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The Composition of Breast Milk: Does Maternal Diet Matter?

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

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The Composition of Breast Milk: Does Maternal Diet Matter?

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  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 • Classes of Nutrients • Mechanisms of Maternal->Milk Transport • Milk Volume • Macronutrients • Transport; IOM Recommendations • Selected Micronutrients • Transport; IOM Recommendations • Vitamins • Transport; IOM Recommendations

  3. 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

  4. 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)

  5. 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)

  6. The Mammary Epithelial Cell

  7. Water (Volume)

  8. 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

  9. 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)

  10. Macronutrients Carbohydrates Fat

  11. 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

  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 • 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

  13. 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

  14. 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)

  15. 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)

  16. 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

  17. Influence of Country of Origin on Milk DHA (Innis et al, 1992)

  18. 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)

  19. Minerals Sodium Potassium Chloride Calcium

  20. 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

  21. 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

  22. Calcium: IOM AI for Daily Calcium Intake by Lactating Mothers 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 Maternal Blood Milk 4Fe2+ Nutrient Intracellular Unloading Protein binding Exporter (FPN, Znt, ATP7) Nutrient (maternal) Nutrient Importer Receptor (TfR, Zip3,Ctr1) Transporter Nutrient (fetal) Endosome 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) • 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)

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

  27. 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

  28. IOM RDA for Iron Intake by Lactating Mothers * Assumes that lactation inhibits menstrual cycle Source: IOM DRIs, 2001

  29. 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

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

  31. IOM RDA for Zinc Intake by Lactating Mothers Source: IOM DRIs, 2001

  32. 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

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

  34. IOM RDA for Copper Intake by Lactating Mothers Source: IOM DRIs, 2001

  35. 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)

  36. IOM Recommendations for Selenium, Iodine, Fluoride and Manganese during Lactation Source: IOM DRIs, 2001

  37. Selected Vitamins Folate B6 B12 Vitamin A Vitamin D

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

  39. 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

  40. IOM RDA for Folate Intake by Lactating Mothers Source: IOM DRIs, 2001

  41. 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

  42. IOM RDA for B6 Intake by Lactating Mothers Source: IOM DRIs, 2001

  43. 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

  44. IOM RDA for B12 Intake by Lactating Mothers Source: IOM DRIs, 2001

  45. 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

  46. 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

  47. 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

  48. IOM AI for Vitamin D Intake by Lactating Mothers Source: IOM DRIs, 2001

  49. Summary of Micronutrient Groups in Lactation 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 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

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