Breast-feeding and cognitive development: a meta-analysis.

Distribution, interconversion, and dose response of n−3 fatty acids in humans

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) deals with the setting of Dietary Reference Values (DRVs) for fats. A lower bound of the reference intake range for total fat of 20 energy % (E%) and an upper bound of 35 E% are proposed. Fat intake in infants can gradually be reduced from 40 E% in the 6 12 month period to 35–40 E% in the 2nd and 3rd year of life. For specific fatty acids the following is proposed: saturated fatty acid (SFA) and trans fatty acid intake should be as low as possible; not to set any DRV for cis-monounsaturated fatty acids; not to formulate a DRV for the intake of total cis-polyunsaturated fatty acids (PUFA); not to set specific values for the n-3/n-6 ratio; to set an Adequate Intake (AI) of 4 E% for linolenic acid; not to set any DRV for arachidonic acid; not to set an UL for total or any of the n 6 PUFA; to set an AI for alpha-linilenic acid (ALA) of 0.5 E% not to set an UL for ALA; to set an AI of 250 mg for eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) for adults; to set an AI of 100 mg DHA for infants (>6 months) and young children <24 months; to increase by 100 200 mg preformed DHA in addition to the AI for adults as an adequate supply of n-3 long chain PUFA during pregnancy and lactation; not to set any DRV for conjugated linoleic acid. For cholesterol it was decided not to propose a reference value beside the limitation on the intake of SFA.

https://orbit.dtu.dk/files/6355881/prod11324452634179.Scientific.pdf

Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol

The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina.

The brain is highly enriched with fatty acids. These include the polyunsaturated fatty acids (PUFAs) arachidonic acid and docosahexaenoic acid, which are largely esterified to the phospholipid cell membrane. Once PUFAs are released from the membrane, they can participate in signal transduction, either directly or after enzymatic conversion to a variety of bioactive derivatives ('mediators'). PUFAs and their mediators regulate several processes within the brain, such as neurotransmission, cell survival and neuroinflammation, and thereby mood and cognition. PUFA levels and the signalling pathways that they regulate are altered in various neurological disorders, including Alzheimer's disease and major depression. Diet and drugs targeting PUFAs may lead to novel therapeutic approaches for the prevention and treatment of brain disorders.

Polyunsaturated fatty acids and their metabolites in brain function and disease

Dietary NT are reported to have significant effects upon lymphoid, intestinal and hepatic tissues, and lipid metabolism (Table 3). The mechanism remains unknown, and the nutritional role of NT remains controversial. However, maintenance of the endogenous NT supply via de novo synthesis and salvage is metabolically costly. Preformed NT supplied by the diet may contribute to tissue NT pools and thus optimize the metabolic function of rapidly dividing tissues such as those of the gastrointestinal and immune systems. An exogenous source of NT may be particularly important for individuals whose dietary intake of NT is low and/or whose tissue needs are increased, for example, rapidly growing infants fed most cow's milk-based formulas and individuals with disease related immunosuppression, intestinal, or liver injury. Under these conditions, dietary NTs may play a role as conditionally essential nutrients. In addition to serving as nucleic acid precursors, NTs and their related metabolic products are potent inter- and intracellular biological mediators. Certain effects of dietary NT may relate to one or more of these important functions. Area for future study include: 1. 1. The absorption and metabolism of nucleic acids, NTs, NSs, bases, and related metabolic products in humans, and the effects of age and disease upon these activities. 2. 2. Dietary NT effects upon gut-associated lymphoid tissues. 3. 3. The content of nucleic acid, NTs, NSs, bases, and their related metabolic products in human milk. 4. 4. The relative contribution of nucleic acid, NTs, NSs, and free bases to observed biologic effects, and the effects of individually administered purine and pyrimidine compounds.

The role of nucleotides in human nutrition

The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects

Investigations with animals demonstrate that dietary nucleotides influence immune function. Restriction of dietary nucleotides in mice decreases several indices of cell-mediated immunity as well as resistance to challenge with Staphylococcus aureus or Candida albicans. Spleen cells of mice maintained on nucleotide-free diet produce less interleukin-2 and have lower natural killer cell cytotoxicity and macrophage activation than those of animals fed nucleotide-supplemented diets. In vivo lymphoproliferative response, macrophage phagocytic activity and expression of interleukin-2 receptor and lyt1 surface marker are also lower in animals fed nucleotide-free diets. At 2 mo of age, infants fed breast milk or nucleotide-supplemented infant formula exhibit increased natural killer cell activity compared with infants fed unsupplemented formula. Dietary nucleotide restriction in animals may also result in hepatic lipid accumulation and decreased mucosal height and gut wall thickness. Adenosine monophosphate, a mediator of hepatic and small bowel blood flow, may play a unique role among the nucleotides studied. In conclusion, de novo synthesis and salvage of nucleotides is a metabolically costly process. An exogenous source of nucleotides from the diet may optimize the function of rapidly dividing tissues, particularly when growth is rapid and the diet is low in nucleotides.

Dietary Nucleotides: Cellular Immune, Intestinal and Hepatic System Effects

Nucleotides (NT) and their related metabolic products play key roles in many biological processes. NT can be synthesized endogenously and thus are not considered essential nutrients. Studies have demonstrated, however, that dietary NT can have beneficial effects; the term "conditionally essential" has been used to describe their role in human nutrition. These nutrients may become essential when the endogenous supply is insufficient for normal function, even though their absence from the diet does not lead to a classic clinical deficiency syndrome. Most dietary NT are rapidly metabolized and excreted. However, some are incorporated into tissues, particularly at younger ages and with fasting. Under conditions of limited NT intake, rapid growth or certain disease states, dietary NT may spare the cost of de novo NT synthesis and optimize the function of rapidly dividing tissues such as those of the gastrointestinal and immune systems. Animals fed NT-supplemented versus non-NT supplemented diets have enhanced gastrointestinal growth and maturation, and improved recovery following small and large bowel injury. Indices of humoral and cellular immunity are enhanced, and survival rates are higher following infection with pathogens. Infants receive NT in human milk, where they are present as nucleic acids, nucleosides, nucleotides and related metabolic products. The NT content of human milk is significantly higher than most cow's milk-based infant formulae. Dietary NT are reported to enhance the gastrointestinal and immune systems of formula-fed infants. Infants fed NT-supplemented versus non-supplemented formula have a lower incidence of diarrhea, higher antibody titers following Haemophilus influenzae type b vaccination and higher natural killer cell activity. These data suggest that human milk NT may contribute to the superior clinical performance of the breastfed infant.

Dietary nucleotides: effects on the immune and gastrointestinal systems

Nucleotide (NT) nitrogen, a component of nonprotein nitrogen, accounts for approximately 0.1% to 0.15% of the total nitrogen content of human milk. The results of studies in animals indicate that dietary NTs may be required for maintenance of normal immune function. Thirty-seven healthy term infants were either breast-fed (n = 9) or fed SMA formula supplemented with 33 mg of NTs per liter (n = 13, NT+) or standard SMA formula (n = 15; NT-). At 2 months of age, natural killer cell percent cytotoxicity was significantly higher in the breast-fed and NT+ groups compared with the NT- group (41.7 +/- 4.7, 32.2 +/- 3.4, 21.7 +/- 2.2%, respectively). Interleukin-2 production by stimulated mononuclear cells was higher in the NT+ compared with the NT- group at 2 months of age (0.90 +/- 0.28 U/mL, 0.27 +/- 0.11 U/mL, respectively); neither formula-fed group differed significantly from the breast-fed group. Rate of growth and incidence and severity of infections did not differ significantly among dietary groups. Nucleotides may be a component of human milk that contributes to the enhanced immunity of the breast-fed infant.

Jane D. Carver

Papers

The role of nucleotides in human nutrition

The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects

Dietary Nucleotides: Cellular Immune, Intestinal and Hepatic System Effects

Dietary nucleotides: effects on the immune and gastrointestinal systems

Dietary Nucleotide Effects upon Immune Function in Infants