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
Vitamins

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 Minerals
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
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)
Country/Culture
% Milk fat as DHA
Inuit Eskimo
1.4
Dominica
0.9
Malaysia
St. Lucia
0.7
Canada/Vancouver
0.4
Australia
0.35
Sweden
0.30
USA
0.25
Germany
0.2

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. Sodium Potassium Chloride Calcium
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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 years
1300 mg
1000 mg
Source: IOM DRIs, 2001

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

24. Vectoral Micronutrient Transport by MEC
Maternal Blood
Milk
4 Fe2+
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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 years
15 mg
18 mg
10 mg*
9 mg*
* 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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 years
8 mg
13 mg
12 mg
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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 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
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
Nutrient
Non-lactating
14-18 y
18-50y
Lactating
14-18y
Selenium
55 mcg
70 mcg
Iodine
150 mcg
290 mcg
Fluoride
3 mg
3mg
Manganese
1.6 mg
1.8 mg
2.6 mg
Source: IOM DRIs, 2001

37. Folate B6 B12 Vitamin A Vitamin D
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 Actively transported from mother to fetus
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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 years
400 mcg
500 mcg
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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 years
2 mg
1.2 mg
1.3 mg
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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 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
“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
Non-lactating years
Non-lactating years
Lactating
14-18 years
18-50 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
Vitamin B-6
Vitamin B-12
Vitamin A
Iodine
Selenium
Examples: Folate
Calcium
Iron
Copper
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 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

51. 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.)