EPA and DHA intakes in children

The richest food sources of both EPA and DHA are fatty fish, with smaller amounts in lean fish and other seafood⁽Reference Innis and Elias^9, Reference Meyer, Mann and Lewis¹⁰⁾. The distributions of dietary EPA and DHA intakes within populations are generally skewed with lower median than mean intakes, explained by a substantial number of individuals eating no or very little fish⁽Reference Meyer, Mann and Lewis^10–Reference Welch, Lund and Amiano¹²⁾. However, information of dietary intakes of EPA and DHA, particularly among children, is limited. This has several reasons, including the limitations of dietary intake methodology, collecting accurate information on dietary intakes from children, and the completeness of fatty acid data on foods listed in databases. For example, the fat and fatty acid composition of fish varies widely, meaning that specific information on the types of fish and seafood consumed is essential; eggs can be an important source of fatty acids and are often hidden in other foods such as cakes and puddings, but depending on the recall method their intake may be missed. Moreover, children frequently consume food outside of the home, and without the parents' knowledge.

The rather limited available information on dietary intake in children suggests that EPA and DHA intake tends to be lower than in adults⁽¹³⁾. Similarly, the intake of children may also be lower per kg body weight than in infants who are breast-fed or fed infant formulas containing DHA⁽Reference Koletzko, Lien and Agostoni^7, Reference Koletzko, Rodriguez-Palmero and Demmelmair¹⁴⁾. Children's current dietary intake of EPA and DHA may also be lower than some decades ago⁽Reference Ailhaud, Massiera and Weill¹⁵⁾. Whether current intakes of EPA and DHA among children are adequate for optimal functional and health outcomes requires information on dietary intakes of children following different diets together with measures of functional endpoints sensitive to potential biological effects of these fatty acids. It is conceivable that EPA and/or DHA intakes might contribute to health promotion and chronic disease prevention, but reliable and comparable data on dietary intake of n-3 fatty acids and on biochemical markers of status in different populations of children are scarce. The available data do not allow us to conclude that changing intakes of EPA and/or DHA can affect physical or mental development or yield specific functional benefits.

The effects of EPA and DHA on biological function, health and prevention of disease

Historically, recommended intake levels for nutrients have been defined to prevent signs of deficiency in the general population. In recent years, however, nutritional recommendations and guidelines are being progressively formulated based on evidence linking specific nutrients at given intakes to disease prevention and optimal performance and health⁽¹⁶⁾. An example is the Acceptable Macronutrient Distribution Range used by the Institute of Medicine⁽¹⁷⁾, which represents the range of energy intakes from the different macronutrient intakes that, when consumed as part of a diet providing an appropriate amount of energy to maintain ideal body weight, are associated with low risk of chronic disease.

Individuals that have low EPA and/or DHA intakes but eat plentiful sources of α-linolenic acid, such as vegans and vegetarians, do have a lower EPA and DHA status than omnivores, but are not known to develop signs of deficiency⁽Reference Davis and Kris-Etherton¹⁸⁾. Higher intake levels of EPA and DHA have been associated with a range of possible physiological and health benefits in humans⁽Reference Akabas and Deckelbaum¹⁹⁾, such as the improvement in neurological functions in infancy⁽Reference Cheatham, Colombo and Carlson²⁰⁾, the primary and secondary prevention of CVD and the metabolic syndrome in adults⁽Reference Mozaffarian and Rimm^1, Reference Carpentier, Portois and Malaisse²¹⁾, modulation of immune response⁽Reference Sijben and Calder²²⁾ and improved pregnancy outcomes⁽Reference Szajewska, Horvath and Koletzko^3–Reference Makrides, Duley and Olsen⁵⁾. The evidence for beneficial effects of EPA and DHA intakes on health outcomes in children is limited and will be summarised here.

The importance of attaining optimal brain and retina DHA for visual and neurological development and function is considered critical in the perinatal period⁽Reference Eilander, Hundscheid and Osendarp²³⁾. Beyond infancy, evidence linking DHA intake or blood levels of DHA with neurological benefits is limited to children following restricted diets with very low dietary intakes of EPA and DHA, such as children with phenylketonuria⁽Reference Beblo, Reinhardt and Muntau^24–Reference Agostoni, Massetto and Biasucci²⁶⁾. These studies show that increasing DHA status with fish oil supplements is consistent with improvements in speed of information processing in the central nervous system as assessed by latencies of visual evoked potentials⁽Reference Beblo, Reinhardt and Muntau²⁴⁾, as well as significant improvements of coordination and fine motor skills⁽Reference Beblo, Reinhardt and Demmelmair²⁵⁾. These findings indicate that a continuous dietary supply of preformed DHA and/or EPA may be essential for achieving optimal neural function even in children who have a high intake of the precursor α-linolenic acid with restricted diets due to phenylketonuria⁽Reference Agostoni, Verduci and Massetto²⁷⁾. This conclusion may be relevant for healthy children as well, since children with early treated phenylketonuria are generally healthy and have no detectable alterations of energy and fatty acid metabolism.

EPA and DHA in combination with n-6 fatty acids have also been reported to improve behaviour in children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder and dyspraxia in some⁽Reference Stevens, Zhang and Peck^28–Reference Richardson and Montgomery³⁰⁾ but not all⁽Reference Hirayama, Hamazaki and Terasawa^31, Reference Voigt, Llorente and Jensen³²⁾ studies. A recent systematic review of these studies concluded that there is insufficient evidence to identify any effect of nutrition, diet and dietary change on learning, education or performance of school-aged children from the developed world⁽Reference Ells, Hillier and Summerbell³³⁾. Further research of high quality, representative of all populations, undertaken for longer durations and using universal standardised measures of educational attainment is needed⁽Reference Ells, Hillier and Summerbell³³⁾ and should evaluate the potential relative roles of EPA and DHA, respectively, in children with neurodevelopmental disorders.

High intakes of EPA and/or DHA may beneficially modulate the immune system by decreasing the synthesis of pro-inflammatory arachidonic acid-derived eicosanoids⁽Reference Calder³⁴⁾ and by shifting the balance of T helper 1 (Th1), T helper 2 (Th2) and T regulatory cells⁽Reference Krauss-Etschmann, Hartl and Rzehak³⁵⁾. Evidence for beneficial effects on asthma in children is not established, but some studies suggested that for certain subgroups of respondent children, symptoms of asthma may be alleviated with DHA/EPA supplementation⁽Reference Nagakura, Matsuda and Shichijyo³⁶⁾. It is unclear to what extent these and other observations using high dosages of EPA and DHA supplements relate to possible effects with lower intakes achieved with foods.

A regular intake of fatty fish is widely advised to adult populations for the prevention of CVD, and a large part of associated beneficial effects is thought to be mediated by the supply of EPA and DHA with fatty fish⁽Reference Mozaffarian and Rimm¹⁾. Potential beneficial effects of EPA and DHA intakes in children on their future risk of developing CVD have not been documented. However, food preferences and eating habits that are established in childhood appear to show a certain degree of tracking into adulthood⁽Reference Parsons, Manor and Power^37, Reference Lanigan, Turnbull and Singhal³⁸⁾. Therefore, it seems desirable to accustom children to dietary patterns that are likely to promote health in adulthood.

Approaches to develop possible advice on dietary intakes of EPA and DHA

Advice on dietary nutrient intake values for children is based on a variety of different methodological approaches, including consideration of deficiency states, usual intake levels, factorial approaches to calculate needs for maintenance and growth, effects on physiological function and health⁽Reference Prentice, Branca and Decsi³⁹⁾ and extrapolation from reference values established for other age groups such as adults or infants⁽Reference Atkinson and Koletzko⁴⁰⁾. The authors of the present paper conclude that the current lack of reliable data on the relationship between EPA and DHA intake or status and functional and health outcomes in 2- to 12-year-old children does not allow determination of physiological requirements or nutrient intake levels using classical approaches to derive dietary recommendations. Extrapolating n-3 fatty acid intake levels, including those for EPA and DHA, for children from existing reference values for either adults or infants (Table 1) seems inappropriate, not only because there is still considerable uncertainty regarding nutrient intake levels for DHA and/or EPA in both adults and infants, but also because extrapolation based for example on body mass or energy expenditure is expected to inadequately reflect age-specific physiological requirements, such as continuing neurological development and lean tissue growth, that determine dietary nutrient needs⁽Reference Atkinson and Koletzko⁴⁰⁾. Thus, at present the available evidence is insufficient to formulate quantitative nutrient intake values for EPA and DHA in children. However, it seems reasonable that dietary advice for children should be consistent with advice for the adult population, such as regular intake of one to two fatty fish meals per week providing DHA and EPA associated with the risk reduction of CVD. If such a habit can be established early in life and be maintained, it may also support a desirable long-chain n-3 fatty acid supply among females of child-bearing age to support optimal pregnancy outcomes. There is no reason why children in a family setting should be excluded from the consumption of at least one to two meals of fatty fish per week, which is recommended for the adult population⁽Reference Kris-Etherton and Innis²⁾.

Present and future research

The possible relationships between intake and effects of DHA and/or EPA need to be studied in detail. Presently, the research project ‘Nutrition and Mental Health’ funded by the European Commission's 7th Framework Research Programme will try to establish whether there is a relationship between the level of dietary DHA supply and neurological functions in children. Further studies should also include evaluating effects of the intake of α-linolenic acid, as well as factors affecting its endogenous conversion to EPA and DHA, such as the concomitant intake of linoleic acid⁽Reference Blank, Neumann and Makrides⁴¹⁾ and the role of genetic polymorphisms of the desaturating enzymes Δ-6 and Δ-5 desaturases⁽Reference Schaeffer, Gohlke and Muller⁴²⁾.

Relevant public health outcomes that are likely to be linked to lifelong intakes of EPA and DHA include the risk of (future) CVD and the metabolic syndrome, optimal mental development and behaviour, and immune response.

Dietary studies should be carefully conducted and analysed, with a specific and standardised methodology, considering the substantial challenges in assessing individual intakes of EPA and DHA in children. Since assessment methods for dietary intake are imprecise, age-specific information on fatty acid status based on biological markers are also required. Cross-sectional analyses from prospective birth and childhood cohort studies are likely to provide valuable insights that can contribute to designing intervention trials. Age-specific effects of different fatty acid intakes and dosages on relevant endpoints should be assessed in controlled intervention studies. The data obtained should aim at establishing the effect of different doses of individual fatty acids, and of different combinations and ratios of PUFA, on well-defined and quantifiable outcomes. Such outcomes may include:

1. (1) Markers of cardiovascular risk and the metabolic syndrome;

2. (2) Measures of neural function, cognition and behaviour;

3. (3) Markers of inflammatory response, immune function and their related diseases, such as allergy or autoimmune disease.

Studies in children aiming at evaluating these and other outcomes must respect the limitations determined by the ethical rules for research with children⁽Reference Ungar, Joffe and Kodish^43, Reference Knudson⁴⁴⁾.

Although recent risk analyses tend to support the safety and overall benefit of increased fish consumption⁽Reference Cohen, Bellinger and Connor^45, Reference Sioen, De and Verbeke⁴⁶⁾, potential adverse effects of recommending increased dietary intakes of EPA and DHA from fish oil concentrates or fatty fish, such as the risk of adverse effects of contamination with environmental pollutants⁽Reference Oken, Radesky and Wright^47, Reference Halldorsson, Meltzer and Thorsdottir⁴⁸⁾, should be taken into account.