Long chain omega-6 (AA) and omega-3 (DHA, EPA) polyunsaturated fatty acids (LC-PUFAs) are key structural components of cell membranes, affecting fluidity, flexibility, permeability and the activity of membrane-bound enzymes (3) (305, 306). Moreover, LC-PUFAs (AA, DHA, EPA) play an important role in cell signalling, cell division, gene expression and lipid mediator production (305, 306).
The omega-3 fatty acid docosahexaenoic acid (DHA) is selectively incorporated into the cell membranes of the retina; the light sensitive tissue lining the inner surface of the eye (4). Animal studies indicate that DHA is required for the normal development and function of the retina, and thus for vision. Research indicates that DHA is needed for the regeneration of the visual pigment ‘rhodopsin’, which plays a critical role in the visual transduction system that converts light hitting the retina to visual images in the brain (5).
The structural components of cell membranes in the brain contain high proportions of DHA and the omega-6 fatty acid arachidonic acid (AA), which suggests they are important to central nervous system function (6). Multiple mechanisms account for how DHA affects brain function. DHA content in neuronal cell membranes alters the availability of neurotransmitters (7), modulates signal transduction molecules and G-protein coupled receptors (230), and affects synaptogenesis (231, 232) and neuronal differentiation (233). DHA is also involved in the generation of active metabolites, such as docosanoids (234), which may play a neuroprotective role against inflammation and oxidative stress in neuronal tissue.
Eicosanoids, derived from the omega-6 fatty acid arachidonic acid (AA) and the omega-3 fatty acid eicosapentaenoic acid (EPA), are potent chemical messengers that play critical roles in immune and inflammatory responses. During an inflammatory response, AA and EPA in cell membranes can be metabolized by enzymes to form the eicosanoids ‘prostaglandins’ and ‘leukotrienes’, respectively. Eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and coagulation than eicosanoids derived from AA (2, 8).
The results of cell culture and animal studies indicate that omega-6 and omega-3 fatty acids can modulate the expression of a number of genes, including those involved with fatty acid metabolism and inflammation (8, 9). Although the mechanisms require further clarification, omega-6 and omega-3 fatty acids may regulate gene expression by acting like ‘steroid’ hormones (10, 11, 12, 13, 14).
The European Food Safety Authority (EFSA), which provides scientific advice to assist policy makers, has confirmed that clear health benefits have been established by the dietary intake of the polyunsaturated omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), since they contribute to:
· the maintenance of normal blood pressure;
· the maintenance of normal blood triglyceride levels (2 grams/day);
· the normal function of the heart (250 mg/day).
In addition, DHA contributes to:
· the maintenance of normal blood triglyceride levels (2 grams/day);
· the maintenance of normal brain function (250 mg/day);
· the maintenance of normal vision (250 mg/day).
Health benefits throughout pregnancy and infancy
Pregnancy and breast feeding
Breastfeeding is the most complete and beneficial method of infant feeding. Docosahexaenoic acid (DHA) and arachidonic acid (AA) are always found in human milk (235, 236, 237, 238, 239). While AA levels are quite consistent, the DHA content of breast milk is dependent on the maternal intake of DHA (237, 239).
Sources of preformed dietary DHA are the best method for increasing breast milk DHA. Increasing maternal intake of alpha-linolenic acid (ALA) does little to influence the content of breast milk DHA (240). Breast milk levels of DHA worldwide vary from as little as 0.1 to over 1.4% of total fatty acids (235, 238). The global mean DHA level is approximately 0.3%. In the United States, the mean DHA composition is 0.17%, an amount lower than many other countries. By increasing DHA in the maternal diet, breast milk DHA levels increase (241, 242, 243, 244,245). In turn, the infant’s blood DHA levels continually increase as breast milk DHA composition approaches 0.8%. At this point, infant DHA accretion begins to stabilize (237, 239, 246). A follow-up study of a RCT in pregnant women showed that maternal supplementation with DHA during pregnancy contribute to improved sustained attention in children at 5 years of age (307).
The increase in DHA status of mother and child is associated, in many but not all studies, with higher scores on tests of cognitive function and vision during infancy and into childhood (245, 247, 248, 249) (308). In addition, RCT and meta-analysis indicate that consumption of DHA by pregnant women reduced the risk of early and preterm delivery, improving pregnancy outcomes and reducing hospital costs (308-311)
Infants and children
The period from late gestation to four years of age is one in which the central nervous system sees critical and rapid growth, especially in the brain and eye. During this time, DHA and AA accretion is also rapidly contributing to both structural and functional development (250) (308, 312).Breast feeding is the gold standard for feeding the term infant and provides a source of DHA and ARA. Although infant formulas can never equal breast milk, they are formulated in an attempt to ensure that the most nutritionally complete substitute possible is made available for babies who are not breastfed. Many of these formulas are supplemented with both DHA and AA (306, 308, 3012). Observational and intervention studies show that DHA/AA-supplemented formula provides developmental benefits for the infant as compared to unsupplemented formula (306, 308, 312-314).
In formula-fed infants, blood and tissue levels of DHA and AA are lower than those of breastfed infants unless a DHA- and AA-supplemented formula is provided (251). By providing preformed DHA and AA in infant formula at levels generally found in human milk, blood levels of these fatty acids increase and developmental benefits can be measured as compared to controls. The benefits observed in infants fed a DHA/AA-supplemented formula include enhancement of visual, neurocognitive and immune development (306, 308, 312-315).
Visual development
As compared to the use of an unsupplemented formula, DHA/AA supplementation reported by several researchers results in more mature retinal function as measured by electroretinography and visual-evoked potential acuity (252, 253). The improvement in visual acuity is frequently described as being equivalent to “one line on the eye chart” at one year of age (254).
The early visual benefits exhibit a long-lasting effect on visual function. Research suggests that the level and duration of LCPUFA supplementation is significantly and positively related to visual acuity at one year of age(253). These findings suggest a continued need for these nutrients for at least the first 12 months of life (251, 255).
Systematic reviews and Meta-analyses of the current literature support the efficacy of DHA/AA supplementation for visual development (256, 257)(312, 314).
Neurocognitive development
DHA/AA supplementation also proves to be important for neural and cognitive development in some, but not all studies of formula fed infants. Several systematic reviews and meta-analyses have been published with mixed results (258, 259). These authors note that due to differences in design, difference in timing, and type of outcome measures, the literature remains too heterogeneous for successful meta-analysis.
A series of experiments shows improved scores on tests of problem-solving ability and ‘look duration to novel visual stimuli’ as the result of DHA/AA supplementation (260, 261). In another report, a test of problem solving ability was used to determine potential benefit from a formula containing 0.36% DHA and 0.72% ARA supplied throughout the first year of life (262). The formula was given as the sole feeding or as a follow-up formula when breast-feeding was discontinued. The supplemented and supplemented/breast-fed infants achieved more ‘intentional solutions to the task’ and higher intentional scores than those without LCPUFA supplementation. Similarly, a separate problem solving test of DHA/AA-supplemented infants showed increased cognitive function at 10 months compared to controls (261).
Such neurological benefits extend beyond the period of supplementation and are measureable using the Bayley Scales of Development. Several studies of early infant DHA/AA supplementation resulted in higher scores on tests of mental skills such as the Bayley Scales extending to 12 and 18 months of age (263, 264).
In a long-term, follow-up study, children who received DHA/AA supplementation during infancy demonstrated more efficient information processing than controls at six years of age (263). From the study, Birch et al. reported positive cognitive and visual outcomes in four-year-old children as the result of supplementation during infancy (265). At a follow up at six years of age, the authors concluded that use of DHA/AA-supplemented formula in infancy supports visual acuity and IQ maturation similar to that of breast-fed infants. In healthy boys dietary supplementation with DHA was associated with brain activation during sustained attention (266). Reviews of the evidence of RCT and prospective studies in health children age 4 to 18 years suggest that consumption of DHA may improve learning, behaviour and cognitive performance, particularly in those with low intake of omage-3 LC-PUFAs and/or low literacy (316,317).
Preterm infants
Preterm infants are born prior to the major period of intrauterine LCPUFA accretion and are not able to rely on sufficient endogenous DHA and AA synthesis for their rapid growth and neurological development (267). Despite variance in measuring visual and behavioral outcomes in this population, study results show more consistent benefits of DHA and AA supplementation on visual and cognitive function (268, 269). While some regulatory groups recommend, but do not mandate DHA/AA supplementation for term infants, such supplementation for preterm infants is more strongly supported (ESPGHAN preterms).
Authored by Dr. Peter Engel in 2010, reviewed and revised by Dr. D. Raederstorff and S. Gautier on 24.05.17
