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The Composition of Breast Milk: Does Maternal Diet Matter? Michael K. Georgieff, M.D. Professor of Pediatrics and Child Development Director, Center for.

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Presentation on theme: "The Composition of Breast Milk: Does Maternal Diet Matter? Michael K. Georgieff, M.D. Professor of Pediatrics and Child Development Director, Center for."— Presentation transcript:

1 The Composition of Breast Milk: Does Maternal Diet Matter? Michael K. Georgieff, M.D. Professor of Pediatrics and Child Development Director, Center for Neurobehavioral Development University of Minnesota

2 Overview Role of Breast Milk in Infant Nutrition Role of Breast Milk in Infant Nutrition Classes of Nutrients Classes of Nutrients Mechanisms of Maternal->Milk Transport Mechanisms of Maternal->Milk Transport Milk Volume Milk Volume Macronutrients Macronutrients –Transport; IOM Recommendations Selected Micronutrients Selected Micronutrients –Transport; IOM Recommendations Vitamins Vitamins –Transport; IOM Recommendations

3 Role of Breast Milk in Infant Nutrition Human Breast Milk is the Gold Standard for human nutrition Human Breast Milk is the Gold Standard for human nutrition Usually, complete nutrition for first 6 months in term infants Usually, complete nutrition for first 6 months in term infants –Vitamin D –Iron Preferred base for feeding preterm infants Preferred base for feeding preterm infants –Reduction of NEC rates –Needs fortification

4 Classes of Nutrients Water (volume) Water (volume) Macronutrients Macronutrients –Carbohydrate –Fat »LC-PUFAs Minerals Minerals –Sodium, Potassium, Chloride, Calcium Selected Micronutrients Selected Micronutrients –Iron, Zinc, Copper Vitamins Vitamins –Water Soluble (C, Bs, Folate) –Fat Soluble (A,E,D,K)

5 Mechanisms of Maternal Milk Production Nutrients transported across single cell layer from maternal serum into milk Nutrients transported across single cell layer from maternal serum into milk –Mammary Epithelial Cell Transport can be passive or active based on Transport can be passive or active based on –Nutrient –Developmental time period Active transporters similar to those found at other single cell transport surfaces Active transporters similar to those found at other single cell transport surfaces –Placenta, intestine, blood-brain barrier –Typically involve »Transporter from maternal serum into MEC (apical) »Exporter from MEC to milk (basal)

6 The Mammary Epithelial Cell

7 Water (Volume)

8 Water (Milk Volume) Water is a nutrient! Water is a nutrient! –Important for metabolic processing –Consumed and produced by numerous enzymatic processes Low milk volume a common cause of lactation failure Low milk volume a common cause of lactation failure –Premature delivery –Intrauterine growth-retardation (maternal hypertension) Milk volume not a function of maternal hydration (within reason) Milk volume not a function of maternal hydration (within reason) –Drinking more water doesnt help Milk volume is a function of amount of lactose secreted by MEC Milk volume is a function of amount of lactose secreted by MEC

9 Water (Milk Volume) Mammary epithelial cell assembles and secretes lactose Mammary epithelial cell assembles and secretes lactose Water (milk volume) follows osmotically Water (milk volume) follows osmotically Strategies to increase lactose production and secretion lead to increased milk volume Strategies to increase lactose production and secretion lead to increased milk volume –Growth hormone administration –Diet manipulations (increased CHO intake) »Does not work in non-fasting state –Genetic variability (polymorphisms of CHO metabolism)

10 Macronutrients CarbohydratesFat

11 Macronutrients: Carbohydrates Current recommendation is for an additional 400 Kcal/day for lactating mothers Current recommendation is for an additional 400 Kcal/day for lactating mothers –No recommendation re: carbohydrate/fat ratio Lactose is the primary carbohydrate in mothers milk Lactose is the primary carbohydrate in mothers milk Dietary lactose is broken down by intestinal lactase into glucose and galactose Dietary lactose is broken down by intestinal lactase into glucose and galactose –No circulating lactose in mothers blood Milk lactose must be synthesized from serum glucose and galactose Milk lactose must be synthesized from serum glucose and galactose –Hexoneogenesis (Sunehag et al, 2002, 2003) –Source of glucose and galactose are serum glucose, glycerol and dietary galactose

12 Macronutrients: Carbohydrates In fed (non-fasting state), 98% of glucose and 68% of galactose that ends up as lactose in milk is derived from plasma glucose In fed (non-fasting state), 98% of glucose and 68% of galactose that ends up as lactose in milk is derived from plasma glucose After 24 hour fast, percentages derived from plasma glucose drop to 72% and 51% respectively After 24 hour fast, percentages derived from plasma glucose drop to 72% and 51% respectively –Mammary cells use glycerol as source of carbon molecules Dietary galactose contributes 7 and 12% respectively if provided. Dietary galactose contributes 7 and 12% respectively if provided. Conclusion: Dietary state and CHO intake matters, but unclear if it matters much in fed state. Adaptations appear important for survival Conclusion: Dietary state and CHO intake matters, but unclear if it matters much in fed state. Adaptations appear important for survival Sunehag et al, 2002,2003

13 Macronutrients: Fat Fat is main source of calories in human milk Fat is main source of calories in human milk –Rat milk is low fat –Seal milk is up to 95% fat calories! Fat content varies considerably (Koletzko et al, 1992) Fat content varies considerably (Koletzko et al, 1992) –Between women of different cultures/diets »Chinese (hi CHO, low fat) < Swedish (hi fat, low CHO) –Between women of same culture/diet »Urban < Rural South African Women –Within women over time No specific IOM recommendations for fat amount or fat source during lactation No specific IOM recommendations for fat amount or fat source during lactation

14 Macronutrients: Fat Fats are assembled and transported into milk fat globules Fats are assembled and transported into milk fat globules Fat quantity and quality in diet does influence milk fat content Fat quantity and quality in diet does influence milk fat content –Low fat diet causes MEC to synthesize more fat (6x) »Mostly C10, C12 and C14 species –DHA supplementation increases DHA content of milk Fat Source does influence milk fat concentration Fat Source does influence milk fat concentration –Animal source vs vegetable source dietary fat –Role of trans fatty acids (TFAs) and conjugated linoleic acid (CLAs)

15 Macronutrients: Effect of Dietary Fat Content Partially hydrogenated vegetable oil (high TFAs) found in processed foods (some margarines) Partially hydrogenated vegetable oil (high TFAs) found in processed foods (some margarines) McGuire fed one of three diets to lactating mothers; measured fat content of milk McGuire fed one of three diets to lactating mothers; measured fat content of milk –High PHVO margarine, low PHVO margarine or low PHVO butter –In obese women, diet made no difference –In lean women, diet made large difference »Mothers fed high PHVO margarine made 2% milk »Mothers fed butter or low PHVO margarine made 3.5% milk (essentially whole milk)

16 Macronutrients: Specific Fats Long Chain Polyunsaturated Fatty Acids Long Chain Polyunsaturated Fatty Acids –Docosohexanoic Acid (DHA) production is rate limited in neonates –Essential fatty acids for preterm and probably term infants –Necessary for cell membranes in all organs –Important for visual system and brain development –Transported »Across placenta »Into human milk »Assures constant flow of LC-PUFA to young human

17 Influence of Country of Origin on Milk DHA (Innis et al, 1992) Country/Culture Country/Culture % Milk fat as DHA Inuit Eskimo 1.4 Dominica0.9 Malaysia0.9 St. Lucia 0.7 Canada/Vancouver0.4 Australia0.35 Sweden0.30 USA0.25 Germany0.2

18 Maternal Diet Influences LC-PUFA Content of Human Milk DHA supplementation to late gestation and lactating women works DHA supplementation to late gestation and lactating women works Boris et al (2004) fed mothers high DHA fish oil or low DHA olive oil Boris et al (2004) fed mothers high DHA fish oil or low DHA olive oil –Milk content of DHA in fish oil supplemented women at 4, 16 and 30 days was 2.3, 4.1 and 3.3 times higher than olive oil supplemented Henderson et al (1992) supplemented lactating women with 6 g/d of fish oil for 21 days Henderson et al (1992) supplemented lactating women with 6 g/d of fish oil for 21 days –Milk DHA increased from 0.37% to 0.70% of total fat (by weight)

19 Minerals SodiumPotassiumChlorideCalcium

20 Minerals Major minerals are sodium, potassium, chloride Major minerals are sodium, potassium, chloride Determined largely by osmotic forces (milk volume) Determined largely by osmotic forces (milk volume) –Active Na and K pumps Na, K, Cl are determined by electrical gradient in secretory cells and not affected by maternal diet Na, K, Cl are determined by electrical gradient in secretory cells and not affected by maternal diet No specific IOM recommendations for these minerals No specific IOM recommendations for these minerals

21 Calcium Calcium transported actively, but mechanisms are poorly understood Calcium transported actively, but mechanisms are poorly understood Maternal diet does not influence milk calcium concentrations Maternal diet does not influence milk calcium concentrations –Does not appear that drinking more milk, calcium supplements alter MEC excretion of calcium into milk Different than Vit D, where maternal diet makes a difference Different than Vit D, where maternal diet makes a difference

22 Calcium: IOM AI for Daily Calcium Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 1300 mg 1000 mg 1300 mg 1000 mg Source: IOM DRIs, 2001

23 Micronutrients Independent of Mom: Fe, Zn, Cu Dependent on Mom: Se, I, Fl, Mn

24 Vectoral Micronutrient Transport by MEC 4 Fe 2+ Milk Nutrient (maternal) Nutrient (fetal) Importer Receptor (TfR, Zip3,Ctr1) Nutrient Transporter Intracellular Unloading Exporter (FPN, Znt, ATP7) Nutrient Protein binding Endosome Maternal Blood Binding Protein

25 Micronutrients: Iron Breast milk quite low in iron concentration compared to formula (0.3 to 0.5 mg/L vs 4.5 to 12 mg/L) Breast milk quite low in iron concentration compared to formula (0.3 to 0.5 mg/L vs 4.5 to 12 mg/L) –More bioavailable (50% vs 4-33%) Iron transported actively across MEC using typical transporters Iron transported actively across MEC using typical transporters –Transferrin Receptor (uptake from serum) –Divalent Metal Transporter-1 (off loading intracellularly) –Ferroportin (export to milk)

26 Picture of Iron transport in MEC Kelleher and Lonnerdal, 2005

27 Iron: Does Maternal Diet Matter? Iron deficient mothers produce iron sufficient milk Iron deficient mothers produce iron sufficient milk –Unclear if iron deficiency increases transporter expression to maintain milk iron content (as seen with intestine and placenta) However, no evidence in humans that increased iron intake influences milk iron content However, no evidence in humans that increased iron intake influences milk iron content –Likely due to highly regulated iron transport process »Iron sufficiency decreases activity of iron transporters »Protects from iron overload in other systems –In rats, increased maternal dietary iron does increase maternal milk iron More research needed More research needed

28 IOM RDA for Iron Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 15 mg 18 mg 10 mg* 9 mg* Source: IOM DRIs, 2001 * Assumes that lactation inhibits menstrual cycle

29 Micronutrients: Zinc Milk zinc concentrations decrease over duration of lactation Milk zinc concentrations decrease over duration of lactation –Drop rapidly after 6 months Zinc is actively transported across MEC Zinc is actively transported across MEC –Zip family of transporter for uptake from maternal serum –ZnT families of transporters for secretion into milk Zinc content of milk not influenced by maternal diet Zinc content of milk not influenced by maternal diet

30 Picture of Zinc transport in MEC Kelleher and Lonnerdal, 2005

31 IOM RDA for Zinc Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 8 mg 13 mg 12 mg Source: IOM DRIs, 2001

32 Micronutrients: Copper Milk copper concentrations decrease over duration of lactation Milk copper concentrations decrease over duration of lactation –Drop rapidly after 6 months Copper is actively transported across MEC Copper is actively transported across MEC –CTR1 transporter for uptake from maternal serum –ATP7a transporter for secretion into milk Copper content of milk not influenced by maternal diet Copper content of milk not influenced by maternal diet

33 Picture of Copper transport in MEC Kelleher and Lonnerdal, 2005

34 IOM RDA for Copper Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 1300 mcg 900 mcg Source: IOM DRIs, 2001

35 Micronutrients That are Dependent on Maternal Serum Concentration Se, I, Fl, Mn are related to maternal intake Se, I, Fl, Mn are related to maternal intake Selenium Selenium –Necessary for normal iodine/thyroid status Iodine Iodine –Necessary for normal thyroid status Fluoride Fluoride –Necessary for bone/teeth –No studies of metabolism of fluoride during lactation Manganese Manganese –Necessary in enzymatic reactions (metabolism)

36 IOM Recommendations for Selenium, Iodine, Fluoride and Manganese during Lactation Nutrient Non- lactating y Non- lactating 18-50yLactating14-18yLactating18-50y Selenium 55 mcg 70 mcg Iodine 150 mcg 290 mcg Fluoride 3 mg 3mg3mg3mg Manganese 1.6 mg 1.8 mg 2.6 mg Source: IOM DRIs, 2001

37 Selected Vitamins FolateB6B12 Vitamin A Vitamin D

38 Three Patterns of Maternal Status-Milk Status Relationship Courtesy of Kay Dewey

39 Folate Necessary for Necessary for –1-carbon metabolism, cell division –Neurodevelopment »Neural tube closure (peri-conceptional) »Cognitive development (late fetal, neonatal) Actively transported from mother to fetus Actively transported from mother to fetus Maternal diet does not affect milk unless mom very deficient Maternal diet does not affect milk unless mom very deficient

40 IOM RDA for Folate Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 400 mcg 500 mcg Source: IOM DRIs, 2001

41 Vitamin B6 Low B6 levels associated with Low B6 levels associated with –Abnormal maternal and infant behaviors –Slower growth, especially after 4-6 months Maternal diet influences B-6 levels Maternal diet influences B-6 levels –India –USA

42 IOM RDA for B6 Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 2 mg 1.2 mg 1.3 mg Source: IOM DRIs, 2001

43 Vitamin B12 Low meat intake causes low B12 in milk Low meat intake causes low B12 in milk High prevalence in developing countries High prevalence in developing countries –32% in Guatemalan lactating women Increased risk in subpopulations of developed countries Increased risk in subpopulations of developed countries –Maternal avoidance of animal source foods x 4 years causes low milk B12 –Vegan mothers Effect on behavior and motor development in offspring Effect on behavior and motor development in offspring –Mechanism unknown

44 IOM RDA for B12 Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 2.4 mcg 2 mcg 2.8 mcg Source: IOM DRIs, 2001

45 Vitamin D, Breastfeeding and Rickets Rickets thought to be disease of the past Rickets thought to be disease of the past –Disappeared in early 1960s due to: » Recognition of role of sunlight in vitamin D homeostasis; fortification of milk » Use of multivitamin preps » Higher prevalence of formula use » AAP CON recommended 200 IU/d starting at 2 weeks of age

46 Prevalence: Is This A Real Problem? Case reports of nutritional rickets pop up in late 1970s Case reports of nutritional rickets pop up in late 1970s Increased case reports in last 20 years Increased case reports in last 20 years Exact prevalence remains unknown but prevalence of risk factors increasing Exact prevalence remains unknown but prevalence of risk factors increasing –Less sun exposure –Higher prevalence of nursing –Decreased prescription of vitamins for nursing infants

47 Milk Content of Vitamin D Human milk (22 to 100 IU/L) Human milk (22 to 100 IU/L) –Varies with maternal diet, pigmentation/sun exposure –Light pigmentation 68 IU/L –Dark pigmentation 35 IU/L –Both fall far short of RDA/DRI (infant does not consume 1L until 14 lbs=5-6 months of age) –Maternal 3000 IU/d supplement-> 100 IU/L –New data from Bruce Hollis group-> Maternal supplementation with 10,000 IU/d is safe and keeps infants vitamin D sufficient »Not in practice yet pending larger study

48 IOM AI for Vitamin D Intake by Lactating Mothers Non-lactating years Non-lactating years Lactating years Lactating years 200 IU 200 IU* Source: IOM DRIs, 2001

49 Summary of Micronutrient Groups in Lactation Group I Milk concentration correlated with maternal status, infant rapidly depleted. Supplements level in milk. Group II Milk concentration relatively independent of maternal status, mother may become depleted. Supplements have little or no effect on milk level. Examples: Thiamin Riboflavin Riboflavin Vitamin B-6 Vitamin B-6 Vitamin B-12 Vitamin B-12 Vitamin A Vitamin A Iodine Iodine Selenium Selenium Examples: Folate Calcium Calcium Iron Iron Copper Copper Zinc Zinc Table courtesy of Dr. Kay Dewey

50 Summary: Clinical Implications Some nutrients in human milk are not influenced by maternal diet unless the mother is very deficient; supplementation of sufficient mother doesnt change milk Some nutrients in human milk are not influenced by maternal diet unless the mother is very deficient; supplementation of sufficient mother doesnt change milk Some nutrients are highly dependent on maternal diet Some nutrients are highly dependent on maternal diet Milk volume can potentially be increased by increasing carbohydrate content of milk Milk volume can potentially be increased by increasing carbohydrate content of milk –No clinical strategy to do this yet

51 Summary: Clinical Implications Milk fat content and composition highly influenced by maternal diet Milk fat content and composition highly influenced by maternal diet –Butter vs margarine? Ice cream? –Fish oil vs vegetable oil to increase DHA Iron, zinc and copper all become very low after 6 months of lactation Iron, zinc and copper all become very low after 6 months of lactation –Argument to start complimentary food Low meat consumption places B12 at risk Low meat consumption places B12 at risk Maternal supplementation with high dose Vitamin D may get around supplementing infant (AAP rec.) Maternal supplementation with high dose Vitamin D may get around supplementing infant (AAP rec.)


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