The Composition of Breast Milk: Does Maternal Diet Matter?

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