Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One. 2013;8(6):e66697.
Cross-sectional observational study
The study included 493 children (ages 7–9 years old) from mainstream schools in Oxfordshire, UK. Children were eligible if their reading ability was below average according to national assessments but they had no significant learning disability.
Primary Outcome Measures
Whole blood samples were analyzed for fatty acid composition. Reading and working memory were assessed using the British Ability Scales (II). Behavior was rated using the revised Connors’ rating scales. Associations between blood fatty acid concentrations and cognitive function and behavior were examined.
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) accounted for only 1.9% and 0.55% respectively of total blood fatty acids. Lower DHA concentrations were associated with poorer reading ability (P<0.042), poorer working memory performance (P<0.001), and higher levels of parent-rated oppositional behavior and emotional lability (P<0.0001 for both).
DHA is well known for its importance in early brain and visual development.1,2 Naturopathic physicians routinely recommend DHA supplementation during pregnancy and lactation, and for infants who are not breastfed. Recent studies suggest that the benefit of DHA supplementation extends beyond the first 12 months of life into early childhood.3,4 Research supports the use of omega-3 supplementation in school-age children to treat attention-deficit hyperactivity disorder (ADHD) and other neuropsychiatric conditions.5,6 The importance of DHA to healthy children, however, has received little attention. This study is one of a small number that examine the role of DHA in cognition and behavior in otherwise healthy and mainstream children.
An excellent review completed in 2013 of the literature on the relationship between DHA and measures of learning and behavior in healthy school-age children identified 15 relevant publications.7 The studies varied in size and duration, from 33 to 598 subjects and from 2 to 12 months. DHA dosages also varied, ranging from 88 to 1,200 mg per day. Out of 7 studies on DHA supplementation and school performance, 5 reported that DHA improved measures of learning ability, reading, or spelling. Out of 6 studies measuring behavioral outcomes, 5 reported at least 1 significant improvement related to DHA supplementation or status. Two studies directly assessed brain activity, and both reported benefit as the result of DHA intake or status. While the number of studies was limited and the design features diverse, the review does suggest a connection between learning problems, behavior problems, and DHA deficiency.
The above study is a cross-sectional observational study that gives us important data on whole blood levels of omega-3 fatty acids in healthy children with below-average reading ability. The results are robust. This study benefits from a large sample size, an objective measure of omega-3 status, and well-validated tests of behavior and cognition. Lower levels of DHA correlated significantly with poorer reading ability, poorer working memory, and higher levels of behavioral problems. But what may be more striking is the actual value of omega-3 fatty acids detected in these children. The average omega-3 index in the study sample was only 2.46% (DHA and EPA accounted for 1.9% and 0.55% respectively).
In order to put this number in perspective, we need to understand the “omega-3 index.” The omega-3 index was developed as a risk assessment for cardiovascular disease in adults. It is conventionally defined as the percentage of EPA + DHA in red blood cell membranes. A value <4% correlates with high cardiovascular risk; 4–8% correlates with intermediate cardiovascular risk; and >8% correlates with low cardiovascular risk.8 Although the results in the study of children discussed here were obtained from whole blood (reflecting plasma plus erythrocyte stores), studies on whole blood and erythrocyte omega-3 index yield similar results. In fact a whole blood omega-3 index <4.32% correlates with the highest rate of cardiovascular disease.9 While the purpose of this commentary is not to discuss cardiovascular risk, these are the only reference ranges that are currently available to make sense of the omega-3 index. Although there is no reference range for omega-3 index in children, it is clear that the average level of 2.46% found in this study reflects a suboptimal value. Because subjects were screened for reading ability, this means that on average, children with below-average reading ability also have below-optimal blood levels of omega-3 fatty acids.
Taken together, the screening and intervention stages of the DOLAB trial provide strong evidence for the benefits of DHA supplementation in healthy mainstream children.
It is no surprise to find suboptimal omega-3 levels even in these mainstream healthy children. Although this data comes from a British study, it is likely that similar values would be found in the United States. Whereas humans evolved on an omega-6:omega-3 ratio closer to 1:1, modern diets provide a ratio between 10:1 and 20:1.10 According to USDA statistics, we have seen a steep increase in the intake of salad oils and cooking oils over the last 10 years.11 These vegetable oils, such as corn, soybean, cottonseed, and safflower oil, are all relatively high in omega-6 and low in omega-3 fatty acids. A 2011 study suggested that increased intake of omega-6 fatty acids has likely decreased tissue levels of omega-3 fats over the course of the 20th century.12 It is these dietary trends that underlie the deficient omega-3 status detected in healthy children in this study.
This cross-sectional observational study formed the screening stage of an intervention trial, the DHA Oxford Learning and Behavior (DOLAB) study. The DOLAB study was designed to determine whether supplementation with 600 mg per day DHA for 16 weeks would improve reading, working memory, and behavior.13 Results of the DOLAB study showed that parent-rated (but not teacher-rated) behavior problems were significantly reduced by supplementation with DHA. While there was no effect of DHA on reading in the full sample, significant benefit was seen in children whose initial reading performance was ≤20th percentile. Those whose initial reading performance was ≤10th percentile experienced the most significant gains from treatment. Over the 4-month intervention, these children experienced an additional reading age gain of 1.9 months. This is evidence that the improvements seen in a healthy childhood population may be subtle and that those who are most vulnerable benefit the most. Taken together, the screening and intervention stages of the DOLAB trial provide strong evidence for the benefits of DHA supplementation in healthy mainstream children.
Currently there is no specific recommendation for DHA intake in healthy children. The World Health Organization recommends 200–250 mg EPA + DHA combined for children ages 6–10 years old.14 The American Academy of Pediatrics defers to the American Heart Association’s recommendation to eat fish 2 times per week.15 Concerns about PCBs and mercury, however, may be good reason to limit fish consumption in children. Fish toxicity is beyond the scope of this commentary but deserves further discussion. If using supplements, the ideal source and dosage is also up for debate. The intervention stage of the DOLAB trial used 600 mg DHA per day. This is equivalent to the amount a child would get in 1 teaspoon of cod liver oil. While some children will readily take cod liver oil from a spoon, there are now many DHA supplements available for kids. Most children think they are treats. This study may convince parents that these fish oil treats are worth it.
- Docosahexaenoic acid (DHA). Monograph. Altern Med Rev. 2009;14(4):391-399.
- Jensen CL, Voigt RG, Prager TC, et al. Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants. Am J Clin Nutr. 2005;82(1):125-132.
- Colombo J, Carlson SE, Cheatham CL, et al. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Am J Clin Nutr. 2013;98(2):403-412.
- Willatts P, Forsyth S, Agostoni C, Casaer P, Riva E, Boehm G. Effects of long-chain PUFA supplementation in infant formula on cognitive function in later childhood. Am J Clin Nutr. 2013;98(2):536S-542S.
- Grassmann V, Santos-Galduroz RF, Galduroz JC. Effects of low doses of polyunsaturated fatty acids on the attention deficit/hyperactivity disorder of children: a systematic review. Curr Neuropharmacol. 2013;11(2):186-196.
- Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2011;50(10):991-1000.
- Kuratko C, Barrett E, Nelson E, Salem N. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients. 2013;5(7):2777-2810.
- Harris WS. The omega-3 index as a risk factor for coronary heart disease. Am J Clin Nutr. 2008;87(6):1997S-2002S.
- Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med. 2002;346 (15):1113-1118.
- Simopoulos AP. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol Neurobiol. 2011;44(2):203-215.
- Liebman B. The Changing American Diet. A Report Card. Nutrition Action Health Letter. 201310-11.
- Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011;93(5):950-962.
- Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P. Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLoS One. 2012;7(9):e43909.
- Food and Agriculture Organization of the United Nations. Fats and Fatty Acids in Human Nutrition. Report of an expert consultation. FAO Food And Nutrition Paper. 2010;91:10.
- Gidding SS, Dennison BA, Birch LL et al. Dietary recommendations for children and adolescents: a guide for practitioners. Pediatrics. 2006;117(2):544-559.