Long-chain polyunsaturated fatty acids in human milk

Arachidonic acid and docosahexaenoic acid are the most representative long-chain polyunsaturated fatty acids (LCPUFA) since they may affect infants' growth and development. LCPUFA are present in the milk of all lactating women throughout lactation. The mothers' dietary habits may affect the levels of these fatty acids in maternal blood lipids and then in milk. LCPUFA show marked differences in levels as wt%, particularly from colostrum to mature human milk, but only mild differences in absolute content. Both the major presence of LCPUFA in human milk phospholipids and some regulatory mechanisms in the mammary gland cells could contribute to the LCPUFA levels in milk beyond those in maternal plasma.     

Long-chain polyunsaturated fatty acids in human milk and brain growth during early infancy

Long-chain polyunsaturated fatty acids are essential for growth and development, and their crucial role in the development of the central nervous system and in retinal function has been the subject of many studies. As the balance between n-6 and n-3 fatty acids has to be optimal, their concentrations in the milk given to infants who are exclusively breastfed is of major importance. In this study, the composition of fatty acids in mothers' milk and the growth rate of the infant brain were analysed. Nineteen mother-term infant pairs from Stockholm, Sweden, were studied from birth to 1 mo and 3 mo of age, during which time the infants were breastfed exclusively. The dietary intake of the mothers was calculated and found to concur with the recommended daily dietary allowances of Swedish lactating women as regards energy, protein, fat and carbohydrates. The amounts of linoleic acid and alpha-linolenic acid in the diet were similar to those reported for European and North American women. The ratio between arachidonic acid (AA) and docosahexaenoic acid (DHA) in the milk from Swedish mothers is approximately the same as in the brain of infants, and was found to be positively correlated with the rate of gain of the occipito-frontal head circumference and of the calculated brain weight at 1 mo (p < 0.01) and 3 mo (p < 0.01) of age, respectively. However, further studies are needed to establish the exact requirements of AA and DHA for optimal growth and development during early infancy in exclusively breastfed infants.     

Nutritional relevance of trans isomeric fatty acids in human milk

Trans isomeric fatty acids amount to about 2% of the fatty acid composition of human milk in Europe, whereas lower values were seen in Africa, and higher values were reported for North-America. At least five human studies indicate that trans fatty acids may interfere with the metabolism of long-chain polyunsaturated fatty acids.

Conclusion: Trans isomeric fatty acids in human milk should be regarded as a potential confounding variable in studies investigating the role of long-chain polyunsaturated fatty acids in the development of breastfed infants.     

The difficult balance between dietary polyunsaturated fatty acids

The evidence emerging from developing countries indicates a wide variability in the fat composition of human milk. The linoleic:alpha linolenic acid ratios, suggested to be included within the range of 5:1 and 15[20]:1, tend to fluctuate, and could indicate the capability of humans to self-adapt according to different dietary and environmental conditions.

Conclusion: When referring to optimal “standard” dietary intakes for infants, the complex interactions between genetics and environment should be considered in interpreting observations from different settings.     

Relation between polyunsaturated fatty acids and growth

Although it was discovered in the late 1920s that polyunsaturated fatty acids (PUFA) are essential for proper growth and development in animals, their nutritional importance in humans has not attained general interest until the 1990s, when the role for growth and development has been extensively studied in both humans and animals. It is now known that PUFA regulate various developmental and physiological processes, and that they are of essential importance for early human growth and development. Thus, linoleic acid is the precursor of arachidonic acid, from which hormone-like compounds, such as prostaglandins and leukotrienes, are formed, whereas a -linolenic acid is the precursor of docosahexaenoic acid, which is an essential compound in cell membranes and occurs in particularly high concentration in the photoreceptors. In this paper the role of PUFA for human growth will be reviewed.     

Breastfeeding and long-chain polyunsaturated fatty acid intake in the first 4 post-natal months and infant cognitive development: an observational study

The aim of this study was to examine infant feeding and the long-chain polyunsaturated fatty acid (LCPUFA) concentration of breast milk and formulas in relation to infant development. The prospective Pregnancy, Infection and Nutrition Study (n=358) collected data on breastfeeding, breast milk samples and the formulas fed through 4months post-partum. At 12months of age, infants' development was assessed (Mullen Scales of Early Learning). Linear regression was used to examine development in relation to breastfeeding, breast milk docosahexaenoic acid (DHA) and arachidonic acid (AA) concentration, and DHA and AA concentration from the combination of breast milk and formula. The median breast milk DHA concentration was 0.20% of total fatty acids [interquartile range (IQR)=0.14, 0.34]; median AA concentration was 0.52% (IQR=0.44, 0.63). Upon adjustment for preterm birth, sex, smoking, race and ethnicity and education, breastfeeding exclusivity was unrelated to development. Among infants exclusively breastfed, breast milk LCPUFA concentration was not associated with development (Mullen composite, DHA: adjusted β=-1.3, 95% confidence interval: -10.3, 7.7). Variables combining DHA and AA concentrations from breast milk and formula, weighted by their contribution to diet, were unassociated with development. We found no evidence of enhanced infant development related to the LCPUFA content of breast milk or formula consumed during the first four post-natal months.     

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg⁻¹) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.     

Impact of maternal overweight and obesity on milk composition and infant growth

Overweight and obesity (OW/OB) impact half of the pregnancies in the United States and can have negative consequences for offspring health. Studies are limited on human milk alterations in the context of maternal obesity. Alterations in milk are hypothesized to impact offspring development during the critical period of lactation. We aimed to evaluate the relationships between mothers with OW/OB (body mass index [BMI] ≥25 kg/m²), infant growth, and selected milk nutrients. We recruited mother–infant dyads with pre‐pregnancy OW/OB and normal weight status. The primary study included 52 dyads with infant growth measures through 6 months. Thirty‐two dyads provided milk at 2 weeks, which was analysed for macronutrients, long‐chain fatty acids, and insulin. We used multivariable linear regression to examine the association of maternal weight status with infant growth, maternal weight status with milk components, and milk components with infant growth. Mothers with OW/OB had infants with higher weight‐for‐length (WFL) and BMI Z‐scores at birth. Mothers with OW/OB had higher milk insulin and dihomo‐gamma‐linolenic, adrenic, and palmitic acids and reduced conjugated linoleic and oleic acids. N6 long‐chain polyunsaturated fatty acid (LC‐PUFA)‐driven factor 1 was associated with higher WFL, lower length‐for‐age (LFA), and lower head circumference‐for‐age Z‐scores change from 2 weeks to 2 months in human milk‐fed infants, whereas N6 LC‐PUFA‐driven factor 5 was associated with lower LFA Z‐score change. Human milk composition is associated with maternal pre‐pregnancy weight status and composition may be a contributing factor to early infant growth trajectory.     

Different quantities and quality of fat in milk products given to young children: effects on long chain polyunsaturated fatty acids and trans fatty acids in plasma

In this study we compared plasma contents of long-chain polyunsaturated fatty acids (LC-PUFAs) and trans fatty acids in triglycerides (TG), phospholipids (PL) and cholesterolesters (CE) in young children fed milk diets containing different amounts of linoleic (LA) and alpha-linolenic acid (ALA). Because the diets differed in vitamin A and E content, plasma concentrations of vitamin A and E were also studied. Thirty-seven 1-y-old children were randomly assigned to one of four feeding groups: (1) low-fat milk (LF) (1.0 g cow's milk fat/dL); (2) standard-fat milk (SF) (3.5 g cow's milk fat/dL); (3) partially vegetable fat milk (PVF) (3.5 g fat/dL; 50% vegetable fat from rapeseed oil, 50% milk fat); and (4) full vegetable fat milk (FVF) (3.5 g fat/dL; 100% vegetable fat from palm-, coconut- and soybean oil). We found higher amounts of plasma LA in the FVF group than in the LF and SF groups (p < 0.001) and higher amounts of ALA in the PVF group than in the SF (p < 0.001 in TGs, p < 0.05 in CEs) and LF (p < 0.01 in PLs and CEs, p < 0.05 in TGs) groups. However, amounts of plasma arachidonic acid (AA) were similar between groups as well as the amounts of docosahexaenoic acid (DHA) in CEs and PLs. Total trans FAs were lower in CEs in the PVF and FVF groups than in the SF group (p < 0.05 SF vs PVF; p < 0.01 SF vs FVF). Plasma concentrations of alpha-tocopherol were higher in the FVF group than in the other groups (p < 0.05 FVF vs SF, p < 0.01 FVF vs SF and PVF). Conclusion: Children consuming milk diets containing high amounts of vegetable fat present with higher plasma LA and ALA without any effects on amounts of plasma LC-PUFA. The plasma LC-PUFA status is not adversely affected by a low-fat milk diet. AHA and DHA in plasma are not affected by the diets studied, presumably because 15-mo-old children may be able to compensate for dietary influences through endogenous LC-PUFA metabolism.     

The composition of polyunsaturated fatty acids in erythrocytes of lactating mothers and their infants

Long-chain polyunsaturated fatty acids (LCPUFA) in breastmilk, specifically docosahexaenoic acid (DHA), are important for infant brain development. Accretion of DHA in the infant brain is dependent on DHA-status, intake and metabolism. The aim of this study was to describe changes in maternal and infant erythrocyte (RBC) DHA-status during the first four months of lactation. We examined 17 mothers and their term infants at 1, 2 and 4 months of age. Milk samples and RBC from the mothers and infants were obtained and analysed for fatty acid composition. Comparative analysis of the results showed that the content of DHA in maternal RBC-phosphatidylcholine (PE) decreased over the four month period and this was not accompanied by a decrease in DHA in infant RBC-PE (P = 0.005). The ratio of n-6 PUFA to n-3 PUFA increased over time in maternal RBC-PE, but not in infant RBC-PE (P < 0.001). The level of 22:5n-6 and the ratio of LCPUFA to precursor PUFAs in infant RBC was higher than in maternal RBC phospholipids. (P = and P < 0.001 respectively). We found a decrease in the level of LCPUFA in milk, specifically AA. However, we did not observe a significant decrease in milk DHA, which may have been due to two outliers. These results indicate better DHA-status and a higher n-3/n-6 PUFA in RBC of infants than in mothers. Whether these differences reflect preferential n-3 PUFA transfer via breastmilk or differences in PUFA-metabolism and utilization remains to be shown.     

Fatty acid balance studies in preterm infants fed formula milk containing long-chain polyunsaturated fatty acids (LCP) II

A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n = 10) and standard Prematil (n = 10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n = 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n -6 LCP (p <0:01). Nevertheless, excreted LCP equated to <30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.     

Compliance of present recommendations of fatty acids in formulas for term infants with the actual human milk fatty acid composition in different populations

Fats are the only dietary agents possibly modulating the individual membrane composition, which otherwise is “genetically” determined. In infancy, human milk represents the first natural source of fats. Although the fat intake of breastfed infants is quantitatively and qualitatively unique, it is not known to what extent their varying requirements are met by the fat composition in the milk of their mothers.

Conclusion: The fat composition of arbitrarily chosen human milk is not always the best standard for that in infant formula.     

Long-chain polyunsaturated fatty acids in Chinese and Swedish mothers: diet, breast milk and infant growth

Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential dietary nutrients required for the optimal growth and development of infants, particularly of the brain and retina. It is important for exclusively breastfed infants to receive milk of a correct balance between omega-6 and omega-3 fatty acids. In this study, we compared the composition of LC-PUFAs in the diet and milk of mothers and their infants' growth between Chinese and Swedish. Twenty-three and 19 mother-term infant pairs from a rural area of northern Beijing, China, and Stockholm, Sweden, who were 3 mo old and exclusively breastfed, were studied. The Chinese diet was higher in carbohydrate (17% of energy) but lower in protein (4% of energy) and fat (12% of energy) than the Swedish diet. The intake of Chinese mothers contained more linoleic acid (LA, C(18 ratio 2 omega-6)) and less arachidonic acid (AA, C(20 ratio 4 omega-6)), eicosapentaenoic acid (EPA, C(20 ratio 5 omega-3)) and docosahexaenoic acid (DHA, C(22 ratio 6 omega-3)) than that of Swedish mothers. The breast milk of the Chinese mothers had significantly higher LA and lower EPA and DHA levels than that of the Swedish mothers. However, in Chinese breast milk the AA level was significantly higher than that in Swedish breast milk. The recommended ranges of the ratios of LA to alpha-linolenic acid (LNA, C(18 ratio 3 omega-3)) and of AA to DHA in human milk are 5-10 and 0.5-1 compared with 23.0 and 3.1 in the Chinese breast milk, and 7.5 and 1.6 in the Swedish breast milk, respectively.Conclusion: The diet of the studied Chinese mothers is less balanced with regard to the levels of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) than that of the Swedish mothers, which is also mirrored in the breast milk of these mothers. The clinical relevance of the difference between the levels of LC-PUFAs in the breast milk of Chinese and Swedish mothers may be elucidated by a follow-up study of the cognitive and visual functions of the infants involved.     

Long-chain polyunsaturated fatty acids and development of human infants

Human infants require n -6 and n -3 long-chain polyunsaturated fatty acids (LCPUFA), derivatives of the essential fatty acids, linoleate ( n -6) and linolenate ( n -3), for growth and neural development. Animals fed diets deficient in the essential fatty acids have low neural LCPUFA and behavioral changes that imply adverse effects on brain function. Studies of animals deficient in essential fatty acids have provided the rationale and outcomes for studies to determine whether human infants need dietary LCPUFA. After including n -3 LCPUFA in formula, preterm infants showed higher sensory function (retinal responses to light, visual acuity), visual attention characteristic of higher maturity during infancy, and higher scores on test of global development (6- and 12-mo Bayley Mental Developmental Index). In term infants, some but not all studies found higher visual acuity, 4-mo Brunet-Lezine psychomotor development, and 10-mo means-end problem solving with LCPUFA-containing formulae compared to formulae in general use. Because preterm infants have lower LCPUFA accumulation at birth than term infants, it may be easier to show benefits of dietary LCPUFA for neural development in the former group. In addition to low gestational age, other variables may influence LCPUFA accumulation at birth and determine whether a particular group of infants will respond to dietary LCPUFA. One current challenge is to identify and characterize the effects of those variables. Another is to learn the mechanisms by which LCPUFA status may influence behavior.     

Trans fatty acids from milk of Brazilian mothers of premature infants

Aim:   The presence of trans fatty acids (TFA) in human milk may be a concern because of their possible adverse nutritional effects on the infant development. TFA may interfere with the metabolism of long-chain polyunsaturated fatty acids (LC-PUFA). Marked variation in TFA of milk appears in different populations. No data have yet been reported in Brazil, particularly as regards the milk of mothers of premature infants. Because of the importance of LC-PUFA in infant growth and development, we investigated the fatty acids composition of the milk of Brazilian mothers of premature infants.
Methods:   We analysed, through gas-liquid chromatography, the content of fatty acids of 37 milk samples obtained from mothers delivering prematurely. Samples were collected from colostrum and mature milk of exclusive breastfeeding.
Results:   All samples contained trans isomers of C18:1 acid with trans isomers of PUFA in lower proportion. The percentage of TFA (mean ± SD) in the colostrum was 2.34 ± 0.75, and 2.19 ± 0.47 in the mature milk. For the LC-PUFA these values were 0.97 ± 0.34 in the colostrum and 0.66 ± 0.25 in the mature milk. The contents of total essential fatty acids and PUFA n-6 were inversely correlated with TFA in colostrum and mature milk. We found a positive correlation between levels of arachidonic acid in mature milk and change in the children's height.
Conclusions:   The study showed that the intake of TFA occupies an intermediate position between the values of North America and European countries, reflecting the ongoing transition to industrialised foods in Brazil.     

Fatty acids in breast milk of allergic and non-allergic mothers: The PIAMA birth cohort study

Fatty acid composition was studied in breast milk of allergic and non-allergic mothers, focusing in particular on concentrations of the n-6 and n-3 long-chain polyunsaturates (LCP) in relation to maternal allergy. Milk samples were obtained from 168 mothers with asthma or inhalant allergies and 107 mothers without asthma and inhalant allergies, between 2 and 35 weeks after delivery. Mean values of fatty acid concentration (weight% of total fatty acids) were estimated for individual fatty acids, for groups of fatty acids and for the metabolic index (the ratio between the sum of n-6 polyunsaturates and linoleic acid). For the most relevant fatty acids, the association with maternal allergy was subsequently analyzed in more detail using multiple regression analysis. The metabolic index in breast milk was significantly lower in the allergic than in the non-allergic mothers, but no significant differences were observed in the concentrations of any of the n-6 fatty acids. Also concentrations of the n-3 fatty acids and nearly all other fatty acids were similar in allergic and non-allergic mothers' breast milk. No differences in fatty acid concentrations were observed between mothers with asthma and mothers with single or with multiple inhalant allergies. Our data suggest that differences in fatty acid composition between breast milk of allergic and non-allergic mothers are small and are unlikely to be responsible for the differential effects of breastfeeding by allergic and non-allergic mothers that have been observed in some studies.     

Breast milk levels of zinc and omega-6 polyunsaturated fatty acids and growth of healthy Chinese infants

AIM: To examine the concentrations of zinc and omega-6 polyunsaturated fatty acids (omega-6 PUFAs) in breast milk, the impact of zinc on omega-6 PUFA metabolism, and the growth rate of infants. METHODS: Forty-one mother-term infant pairs from a rural area of northern Beijing, China, who were 1 month (n = 18, group I) and 3 months (n = 23, group II) old and exclusively breastfed, were studied. The dietary records and the concentrations of zinc and omega-6 PUFAs in the milk of lactating women and the increase in weight and length of their infants during 1 and 3 postnatal months were analysed. RESULTS: The dietary intakes of mothers in the two groups were the same, i.e. high in carbohydrate and low in fat, protein and energy. The maternal zinc intake was 7.5mg/d and thus reached only 34.6% of the current Recommended Nutrient Intake (RNI). The levels of zinc and arachidonic acid (AA, C20:4 omega-6) in the milk of group I were significantly higher than those in group II. Furthermore, significant positive correlations were found between the concentrations of zinc and AA in the breast milk and between the level of milk AA and weight gain. CONCLUSION: Zinc may be a co-factor and essential for essential fatty acids (EFA) metabolism. Thus suboptimal zinc intake may cause EFA imbalance. Further studies of Chinese rural mother-infant pairs are necessary to determine whether zinc supplementation should be recommended when lactation exceeds 3 months.     

Essential fatty acids in human colostrum

We analyzed the colostrum of 11 mothers, consuming a normal hospital diet, for total fat content and various fatty acids. Three of the mothers had given birth four weeks prematurely. Total fat content of the colostrum ranged from 2.16 to 3.65 g/100 ml. The major fatty acids were palmitic acid (16:0) and oleic acid (18:1) (24.3 and 39.7% (w/w), respectively). The dominating polyunsaturated fatty acid was linoleic acid (18:2n-6) (11.5% of the total fatty acids). Linolenic acid (18:3n-3) and docosahexaenoic acid (22:6n-3) accounted for 0.7 and 0.6%, respectively, of the sum of total fatty acids. The ratio of polyunsaturated to saturated fatty acids was 0.42, ranging from 0.28 to 0.5, and the ratio of n-6/n-3 fatty acids was 6:1. Linoleic acid and linolenic acid were positively correlated with each other (p < 0.02), whereas palmitic acid was negatively correlated with oleic acid (p < 0.05). We conclude that the average human colostrum contains the recommended level and balance of the essential fatty acids required by the newborn baby.     

Fatty acids in formulae for term infants: compliance of present recommendations with the actual human milk fatty acid composition of geographically different populations

Aim: Recommendations for formula fatty acids (FA) are largely based on the mature human milk FA composition. This study aimed to investigate whether current recommendations for formula FA for term infants comply with the actual breast-milk FA composition of geographically distinct populations and to provide more realistic grounds for future recommendations. Methods: 455 mature breast-milk samples were collected in different countries over 25 y. Recommendations of different organizations were projected on their FA data. FA interrelationships were calculated with Spearman's rank tests. FA compositions of 30 formulae were compared with those of breast milk. Results: Many samples from non-Western communities did not meet the recommendations for formula 12:0, 14:0 and 18:2ω6, since these are mainly based on breast milk of mothers living in Western countries. Recommendations for 18:3ω3, 18:2ω6/18:3ω3, 20:4ω6 and 22:6ω3 were not met by many milk samples, which may point to the poorly developed recommendations for long-chain polyunsaturated FA. Most of the investigated breast-milk FA (12:0, 14:0, 16:0, 18:0, 18:3ω3, 22:6ω3, 18:2ω6, 20:4ω6, 18:1ω9) were either positively or negatively interrelated. Many formulae had FA compositions that were not consistent with the physiological interrelationships of FA in breast milk. Conclusion: Future recommendations, if based on human milk, should derive from its FA balance, as indicated by the FA interrelationships. A “humanized” formula FA composition would in this sense be any composition that cannot be distinguished from that of breast milk by techniques such as principal component analysis.