Long-chain n-3 fatty acids in seafood and child nutrition

Transcription

1 Long-chain n-3 fatty acids in seafood and child nutrition Lotte Lauritzen, Faculty of Life Sciences, Copenhagen University, Denmark LL 24/4-2007, DTU ph.d.course Nordic recommendations Infants 6-12 mo Children 1-2 y Adults (>2 y) Total polyunsaturated acids (PUFA, essential fatty acids) 5-10 E% min. 5 E% 5-10 E% 5-10 E% min. 3 E% Pregnant & lactating = infant n-6/n n-3 PUFA Estimated intake in g/d at a typical energy intake Min. 1 E% 0.75 g/d 1.07 g/d Min. ½ E% Recommended ~1 E% g/d Fish 2 /wk for main meal = g fish/wk (=30-40 g/d), varying between fatty and lean fish types. Dias 2 Nordic Nutrition Recommendations

2 Danish intake Fish Adults (15-85 y) in 1995: 22 g/d and in 2000/2001:17 g/d 85% of the adults eat less fishthanrecommended. Approximately 50% eats fish 1-2 /wk. Children (1-3 y) in 1995: 11 g/d Only approx. 33% eats fish 1-2 /wk. >50% do not eat any fish as main meals. n-3 PUFA Adults: Approx. 2 g/d ALA & 0.4 g/d n-3 LCPUFA Children (1-3 y): 8 g/d PUFA ~ 1.4 g/d n-3 PUFA Dias 3 RBC n-3 PUFA status in Danes RBC 22:6n-3 (FA%) Males Females 4 mo 6.96± ± mo 5.12± ± y 5.25± ±1.51 2½ y 5.49± ± y 3.85± y 4.99± ±0.99 Adults (40-70 y & pregnant, resp.) 4.60± ±1.27 Dias 4 Data from papers by Lauritzen et al

3 Questions in need of answers Which functions are affected by n-3 PUFA? What is an optimal RBC 22:6n-3 status? Does the status-function-relationship differ with age? Does the relationship between intake and status differ with age? Dias 5 n-3 PUFA functions/effects n-3 PUFA deficiency in animals Impaired visual functions and effects on learning n-3 PUFA intake in infants Maturation of visual acuity and cognitive development n-3 LCPUFA supplementation in healthy adults (Meta-analysis of RCT): Plasma lipid profile: reduced TG, possible increase in HDL-c, but not in LDL-c (Cochrane 2004, Hartweg et al. Diabetologia 2007;50: ) Blood pressure: 2 mmhg reduction in systolic & diastolic blood pressure (Geleijnse et al. Hypertens, 2002;20:1493-9) Heart rhythm: slower heart rate and possible increase in variability (Mozaffarian et al. Circulation 2005;112: ) Dias 6 3

4 Dias 7 Fatty acid composition of human milk & infant formula % of fatty acids (FA%) Human milk Formula Europeans Vegans Eskimos DK 2003 SFA MUFA PUFA (= 8 E%) 18:2n :4n :3n :6n n-6/n Brain 22:6n-3 accretion during growth spurt depends on diet Brain 22:6n-3 accretion during 1 year ~ 4g Martinez Dias Brain 8 Res. 1992; 583: & Makrides et al. Am.J.Clin.Nutr. 1994; 60:

5 Faster visual acuity development in breast-fed infants - due to 22:6n-3? Metaanalysis BF vs. FF at 2-7 mo, p<0.05 SanGiovanni et al. Early Hum.Dev. 2000; 57: Breast-fed Formula-fed Dias 9 Jørgensen et al. Lipids 1996, 31: Consensus: Premature need 22:6n-3 for optimal visual development with fat lines: Metaanalysis results, p<0.001 at 2 & 4 mo Benefit from 22:6n-3 addition Unfavourable effect of 22:6n-3 Dias 10 SanGiovanni et al. Pediatrics 2000; 105:

6 Dose-response between 22:6n-3 intake & visual acuity improvement in term infants Relative visual acuity (+22:6n-3/control) p=0.001 Line of equality Improvement with 22:6n-3 Birch et al Experimental formula 22:6n-3 equivalents (mg/d, 18:3n-3 =10%) Uauy et Dias al. J 11 Pediatr. 2003; 143: S17-25 & SanGiovanni et al. Pediatrics 2000; 105: Visual acuit y at 4 mo. (logmar) 0,9 0,8 0,7 0,6 0,5 0,4 2,0 Dias 12 Group Dose-response relationship between infant RBC 22:6n-3 and visual acuity Regression line: r 2 =0.04, p=0.049 p=0.002 adj. for sex, GA, age, siblings OO FO 8 wks 0.85 ± ± wks 0.64 ± ± 0.09 No effect by group comparisons in this or other trials. 4,0 6,0 8,0 10,0 12,0 14,0 Infant RBC 22:6n-3 at 4 mo (FA%) Lauritzen et al. Lipids 2004, 39: FO OO High fish 6

7 The effect of breast-feeding on IQ depends on Δ 6 -desaturase-genotype Dias 13 Caspi et al. PNAS 104(47): , 2007 Maternal seafood consumption and neurodevelopment in childhood % of children in lowest quartile for verbal IQ The ALSPAC-study Diet by FFQ on British pregnant women WISC-III on a subgroup of 5407 children at 8 years Curve fit: r 2 =0.92, p=0.017 Toxic effect of MeHg Dias 14 Hibbeln et al. Lancet 2007; 369:

8 Associations of maternal fish intake and developmental in Danish children DNBC: children. Development score at 18 mo. adjusted for SES and breast-feeding duration Oken, E. et al. Am J Clin Nutr 2008;88: Copyright 2008 Dias 15 The American Society for Nutrition Maternal fish oil supplementation enhance problem solving at 4 year Supplementation: 18 gest.wk-3 mo after birth MPCOMP: Mental processing composite SEQ & SIM-PROC: Sequential & simultaneous problem solving & information processing NONVERB: Non-verbal abilities RCT at present far from conclusive. Dias 16 Helland et al., Pediatrics 2003; 111: e39-e44 8

9 Maternal fish oil supplementation gave slower language development Age (mo) n OO FO HF 12.2± ± ± y comprehension 72±45 52±38* 63±40 1y production 7.9± ±5.4* 6.1±5.6 Age (mo) n 24.6± ± ± y production 287± ± ±148 Longest sentence 3.5± ± ±2.1 Determined by parental questionnaires (Danish MacArthur CDI) at 12 & 24 mo Data are given as mean±sd (n) and * gives t-test p<0.05 vs OO. Language production at 1 y is positively associated with parental education (Pearson r=-0.159, p=0.034, n=132) Positive or negative?? Dias 17 Lauritzen et al. Reprod. Nutr. Develop. 2005; 45: Formula LCPUFA-supplementation affects blood pressure at 6 years Blood pressure (mmhg) LCPUFA formula Control formula Mean difference (95% CI) P Mean (-5.4 to -0.5) Diastolic (-6.5 to -0.6) Systolic (-5.3 to 0.7) LCPUFA formula added 0.35 % 20:4n-6 & 0.2 % 22:6n-3 18:2n-6 & 18:3n-3 in control formula 11.4 % & 0.7 % No or possible opposing effect in maternal FO-supplementation trials Dias 18 Forsyth et al. BMJ 2003; 326:

10 CVD-effects of 1 teaspoon/d of fish oil in RCT with infants from 9 to 12 mo After intervention values: RBC 20:5n-3 (FA%) 22:6n-3 (FA%) Systolic blood pressure (mmhg, adj. 9mo, age, breast-feeding & cuff) No fish oil Fish oil p 0.7± ± ±2 (n=27) 3.2± ± ±2 (n=26) <0.001 < Corr. RBC-DHA (p=0.05) Plasma TAG (mmol/l, adj. 9mo, sex, age, last meal energy) 1.50±0.09 (n=19) 1.29±0.09 (n=20) 0.10 Corr. RBC-EPA (p<0.01) Heart rhythm (msec) Higher RR = slower pulse 455 (n=33) 458 (n=28) ΔRR corr. RBC- EPA (p=0.010) Dias 19 Damsgaard et al. J. Nutr.2006;136:94-99, Lauritzen et al. (in prep) Higher ex vivo IFN-γ production in infant whole blood after fish oil ( ) Adj. IFN-γ concentration (pg/ml Fish oil p=0.05 ) No fish oil mo infant 3½ ml/d fish oil vs. no oil Cytokine production measured ex vivo in whole blood cultures for 22 h with L. paracasei and adj. for for baseline Dias 20 Damsgaard et al. J.Nutr. 2007; 137:

11 General n-3 PUFA need during growth? Dias 21 Breast-feeding is associated with IQ Test age (cognitive developmental/iq) 8 & 15 y 3, 5 & 7 y 7½ y IQ-differences detected in adults. Mortensen et al. JAMA 2002; 18: ½ y ½, 1 & 2 y 2, 5 & 8 y 4 y 7½-8 y ½, 1, 1½, 2, 3, 4 & 5 y 1½-2½ y 1½ y Overall effect only small, but a reduction in frequency with low IQ Dias 22 Anderson et al. AJCN 1999;70:

12 Effect of human milk in preterm RCT on teenage blood pressure & leptin RCT: Mean MAP (mmhg) Leptin (μg/(l kg fat mass)) Human milk-group 81.9±7.8 (n=66) 0.79 (cv%=85) (n=66) Formula-group 86.1 ±6.5 (n=64) 0.60 (cv%=90) (n=58) Difference (95% Cl) -6.6 to -1.6 (p=0.001) -5.2 to 58.2 % (p=0.10) Diastolic blood pressure (mmhg) β=-0.3 mmhg per 10% increase in human milk [95% CI -05 to -0.1]; p=0.006 Serum leptin rel. to fat mass (μg/(l kg)) n=191, p for trend = Distribution by tertiles of the percentage of human milk Dias 23Singhal et al. Lancet, 2001, 357: 413-9, Singhal et al. AJCN 2002: 75:993 12