determine whether these biomarker changes translate into meaningful clinical outcomes.
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