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 Overview Role of Breast Milk in Infant Nutrition Classes of Nutrients Mechanisms of Maternal->Milk Transport Milk Volume Macronutrients – Transport; IOM Recommendations Selected Micronutrients – Transport; IOM Recommendations Vitamins – Transport; IOM Recommendations Role of Breast Milk in Infant Nutrition Human Breast Milk is the Gold Standard for human nutrition Usually, complete nutrition for first 6 months in term infants – Vitamin D – Iron Preferred base for feeding preterm infants – Reduction of NEC rates – Needs fortification Classes of Nutrients Water (volume) Macronutrients – Carbohydrate – Fat » LC-PUFAs Minerals – Sodium, Potassium, Chloride, Calcium Selected Micronutrients – Iron, Zinc, Copper Vitamins – Water Soluble (C, Bs, Folate) – Fat Soluble (A,E,D,K) Mechanisms of Maternal Milk Production Nutrients transported across single cell layer from maternal serum into milk – Mammary Epithelial Cell Transport can be passive or active based on – Nutrient – Developmental time period 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) The Mammary Epithelial Cell Water (Volume) Water (Milk Volume) Water is a nutrient! – Important for metabolic processing – Consumed and produced by numerous enzymatic processes 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) – Drinking more water doesn’t help Milk volume is a function of amount of lactose secreted by MEC Water (Milk Volume) Mammary epithelial cell assembles and secretes lactose Water (milk volume) follows osmotically 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) Macronutrients Carbohydrates Fat Macronutrients: Carbohydrates Current recommendation is for an additional 400 Kcal/day for lactating mothers – No recommendation re: carbohydrate/fat ratio Lactose is the primary carbohydrate in mother’s milk Dietary lactose is broken down by intestinal lactase into glucose and galactose – No circulating lactose in mother’s blood 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 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 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. 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 Macronutrients: Fat Fat is main source of calories in human milk (@55%) – Rat milk is low fat – Seal milk is up to 95% fat calories! 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 Macronutrients: Fat Fats are assembled and transported into milk fat globules 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 – Animal source vs vegetable source dietary fat – Role of trans fatty acids (TFAs) and conjugated linoleic acid (CLAs) Macronutrients: Effect of Dietary Fat Content 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 – 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) Macronutrients: Specific Fats 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 Influence of Country of Origin on Milk DHA (Innis et al, 1992) Country/Culture % Milk fat as DHA Inuit Eskimo 1.4 Dominica 0.9 Malaysia 0.9 St. Lucia 0.7 Canada/Vancouver 0.4 Australia 0.35 Sweden 0.30 USA 0.25 Germany 0.2 Maternal Diet Influences LC-PUFA Content of Human Milk DHA supplementation to late gestation and lactating women works 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 – Milk DHA increased from 0.37% to 0.70% of total fat (by weight) Minerals Sodium Potassium Chloride Calcium Minerals Major minerals are sodium, potassium, chloride 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 No specific IOM recommendations for these minerals Calcium Calcium transported actively, but mechanisms are poorly understood 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 Calcium: IOM AI for Daily Calcium Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years Lactating 18-50 years 1300 mg 1000 mg 1300 mg 1000 mg Source: IOM DRIs, 2001 Micronutrients Independent of Mom: Fe, Zn, Cu Dependent on Mom: Se, I, Fl, Mn Vectoral Micronutrient Transport by MEC Milk Maternal Blood Intracellular Unloading Nutrient (maternal) Importer Receptor (TfR, Zip3,Ctr1) Exporter (FPN, Znt, Nutrient ATP7) 2+ 4 Fe Transporter Endosome Binding Protein Nutrient Protein binding Nutrient (fetal) 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) – More bioavailable (50% vs 4-33%) Iron transported actively across MEC using typical transporters – Transferrin Receptor (uptake from serum) – Divalent Metal Transporter-1 (off loading intracellularly) – Ferroportin (export to milk) Picture of Iron transport in MEC Kelleher and Lonnerdal, 2005 Iron: Does Maternal Diet Matter? 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 – 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 IOM RDA for Iron Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years Lactating 18-50 years 15 mg 18 mg 10 mg* 9 mg* * Assumes that lactation inhibits menstrual cycle Source: IOM DRIs, 2001 Micronutrients: Zinc Milk zinc concentrations decrease over duration of lactation – Drop rapidly after 6 months 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 Picture of Zinc transport in MEC Kelleher and Lonnerdal, 2005 IOM RDA for Zinc Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years Lactating 18-50 years 8 mg 8 mg 13 mg 12 mg Source: IOM DRIs, 2001 Micronutrients: Copper Milk copper concentrations decrease over duration of lactation – Drop rapidly after 6 months 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 Picture of Copper transport in MEC Kelleher and Lonnerdal, 2005 IOM RDA for Copper Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years 1300 mcg 1300 mcg 900 mcg Lactating 18-50 years 900 mcg Source: IOM DRIs, 2001 Micronutrients That are Dependent on Maternal Serum Concentration Se, I, Fl, Mn are related to maternal intake Selenium – Necessary for normal iodine/thyroid status Iodine – Necessary for normal thyroid status Fluoride – Necessary for bone/teeth – No studies of metabolism of fluoride during lactation Manganese – Necessary in enzymatic reactions (metabolism) IOM Recommendations for Selenium, Iodine, Fluoride and Manganese during Lactation Nutrient Nonlactating 18-50y 55 mcg Lactating 14-18y Lactating 18-50y Selenium Nonlactating 14-18 y 55 mcg 70 mcg 70 mcg Iodine 150 mcg 150 mcg 290 mcg 290 mcg Fluoride 3 mg 3mg 3mg 3mg Manganese 1.6 mg 1.8 mg 2.6 mg 2.6 mg Source: IOM DRIs, 2001 Selected Vitamins Folate B6 B12 Vitamin A Vitamin D Three Patterns of Maternal Status-Milk Status Relationship Courtesy of Kay Dewey Folate Necessary for – 1-carbon metabolism, cell division – Neurodevelopment » Neural tube closure (peri-conceptional) » Cognitive development (late fetal, neonatal) Actively transported from mother to fetus Maternal diet does not affect milk unless mom very deficient IOM RDA for Folate Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years Lactating 18-50 years 400 mcg 400 mcg 500 mcg 500 mcg Source: IOM DRIs, 2001 Vitamin B6 Low B6 levels associated with – Abnormal maternal and infant behaviors – Slower growth, especially after 4-6 months Maternal diet influences B-6 levels – India – USA IOM RDA for B6 Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years Lactating 18-50 years 2 mg 2 mg 1.2 mg 1.3 mg Source: IOM DRIs, 2001 Vitamin B12 Low meat intake causes low B12 in milk High prevalence in developing countries – 32% in Guatemalan lactating women 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 – Mechanism unknown IOM RDA for B12 Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years Lactating 18-50 years 2.4 mcg 2 mcg 2.8 mcg 2.8 mcg Source: IOM DRIs, 2001 Vitamin D, Breastfeeding and Rickets 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 » Prevalence: Is This A Real Problem? Case reports of nutritional rickets pop up in late 1970s Increased case reports in last 20 years Exact prevalence remains unknown but prevalence of risk factors increasing – Less sun exposure – Higher prevalence of nursing – Decreased prescription of vitamins for nursing infants Milk Content of Vitamin D 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 IOM AI for Vitamin D Intake by Lactating Mothers Non-lactating 14-18 years Non-lactating 18-50 years Lactating 14-18 years Lactating 18-50 years 200 IU 200 IU 200 IU* 200 IU* Source: IOM DRIs, 2001 Summary of Micronutrient Groups in Lactation Group I Group II Milk concentration correlated with maternal Milk concentration relatively independent status, infant rapidly depleted. Supplements of maternal status, mother may become depleted. Supplements have little or no level in milk. effect on milk level. Examples: Thiamin Riboflavin Vitamin B-6 Vitamin B-12 Vitamin A Iodine Selenium Examples: Folate Calcium Iron Copper Zinc Table courtesy of Dr. Kay Dewey Summary: Clinical Implications Some nutrients in human milk are not influenced by maternal diet unless the mother is very deficient; supplementation of sufficient mother doesn’t change milk Some nutrients are highly dependent on maternal diet Milk volume can potentially be increased by increasing carbohydrate content of milk – No clinical strategy to do this yet Summary: Clinical Implications 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 – Argument to start complimentary food Low meat consumption places B12 at risk Maternal supplementation with high dose Vitamin D may get around supplementing infant (AAP rec.)