Effect of n−3 PUFA supplementation on cognitive function throughout the life span from infancy to old age: a systematic review and meta-analysis of randomized controlled trials

Background: n−3 PUFAs play an important role in cognitive function.

Objective: The objective was to investigate the effect of n−3 PUFA supplements on cognitive development, function, and decline throughout the life span.

Design: The study included randomized controlled trials and provided ≥3 mo of treatment. Potential studies were independently screened in duplicate, and study characteristics and outcomes were extracted. A meta-analysis was performed by using fixed- or random-effects models. The results are presented as standardized mean differences (SMDs) with 95% CIs.

Results: Of the 3692 citations retrieved, 34 studies of a total of 12,999 participants (1031 infants, 1517 children, 3657 adults, and 6794 elderly individuals) were included. Compared with placebo, n−3 PUFA supplements significantly improved the cognitive development in infants, including the Mental Development Index (SMD: 0.33; 95% CI: 0.15, 0.52), the Psychomotor Development Index (0.27; 95% CI: 0.09, 0.45), and language (0.27; 95% CI: 0.13, 0.42), motor (0.29; 95% CI: 0.14, 0.43), and cognitive (0.31; 95% CI: 0.16, 0.45) abilities. However, n−3 PUFAs did not promote cognitive function in terms of composite memory, executive function, and processing speed domains in children, adults, and the elderly, except for the attention domain. No association was found between n−3 PUFA intake and improvements in cognitive performance in terms of recognition, immediate and delayed word recall, digit span backward and forward tests, rapid visual information processing, verbal fluency, and simple and choice reaction times. In addition, n−3 PUFA supplements were not associated with improvements in cognitive decline or with any effects on Alzheimer disease in elderly people.

Conclusions: n−3 PUFA supplements may significantly improve cognitive development in infants but do not improve cognitive performance in children, adults, or the elderly. n−3 PUFA intake, especially that of DHA supplements, may benefit cognitive development during infancy.


Alex’s Notes: I’m going to try and stay brief. There is seemingly relentless hype around fish oil and omega-3s – and not without good reason – but we are still premature in understanding if that hype is deserved. Many studies look into the benefits of omega-3 fatty acids on cognition in the elderly, general health in the general public, and neural development in children, so what effect does age have on the benefits of omega-3 supplementation? It is a question this meta-analysis sought to answer.

The researchers focused only on studies that used omega-3 supplements (so any omega-3 diet trials were excluded) for durations greater than three months. Moreover, if the omega-3s were administered with other nutrients then those trials were excluded as well. Cognition throughout life was assessed via numerous questionnaires.

  1. The Mental Development Index (MDI) and the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development were taken as the primary outcomes during infancy, in addition to language, motor, and cognitive abilities as secondary outcomes.
  2. Composite memory, executive function, attention, and processing speed were used as the representative cognitive domains and were regarded as the primary outcomes during the child, adult, and the elderly stages of the life span. To further describe these domains, other secondary outcomes, including recognition, immediate word recall, delayed word recall, digit span backward, digit span forward, the Stroop effect, rapid visual information processing, verbal fluency, simple reaction time, and choice reaction time were also included.
  3. The Mini-Mental State Examination (MMSE) result was used as a primary outcome to screen for cognitive decline in elderly people. Considering the prevalence of Alzheimer’s Disease (AD), the Cognitive Subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog) was an additional secondary outcome.

Thirty-four randomized controlled trials were included for review, of which seven investigated infants (n=1031), 15 investigated children and adults (n=5174), and 12 investigated the elderly (n=6794). I summarized the group characteristics in the table below.



Children & Adults


# of RCTs









.07 (0-18) months

22 (9-30.5) years

71 (69-74) years

Female sex




Treatment duration

7.9 months

4.5 months

6.1 months

n-3 PUFA dose

35% of formula total fatty acids

900 mg/day

1400 mg/day

Cognitive Function, are thou better?

According to the meta-analysis, it is in infants. Omega-3 supplementation significantly improved MDI and PDI by 33% and 27%, respectively, compared to the control groups. Moreover, supplementation led to a significant improvement in all aspects of language (27%), motor (29%), and cognitive (31%) abilities relative to placebo. To be fair, this is not entirely surprising given that EPA and especially DHA play such a central role in neural development and infant growth. No doubt, DHA is capable of influencing gene transcription and modifying the fluidity and thickness of neuronal membranes, ultimately affecting receptor function and brain function.

The results are less encouraging as we age. Out of all the tested variables (from #2 and #3 above), only attention was significantly improved (29%) in the elderly from treatment with omega-3 supplementation. This is despite many of the included trials reporting increased levels of plasma omega-3 concentrations. Still though, most of the trials were from developed countries, so it would be interesting to see how economic status plays a role. Moreover, omega-3 rich diets were excluded from analysis, and thus we cannot extrapolate these results to fish-heavy diets such as the Mediterranean diet, thus raising another important question: would it make a difference?


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