Only for HIFSA SHAUAKT

contentserver.asp-3.pdf

Home >Psychology homework help >Only for HIFSA SHAUAKT

Review

Omega-3 polyunsaturated fatty acids and cognition throughout the lifespan: A review Justin E. Karr, Joel E. Alexander, Robert G. Winningham

Psychology Division, Western Oregon University, Monmouth, OR, USA

With increasing awareness of the effects of nutrition on physical and mental health, researchers have begun to further investigate the benefits of omega-3 polyunsaturated fatty acids (n-3 PUFA) on health and the brain; however, these benefits remain unclear across different age groups. Objectives: The purpose of this article is to summarize the current evidence on the cognitive effects of n-3 PUFA throughout the lifespan. Methods: An exhaustive review of the literature on the effects of n-3 PUFA on various aspects of cognition, across the lifespan, was conducted. Results: The research suggests that n-3 PUFA positively affect pre-natal neurodevelopment; however, this cognitive-enhancing effect might diminish post-natally with maturation, as no research on child populations has clearly tied dietary n-3 PUFA to improved cognitive skills. Overall, few studies have examined the cognitive effects of n-3 PUFA through childhood, young adulthood, and middle age. At later ages, multiple studies found evidence suggesting that n-3 PUFA can protect against neurodegeneration and possibly reduce the chance of developing cognitive impairment. Discussion: Age groups central to the lifespan require further investigation into the effects that n-3 PUFA might have on their cognitive skills. The research examining the extremities of the lifespan provides evidence that n-3 PUFA are essential for neurodevelopment and cognitive maintenance in older adulthood. Future research must develop more consistent methodologies, as variable dosages, supplementation periods, and cognitive measures across different studies have led to disparate results, making the evidence less comparable and difficult to synthesize.

Keywords: Cognition, Lifespan, Omega-3 polyunsaturated fatty acids, Neuroprotection

Recent research has found relationships between dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) and the prevalence or treatment of 5 of the 10 leading causes of American deaths in 2006.1

These causes of mortality include cardiovascular disease,2 cancer,3 cerebrovascular accidents,4 diabetes mellitus,5 and Alzheimer’s disease.6 To counteract such health epidemics, policymakers and advisory organizations have worked to improve consumers’ knowledge about nutrition and other lifestyle beha- viors that may affect quality of life.7 Alongside a wide- spread concern for a health-oriented diet, nutrition researchers have begun investigating the nutrients necessary for optimal brain health and cognition. Cognitive-nutritional research has rapidly accumu-

lated in recent years, branching into a new field known as neuro-nutrition, which attempts to further our understanding of the relationship between

nutrition and brain health. Scientists have become increasingly interested in the relationship between human health and the essential fatty acids (EFA), meaning the omega-3 (n-3) and omega-6 (n-6) PUFA which appear mutually necessary for a ben- eficial human diet. Numerous researchers have repeat- edly found novel and potentially significant results related to n-3 PUFA in the diet.2,8–11

Biological components to PUFA The biochemistry of fatty acids helps explain the dietary need that humans have for PUFA. Typically, fatty acids have an even number of carbon atoms, ranging from 16 to 26 total carbon atoms along the hydrocarbon chain.12 Fatty acids with only single bonds are con- sidered saturated fatty acids, while fatty acids with at least one double bond between carbon atoms are con- sidered unsaturated; therefore, fatty acids with multiple double bonds between carbon atoms are labeled poly- unsaturated. These double bonds create kinks in the hydrocarbon chain disabling the fatty acids from

Correspondence to: Justin Elliott Karr, Psychology Division, Western Oregon University, 345 N. Monmouth Avenue Monmouth, OR 97361, USA. Email: [email protected]

mailto:[email protected]

condensing enough to solidify at room temperature, while saturated fatty acids retain straight hydrocarbon chains, allowing them to compact enough to solidify at room temperature.13

Certain PUFA have piqued the attention of research- ers, specifically docosahexaenoic acid (DHA) and eico- sapentaenoic acid (EPA). DHA and EPA are both n-3 PUFA, with the omega value denoting the location of the first double bond along the carbon chain. DHA and EPA are synthesized from the n-3 precursor alpha- linolenic acid (ALA).12,14,15 Endogenously, EPA can be converted to docosapentanoic acid and then DHA through the addition of two carbon atoms and desatura- tion of a bond along the carbon chain.16 In addition to n-3 PUFA, n-6 PUFA also has a critical place in the human diet. The n-6 PUFA arachidonic acid (AA) is synthesized from the precursor linoleic acid (LA), and accordingly both ALA and LA are essential for the human diet, as neither is synthesized endogenously by humans.12,15 Moreover, the n-3 and n-6 families cannot be interconverted, as mammalian cells lack the converting enzyme n-3 desaturase.15,17 Therefore, both n-3 and n-6 PUFA must have a place in the diet in order for humans to receive the proper nutrients from each variety of fatty acid. The nutritional importance of the EFA has a rich

evolutionary history that is mostly ignored in the modern diet due to increased consumption of satu- rated fatty acids and reduced consumption of n-3 PUFA.18 Evaluations of paleolithic and modern hunter-gatherer nutritional habits suggest that humans evolved while consuming a diet much lower in saturated fatty acids than modern diets and small but nearly equal amounts of n-3 and n-6 PUFA.19

This low dietary ratio of the EFA among human ancestors continued for millions of years, leading to genetic changes during the evolution of the genus Homo.17 However, the current western diet has disre- garded the traditional diet of humans, grossly increas- ing the dietary ratio of the EFA over the last 150 years, with n-3 to n-6 ratios estimated as high as 1:15–20 in the modern western world.17,18,20

The dramatic alteration of the n-3 to n-6 PUFA ratio might have a greater influence on the nervous system than the levels of either fatty acid alone. Among animal studies a 1:4 ALA to LA ratio effec- tively enhanced learning performance, pain threshold, sleep quality, and thermoregulation.21 If the ratio becomes too large, it can affect both the absorption of the nutrients and the overall health of the individ- ual. According to one group of researchers, the EFA compete for absorption leading to increased n-6 PUFA absorption alongside decreased DHA absorp- tion.22 The increased ratio notably affects absorption and nervous system physiology, but also has ties to sig- nificant health disparities.

Mammalian cells cannot convert n-6 to n-3 without the converting enzyme n-3 desaturase.17 A group of researchers recombined a gene for this enzyme into human breast cancer cells through an adenovirus and effectively reduced the n-3 to n-6 PUFA ratio to nearly 1:1.23 After reducing the ratio, cancer cells expressing the enzyme n-3 desaturase with the low PUFA ratio underwent apoptotic death, while the control cancer cells with a high PUFA ratio continued to proliferate. The large PUFA ratio has a notable influence on the nutrition of western populations, and the relationship between n-3 PUFA and better health outcomes might result from a reduced ratio.15

PUFA and health disparities With this relatively recent distortion of the human diet, researchers have begun to investigate the relationships between rates of certain diseases and n-3 PUFA con- sumption, discovering significant relationships between malnourished populations (consuming little n-3 PUFA) and an array of diseases and disorders. In an epidemiological study, one research team sur- veyed 57 972 Japanese men and women with a food frequency questionnaire (FFQ), hypothesizing that reported n-3 PUFA intake, most commonly associated with the consumption of fish, would have an inverse relationship with incidents of various heart problems.2

After a 12.7-year follow-up on the participants, the researchers found an 18–19% lower risk of overall mortality from cardiovascular disease among fish and n-3 PUFA consuming individuals, implying some protective qualities of n-3 PUFA for the heart. Another group of researchers found that the con-

sumption of walnuts, a botanical source of n-3 PUFA, provides optimal proportions of fat intake without adverse effects in patients with diabetes melli- tus.5 Examining the relationship between n-3 PUFA and cancer, a research team hypothesized that n-3 PUFA would protect against carcinogenesis and inflammation in the prostate.3 In their design, the researchers used an FFQ to survey the diets of 466 men with aggressive prostate cancer alongside 477 control men. Associating n-3 PUFA intake with genes related to the cancer, they discovered cancer- protective qualities of n-3 PUFA in the COX-2 enzy- matic pathway. Among cancer, diabetes mellitus, and heart disease, many other diseases have propagated throughout recent history in industrialized countries at astounding rates seemingly due to mass malnourish- ment17,18 of generally overnourished western populations.24

Another deadly disease associated with n-3 PUFA deficiency is Alzheimer’s disease.6 Scientists have observed n-3 PUFA as being efficacious in treating dementia and age-related cognitive declines. After the age of 65, incidences of Alzheimer’s disease

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5 217

double across the population every 5 years, with half of the population over 100 years of age afflicted with the disease.25 No cure for Alzheimer’s disease exists, but some studies have found ways to delay or avoid the onset of cognitive decline by changing the diet. An elderly population consuming fish at least once weekly showed a 60% lower risk of developing Alzheimer’s disease over a 4-year period,6 while another study associated frequent fish consumption during midlife with better semantic memory and cog- nitive function in later life.8

Similarly, a longitudinal study investigated the relationship between PUFA consumption and cogni- tive decline, tracking 95 elderly participants (between 65 and 84 years of age) across 8.5 years.11 The researchers used an FFQ and the mini-mental status exam to measure PUFA intake and cognition, respect- ively. They noticed that individuals with a typical Mediterranean diet, high in PUFA, performed signifi- cantly better cognitively than individuals consuming less PUFA. A worldwide group of researchers exten- sively examined the prevalence of dementia in associ- ation with fish and meat intake across an international pool of 14 960 participants over 65 years of age.26 Participants came from five Latin American countries, China, and India, and in all countries assessed aside from India, reported fish intake inversely correlated with dementia prevalence. Overall, the research seems to indicate a potential pro- tective effect against cognitive decline associated with higher n-3 PUFA consumption.

PUFA and mental health Researchers have also observed links between n-3 PUFA and various pathologies or cognitive disorders that afflict humans throughout their lifespan. Some efficacy may exist for n-3 PUFA in the treatment of certain developmental disorders. A trial study of 75 patients diagnosed with attention deficit/hyperactivity disorder (ADHD) assessed the effects of 174 mg DHA, 558 mg EPA, and 60 mg gamma LA on the treatment of ADHD symptoms.27 The study involved a 3-month placebo-controlled phase and then a second 3-month phase where all participants received n-3 PUFA. After the first 3 months, 26% of the n-3 PUFA group experienced a 25% or greater reduction in symptoms; and after the second 3 months, 47% of all participants experienced a 25% or greater reduction in symptoms. In addition to ADHD, researchers have investigated

the relationship between n-3 PUFA and autism spec- trum disorder. Researchers have begun to experimen- tally assess the efficacy of n-3 PUFA in the treatment of autism. One research team supplemented children with autism for 4 weeks with 700 mg DHA and 840 mg EPA per day.28 This pilot study reported that

when compared with a placebo group, children with autism supplemented with n-3 PUFA showed signifi- cant improvement in hyperactivity and stereotypy. In contrast, another group of researchers found no effect of fish oil supplementation on the severity and frequency of problem behaviors among young adults with autism.29 Researchers examining the relationship between autism spectrum disorder and n-3 PUFA have found counterintuitive results, but this area of research remains in the preliminary stages.

Multiple research teams have also examined n-3 PUFA and their relationship with depression and mood disorders, and – much like the studies on autism – they too have found mixed results. A series of studies have found convincing results regarding the mood-stabilizing capabilities of n-3 PUFA. According to one research team,30 patients with major depressive disorder had lower levels of DHA in the orbitofrontal cortex at autopsy when compared with control individuals of the same age. Two studies with similar treatments of DHA/EPA found disparate results regarding changes in mood from baseline as measured by the profile of mood states. According to mood results, one group of researchers found that 35 days of n-3 PUFA supplementation increased vigor and reduced anxiety, aggression, and depressive states;9 however, the other researchers found only a slight reduction in distress, which they interpreted with caution.31 Similarly, a population study of 29 133 men found no association between reported dietary intake of n-3 PUFA and mood scores.32

Additional mood research showed that across 2982 participants of varying ages, very-high and very-low consumption of n-3 PUFA was associated with high depressed mood scores;33 however, the researchers suggested that the association with high n-3 PUFA intake might derive from nutritional self-medication of depressed individuals. Cumulatively, these results present an unclear relationship between n-3 PUFA and mood. Other reviewers have also verified that although some research shows beneficial mood-alter- ing properties to the nutrients, many effects of n-3 PUFA on various mood disorders are yet to be entirely understood.34

Another developing area of research involves asses- sing the treatment benefits of n-3 PUFA on psychotic disorders. One research team assessed the effects of DHA and EPA supplementation on the positive and negative schizophrenia symptoms.35 Using the Positive and Negative Syndrome Scale (PANSS), the researchers supplemented 45 patients diagnosed with schizophrenia with 2000 mg DHA, 2000 mg EPA, or placebo for 12 weeks, finding greater improvement on PANSS scores through EPA treatment compared with the DHA or placebo groups. The researchers con- cluded that EPAwas superior to DHA in the treatment

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5218

of positive symptoms. In their second study on 30 patients, the same researchers found that EPA again reduced PANSS scores more than placebo especially pertaining to positive symptoms, while EPA also sig- nificantly reduced the need for antipsychotic medi- cation. Another study focusing on the prodromal stage of psychosis found a greater reduction in posi- tive, negative, and general symptoms and improved functioning for the group supplemented with 480 mg DHA, 700 mg EPA, and 220 mg of other n-3 PUFA.36 From a preventative perspective, these results indicated a lower chance of developing psycho- sis among the n-3 PUFA group. These preliminary findings suggest that n-3 PUFA could have a role in the treatment of mental health disparities alongside the chronic diseases mentioned earlier (Table 1). Aside from psychiatric disorders, damages to the

nervous system have also received attention from scientists. Research on neurological injuries has been extensively reviewed elsewhere, specifically regarding the neuroprotective effects of DHA against acute spinal injury.37 Preliminary research involving rats has found rehabilitative properties of n-3 PUFA for dopaminergic neurotransmission38 and brain homeo- stasis39 after traumatic brain injury. These neuro- restorative properties may derives from the notable

anti-inflammatory properties of n-3 PUFA,15 as they further emphasize the benefits of the nutrients within the nervous system.

PUFA and the central nervous system n-3 PUFA have reportedly protected against certain diseases of the central nervous system (CNS) like Alzheimer’s disease6 and multiple sclerosis.40

Accordingly, a linkage exists between the EFA and the CNS. Possibly identifying myelinating qualities of n-3 PUFA, the results of one study showed EPA sti- mulating the expression of myelin-related proteins within the CNS of rats.41 Thicker myelin might better insulate electrochemical signals transmitted down the axons, thereby leading to a quicker speed of processing and more effective cognition among high n-3 PUFA consumers.42

Aside from affecting myelination, n-3 PUFA such as DHA and EPA play an important role in the CNS. Altogether, PUFA comprises 15–30% of the brain’s dry weight.20 About 60% of the brain’s structural material is lipid, composed of cholesterol and phosphoglycerides rich in both AA and DHA.14

For example, in the retinal rods, DHA accounts for some 50–60% of the fatty acids used in the polar phosphoglycerides of the plates.14,43 DHA also

Table 1 Cited studies on n-3 PUFA and mental health

Diagnosis Author Age Type of study

Supplement composition/ dietary routine

Period of treatment Effect of n-3 PUFA

ADHD Johnson et al.27 8–18 Supplementation 174 mg DHA/ 558 mg EPA/60 mg gamma LA

6 month, one-way cross-over

Symptom reductions of 25–50% for 47% of patients

Amminger et al.28 5–17 Supplementation 700 mg DHA/ 840 mg EPA

6 weeks Significant improvement in hyperactivity and stereotypy

Autism Politi et al.29 18–40 Supplementation 930 mg DHA/ EPA

6 weeks No effect on severity and frequency of behaviors

Appleton et al.33 – FFQ – – Very low and very high n-3 PUFA intake associated with higher depressed mood

Hakkarainen et al.32 50–69 FFQ – – No association between low mood and n-3 PUFA

Depression and mood disorders

McNamara et al.30 – Brain PUFA Levels at Autopsy

– – Significantly lower DHA in orbitofrontal cortex

Amminger et al.36 13–25 Supplementation 480 mg DHA/ 700 mg EPA/ 220 mg other n-3 PUFA

12 weeks Less positive, negative, and general symptoms; better functioning; lower chance of developing psychosis

Peet et al.35

Experiment 1 – Supplementation 2000 mg DHA

vs. 2000 mg EPA

12 weeks EPA-treated positive symptoms and improved PANSS over DHA

Schizophrenia and psychosis

Peet et al.35

Experiment 2 – Supplementation 2000 mg EPA 12 weeks Lower PANSS and

reduced need of antipsychotic drugs

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5 219

affects neuronal membrane fluidity and blood–brain barrier function, along with regulating dopaminergic, serotonergic, acetylcholinergic, and norepinephriner- gic neurotransmission.9,43

The cognitive effects of PUFA throughout the lifespan The EFA are integrally involved with the architecture and functioning of the CNS, demonstrated, in part, through a dependence on PUFA throughout the life- span. n-3 and n-6 PUFA are both required for proper brain development and functioning of the mature brain through their effects on cell membrane structures and electrophysiology.44 The psychophysiol- ogy of n-3 PUFA illustrates the potential of n-3 PUFA to direct changes in the brain, implying a probable effect on cognitive measures. Mothers consuming fish four times a week during pregnancy had babies with higher developmental scores than non-fish consu- mers at 18 months after birth.45 Another group of researchers hypothesized this relationship between developmental nutrition and later cognitive perform- ance.10 At the age of 4, the researchers found that chil- dren of mothers supplemented with 1180 mg DHA and 800 mg EPA per day through cod liver oil during pregnancy from week 18 until 3 months after delivery had significantly higher IQ scores than chil- dren of mothers supplemented with corn oil. However, the researchers did not find a significant effect of post-natal cod liver supplementation on the later neurodevelopment of breast-fed infants. Fatty acid composition of human milk depends on

both the short-term and long-term maternal diet,46

and the early diet could render the amount of DHA and n-6 PUFA in the infant brain.22 During the third tri- mester of pregnancy, fetuses require approximately 40–60 mg of n-3 PUFA per kilogram body weight per day.47 The last trimester and first post-natal months experience a growth spurt in the human brain, with a large increase in cerebral content of AA and DHA.10

During pre-natal and perinatal growth, significant amounts of AA and DHA accumulate in the brain, showing a physiological demand for these nutrients.47

Among 73 children, a group of researchers found that 76% of IQ variance in a regression analysis, among participants at 6.5 years of age, could be accounted for by breastfeeding duration, week of ges- tation, and the DHA/AA quotient.48 Similarly, another study correlated milk DHA with fish intake and visual acuity among 39 entirely breast-fed infants at 4 months of age.46 Two meta-analyses con- cluded that DHA-fortified formula in the early infant diet could positively support the development of the visual system; however, the researchers could not confirm a lasting positive influence of the formula on the visual system at later stages of the

lifespan.49,50 All of these studies present a relationship between the early diet, n-3 PUFA, and perinatal cog- nitive development; however, as the child continues to mature the influence of n-3 PUFA on cognition becomes more unclear.

Another research group concluded that only some DHA and AA supplemented infants performed better on visual and cognitive measures, implying a trend toward less significant cognitive effects of n-3 PUFA as a child matures.51 However, relatively few studies have delved into the cognitive effects of n-3 PUFA post-infancy,52 but researchers have recently begun to grasp the importance of data regarding the nutritional effects of PUFA among diversely aged populations.

A recent study into school nutrition found disparate results regarding the relationship between n-3 PUFA and intellect among school-aged children. The researchers investigated the effects of fortified nutri- tion in school meals, sampling 598 Indian school chil- dren ranging between 6 and 10 years of age.53 The children received foods containing either low or high levels of micronutrients and n-3 PUFA. The high n-3 PUFA level contained 900 mg ALA and 100 mg DHA, while the low n-3 PUFA level contained 140 mg ALA and no DHA.

During the 12 months of dietary intervention, psy- chologists assessed cognitive performance at baseline, 6 months, and 12 months through a cognitive test battery of 11 measures (i.e. Wechsler Intelligence Scale for Children, Auditory–Verbal Learning Test, etc.). The study yielded no significant difference in these cog- nitive measures between the low- and high-n-3 PUFA conditions alongside no interaction between the fatty acids and the micronutrients. However, a shortcoming of this study derives from its high use of ALA in place of DHA/EPA, as ALA does not serve as an effective source of DHA/EPA,43 with DHA/EPA represented in more studies and producing more positive results.9,10,41 These preliminary results indicate no posi- tive cognitive effects of ALA during childhood; however, they provide little insight into the effects of DHA/EPA on this age group.

Another recent study examined many critical groups of PUFA in relation to cognitive skills among children between the ages of 8 and 10. This research team inves- tigated cheek cell levels of n-3 and n-6 PUFA among 411 typically developing children.54 The researchers found some associations between fatty-acid levels and behavior, but took caution when interpreting their findings. DHA had a weak correlation with higher non-verbal IQ, while LA inversely correlated with one measure of attention. Tests of working memory and reading/spelling abilities did not corre- late with any PUFA levels.

Although no dietary intervention occurred in the study, ALA had a much greater presence than

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5220

DHA/EPA in the mean PUFA status of the partici- pants. Examining the percent proportion of cheek cell fatty acids, the ALA to DHA to EPA ratio was 0.59:0.08:0.05. With a much smaller proportion of DHA/EPA compared to ALA, DHA/EPA may have been present at too low of levels for any influence. However, among a group of children 10–12 years of age, another research group found no significant effects of n-3 PUFA on cognition across two sup- plementation groups consuming either 400 mg or 1000 mg DHA per day over an 8-week period of sup- plementation.55 These exploratory studies illustrate the discrepancies in the methodologies of n-3 PUFA research on cognition in children; however, these results remain preliminary and require further research before any firm conclusions can be made, especially for this age group. Researchers have provided concrete evidence for the

neurodevelopmental benefits of dietary PUFA throughout pregnancy and into infancy.10,45,51 As well, multiple studies have observed cognitive benefits among elderly populations consuming high levels of n-3 PUFA.6,8,11 However, disparate results from child- hood to middle adulthood have made the cognitive effects of n-3 PUFA unclear throughout the lifespan. Presenting cognitive benefits of the fatty acids, two separate research groups9,56 indicated a distinct relationship between n-3 PUFA intake, attention, and mood among emerging adulthood and midlife populations. As with childhood, few studies have effectively

assessed the benefits of n-3 PUFA on cognition in healthy, young adult, and middle-aged populations, and the possible benefits could be significant. Two particular studies have investigated this population, finding benefits related to n-3 PUFA consumption. The first study by Kalmijn et al.56 assessed a popu- lation between 45 and 70 years of age, while the latter study by Fontani et al.9 assessed a population ranging from 22 to 51 years of age. Both studies related n-3 PUFA in the diet to better performances on cognitive tasks. Kalmijn et al.56 found an inverse relationship between reported n-3 PUFA consumption and impaired cognitive function and time to complete a challenging cognitive task. The researchers assessed cognition through a battery of tests including a Stroop Test and Verbal Learning Test, constructively measuring the executive functioning of the population. Fontani et al.9 also assessed the cognitive effects of

n-3 PUFA, but among a healthy adult population that self-administered an n-3 PUFA supplement. The researchers hypothesized significant effects of n-3 PUFA on both cognition and physiology, considering the possible relationship between n-3 PUFA and CNS health. Participants received either n-3 PUFA sup- plements or olive oil placebos. To assess cognition at

baseline and post-supplementation, participants underwent a battery of tests focusing on attention (i.e. alert, go/no-go, choice, and sustained attention). During these tests, the researchers recorded reaction time and event-related potentials, observing a reduction in reaction time, better sustained attention, and a frequency shift toward the theta and alpha band during electroencephalogram recordings. Kalmijn et al.56 focused on a population of a later

age compared with the young adult to midlife popu- lation of Fontani et al.9 and overall few studies have focused on n-3 PUFA and cognition in young adult populations. Another study investigating a college- aged population of 126 students hypothesized that PUFA supplementation would lower test anxiety.57

After 3 weeks of supplementation, the researchers found reduced cortisol levels and reduced test anxiety among college students consuming a 1:4 n-3 to n-6 PUFA mixture over placebo. The preliminary findings on n-3 PUFA in young adult populations indicate benefits on cognitive performance and brain health. The findings of Fontani et al.9 are consistent with

these results among college-aged participants57 in that both studies found that n-3 PUFA had a ben- eficial cognitive effect for younger adults; however, other research on n-3 PUFA in both similar and younger age groups present disparate results. A 4-week, double-blind supplementation study into depression-related cognition among university stu- dents31 largely replicated the design of Fontani et al.9 but despite similar methodologies, the research- ers did not find any cognitive effects associated with n-3 PUFA consumption. Although Fontani et al.9

reported n-3 PUFA improving performance on the attentional go/no-go task over placebo, n-3 PUFA supplementation did not significantly improve per- formance, among healthy participants, over placebo on the same measure in the replication study.31 The latter study also found no effects of n-3 PUFA on memory or response inhibition among healthy participants. While these dissimilar results31 bring the results of

Fontani et al.9 into question, the findings of Kalmijn et al.56 must also be reexamined. In contrast to the results achieved by Fontani et al.9 the results obtained by Kalmijn et al.56 implied that n-3 PUFA lowered the likelihood of impairment rather than enhanced any cognitive ability. In turn, n-3 PUFA may produce a latent and protective effect on the brain, leading to their preventative qualities against cognitive declines.6,8,11 However, among a 55 and older popu- lation of 485 healthy adults diagnosed with age- related cognitive decline, a recent research team found that 900 mg of daily DHA supplementation for 24 weeks improved memory and learning over

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5 221

placebo.58 The researchers present DHA as cognitively rehabilitative as well as having a neuroprotective effect, possibly explained through the high concen- trations and apparent reliance of the brain on DHA.9,20,43 However, this reliance on DHA may produce no measurable effect on cognitive function prior to late adulthood.31,55

The preliminary research has yielded little clear evi- dence for cognitive-enhancing effects of n-3 PUFA among healthy individuals from young adulthood through midlife. Therefore, further research among these age groups is required for greater insight into n-3 PUFA and cognition throughout the lifespan. Incongruent conclusions on the cognitive effects of n-3 PUFA derive from conflicting results as a function of participants’ ages. Further complicating interpret- ations, many studies differed in terms of n-3 PUFA dosages. Moreover, the length of intervention has varied. For example, the study into school nutrition53

provided participants with a yearlong and extensive n-3 PUFA treatment and still found no efficacy to n-3 PUFA in improving cognitive performance among school-aged students. Whereas another research team55 administered children with 400 mg or 1000 mg DHA for 8 weeks and still found no positive effects on cognition. If DHA has a valid effect on cognition, perhaps studies must adjust their assigned supplements to produce comparable results to Fontani et al.9 or perhaps no valid effect on cognition exists.

Dosage consistency in PUFA research Due to varying dosages of n-3 PUFA and lengths of interventions, results concerning the relationship between n-3 PUFA and cognition at different age groups have become difficult to generalize. A particu- lar concern of n-3 PUFA research pertains to the nutri- ent dosage within supplements or dietary interventions and the method of measuring nutrient intake. Though FFQs have been validated, they possess substantial limitations when describing the diet of a population,59

while supplementation experiments may detach the supplemented nutrient from its natural association with other nutrients.60 Researchers must normalize their protocol, specifically dosage and period of treat- ment, for more standard and consistent results. The use of consistent treatment dosages will elicit more comparable results; however, little consistency cur- rently exists in the suggested nutritional intake of n-3 PUFA by many organizations. A consistent dosage of n-3 PUFA remains difficult to

determine due to the discourse among the organiz- ations advising consumers. Even health advisory organizations differ in their suggested intake of n-3 PUFA. While the American Heart Association has suggested dosages of 1000 mg DHA/EPA per day for individuals with a history of heart problems, they

have also suggested dosages as high as 2000–4000 mg for individuals with high triglycerides.43 Contrarily, the American Diabetes Association61 has advocated for the consumption of two or more servings of fish per week, which equates to roughly 400 mg DHA/ EPA per week.43 Similarly, with greater regard for the brain, the American Psychiatric Association’s Omega-3 Fatty Acid Subcommittee also determined that adults should consume fish twice or more weekly.62 Although different disorders may require different therapeutic dosages, researchers must consist- ently use an effective and standardized dosage of n-3 PUFA on cognition (if one exists) to provide more com- parable research results.

Another problem with dosages concerns the distinc- tions between the various types of n-3 PUFA. While DHA has notable cognitively beneficial properties among the elderly,58 similar treatments of DHA have not produced any comparable effects among younger age groups.55 However, high levels of DHA in formula and breast milk has notably improved visual development among infants,49,50 and higher cheek cells concentrations of DHA weakly correlated with children’s non-verbal IQ.54 Considering combinations of DHA and EPA, studies with comparable amounts of EPA but distinct dosages of DHA found opposite results, as a study with higher DHA reported enhanced cognitive performance at midlife9 while a study with lower DHA observed no cognitive effect at midlife.31 Showing distinctions in the effects of these nutrients, EPA stimulated the expression of a myelin protein in rats without the involvement of DHA.41

Some researchers have also focused on the EPA pre- cursor, ALA, and they have found diverse results, although one researcher labeled ALA as an ineffective source of DHA/EPA.43 While extensive ALA treat- ment produced no cognitive effects among children,53

a short treatment of ALA alongside a higher amount of the LA reduced test anxiety among a college-aged population.57 The various n-3 PUFA might have dis- tinct effects on cognition; however, they are predomi- nantly, and unfortunately, lumped together with one another in various studies.9,10,27–29,31,36 One study on schizophrenia35 considered DHA and EPA separate treatments and discovered that EPA unexpectedly pro- duced a greater reduction in symptoms than DHA. Although they have a common biosynthetic pathway, to facilitate the development of reliable dietary sugges- tions, researchers should clearly delineate the individ- ual combined contributions of various PUFA in order to attribute any positive results to a specific lipid.

The future of neuro-nutritional research on PUFA Regardless of consistent dosages, relatively little data exist regarding the cognitive effects of n-3 PUFA

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5222

into emerging adulthood and prior to middle age. Although only one study9 has confidently observed n-3 PUFA improving cognitive performance within this age group, their results cannot be disregarded as so few studies have investigated similar popu- lations, with similar dosages, for similar durations, measuring similar cognitive functions. The current evidence suggests that n-3 PUFA have different effects throughout the lifespan. While maternal sup- plementation during pregnancy improves the IQ of children at the age of four,10 other researchers observed less significant effects of DHA and AA supplementation on the cognitive and visual skills of infants.51 However, up to 4 months after birth, DHA in breast milk and infant formula produces better development of visual skills, which may or may not be a lasting effect.47–50 It appears that as a child matures, the intellectual and cognitive effects of n-3 PUFA gradually diminish, with studies of children from age 6 to 12 presenting no significant cognitive benefits of a high n-3 PUFA diet.53–55 Thereafter, a gap in the neuro-nutri- tional research leaves room for speculation as to the cognitive effects of n-3 PUFA from adolescence to midlife.9,31 Into middle age and beyond, the research begins to imply the cognitive-protective effects of n-3 PUFA against cognitive decline.56

These protective effects gain momentum into the abundant research on n-3 PUFA among the elderly.6,8,11,58 See Tables 2 and 3 for summaries of

the dosages, age groups, and findings of many of the studies cited above. The lifespan trend above has support through

numerous studies, and a supplementation study on a large range of ages mimics this trend. Supplementing 190 moderately depressed individuals for 12 weeks, researchers found no benefits to 850 mg DHA and 630 mg EPA supplementation over placebo on measures of reaction time, lexical decision making, and impulsivity.63 The population studied in this research ranged from 18 to 70 years of age. Accordingly, researchers are yet to consistently observe any cognitive-enhancing properties of n-3 PUFA throughout the lifespan, but the neuroprotective effects of n-3 PUFA among the elderly remain clear, as they seem to prevent and counteract cognitive declines. The gap of knowledge among children, adolescents,

and young adults leads to disparate and unclear results. Therefore, future research must follow similar periods and dosages of supplementation among healthy and different-aged populations. Although few researchers have so far observed some cognitive enhancement of n-3 PUFA, no definitive study has detailed all clear and comprehensive benefits of n-3 PUFA for the brain, body, and behavior. These nutri- ents still have an essential place in the human diet, and though they may lack apparent cognitive benefits at younger ages, they remain crucial for human health and may provide the means for maintaining cognition into later life.

Table 2 Cited studies on n-3 PUFA and cognition from pre-natal development to pre-adolescents

Age group Author Age Type of study

Supplement composition/dietary routine

Period of treatment Effect of n-3 PUFA

Daniels et al.45 – FFQ 4 fish/week – Higher developmental scores at 18 months

Pre-natal Helland et al.10 – Maternal supplementation

1180 mg DHA/ 800 mg EPA

Week 18 till 12 weeks post-natal

Higher IQ at age 4, but no effect of post-natal supplementation

Gustafsson et al.48 – Breast milk PUFA analysis

DHA/AA concentration in breast milk

– 76% IQ variation accounted for by breast-feeding duration, gestation week, and DHA/AA quotient at age 6.5

Perinatal Jørgensen et al.46 – Breast milk PUFA analysis

DHA concentration in breast milk

– Correlation between DHA in milk and visual acuity

Kennedy et al.55 10–12 Supplementation 400 mg or 1000 mg DHA

8 weeks No cognitive effects

Kirby et al.54 8–10 Cheek cell PUFA levels

Percent of cheek cell FA = 0.59 ALA, 0.08 DHA, 0.05 EPA

– Weak correlation between DHA and non-verbal IQ

Children and pre- adolescents

Muthayya et al.53 6–10 Dietary intervention 900 mg ALA/100 mg DHA or 140 mg ALA

1 year No cognitive effects

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5 223

References 1 Heron M, Hoyert D, Murphy S, Xu J, Kochanek K, Tejada-Vera B. Deaths: final data for 2006. Natl Vital Stat Rep 2009;57: 1–134.

2 Yamagishi K, Iso H, Date C, Fukui M, Wakai K, Kikuchi S, et al. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J Am Coll Cardiol 2008;52:988–96.

3 Fradet V, Cheng I, Casey G, Witte J. Dietary omega-3 fatty acids, cyclooxygenase-2 genetic variation, and aggressive pros- tate cancer risk. Clin Cancer Res 2009;15:2559–66.

4 Iso H, Rexrode K, Stampfer M, Manson J, Colditz G, Speizer F, et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA 2001;285:304–12.

5 Gillen L, Tapsell L, Patch C, Owen A, Batterham M. Structured dietary advice incorporating walnuts achieves optimal fat and energy balance in patients with type 2 diabetes mellitus. J Am Diet Assoc 2005;105:1087–96.

6 Morris M, Evans D, Bienias J, Tangney C, Bennett D, Wilson R, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003;60:940–6.

7 Simopoulos A. N-3 fatty acids and human health: defining strat- egies for public policy. Lipids 2001;36(Suppl):S83–9.

8 Eskelinen M, Ngandu T, Helkala E, Tuomilehto J, Nissinen A, Soininen H, et al. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry 2008;23:741–7.

9 Fontani G, Corradeschi F, Felici A, Alfatti F, Migliorini S, Lodi L. Cognitive and physiological effects of omega-3 polyunsatu- rated fatty acid supplementation in healthy subjects. Eur J Clin Invest 2005;35:691–9.

10 Helland I, Smith L, Saarem K, Saugstad O, Drevon C. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics 2003;111:39–44.

11 Solfrizzi V, Colacicco A, D’Introno A, Capurso C, Torres F, Rizzo C, et al. Dietary intake of unsaturated fatty acids and age-related cognitive decline: a 8.5-year follow-up of the Italian

Longitudinal Study on aging. Neurobiol Aging 2006;27: 1694–704.

12 Ruxton C, Reed S, Simpson M, Millington K. The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. J Hum Nutr Diet 2007;20:275–85.

13 Campbell N, Reece J, Urry L, Cain M, Wasserman S, Minorsky P, et al. Biology. 8th ed. San Francisco: Pearson Education Inc; 2008.

14 Crawford M. The role of dietary fatty acids in biology: their place in the evolution of the human brain. Nutr Rev 1992;50: 3–11.

15 Simopoulos A. Human requirement for n-3 polyunsaturated fatty acids. Poult Sci 2000;79:961–70.

16 Heinrichs S. Dietary omega-3 fatty acid supplementation for optimizing neuronal structure and function. Mol Nutr Food Res 2010;54:447–56.

17 Simopoulos A. Evolutionary aspects of diet, the omega-6/ omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 2006;60:502–7.

18 Simopolous A. Evolutionary aspects of diet, essential fatty acids and cardiovascular disease. Eur Heart J Suppl 2001;3(Suppl D): D8–21.

19 Eaton S, Konner M. Paleolithic nutrition. A consideration of its nature and current implications. N Engl J Med 1985;312: 283–9.

20 Hallahan B, Garland M. Essential fatty acids and mental health. Br J Psychiatry 2005;186:275–7.

21 Yehuda S, Rabinovitz S, Mostofsky DI. Essential fatty acids and cognition. In: Tsai JP (ed.) Leading edge cognitive dis- order research. New York: Nova Science Publishers; 2008. p. 59–63.

22 Novak E, Dyer R, Innis S. High dietary omega-6 fatty acids con- tribute to reduced docosahexaenoic acid in the developing brain and inhibit secondary neurite growth. Brain Res 2008;1237: 136–45.

23 Ge Y, Chen Z, Kang Z, Cluette-Brown J, Laposata M, Kang J. Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells. Anticancer Res 2002;22:537–43.

24 Ford E, Mokdad A. Epidemiology of obesity in the western hemisphere. J Clin Endocrinol Metab 2008;93(Suppl 1):S1–8.

Table 3 Cited studies on n-3 PUFA and cognition from adulthood to late age

Age group Author Age Type of study

Supplement composition/dietary routine

Period of treatment Effect of n-3 PUFA

Antypa et al.31 x ≈ 22 Supplementation 250 mg DHA/1740 mg EPA

4 weeks Most cognitive skills/ mood were unaffected

Fontani et al.9 22–51 Supplementation 800 mg DHA/1600 mg EPA/400 mg other n-3 PUFA

5 weeks Improved attention and mood

Kalmijn et al.56 45–70 FFQ Marine n-3 PUFA – Inverse relationship with cognitive function and speed

Adulthood Yehuda et al.57 College- aged

Supplementation 225 mg ALA/ 900 mg LA

3 weeks Reduced test anxiety

Albanese et al.26 ≥65 Interview for dietary habits

Fish consumption – Associated with lower prevalence of dementia

Eskelinen et al.8 65–80 FFQ/interview >2.1 g PUFA/day – Better memory and executive functioning

Morris et al.6 65–94 FFQ 1 + fish/week – 60% lower likelihood of Alzheimer’s disease

Solfrizzi et al.11 65–84 FFQ High PUFA diet – Protective against cognitive decline

Elderly Yurko-Mauro et al.58 ≥65 Supplementation 900 mg DHA 24 weeks Improved memory and learning in age-related cognitive decline

Across age groups

Rogers et al.63 18–70 Supplementation 850 mg DHA/630 mg EPA

12 weeks No effects on mood or cognition

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5224

25 Czech C, Tremp G, Pradier L. Presenilins and Alzheimer’s disease: biological functions and pathogenic mechanisms. Prog Neurobiol 2000;60:363–84.

26 Albanese E, Dangour A, Uauy R, Acosta D, Guerra M, Guerra S, et al. Dietary fish and meat intake and dementia in Latin America, China, and India: a 10/66 Dementia Research Group population-based study. Am J Clin Nutr 2009;90:392–400.

27 Johnson M, Ostlund S, Fransson G, Kadesjö B, Gillberg C. Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. J Atten Disord 2009;12:394–401.

28 Amminger G, Berger G, Schäfer M, Klier C, Friedrich M, Feucht M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry 2007;61:551–3.

29 Politi P, Cena H, Comelli M, Marrone G, Allegri C, Emanuele E, et al. Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study. Arch Med Res 2008;39:682–5.

30 McNamara R, Hahn C, Jandacek R, Rider T, Tso P, Stanford K, et al. Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder. Biol Psychiatry 2007;62:17–24.

31 Antypa N, Van der Does A, Smelt A, Rogers R. Omega-3 fatty acids (fish-oil) and depression-related cognition in healthy vol- unteers. J Psychopharmacol 2009;23:831–40.

32 Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lönnqvist J. Is low dietary intake of omega-3 fatty acids associ- ated with depression? Am J Psychiatry 2004;161:567–9.

33 Appleton K, Peters T, Hayward R, Heatherley S, McNaughton S, Rogers P, et al. Depressed mood and n-3 polyunsaturated fatty acid intake from fish: non-linear or confounded association? Soc Psychiatry Psychiatr Epidemiol 2007;42:100–4.

34 Owen C, Rees A, Parker G. The role of fatty acids in the devel- opment and treatment of mood disorders. Curr Opin Psychiatry 2008;21:19–24.

35 Peet M, Brind J, Ramchand C, Shah S, Vankar G. Two double- blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr Res 2001;49:243–51.

36 Amminger G, Schäfer M, Papageorgiou K, Klier C, Cotton S, Harrigan S, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-con- trolled trial. Arch Gen Psychiatry 2010;67:146–54.

37 Michael-Titus A. Omega-3 fatty acids and neurological injury. Prostaglandins Leukot Essent Fatty Acids 2007;77:295–300.

38 Shin S, Dixon C. Oral fish oil restores striatal dopamine release after traumatic brain injury. Neurosci Lett 2011;496:168–71.

39 Wu A, Ying Z, Gomez-Pinilla F. Omega-3 fatty acids supplementation restores mechanisms that maintain brain homeostasis in traumatic brain injury. J Neurotrauma 2007;24: 1587–95.

40 Mehta L, Dworkin R, Schwid S. Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis. Nat Clin Pract Neurol 2009;5:82–92.

41 Salvati S, Natali F, Attorri L. Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain. J Neurosci Res 2008;86:776–84.

42 Georgieff M. Nutrition and the developing brain: nutrient priori- ties and measurement. Am J Clin Nutr 2007;85:614S–20S.

43 Kidd P. Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. Altern Med Rev 2007;12: 207–27.

44 Kitajka K, Sinclair A, Weisinger R, Weisinger H, Mathai M, Jayasooriya A, et al. Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression. Proc Natl Acad Sci USA 2004;101:10931–6.

45 Daniels J, Longnecker M, Rowland A, Golding J. Fish intake during pregnancy and early cognitive development of offspring. Epidemiology 2004;15:394–402.

46 Jørgensen M, Hernell O, Hughes E, Michaelsen K. Is there a relation between docosahexaenoic acid concentration in mothers’ milk and visual development in term infants? J Pediatr Gastroenterol Nutr 2001;32:293–6.

47 Clandinin M, Chappell J, van Aerde J. Requirements of newborn infants for long chain polyunsaturated fatty acids. Acta Paediatr Scand Suppl 1989;351:63–71.

48 Gustafsson PA, Duchén K, Birberg U, Karlsson T. Breastfeeding, very long polyunsaturated fatty acids (PUFA) and IQ at 6 1/2 years of age. Acta Paediatr 2004;93:1280–7.

49 SanGiovanni J, Parra-Cabrera S, Colditz G, Berkey C, Dwyer J. Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants. Pediatrics 2000;105:1292–8.

50 SanGiovanni J, Berkey C, Dwyer J, Colditz G. Dietary essential fatty acids, long-chain polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: a systematic review. Early Hum Dev 2000;57:165–88.

51 Larque E, Demmelmair H, Koletzko B. Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: impor- tance for the early development of the nervous system. Ann N Y Acad Sci 2002;967:299–310.

52 Eilander A, Hundscheid D, Osendarp S, Transler C, Zock P. Effects of n-3 long chain polyunsaturated fatty acid supplemen- tation on visual and cognitive development throughout child- hood: a review of human studies. Prostaglandins Leukot Essent Fatty Acids 2007;76:189–203.

53 Muthayya S, Eilander A, Transler C, Thomas T, van der Knaap H, Srinivasan K, et al. Effect of fortification with multiple micronutri- ents and n-3 fatty acids on growth and cognitive performance in Indian schoolchildren: the CHAMPION (Children’s Health and Mental Performance Influenced by Optimal Nutrition) Study. Am J Clin Nutr 2009;89:1766–75.

54 Kirby A, Woodward A, Jackson S, Wang Y, Crawford M. Childrens’ learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels. Res Dev Disabil 2010;31:731–42.

55 Kennedy D, Jackson P, Elliott J, Scholey A, Robertson B, Greer J, et al. Cognitive and mood effects of 8 weeks’ supplementation with 400 mg or 1000 mg of the omega-3 essential fatty acid doco- sahexaenoic acid (DHA) in healthy children aged 10–12 years. Nutr Neurosci 2009;12:48–56.

56 Kalmijn S, van Boxtel M, Ocké M, Verschuren W, Kromhout D, Launer L. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 2004;62: 275–80.

57 Yehuda S, Rabinovitz S, Mostofsky D. Mixture of essential fatty acids lowers test anxiety. Nutr Neurosci 2005;8:265–7.

58 Yurko-Mauro K, McCarthy D, Rom D, Nelson E, Ryan A, Blackwell A, et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 2010;6:456–64.

59 Kristal A, Peters U, Potter J. Is it time to abandon the food fre- quency questionnaire? Cancer Epidemiol Biomarkers Prev 2005; 14:2826–8.

60 Benton D. Micronutrient status, cognition and behavioral pro- blems in childhood. Eur J Nutr 2008;47(Suppl 3):38–50.

61 Bantle J, Wylie-Rosett J, Albright A, Apovian C, Clark N, Franz M, et al. Nutrition recommendations and interventions for dia- betes: a position statement of the American Diabetes Association. Diabetes Care 2008;31(Suppl 1):S61–78.

62 Freeman M, Hibbeln J, Wisner K, Davis J, Mischoulon D, Peet M, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry 2006;67: 1954–67.

63 Rogers P, Appleton K, Kessler D, Peters T, Gunnell D, Hayward R, et al. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cog- nitive function: a randomised controlled trial. Br J Nutr 2008;99: 421–31.

Karr et al. Omega-3 polyunsaturated fatty acids and cognition

Nutritional Neuroscience 2011 VOL. 14 NO. 5 225

emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.

However, users may print, download, or email articles for individual use.