Carol J. Lammi-Keefe

Effect of fish oil on the fatty acid composition of human milk and maternal and infant erythrocytes.

To examine the effect of fish oil supplementation on the fatty acid (FA) composition of human milk and maternal and infant erythrocytes, five lactating women were supplemented with 6 g of fish oil daily for 21d. Usual maternal diets contained 1,147 mg of total n−3 FA, with 120 mg from very long-chain (>C18) n−3 FA. Supplementation increased dietary levels to 3,092 mg of total n−3 FA and 2,006 mg of very long-chain n−3 FA. Milk samples were collected daily, prior to fish oil ingestion, and at 4-h intervals on days 1, 7, 14 and 21. Milk n−3 FA content increased within 8 h and reached steady state levels within one week. The n−6 fatty acid content decreased. Erythrocyte eicosapentaenoic acid content increased from 0.24% to 1.4% (P<0.01) in mothers and from 0.11% to 0.70% (P<0.05) in infants. Docosapentaenoic acid increased from 1.4% to 2.2% (P<0.05) in mothers and from 0.30% to 0.78% (P<0.01) in infants. There was no significant change in docosahexaenoic acid or n−6 fatty acid content. Maternal platelet aggregation responses were variable. No differences in milk or plasma tocopherol levels were noted.

Lipids in Human Milk: A Review. 2. Composition and Fat-soluble Vitamins

Recent work on lipid classes and the fatty acid composition of milk is reviewed. At least 98% of the lipids are triacylglycerols with about 1% phospholipids and 0.3-0.4% cholesterol. Desmosterol has been identified. The major phospholipids (% of total) are: sphingomyelin (32), phosphatidylcholine (25), and phosphatidylethanolamine (28). The 12:0 content of colostrum is lower than that of mature milk. The 18:2 content of mature milk can be altered by diet; otherwise, the fatty acid composition is remarkably constant. Long-chain polyunsaturates appear to be needed for development of the infants brain and nervous system. Data on the contents of these acids are given. The fat-soluble vitamins have been analyzed by high-performance liquid chromatography. The amounts of vitamins D and K in milk, unlike those of A and E, are lower than the quantities required to meet the U.S. Recommended Daily Allowances. Vitamin D sulfate does not appear to be a significant antirachitic component of human milk. Nutritional and analytical aspects are emphasized throughout and areas for future investigations indicated.

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications.

Fetal erythrocyte phospholipid polyunsaturated fatty acids are altered in pregnancy complicated with gestational diabetes mellitus

Insulin resistance and altered maternal metabolism in gestational diabetes mellitus (GDM) may impair fetal arachidonic acid (AA) and docosahexaenoic acid (DHA) status. The objectives were to test the hypothesis that fetal polyunsaturated fatty acids would be altered with GDM and identify factors related to fetal phospholipid (PL) AA and DHA. Maternal and cord vein erythrocyte PL fatty acids were determined in GDM (n=13) and healthy pregnant women (controls, n=12). Cord vein erythrocyte PL AA and DHA concentrations were significantly lower in GDM vs. controls. Maternal blood hemoglobin A1C was inversely correlated to fetal erythrocyte PL DHA and AA in controls and GDM (n=25). Pregravid body mass index was negatively associated with fetal PL DHA. The data support the hypothesis that there is impairment in fetal accretion of DHA and AA in GDM.

The impact of supplemental N-3 long chain polyunsaturated fatty acids and dietary antioxidants on physical performance in postmenopausal women

ObjectivesIdentify relationships and evaluate effects of long chain polyunsaturated fatty acids (LCPUFA) on frailty and physical performance. Design: Randomized, double blind pilot study.SettingUniversity General Clinical Research Center.Participants126 postmenopausal women.Intervention2 fish oil (1.2g eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or 2 placebo (olive oil) capsules per day for 6 months. All participants received calcium and vitamin D supplements.MeasurementsFatty acid levels, frailty assessment, hand grip strength, 8 foot walk, body composition, medical history and co-morbidities, nutrient intake, and inflammatory biomarkers taken at baseline and 6 months.ResultsAt baseline, those with greater red blood cell (RBC) DHA and DHA/arachidonic acid (AA) presented with less frailty (r=−0.242, p=0.007 and r=−0.254, p=0.004, respectively). Fish oil supplementation resulted in higher RBC DHA and lower AA compared to baseline and placebo (p<0.001) and an improvement in walking speed compared to placebo (3.0±16 vs. −3.5±14, p=0.038). A linear regression model included age, antioxidant intake (selenium and vitamin C), osteoarthritis, frailty phenotype, and tumor necrosis factor alpha (TNFα). The model explained 13.6% of the variance in the change in walking speed. Change in DHA/AA (p=0.01) and TNFα (p=0.039), and selenium intake (p=0.031) had the greatest contribution to change in walking speed.ConclusionPhysical performance, measured by change in walking speed, was significantly affected by fish oil supplementation. Dietary intake of antioxidants (selenium and vitamin C) and changes in TNFα also contributed to change in walking speed suggesting LCPUFA may interact with antioxidants and inflammatory response to impact physical performance.

Comprehensive profiling of the human circulating endocannabinoid metabolome: clinical sampling and sample storage parameters

Abstract Background: Endogenous cannabinoid-receptor ligands (endocannabinoids) and over a dozen related metabolites now comprise the “endocannabinoid metabolome”. The diverse (patho)physiological roles of endocannabinoids, the predictive/diagnostic utility of systemic endocannabinoid levels, and the growing interest in endocannabinoid-related pharmacotherapeutics mandate a valid clinical protocol for processing human blood that does not jeopardize profiling of the circulating endocannabinoid metabolome. Methods: We systematically evaluated the potential effect of pre-analytical variables associated with phlebotomy and sample handling/work-up on the human-blood endocannabinoid metabolome as quantified by state-of-the-art liquid chromatography-mass spectrometry. Results: Neither subject posture during phlebotomy nor moderate activity beforehand influenced the blood levels of the 15 endocannabinoid-system lipids quantified. Storage of fresh blood at 4°C selectively enhanced ethanolamide concentrations artifactually without affecting monoglycerides and nonesterified fatty acids, such as arachidonic acid. In marked contrast, ethanolamides and monoglycerides remained stable through three plasma freeze/thaw cycles, whereas plasma arachidonic acid content increased, probably a reflection of ongoing metabolism. Conclusions: Class- and compound-selective pre-analytical influences on circulating human endocannabinoid levels necessitate immediate plasma preparation from fresh blood and prompt plasma apportioning and snap-freezing. Repeated plasma thawing and refreezing should be avoided. This protocol ensures sample integrity for evaluating the circulating endocannabinoid metabolome in the clinical setting. Clin Chem Lab Med 2008;46:1289–95.

Effect of dietary intake of n-6 and n-3 fatty acids on the fatty acid composition of human milk in North America

To determine the effect of maternal dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on the amounts of these fatty acids in human milk, two criteria must be met. These are assessment of the maternal diet and accurate analysis of the milk fatty acids. This type of analysis requires gas-liquid chromatography with capillary columns to resolve important n-6 and n-3 C20 and C22 fatty acid. This type of analytic equipment has only recently become available; thus the amount of complete data on human milk fatty acids is limited. To assess actual fatty acid intakes by the infant, the fat content and volume of milk received by the infant must be known. Alterations in maternal dietary intake of PUFA cause similar changes in milk PUFA. Several investigators have shown that maternal supplementation with fish oils increases the amounts of 20:5n-3 and 22:6n-3 in milk and maternal and infant erythrocyte lipids. A new mathematic index for assessment of essential fatty acid status, the mean melting point of plasma phospholipid fatty acids, has been proposed. We found in some mother-infant pairs that maternal supplementation with fish oil lowered the mean melting points of erythrocyte lipids to levels seen in nonpregnant women.

Elevated lipoprotein lipids and gestational hormones in women with diet-treated gestational diabetes mellitus compared to healthy pregnant controls.

The objective of this study was to describe plasma and lipoprotein perturbations in gestational diabetes mellitus (GDM) compared to controls, and determine if alterations in lipids are related to gestational hormones and/or glucose control. Maternal HbA1c, free fatty acids (FFA), beta-estradiol, progesterone, prolactin, and plasma, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), HDL2 and HDL3 triglyceride (TG), cholesterol, and dietary intake were determined for women with diet-treated GDM and controls in a longitudinal design. Subjects (N = 25/group) were matched for age, race, and body-mass index (BMI). Women with GDM had significantly higher HbA1c than controls, although both groups were within the normal range (4%-6%). However, body weight gain was less for women with GDM. There was a trend for higher plasma FFAs at 37-38 weeks in GDM versus controls. Plasma and lipoprotein TG among the groups increased over the third trimester, and mean concentrations were greater for women with GDM. In GDM versus controls, VLDL and HDL3 TGs were higher at all times, HDL and HDL2 TGs at 33-34 and 37-38 weeks, and LDL TGs at 37-38 weeks. In VLDL, core lipids (TG + cholesterol) increased over gestation and were greater in GDM. In HDL, the TG/cholesterol ratio was greater in GDM. In GDM versus controls, plasma progesterone and prolactin were higher at all times; beta-estradiol was elevated at 37-38 weeks. HbA1c, progesterone, and prolactin correlated with all lipoprotein TG fractions. Exaggerated hypertriglyceridemia, particularly in the VLDL and HDL fractions, is a feature of GDM. The increase in VLDL TG is likely due to an increase in VLDL synthesis, whereas particle enrichment in TG is a plausible explanation for changes in HDL TG. Slight perturbations in glucose control and gestational hormones in diet-treated GDM may contribute to the observed increase in plasma and lipoprotein TG.

Changes in Human Milk at 0600, 1000, 1400, 1800, and 2200 h

Milk from six mothers was collected every 4 h from 0600 to 2200 h. Total lipid and cholesterol, lactose, glucose, protein N, indicator acids 12:0, 14:0, and 18:2, and α- and γ-tocopherols were analyzed. Total calories were calculated. Although considerable variation was seen in the lipid content, this was not significant and was apparently due to individuality. Differences in the other lipid components were not significant and were generally related to the total lipid content. Except for protein N (p < 0.05), none of the other components varied significantly. Based upon these data and the results of others, the time of sampling of human milk should be matched to the population being studied to obtain consistent results, at least with lipids.

Dietary intake of essential and long-chain polyunsaturated fatty acids in pregnancy

The dietary intake of EFA and long-chain PUFA (LCPUFA) by women with (n=14) and without (n=31) gestational diabetes mellitus (GDM) was determined by repeated 24-h recalls. Women with GDM consumed significantly more energy as fat compared with women who had uncomplicated pregnancies; absolute dietary fat did not differ. Dietary n−3 LCPUFA was substantially lower than the current recommendation for pregnancy, whereas intake of saturated FA (SFA) exceeded it. We conclude that replacing dietary sources of SFA with those of EFA and LCPUFA, especially n−3 LCPUFA, would benefit the dietary fat profiles of all pregnant women.