Pregnancy and Youth Omega-3 on Neurodevelopment and Cognition

Shulkin M, Pimpin L, Bellinger D, et al. Effects of omega-3 supplementation during pregnancy and youth on neurodevelopment and cognition in childhood: a systematic review and meta-analysis. FASEB Journal. 2016 April30;(1): S295.5.


Long-chain omega-3 fatty acids are thought to be crucial for optimal neurodevelopment in early life.


To investigate the effect of omega-3 supplementation during pregnancy and infancy on child cognitive and developmental outcomes.


We searched PubMed, Cochrane Library, EMBASE, and PsychInfo through May 2015 without language or publication year restrictions for randomized controlled trials (RCTs) of omega-3 supplementation (>3 months) i.e. docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA), and quantitative measure of neurodevelopment or cognition. Full-text inclusion decisions and data extractions were performed independently and in duplicate. Our primary outcome was the standardized mean difference in Bayley Scales of Infant Development (BSID) score between intervention groups in RCTs. Other outcomes included the Weschler Intelligence Scale for Children, Weschler Preschool and Primary Scale of Intelligence, Kaufman Brief Intelligence Test, Kaufman Assessment Battery for Children, Peabody Picture Vocabulary Test, and other standardized measures.


Among 571 abstracts, we identified 15 trials with 20 intervention arms involving 2,525 children. Trials used DHA + EPA (N=6 arms), DHA only (N=2), DHA + arachidonic acid (AA) (N=10), or DHA + EPA + AA (N=2); either prenatally (mean 20 weeks gestation; N=4 arms) or within the first few days of birth (N=16). Mean supplementation duration was 7.3 months; and age at outcome assessment, 16 months. In pooled analyses, both maternal and infant supplementation similarly improved neurodevelopment: standardized mean difference (SMD) in BSID= 0.21 (95% CI: 0.01, 0.41) and 0.24 (0.00, 0.48) respectively (Figure 1). Among BSID subscales, DHA and/or EPA raised the psychomotor developmental index (N=8 arms; SMD 0.40; 95% CI: 0.10, 0.70), while DHA + AA raised the mental developmental index (N=15 arms; SMD 0.17; 95% CI: 0.00, 0.35). Pooled findings for other outcomes will be presented.


Omega-3 supplementation during either pregnancy or infancy improves child neurodevelopment. These findings indicate the importance of sufficient polyunsaturated fatty acid intake by pregnant women and young children.



Effect of Omega-3 After Acute Myocardial Infarction


Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown.


In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size.


By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (-5.8%, P=0.017), and noninfarct myocardial fibrosis (-5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy.


Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care.


Heydari B1, Abdullah S1, Pottala JV1, Shah R1, Abbasi S1, Mandry D1, Francis SA1, Lumish H1, Ghoshhajra BB1, Hoffmann U1, Appelbaum E1, Feng JH1, Blankstein R1, Steigner M1, McConnell JP1, Harris W1, Antman EM1, Jerosch-Herold M1, Kwong RY2. Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial. Circulation. 2016 Aug 2;134(5):378-91. doi: 10.1161/CIRCULATIONAHA.115.019949.


Australian and New Zealand Fish Oil Products in 2016 Meet Label Omega-3 Claims and Are Not Oxidised

A new paper confirming that omega-3 supplements in the Australian and New Zealand markets are within oxidation limits and contain the labeled contents of EPA and DHA has been published in Nutrients. The work was funded by the Omega-3 Centre in Australia after a paper from the Liggins Institute was published in Scientific Reports last year alleging that fish oils in the New Zealand market were over-oxidised and had as little as half of the EPA and DHA claimed on the labels.

The Liggins Institute paper caused a media uproar in New Zealand and the results seemed contradictory to what industry participants and market surveillance groups had observed. In order to determine if there was a problem in that market, GOED (Global Organisation for EPA and DHA) funded its own tests, as did the Australian Therapeutic Goods Administration and now the Omega-3 Centre. None of these groups’ results substantiated the Liggins Institute’s allegations. The Liggins researchers have said in the media that these results are not valid because they are not peer-reviewed, but now the Omega-3 Centre results have been, and GOED’s tests will be submitted for peer-reviewed publication shortly as well.

The Liggins researchers also published a subsequent study that raised additional questions about oxidised oils. GOED is funding a number of papers in the next year to investigate some of the issues raised.


Exceptional Freshness Levels – Protection from fishy smell, taste, and harmful free radicals

Freshness, which ensures product integrity and biological efficacy, may be the single most important quality of fish oils. Nordic Naturals‘ oxygen–free manufacturing process maintains the freshness of fish oil used in our products, with peroxide values (indicators of freshness) well below the EP (European Pharmacopoeia) Standard limits. The lower the peroxide value, the fresher the fish oil. Nordic Naturals’ third-party analysis verifies adherence to strict standards set out by leading international organisations and experts such as GOED, IFOS, WHO and EP.

Maternal DHA Impacts Pregnancy and Subsequent Child Development

Harris, Stacy, Baker, et al. The omega smart baby project: effect of maternal DHA on infant development. FASEB Journal April 2014 V. 28, No. 1 Supplement 269.1

A randomised placebo controlled trial was conducted to examine the effect of DHA on gestational length and cognitive development. 115 pregnant women were supplemented with 300 mg DHA/d or placebo during pregnancy and thru the first 3 mo of breastfeeding (BF).

Bayley Scales of Infant Development (BSID) were administered at 4 mo and 1y. Dietary DHA intake during pregnancy, was 81.9 +/- 5.8 mg/day (95% CI 72.3,91.5) and increased only slightly during BF. Some took prenatal vitamins with 0– 300 mg DHA per day resulting in total DHA intakes of 80 to 1100 mg/day. RBC and plasma phospholipid DHA at entry (expressed as % total fatty acids) were5.94 +/- 1.52 and 5.04 +/- 1.44 (mean +/- SD), respectively. Breastmilk (BM) % total DHA was .53 +/- .037 (mean +/- sem) at 2 mo and decreased to .35 +/- /039 at 4 mo.

BM DHA was significantly greater in the DHA treatment ( p<.02) and with the highest DHA intake compared to the lowest. BM DHA was lowest in carriers of the minor allele of the delta-5 desaturase gene. Data were analysed by treatment and by DHA intake. DHA supplementation resulted in a 1 wk increase in gestation with a significant (p<.03) 8 d increase in gestational length comparing the highest intake of DHA( > 600 mg/d) to the lowest (< 300 mg/d). BSID cognitive and language scores were 10 points higher with high intake of DHA compared to the lowest (p<.02).

Maternal DHA impacts both pregnancy outcome and subsequent development.



DHA and Human Brain Development

Brenna JT, Carlson SE. Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development. J Hum Evol. 2014 Dec;77:99-106.

Humans evolved a uniquely large brain among terrestrial mammals. Brain and nervous tissue is rich in the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). Docosahexaenoic acid is required for lower and high order functions in humans because of understood and emerging molecular mechanisms.

Among brain components that depend on dietary components, DHA is limiting because its synthesis from terrestrial plant food precursors is low but its utilisation when consumed in diet is very efficient. Negligible DHA is found in terrestrial plants, but in contrast, DHA is plentiful at the shoreline where it is made by single-celled organisms and plants, and in the seas supports development of very large marine mammal brains.

Modern human brains accumulate DHA up to age 18, most aggressively from about half-way through gestation to about two years of age. Studies in modern humans and non-human primates show that modern infants consuming infant formulas that include only DHA precursors have lower DHA levels than for those with a source of preformed DHA.

Functional measures show that infants consuming preformed DHA have improved visual and cognitive function. Dietary preformed DHA in the breast milk of modern mothers supports many-fold greater breast milk DHA than is found in the breast milk of vegans, a phenomenon linked to consumption of shore-based foods. Most current evidence suggests that the DHA-rich human brain required an ample and sustained source of dietary DHA to reach its full potential.



Reduction in Behaviour Problems with Omega-3



While limited evidence suggests that omega-3 supplementation may reduce antisocial behaviour in children, studies have not reported on post-treatment follow-up and most treatment periods have been of short duration. This study tests the hypothesis that omega-3 supplementation over 6 months will reduce behaviour problems in children both at the end of treatment and at 6 months post treatment.



In this randomised, double-blind, placebo-controlled, stratified, parallel-group trial, a community sample of 8-16 year old children were randomised into a treatment group (N = 100) and a placebo-control group (N = 100). The supplementation consisted of a fruit drink containing 1 g/day of omega-3 or a placebo consisting of the same fruit drink without omega-3. Participants, caregivers, and research assistants were blinded to group assignment. The primary outcome measures of externalising and internalising behaviour problems were reported by both caregivers and their children in a laboratory setting at 0 months (baseline), 6 months (end of treatment) and 12 months (6 months post treatment), together with the secondary outcome measures of parental antisocial behaviour. Data were analysed on an intention-to-treat basis including all participants.



Significant group × time interactions were observed with the treatment group showing long-term improvements in child behaviour problems. The average post-treatment effect size was d = -.59. Effects were documented for parent reports, but with the exception of proactive and reactive aggression, child-report data were nonsignificant. Parents whose children took omega-3 showed significant post-treatment reductions in their own antisocial and aggressive behaviour. This improvement in caregiver behaviour partly mediated the improvements observed in child behaviour.



Findings provide initial evidence that omega-3 supplementation can produce sustained reductions in externalising and internalising behaviour problems. Results are the first to report improvements in caregiver behaviour, and to establish this improvement as a part-mechanism for the efficacy of omega-3.


J Child Psychol Psychiatry. 2014 Aug 22.

Omega-3 Fatty Acids and the Body’s Response to Pain and Orthopaedic Injury

Musculoskeletal symptoms and orthopaedic conditions are a common cause of concern for many patients. Concentrated fish oil, providing the omega-3s EPA and DHA, is emerging as a cost effective tool with a favourable safety profile for optimising outcome from traditional treatment strategies. Scientific and clinical evidence shows that EPA and DHA may address all three of the major components of pain and injury: inflammatory response, cellular/tissue structural integrity, and nervous system signalling.

Inflammatory Response
EPA and DHA may significantly modify the class of prostaglandins and leukotrienes produced via COX- and LOX-mediated pathways to encourage a flux away from the 2- and 4- series and towards the 3- and 5- series. In addition, specialised downstream lipid mediators—end products of metabolism from EPA and DHA known as resolvins, protectins, and maresins—are now touted as critical to signalling the termination of acute inflammation toward homeostasis and away from a chronic inflammatory state. Hence, suboptimal EPA and DHA leads to poor tissue repair as a result of insufficient signalling of granulocytes, multi-potent stem cells, macrophages, and fibroblasts.

Cellular / Tissue Structural Integrity
EPA and DHA provide plasma membrane structural support for repairing injured tissue, and provide necessary chemical building blocks for restoring normal function to cell membranes across all tissue types and organ systems. Additionally, by enhancing the novel fibroblast collagen formation, musculoskeletal tissue may undergo structural repair to address a persistent pain generator.

Peripheral and Central Nervous System Signalling
Finally, fish oil may stabilise nerve thresholds and neuroendocrine axes for managing central and peripheral neural pain signalling processes. There is preliminary evidence and rationale for neural pain fiber membrane stabilisation as a result of sufficient EPA and DHA.

Thus, there is powerful construct validity for administering concentrated fish oil to address the biochemical and metabolic processes of musculoskeletal pain and injury.

Supplement Aids Age-Related Macular Degeneration

A supplement containing a combination of lutein, zeaxanthin, and Omega-3 long-chain polyunsaturated fatty acids significantly benefits patients with age-related macular degeneration, according to a study published online March 21, 2013 in JAMA Ophthalmology.


Importance: It has been shown that the functionality of the macula lutea depends on the nutritional uptake of lutein and zeaxanthin and that it is inversely associated with the risk of age-related macular degeneration (AMD). Additionally, Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may also be protective.

Objective: To investigate the effect of a 12-month intervention with macular xanthophylls and Omega-3 LC-PUFAs on xanthophylls and fatty acids in plasma, antioxidant capacity, and optical density of the macular pigment of patients with nonexudative AMD.

Design: The LUTEGA study was a randomized, double-blind, placebo-controlled, parallel clinical trial that was conducted for 12 months.

Setting: University Eye Hospital and Institute of Nutrition, Friedrich Schiller University Jena, Germany.

Participants: A total of 172 individuals with nonexudative AMD.

Intervention: Individuals were enrolled and randomly divided as follows: placebo group, group 1 (a capsule containing 10 mg of lutein, 1 mg of zeaxanthin, 100 mg of docosahexaenoic acid, and 30 mg of eicosapentaenoic acid administered each day), and group 2 (same substances but twice the dose used in group 1). One hundred forty-five participants completed the study successfully.

Main Outcome Measures: Plasma xanthophyll concentrations and fatty acid profiles, optical density of the macular pigment, and antioxidant capacity in plasma (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [Trolox] equivalent antioxidant capacity and photochemiluminescence).

Results: The concentrations of the administered carotenoids in plasma as well as the optical density of the macular pigment increased significantly in the groups randomized to receive supplementary macular xanthophylls and Omega-3 LC-PUFAs after 1 month of intervention and remained at this level through the end of the study. Use of the double dose resulted in a beneficial alteration of the fatty acid profile in the plasma of patients with AMD in comparison with the dose in group 1. The lipophilic antioxidant capacity in plasma was significantly elevated with the intervention.

Conclusions and Relevance: A supplement containing a fixed combination of lutein, zeaxanthin, and Omega-3 LC-PUFAs during 12 months significantly improved plasma antioxidant capacity, circulating macular xanthophyll levels, and the optical density of the macular pigment.


Macular Xanthophylls and Omega-3 Long-Chain Polyunsaturated Fatty Acids in Age-Related Macular DegenerationA Randomized Trial
Christin Arnold, Dipl-Troph; Lisa Winter, Dipl-Troph; Kati Fröhlich, PhD; Susanne Jentsch, Dipl-Ing; Jens Dawczynski, MD; Gerhard Jahreis, PhD; Volker Böhm, PhD
JAMA Ophthalmol. 2013;131(5):564-572. doi:10.1001/jamaophthalmol.2013.2851.

LCPUFA Supplementation in Infancy Reduces Heart Rate and Positively Affects Distribution of Attention—Birth to 12 Months


This study is the first randomized clinical trial of postnatal omega-3 DHA supplementation to measure attention.

DHA and ARA, two nutritional compounds markedly deficient in the American [Western] diet, are derived from:

  • Mothers before birth
  • Breast-feeding, up to age two
  • Some infant formulas


DHA and ARA, positively affect:

  • Brain development, infancy into childhood
  • Eye development
  • Nervous system development
  • Immune support

Read more

Omega-3 PUFAs offer an affordable way to reduce effects of traumatic brain, spinal cord injuries

The omega-3 polyunsaturated fatty acids (PUFAs) found in seafood and marine oils called EPA and DHA may offer a simple, affordable way to reduce the effects of traumatic brain and spinal cord injuries by decreasing inflammation and nerve cell damage. They may also protect against cognitive impairment that can follow surgery or critical illness. These encouraging findings and more are being presented at the 11th Congress of the International Society for the Study of Fatty Acids and Lipids (ISSFAL) in Stockholm 29 June-1 July, 2014.

Traumatic brain injury (TBI), resulting from combat, falls, traffic accidents and sports, is a leading cause of death in children and adults 1-44 years of age. In 2010 alone, there were more than 10 million TBIs worldwide. TBI is associated with long-term complications such as epilepsy, chronic headaches and neuropsychiatric disorders. Spinal cord injury (SCI) from similar causes also results in severe disabilities, impaired sensorimotor function and chronic pain. The consequences of TBI and SCI include reduced blood flow and DHA levels, inflammation, swelling and cell death. Loss of certain types of cells impairs the ability of the brain to repair itself and can affect the nervous system. For both TBI and SCI, there are no specific treatments to protect against such damage.

However, intervention with DHA, EPA and other substances may preserve brain networks and connectivity, maintaining or improving memory, according to Adina Michael-Titus, D.Sc., professor of neuroscience, Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, U.K.

“Research has demonstrated significant neuroprotective effects of DHA and EPA,” she observes. “These omega-3 fatty acids may protect and regenerate nerve cells as well as reduce damaging inflammation. As a result, they have significant potential for the improved treatment of brain and spinal cord injuries.”

Animal studies have shown that the administration of DHA up to two hours after SCI improves neurological function and nerve cell survival, reduces inflammation and decreases oxidative stress. DHA given prior to the injury also promotes cell survival and function. Similar neuroprotective effects have been reported in rats with mild TBI fed DHA and EPA prior to or shortly after injury. Due to these significant results, human trials are now underway.

Niccolò Terrando, Ph.D., assistant professor of physiology and pharmacology at the Karolinska Institutet, Sweden, showed in animals how resolvins – molecules naturally produced from omega-3 fatty acids – can protect against cognitive impairment that often occurs in people post-surgery and during critical illness. Treatment with a single dose of a DHA-derived resolvin protected the brain from memory dysfunction after surgery by “resolving” neuroinflammation.

This treatment also improved nerve cell function when given 24 hours after surgery. Major surgery affects brain function at large, contributing to inflammation and memory impairment.

“It was remarkable that the resolvin displayed such unexpected, positive effects on the central nervous system when administered at very low doses systemically,” says Terrando. “This substance, aside from reversing inflammation, may also promote healing and tissue regeneration critical to patient recovery. We hope to translate these promising findings into patient care.”

Even healthy people may benefit from the anti-inflammatory properties of omega-3 PUFAs. Trevor Mori, Ph.D., research professor at the University of Western Australia, examined the effect of 2.4 grams of EPA and DHA per day for seven days and aspirin for two days on blood levels of resolvins in a trial with healthy men and women.

“Short-term dietary supplementation with moderate amounts of these omega-3 PUFAs resulted in measurable levels of potent, inflammation-resolving substances,” Mori notes. “These substances are highly effective in reducing the symptoms and damage from overactive and chronic inflammation. The increase in resolvins after EPA and DHA supplementation may, in part, explain the benefits of these omega-3s in cardiovascular disease.”


Source: International Society for the Study of Fatty Acids and Lipids (ISSFAL)

Comparative Bioavailability of Omega-3 Fatty Acids from Four Different Natural Health Products

Comparison of the degree to which omega-3 fatty acids (EPA and DHA) from four (4) different natural health products are absorbed in the body.


Study Design:

  • Randomized, Cross-Over Study
  • The bioavailability/absorption of the long-chain omega-3 polyunsaturates eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in Nordic Naturals Ultimate Omega® soft gels were assessed in comparison with three (3) different natural health products.
  • The four (4) products administered included: 1) Fish oil, providing EPA and DHA in the form of triglycerides (Nordic Naturals Ultimate Omega), 2) Fish oil, providing EPA and DHA in the form of ethyl esters (Minami MorEPA Platinum), 3) Krill oil, providing EPA and DHA in the form of phospholipids (Arctic Pure Krill Oil), and 4) Salmon oil (New Chapter’s Whole Omega-3).
  • The degree to which supplementation with each of these four products affected the lipemicr response of 15 healthy participants in the trial was measured by the Lipemic Index™ to a standard reference solution both before and after the treatment period over a 7-month period.



  • The test results clearly illustrate the definitive superiority of Nordic Naturals Ultimate Omega supplement.
  • The combined EPA+DHA change and percentage change for Ultimate Omega, MorEPA, krill oil, and salmon oil were 70% vs. 48%, 14%, and 21%, respectively.
  • These results are corroborated by those in which participants taking the Ultimate Omega supplement exhibited improvement in all five of the parameters beyond any improvement in any of the other supplements.



  • From the results, it has clearly been observed that Nordic Naturals Ultimate Omega omega-3 supplement, at the prescribed daily dose, is superior to krill oil and salmon oil, at their prescribed doses, in the bioavailability of EPA, and is similar to MorEPA in this regard. However, it is superior to all three comparator products in the bioavailability of DHA and in various other calculated ratios,
    including OmegaScore™.
  • In terms of blood lipid and post-prandial triglyceride results, there were only two small but significant changes in lipid biomarkers, but no significant change in post-prandial triglyceride levels. For the MorEPA group, the logTG value showed a small decrease from Day 0 to Day 28, and for the krill oil group, HDL-C increased from Day 0 to Day 28. There was also an increase in LDL-C for the MorEPA group. None of the significant changes were noted in the Ultimate Omega supplementation group.
Laidlaw M, et al. A randomized clinical trial to determine the efficacy of manufacturers’ recommended doses of omega-3 fatty acids from different sources in facilitating cardiovascular disease risk reduction. Lipids Health Dis 2014 Jun 21;13:99.