HS-Omega-3 Index and cognitive performance

Cognitive performance includes executive functions like cognitive flexibility. Executive functions include mental functions, which are used to steer behavior in relation to conditions of the environment: setting targets, planning, deciding on priorities, controlling impulses, regulation of emotions, regulation of attention, targeting and sequencing of actions, motor functions, observation of consequences of actions and self-correction. Cognitive flexibility “has been described as the mental ability to switch between thinking about two different concepts, and to think about multiple concepts” (according to Wikipedia).

The brain is built up from last three months of pregnancy to the third decade. Building up the brain is not just growing of the brain structure (for which DHA is needed), but also cross-linking brain cells by branching out of neurons and axons, which is improved in the presence of EPA and DHA (Innis, 2014). Even with a completed structure, the brain will need DHA from the blood to maintain the structure, which is harder with lower levels of DHA in the blood (Bradbury, 2011). Moreover, complex brain functions depend on the circulation of the brain, with both EPA and DHA being important modulators of brain circulation (Kiso, 2011). For complex brain functions inflammatory processes also play a role. Inflammatory processes develop less, and are resolved faster, in the presence of high levels of EPA and DHA; here cytokines like resolvins, neuroprotectins and maresins are involved (Janssen & Kiliaan, 2014). Although the interplay of all these mechanisms is not yet fully understood, it has become clear that EPA and DHA play a major role for higher brain functions.

Cognitive performance of the infant and toddler

If the diet is supplemented with EPA and DHA during pregnancy, parameters indicating complex brain functions of the infant are improved: visual acuity, attention spans, coordination of eye and hand, problem solving behavior, and others. This has been demonstrated in numerous randomized controlled intervention trials using doses between 0.13 and 3.3 g EPA plus DHA / day, in comparison to placebo or no supplementation (Koletzko et al, 2007, Brenna & Lapillonne, 2009, Lauritsen & Carlson 2009, Innis 2014). Improvement of the performance of the infant correlated with the levels of (EPA+) DHA, if measured: e.g. in case of high levels of EPA plus DHA during pregnancy in the mother, their children had a significantly higher intelligence quotient at age 7 (in comparison with mothers with lower levels, Brenna & Lapillonne, 2009, Helland et al, 2008, Koletzko et al, 2014). A number of scientific societies, among them the German Society for Nutrition, recommend that pregnant women should at least take 200 mg DHA per day. According to our unpublished data, this is not sufficient in more than 50% of pregnant women to achieve a HS-Omega-3 Index between 8 and 11%. In the intervention trials mentioned, higher doses were well tolerated by pregnant women. Therefore, we think that pregnant women should have a HS-Omega-3 Index between 8 and 11%, and if only to supply the growing brain of the infant in an optimal way with EPA and DHA.

In children born at term, data on a positive effect of EPA plus DHA during lactation and afterward are not consistent. In some intervention trials, positive effects were seen on coordination or intellectual capabilities, while in others this was not the case (Koletzko, 2014). This may very well be due to the same methodological problems seen in trials in cardiology: Recruitment of participants irrespective of baseline levels of EPA plus DHA, and ignoring issues of bioavailability. Breast milk should contain 0.3% DHA, if necessary by supplementing the nursing mother (Koletzko et al, 2014). Infants should receive 100 mg DHA / day (Koletzko et al, 2014). In premature infants, the dose of DHA should be adjusted to weight.

Cognitive performance in the adolescent

Only few trials investigated the effects of EPA plus DHA on cognitive performance in adolescents aged between 10 and 18 years. If 15-year olds eat fish regularly, they will have better school grades at age 18, in comparison to adolescents not eating fish (Kim et al, 2010). Similar findings were reported in a comparable study on cognitive performance (Aberg et al, 2009).

Cognitive performance in the adult

The HS-Omega-3 Index in American soldiers with a mean age of 31.4+7.4 years correlated directly with executive function and cognitive flexibility (Johnston et al, 2012). Other complex cognitive performances, like non-verbal thinking or working memory of the brain also depend on levels of omega-3 fatty acids (Muldoon et al, 2010). An intervention trial in persons of this age (mean 33+3.4 years) demonstrated that working memory and attention improved with supplementation of EPA plus DHA (Stonehouse et al, 2013). Since these trials were not performed in children or adolescents, the data indicate that a high HS-Omega-3 is a prerequisite for optimal cognitive performance.

“Age-dependent” cognitive decline

In participants of the Framingham study (mean age 67 years) without clinical dementia, a low HS-Omega-3 Index correlated with a smaller brain volume and a vascular pattern of cognitive decline (logical and optical memory, abstract thinking) (Tan et al, 2012, Bowman et al, 2012, 2013). These results were confirmed and expanded by a trial from Berlin university – Charité: In a six month randomized intervention trial, EPA plus DHA improved not only brain structure and function, but also slowed the “natural” aging process of the brain (Witte et al, 2014). Improvements of executive function correlated with EPA in erythrocytes (Witte et al, 2014).

Low levels of omega-3 fatty acids predispose to later development of Alzheimer’s disease (Lopez et al, 2011). According to the results of randomized intervention trials, EPA plus DHA could be effective in the early, but not in later, stages of Alzheimer’s disease (Mazereeuw et al, 2012, Hashimoto M, 2011). In a randomized intervention trial, EPA plus DHA improved mild to moderate Alzheimer’s only in patients without ApoE4 (Quinn et al, 2014). ApoE4 is a risk factor for Alzheimer’s disease. This gene is responsible for a poor transport of DHA into the brain, and for EPA and DHA being shunted towards ß-oxidation, and not to be available elsewhere (Cunnanne et al, 2013).

In an official statement, American Heart Association, American Stroke Association and other scientific societies point out that the current evidence indicates that “increasing levels of omega-3 fatty acids is associated with better cognitive performance and less cognitive decline” (Gorelick et al, 2011). We suggest as a therapeutic target an optimal HS-Omega-3 Index (8 – 11%).

To summarise, a low HS-Omega-3 Index predisposes to compromised cognitive performance. EPA plus DHA improve cognitive performance in all ages. If it was tested, improvements correlated with the level of the Omega-3 Index.

A Double- Blind, Randomized, and Placebo-Controlled Clinical Trial With Omega-3 Polyunsaturated Fatty Acids for the Prevention of Migraine in Chronic Migraine Patients Using AmitriptylineAA Soares et al. Nutr Neurosci 1-5. 2017 Jan 05.

OBJECTIVE: To determine the prophylactic effect of OPFAϖ-3 in migraine.
SUBJECTS AND METHODS: This was a prospective, experimental, controlled, double-blind, and with comparison groups study. Sixty patients diagnosed with chronic migraine, according to the criteria of the International Classification of Headache Disorders, Third Edition (beta version) (ICHD-3β), were prophylactically treated with amitriptyline. They were divided into two equal groups: in group 1, prophylaxis was associated with OPFAϖ-3 and in group 2 with placebo. After 60 days, both groups were assessed by a second researcher.
RESULTS: Of the 60 patients with chronic migraine, only 51 patients (15 men and 36 women) completed the treatment. The group that received OPFAϖ-3 consisted of 27 (52.9%) patients (six men and 21 women), while the control group was equal to 24 (47.1%) patients (nine men and 15 women). These differences were not significant (χ 2 = 1.428; P = 0.375). In 66.7% (18/27) of the patients who used OPFAϖ-3, there was a reduction of more than 80.0% per month in the number of days of headache, while in the control group, the same improvement occurred in 33.3% (8/24) of patients. This difference was significant (χ 2 = 5.649; P = 0.036).
CONCLUSIONS: Polyunsaturated omega 3 fatty acids are useful for prophylaxis of migraine attacks.
PubMed: 28056704
DOI: 10.1080/1028415X.2016.1266133


Aberg MA, Aberg N, Brisman J, Sundberg R, Winkvist A, Toren K. Fish intake of Swedish male adolescents is a predictor of cognitive performance. Acta Paediatr. 2009;98:555-60.
Bowman GL, Dodge HH, Mattek N, Barbey AK, Silbert LC, Shinto L, Howieson DB, Kaye JA, Quinn JF. Plasma omega-3 PUFA and white matter mediated executive decline in older adults. Front Aging Neurosci. 2013;5:92.
Bowman GL, Dodge HH, Mattek N, Barbey AK, Silbert LC, Shinto L, Howieson DB, Kaye JA, Quinn JF. Plasma omega-3 PUFA and white matter mediated executive decline in older adults. Front Aging Neurosci. 2013;5:92.
Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, Kaye JA, Shannon J, Quinn JF. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology. 2012;78:241-9.
Bradbury J. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain. Nutrients. 2011;3:529-54
Brenna JT, Lapillonne A. Background paper on fat and fatty acid requirements during pregnancy and lactation. Ann Nutr Metab. 2009;55:97-122
Cunnane SC, Chouinard-Watkins R, Castellano CA, Barberger-Gateau P. Docosahexaenoic acid homeostasis, brain aging and Alzheimer’s disease: Can we reconcile the evidence? Prostaglandins Leukot Essent Fatty Acids. 2013;88:61-70.
Hashimoto M, Hossain S. Neuroprotective and ameliorative actions of polyunsaturated fatty acids against neuronal diseases: beneficial effect of docosahexaenoic acid on cognitive decline in Alzheimer’s disease. J Pharmacol Sci. 2011;116:150-62
Helland IB, Smith L, Blomén B, Saarem K, Saugstad OD, Drevon CA. Effect of supplementing pregnant and lactating mothers with n-3 very-long-chain fatty acids on children’s IQ and body mass index at 7 years of age. Pediatrics. 2008;122:e472-9
Innis SM. Impact of maternal diet on human milk composition and neurological development of infants. Am J Clin Nutr. 2014;99:734S-41S.
Janssen CI, Kiliaan AJ. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. Prog Lipid Res. 2014;53:1-17.
Kim JL, Winkvist A, Aberg MA, Aberg N, Sundberg R, Toren K, et al. Fish consumption and school grades in Swedish adolescents: a study of the large general population. Acta Paediatr. 2010;99:72-7.
Kiso Y. Pharmacology in health foods: effects of arachidonic acid and docosahexaenoic acid on the age-related decline in brain and cardiovascular system function. J Pharmacol Sci. 2011;115:471-5.
Koletzko B, Boey CC, Campoy C, Carlson SE, Chang N, Guillermo-Tuazon MA, Joshi S, Prell C, Quak SH, Sjarif DR, Su Y, Supapannachart S, Yamashiro Y, Osendarp SJ. Current information and Asian perspectives on long-chain polyunsaturated fatty acids in pregnancy, lactation, and infancy: systematic review and practice recommendations from an early nutrition academy workshop. Ann Nutr Metab. 2014;65:49-80.
Koletzko B, Cetin I, Brenna JT; Perinatal Lipid Intake Working Group; Child Health Foundation; Diabetic Pregnancy Study Group; European Association of Perinatal Medicine; European Association of Perinatal Medicine; European Society for Clinical Nutrition and Metabolism; European Society for Paediatric Gastroenterology, Hepatology and Nutrition, Committee on Nutrition; International Federation of Placenta Associations; International Society for the Study of Fatty Acids and Lipids. Dietary fat intakes for pregnant and lactating women. Br J Nutr. 2007;98:873-7
Lauritzen L, Carlson SE. Maternal fatty acid status during pregnancy and lactation and relation to newborn and infant status. Matern Child Nutr. 2011;7 Suppl 2:41-58.
Lopez LB, Kritz-Silverstein D, Barrett Connor E. High dietary and plasma levels of the omega-3 fatty acid docosahexaenoic acid are associated with decreased dementia risk: the Rancho Bernardo study. J Nutr Health Aging. 2011;15:25-31
Mazereeuw G, Lanctôt KL, Chau SA, Swardfager W, Herrmann N. Effects of ω-3 fatty acids on cognitive performance: a meta-analysis. Neurobiol Aging. 2012;33:1482.e17-29.
Muldoon MF, Ryan CM, Sheu L, Yao JK, Conklin SM, Manuck SB. Serum phospholipid docosahexaenonic acid is associated with cognitive functioning during middle adulthood. J Nutr. 2010;140:848-53.
Otsuka R, Tange C, Nishita Y, Kato Y, Imai T, Ando F, Shimokata H. Serum docosahexaenoic and eicosapentaenoic acid and risk of cognitive decline over 10 years among elderly Japanese. Eur J Clin Nutr. 2014;68:503-9.
Pase MP, Grima N, Cockerell R, Stough C, Scholey A, Sali A, Pipingas A. The Effects of Long-Chain Omega-3 Fish Oils and Multivitamins on Cognitive and Cardiovascular Function: A Randomized, Controlled Clinical Trial. J Am Coll Nutr. 2015 Jan 7:1-11. [Epub ahead of print]
Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010;304:1903-11
Stonehouse W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Evidence from clinical trials. Nutrients. 2014;6:2730-58
Stonehouse W, Conlon CA, Podd J, Hill SR, Minihane AM, Haskell C, Kennedy D. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr. 2013;97:1134-43.
Tan ZS, Harris WS, Beiser AS, Au R, Himali JJ, Debette S, Pikula A, DeCarli CS, Wolf PA, Vasan RS, Robins SJ, Seshardi S. Red Blood Cell Omega-3 Fatty Acid Levels and Markers of Accelerated Brain Aging. Neurology 2012;78:658-64
Witte AV, Kerti L, Hermannstädter HM, Fiebach JB, Schreiber SJ, Schuchardt JP, Hahn A, Flöel A. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014;24:3059-68.