Omega 3 e omega 6: funzione in età pediatrica

Transcription

1 Omega 3 e omega 6: funzione in età pediatrica Carlo Agostoni Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Dipartimento di Scienze Cliniche e di Comunità Università di Milano [email protected] [email protected]

2 LA FISIOLOGIA

3 ACIDI GRASSI POLINSATURI n-6 Precursori acido linoleico18:2 n-3 acido alfa-linolenico18:3 delta6desaturasi elongasi delta5desaturasi acido arachidonico 20:4 acido eicosapentaenoico 20:5 elongasi delta6 desaturasi LCPUFA acidi grassi polinsaturi beta-ossidazione perossisomale a lunga catena acido docosaesaenoico 22:6

4 Hwang D et al

5 J Nutr. 128: 427S 433S, EPA DHA The effect of dietary level of a-linolenic acid (18:3v3) on the content of its metabolites in liver lipids.

6 ARA Left panel: Suppression of the metabolism of 0.6% of dietary calories of 18:2v6 by increasing levels of dietary 18:3v3, as measured in liver lipids. Right panel: Suppression of the metabolism of 1% of calories of 18:3v3 by increasing levels of dietary 18:2v6 as indicated by changes in liver fatty acids.

7 Hulbert AJ et al

8 nelle Quale rapporto ottimale omega6/omega3? Nel corso dell evoluzione circa 1 Oggi nelle diete occidentale circa 15:1 Consigliato da 10:1 a 5:1 ( età evolutiva) Forse ottimale da 3:1 a 5:1

9 LA FISIOPATOLOGIA

10 P Calder et al

11 Fatty acids and eicosanoids are peroxisome proliferator activated receptor (PPAR) ligands Hwang D

12 P Calder et al

13 Mazurak V et al randomized, double-blind, placebo-controlled trial provided children, (ages 5 7 years; n¼37) who had low intakes of DHA, with a dietary supplement containing AA (20 30mg daily) and DHA (14 21mg daily) or a placebo supplement for 7 months. Unstimulated (US), b-lactoglobulin (BLG), ibuprofen (IB) or lipopolysaccharide (LPS) Journal of Pediatric Gastroenterology and Nutrition 2008; 46:570

14 Miles BA et al A systematic review included 23 studies. Evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs..

15 Nobili V et al, Pediatr Obes 2012, on-line

16 Steatosic patients Liver biopsy at months after starting DHA supplementation effect on statosis but not on fibrosis (inflammation?)

17 n-3 PUFA enhance hepatic fatty acid oxidation and inhibit fatty acid synthesis and VLDL secretion by regulating gene expression PUFA (DHA) control of hepatic metabolic processes Chem Phys Lipids 2008;153:3-13

18 LA GENETICA

19 Ameur A et al

20 Haplotype D is associated with increased FADS activity. Intriguingly, the distance between FADS1 and FADS2 has been reduced (through a deletion) from over 75 kb in monkeys to only 11 kb in humans. This deletion brought the promoters of FADS1and FADS2 closer to each other, with a resulting coordinated regulation of FADS expression.

21 DIFFERENT RESULTS WITH LCPUFA trials Different capacity of endogenous synthesis based on individual genetic background

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23 Glaser C, Maternal and Child Nutr 2011; 7(S2): 27 FADS3 function not characterized

24 No association was found between genetic variants and DHA variance, which would support the concept that little DHA is synthesized endogenously, and DHA serum concentrations are primarily determined by the dietary supply of preformed DHA from fish and other sources. The effect size of SNPs was very high: genetic variants explained as much as 28.5% of the variation in serum AA contents in this cohort of free-living individuals with considerable variation in lifestyle and dietary habits. The reconstructed haplotypes predicted some 12% and 10% of the variation of the AA precursors Glaser C et al, Maternal and Child Nutrition 2011;7 (Suppl 2): 27

25 DHA in forebrain in 34 infants up to 2 years EPA

26 ARACHIDONIC ACID ADRENIC ACID LINOLEIC ACID

27 OLEIC ACID

28 GENETIC VARIATIONS AND PUFA METABOLISM FIRST MODEL Adapted from Lattka E et al, Ann Nutr Metab 2012; 60 (Suppl 3):8-17

29 Association between breastfeeding and IQ moderated by the genetic polymorphism Rs in the FADS2 gene in 2 independent birth cohorts. BF children carrying the C allele showed an IQ point advantage an IQ advantage relative to those not BF. Breastfeeding had no effect on IQ of GG homozygotes. Caspi A, PNAS 2007; 104:18860

30 Steer CD, Plos One 2010;5:e11570 In contrast to Caspi study, GG children exhibited the greatest difference between feeding methods. Breastfed children performed similarly irrespective of child genotype whereas formula fed GG children performed worse than other children on formula milk.

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32 GENETIC VARIATIONS AND PUFA METABOLISM SECOND MODEL inflammation Adapted from Lattka E et al, Ann Nutr Metab 2012; 60 (Suppl 3):8-17

33 High-Oleic acid Sunflower Oil

34 inflammation These results are the first to show that intake of EPA+DHA for 26 wk can alter the gene expression profiles of PBMCs to a more antiinflammatory and antiatherogenic status.

35 GENETIC VARIATIONS AND PUFA METABOLISM THIRD MODEL Other than FADS CVD risk factors Adapted from Lattka E et al, Ann Nutr Metab 2012; 60 (Suppl 3):8-17

36 Scaglioni S et al BACKGROUND

37 GENETIC VARIATIONS AND PUFA METABOLISM FINAL MODEL Other than FADS inflammation CVD risk factors Adapted from Lattka E et al, Ann Nutr Metab 2012; 60 (Suppl 3):8-17

38 GLI STILI DI VITA: IL MODELLO DEL FUMO

39 Agostoni et al, Lancet 1998; 352:1703 LC-PUFA daily intakes by the infant (mg/kg)1 1st day 3rd month S NS S NS AA 8.1± ± ± ±1.8 DHA 5.3± ± ± ±1.1

40 Agostoni et al, Arch Dis Child 2008;93:414 non-smokers (reference), smokers (>5 cigarettes per day) who either stopped within the first trimester of pregnancy (early smokers) or who continued througout pregnancy (late smokers). Agostoni et al, Arch Dis Child 2008;93:414

41 Neonatal sample at 4 days Agostoni et al, J Pediatr 2005;147:857

42 Omega 3 e omega 6: funzione in età pediatrica La composizione lipidica delle membrane dipende da fattori genetici ed ambientali. La quota e composizione degli omega 3 dipende più di altri acidi grassi dalla dieta La quota degli omega 3 ( DHA) si associa allo sviluppo strutturale e funzionale degli organi a maggiore componente lipidica (fegato, sistema nervoso centrale) Il bilancio tra omega3 ed omega6 è un elemento regolatore di processi infiammatori ed immunitari Fabbisogni ed effetti sono significativamente associati alla componente genetica