Importance of a supplemental source of DHA during Pregnancy and Lactation

Transcription

1 Importance of a supplemental source of DHA during Pregnancy and Lactation Catherine J. Field PhD RD Professor of Nutrition, Co-Director of the Cancer Research Institute Faculties of Agriculture, Life and Environmental Sciences and Medicine and Dentistry University of Alberta, Edmonton, Alberta, Canada

2 Outline What is DHA? Why is it important? Mom Infants Should we be concerned about maternal status of DHA? What are the opportunities for the functional nutrition, nutraceutical and supplement?

3 Objectives for this presentation 1. Understand the importance of docosahexaenoic acid (DHA) for maternal infant health 2. Learn the sources of DHA in the diet of mothers during pregnancy and when breast feeding 3. See evidence of why a supplement containing DHA improves moms status and the composition of her breast milk

4 What is Docosahexaenoic Acid (DHA)?

5 corn oil sunflower n-6 n-3 LA (linoleic acid) 18:2(n-6) Plant oil flax canola Δ6 desaturase ALA ( -linolenic acid) 18:3(n-3) 18:3(n-6) 20:3(n-6) elongase 18:4(n-3) 20:4(n-3) LCPUFA= n-3 and n-6 fatty acids 20C animal tissues AA 20:4(n-6) Δ5 desaturase EPA 20:5(n-3) elongase 24:5(n-3) 22:4(n-6) 22:5(n-6) elongase Δ4 desaturase Fish or supplement 22:5(n-3) DHA 22:6(n-3) Δ6 desaturase 24:6(n-3) b-oxidation

6 LCPUFA concentration in cell membranes Cell growth demand for new phospholipid Diet fat changes membrane phospholipid composition Changes in phospholipid fatty acid composition alter fluidity & impact function Micro environments- lipid rafts

7 LCPUFAs are pre-cursors of functional lipids (eicosanoids) Eicosanoids are signaling proteins that influence many biological functions i.e. labour induction, immune function,?neurofunction Families of eicosanoids Prostaglandins Prostacyclins Thromboxanes Leukotrienes Resolvins, Protectins, lipoxin Depending on the substrate (n-3 or n-6 LCPUFA) the eicosanoid has a different effect in the body

8 Summary of mechanisms Change in LCPUFA supply Altered composition of membrane phospholipids Membrane alterations: rafts; fluidity Signal transduction pathways Eicosanoids cell function (adapted from Calder, 1990) Change maternal/infant health

9 Importance of DHA to mother and child

10 Importance of DHA to mom Association with low DHA status and risk of maternal depression Experimental studies suggest benefits to placental health Meta-analyses of studies concluded that maternal DHA supplementation was associated with an increase in gestation ( days) Plus all the other health benefits of DHA: risk of cancer, CVD, insulin resistance etc.

11 Importance of DHA to infant Growth & Development Brain & cognitive development DHA deposited in second half of gestation, continues to accumulate postnatally (4 g DHA 2-4y) DHA status of mom/infant is associated with improved cognitive development Visual development Structural component of retinal lipids (comprises as much as 50% of total rod & cone outer segment) (Reviews: Gould et al. AJCN 97:531, 2013; Janssen & Kiliaan Prog Lipid Res 53:1, 2014)

12 Immune Function

13 Immunity in the 1 st year of life Infant has a different immune system than an adult ability of T cells to respond to immune challenges (i.e. proteins, pathogens, toxins) Infant relies on their innate immune system Are in the process of developing tolerance to proteins in the environment Compared to adults, infants have a delayed immune response and risk of infection & atopic diseases

14 Our RCTs in infants who were not breast fed has suggested that adding DHA+AA to full (and preterm) formula: modifies type of immune cells in blood closer to that of the breast-fed infant facilitates the maturation of peripheral CD4 + cells improves the ability of T cells to respond to an immune challenge increases the ability of immune cells to produce the regulatory cytokine (IL-10) when challenged Improves ex vivo tolerance to dietary proteins Suggests improved/faster immune development (Field et al., 2008, 2009,2010)

15 Applied Physiology Nutrition and Metabolism In press, available on line (April 2016)

16 Conclusion Epidemiological studies suggest an inverse association between breast milk DHA content and the development of atopic disease in children with family history of atopic disease Evidence from epidemiological studies : Maternal DHA intake influences breast milk DHA content Breast milk AA and DHA content negatively associated with the development of atopic diseases in children at risk of atopic disease Richard et al. APNM, 2016 (in press)

17 Conclusion nutritional intervention studies suggest that supplementing the maternal diet with fish oil (late pregnancy and/or lactation) and feeding infant formula enriched in AA/DHA alters markers of immune function in a direction that is thought to be beneficial. DHA in maternal diet (n=3) DHA in infant diet (n=6) All were RCTs 2.2 to 4 months postpartum Daily fish oil EPA (range: mg/d) and DHA ( mg/d) Immune function or incidence of allergic and atopic diseases were 1º or 2 nd outcome RCTs (4), observational open label (2) 4 wk to 12 months. 5 studies provided infant formula enriched in AA (range %) and DHA (range %); 1 provided fish oil supplement (110 mg EPA & 280 mg DHA) Immune function or incidence of allergic and atopic diseases was the 1º or 2 nd outcome Richard et al. APNM, 2016 (in press)

18 Summary of our animal studies A maternal diet during lactation supplemented with DHA (0.9% fat) Did not change growth of the pups the DHA content in breast milk to levels (1% w/w fat) similar to that in human populations % of mature B cells(cd80 + and CD71 + ) and a better Th1 response to mitogens (maturation response) Improved the tolerance response ( serum IgE) to a dietary protein at the end of suckling This improved tolerance to vaccination with a dietary protein was maintained after suckling, even when a diet without DHA was fed. Richard et al, 2016 (Eur J Nutr, J Nutr Biochem) in press

19 Is Mom getting enough DHA?

20 corn oil sunflower animal tissues N-6 N-3 LA (linoleic acid) 18:2(n-6) 18:3(n-6) 20:3(n-6) AA 20:4(n-6) 22:4(n-6) 22:5(n-6) Δ6 desaturase elongase Δ5 desaturase elongase Δ4 desaturase Plant oils flax canola 0.1-9% ALA (linolenic acid) 18:3(n-3) 18:4(n-3) 20:4(n-3) EPA 20:5(n-3) 22:5(n-3) DHA 22:6(n-3) elongase Conversion depends on: ALA in the diet LA in the diet Adipose tissue lipolysis Genetics Hormones Environment 24:5(n-3) Δ6 desaturase 24:6(n-3) At 3 mos post partum a lactating mon secrets b-oxidation mg DHA each day into breast milk

21 Br J Nutr 98, , 2007 Recommendations for DHA during pregnancy/lactation Consensus recommendations on behalf of the European Commission research projects Perinatal Lipid Metabolism and Early Nutrition Programming developed jointly with representatives of (Child Health Foundation, the Diabetic Pregnancy Study Group, the European Association of Perinatal, the European Society for Clinical Nutrition and Metabolism, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, the International Federation of Placenta Associations and the International Society for the Study of Fatty Acids and Lipids) Pregnant and lactating women require 200 mg DHA each day

22 . Relationship between DHA intake and DHA content in human milk (r = 0.84, P = 0.002; study day 14) in 10 lactating women Nataša Fidler et al. J. Lipid Res. 2000;41: by American Society for Biochemistry and Molecular Biology

23 Yuhus et al., 2006 Variation in DHA proportion in human milk between countries

24 Apron Cohort Large cohort of women & their infants in Alberta Canada

25 Study Design Pregnant women from Edmonton /Calgary, AB, Canada Trimester 1

26 Estimated daily intake of EPA, DPA and DHA (mg) Estimated Daily Intake of n-3 LCPUFAs Food + Supplements during Pregnancy & 3 Postpartum DHA recommendation DHA EPA DPA 50 Average intake of DHA from diet 120 mg 0 trimesters Jia et al. APNM 40:474, 2015

27 Relative Contribution of Food Categories to Total Dietary n-3 LCPUFAs Intake 0.9% 1.1% Salmon 1.5% 2.1% 2.4% Whitefish 5.4% 78.9% 61.3% Shellfish & crustaceans 7.8% Tuna Others Small oily fish Seafood and fish Seaweed Poultry (Chicken and Turkey Products) Egg products Meat (beef and pork products) Fast foods and convenience foods Dairy products Baked products Others Jia et al. APNM 40:474, 2015

28 Estimated daily intake of DHA (mg) Published in Appl. Physiol. Nutr. Metab. 40: DOI: /apnm mg 225 mg * * Women who reported to take an EPA and DHA supplement were 11 and 16 times more likely to DHA meet Supplement current User Non recommendation DHA Supplement during User pregnancy and at 3 month postpartum respectively (P 0.001) DHA recommendation Average supplement contained 299 mg DHA 0 n= n=415 n=109 n=372 Pregnancy Postpartum

29 Infant Feeding Status at 3 months postpartum n=772

30 Yuhus et al., 2006 Variation in DHA proportion in human milk between countries 0.26 ± 0.25 (APrON cohort)

31 Effect of reported supplement use on breast milk DHA content Fatty acid Supplement users (n=49) Non-supplement users (n=285) % of fat DHA * EPA * AA ALA LA *P<0.05

32 Breast Milk DHA (%w/w) Relationship between maternal plasma DHA and content in breast milk R² = (p<0.001) Plasma phospholipid DHA (%w/w)

33 Summary A supply/source of DHA is essential for maternal & infant health The majority of women in the 1 st cohort of APrON study (80% in pregnancy and 83% 3month postpartum) did not meet current recommendations for DHA Fish, more specifically salmon, were the major contributors of dietary n- 3 LCPUFAs in this population Maternal intake/status influences the DHA available to the infant during lactation Taking a daily supplement containing DHA increased the content of DHA in breast milk to levels believed to be optimal

34 What are the opportunities for the functional nutrition, nutraceutical and supplement industry?

35 ?Opportunities Create and make available sources of DHA (at least 200 mg) for women during pregnancy and lactation Supplements Ingredients Functional foods

36 Acknowledgements Dr. Caroline Richard Students Xiaoming Jia MSc RD Yara Assad MSc Nour Wattar RD Erin Lewis PhD A whole gang of amazing undergraduate students Technicians Susan Goruk Marnie Newell Nicole Coursen Collaborators The APrON team and participants Dr. Linda McCargar Funding: NSERC CIHR Alberta Innovates Health Solutions: APrON Study

37 Questions

38 Extra slides

39 AA levels in Human Milk 0.46 ±0.16 Yuhus et al., 2006