Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women

Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 ± 38.7 and 90.2 ± 40.3 μmol/L, respectively) and menhaden oil (131.8 ± 28.0 and 149.9 ± 30.4 μmol/L, respectively) groups than in the control group (2.9 ± 13.8 and −1.1 ± 32.4 μmol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (−2.2 ± 2.0 mm Hg) group than in the control group (3.3 ± 1.5 mm Hg), and the response in the krill oil group (−0.8 ± 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters.     

Effects of a combined micronutrient supplementation on maternal biological status and newborn anthropometrics measurements: a randomized double-blind, placebo-controlled trial in apparently healthy pregnant women

OBJECTIVE: To investigate the possible beneficial effects of a micronutrient supplementation to apparently healthy pregnant women on maternal biological status and new born anthropometric characteristics. SETTING: Departments of Obstetric of the University Hospital of Grenoble (France) and Lyon (France), Laboratoire of Biology of Oxidative Stress, UFR de Pharmacie. Grenoble (France). STUDY DESIGN: Double-blind, randomized placebo-controlled intervention trial. SUBJECTS: A total of 100 apparently healthy pregnant women were recruited at 14+/-2 weeks of gestation to delivery. At the end, they were 65 women to follow out the study. INTERVENTIONS: Daily consumption over gestation of a micronutrients supplement or placebo. MAIN OUTCOME MEASURES: Plasma micronutrient levels and oxidative stress parameters were measured in mothers at 14 and 38 weeks of gestation. New born's anthropometric characteristics were measured at delivery. RESULTS: In the supplemented group, folic acid, vitamin C, E, B2, B6 and beta-carotene levels were higher than in the placebo group. Oxidative stress parameters were not different between the groups. Birth weights were increased by 10% and the number of low newborn weights (<2700 g) decreased significantly when the mother received the supplementation. Maternal plasma Zn levels were positively correlated to the newborn heights. CONCLUSION: A regular intake of a micronutrient supplement at nutritional dose may be sufficient to improve micronutrient status of apparently healthy pregnant women and could prevent low birth weight of newborn.     

Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women

OBJECTIVE: Our aim was to determine if a once-a-week folic acid supplement increases women's red blood cell folate to concentrations (>905 nmol/l) that are associated with a low risk of bearing a child with a neural tube defect. DESIGN: Randomized control trial. SETTING: General community. SUBJECTS: In total, 114 nonpregnant women (18-40 y) volunteers, with red blood cell folate concentrations between 295 and 905 nmol/l at screening. INTERVENTION: Women were randomized to receive a once-a-week 2800 microg folic acid supplement, a daily 400 microg folic acid supplement or a daily placebo for 12 weeks. RESULTS: The mean (95% CI) red blood cell folate concentrations increased during the 12-week intervention from 608 (553-668) to 900 (828-978) in the weekly folic acid group (P<0.05) and from 615 (560-677) to 1053 (957-1158) nmol/l in the daily group (P<0.05) during the trial. At week 12, 49% of women ingesting the weekly folic acid supplement had red blood cell folate concentrations greater than 905 nmol/l compared to 74% of women ingesting the daily supplement. CONCLUSION: A once-a-week 2800 microg folic acid supplement can increase women's red blood cell folate to concentrations associated with a reduced risk of bearing a child with a neural tube defect, but is less effective than a 400 microg daily supplement. Use of a weekly folic acid supplement over at least 12 weeks before conception by women of child-bearing age may prevent neural tube defects. FUNDING: The Otago Medical Research Foundation (Laurenson Award). Healtheries (New Zealand) provided the supplements.     

Estimation of eicosapentaenoic acid and docosahexaenoic acid intakes in pregnant Japanese women without nausea by using a self-administered diet history questionnaire

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes during pregnancy affect fetal development and maternal mental health; therefore, an accurate assessment of EPA and DHA intakes is required. We hypothesized that a self-administered diet history questionnaire (DHQ) that was developed for non-pregnant adults could be used for estimating EPA and DHA intakes in pregnant Japanese women; thus, we evaluated the validity and reproducibility of the DHQ during pregnancy. We recruited 262 healthy participants with singleton pregnancies during their second trimester at a university hospital in Tokyo between June 2010 and July 2011. Plasma concentrations of EPA and DHA were measured as reference values. Fifty-eight women completed the DHQ twice, within a 4- to 5-week period to assess the reproducibility of the results. Among the participants without pregnancy-associated nausea (n = 180), significantly positive correlations were observed between energy-adjusted intakes and plasma concentrations of EPA (r_s = 0.388), DHA (r_s = 0.264), and EPA + DHA (r_s = 0.328). More than 60% of the participants without nausea fell into the same or adjacent quintiles according to energy-adjusted intakes and plasma concentrations of EPA, DHA, and EPA + DHA. Meanwhile, among the participants with nausea, a low correlation for EPA and no correlation for DHA and EPA + DHA were found. Intraclass correlation coefficients for the 2-time DHQ measurements were 0.691 (EPA) and 0.663 (DHA). The results indicate that the DHQ has an acceptable level of validity and reproducibility for assessing EPA, DHA, and EPA + DHA intakes in pregnant Japanese women without nausea.     

Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal

BACKGROUND: We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15%. OBJECTIVE: We examined the effect of daily maternal micronutrient supplementation on fetal loss and infant mortality. DESIGN: The study was a double-blind, cluster-randomized, controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal. In addition to vitamin A (1000 microg retinol equivalents), the intervention groups received either folic acid (FA; 400 microg), FA + iron (60 mg), FA + iron + zinc (30 mg), or multiple micronutrients (MNs; the foregoing plus 10 microg vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 2.2 mg vitamin B-6, 2.6 microg vitamin B-12, 100 mg vitamin C, 64 microg vitamin K, 20 mg niacin, 2 mg Cu, and 100 mg Mg). The control group received vitamin A only. RESULTS: None of the supplements reduced fetal loss. Compared with control infants, infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15-20% lower 3-mo mortality; this pattern was not observed with MNs. The effect on mortality was restricted to preterm infants, among whom the relative risks (RRs) were 0.36 (95% CI: 0.18, 0.75) for FA, 0.53 (0.30, 0.92) for FA + iron, 0.77 (0.45, 1.32) for FA + iron + zinc, and 0.70 (0.41, 1.17) for MNs. Among term infants, the RR for mortality was close to 1 for all supplements except MNs (RR: 1.74; 95% CI: 1.00, 3.04). CONCLUSIONS: Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality. Among preterm infants, FA alone or with iron reduced mortality in the first 3 mo of life. MNs may increase mortality risk among term infants, but this effect needs further evaluation.     

Oxidation of plasma proteins is not increased after supplementation with eicosapentaenoic and docosahexaenoic acids

BACKGROUND: It is generally thought that as the intake of dietary polyunsaturated fatty acids increases, so should that of alpha-tocopherol, to protect the polyunsaturated fatty acids from increased in vivo peroxidation. However, there are little quantitative data about the concentration of alpha-tocopherol that is necessary when eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are consumed. OBJECTIVE: The purpose of this study was to measure changes produced in 2 indexes of lipid oxidation after supplementation with EPA and DHA from fish oil and 3 doses of RRR-alpha-tocopheryl acetate in postmenopausal women. DESIGN: Daily supplements of fish oil providing 2.5 g EPA and 1.8 g DHA and 0, 100, 200, or 400 mg alpha-tocopheryl acetate were given to 46 postmenopausal women in a 4-treatment, 4-period crossover design. RESULTS: The supplements increased plasma concentrations of EPA, DHA, and alpha-tocopherol. The fish-oil supplement increased the plasma concentration of thiobarbituric acid-reactive substances (TBARS) (P: = 0.0001) but not that of oxidatively modified protein, as indicated by the carbonyl content. The alpha-tocopheryl acetate and fish-oil supplements had no significant effect on plasma concentrations of TBARS or oxidized protein. CONCLUSIONS: Although these data show a small but statistically significant increase in oxidative stress on the basis of plasma TBARS concentrations after the consumption of EPA and DHA, the clinical relevance of this change is questionable. In addition, as supplements of alpha-tocopheryl acetate were added to the diet, neither the plasma TBARS concentration nor the protein oxidation changed. Consequently, the results of this study indicate that there is no basis for vitamin E supplementation after consumption of EPA and DHA.     

Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial

BACKGROUND: It is suggested that a low intake of fish and/or n-3 PUFA is associated with depressed mood. However, results from epidemiologic studies are mixed, and randomized trials have mainly been performed in depressed patients, yielding conflicting results. OBJECTIVE: We investigated the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mental well-being in a double-blind, placebo-controlled trial. DESIGN: Independently living individuals (n = 302) aged > or =65 y were randomly assigned to consume 1800 mg/d EPA+DHA, 400 mg/d EPA+DHA, or placebo capsules for 26 wk. Changes in mental well-being were assessed as the primary outcome with the Center for Epidemiologic Studies Depression Scale (CES-D), Montgomery-Asberg Rating Scale (MADRS), Geriatric Depression Scale (GDS-15), and Hospital Anxiety and Depression Scale (HADS-A). RESULTS: Plasma concentrations of EPA+DHA increased by 238% in the high-dose and 51% in the low-dose fish-oil group compared with the placebo group, reflecting excellent compliance. Baseline CES-D scores ranged from 5.9 to 6.8 in the 3 groups and were not significantly different between groups. Mean changes in CES-D scores after 26 wk were -0.2, 0.2, and -0.4 (P = 0.87) in the high-dose fish oil, low-dose fish oil, and placebo groups, respectively. Treatment with neither 1800 mg nor 400 mg EPA+DHA differentially affected any of the measures of mental well-being after 13 or 26 wk of intervention compared with placebo. CONCLUSIONS: In this randomized, double-blind, placebo-controlled trial we observed no effect of EPA+DHA supplementation for 26 wk on mental well-being in the general older population studied. This trial was registered at clinicaltrials.gov as NCT00124852.     

Trivalent influenza vaccination randomized control trial of pregnant women and adverse fetal outcomes

IntroductionThe purpose of this study was to evaluate the association of influenza vaccine during pregnancy and adverse fetal outcomes. Preventing fetal death, low birth weight, small for gestational age birth and preterm birth are important potential effects of antenatal maternal influenza immunization for which there are conflicting data.Materials and methodsA double-blind, randomized, placebo-controlled clinical trial of trivalent inactivated influenza vaccine was conducted in South Africa from March 2011 until after the 2012 influenza season when the infants born had reached the age of 24 weeks. Mothers were administered the vaccine or placebo during pregnancy at a gestation of 20 to 36 weeks. A comparison of rates of fetal death, low birth weight, small for gestational age birth, and preterm birth, between vaccinated and placebo groups was made. Fetal outcome differences between the groups were measured using Student’s t-tests, vaccine efficacy with 95% confidence intervals, and Poisson regression for incidence rates. All analyses except fetal death excluded mothers who were administered vaccine or placebo after 34 weeks gestational age.ResultsThere were 2116 HIV-uninfected pregnant women age 18 to 38 years in the trial; 2005 infants were born to mothers where vaccine or placebo had been administered ≥ 14 days prior to delivery, and there were 6 miscarriages and 23 stillbirths. There was no significant vaccine efficacy (with [95% confidence interval]) on fetal death (−21.2% [−150.8, 41.4]), low birth weight (−11.1% [−42.3, 12.5]), small for gestational age birth (−9.9% [−35.6, 11.0]), or preterm birth (−21.3% [−60.5, 8.3]). Neither was vaccine efficacy demonstrated when the analysis was restricted to infants of mothers who were exposed to an influenza season (1832 outcomes available).ConclusionWe did not find a beneficial effect of trivalent inactivated influenza vaccine during pregnancy on adverse fetal outcomes.     

Leptin and phospholipid-esterified docosahexaenoic acid concentrations in plasma of women: observations during pregnancy and lactation

BACKGROUND: The n-3 fatty acid status changes during pregnancy and lactation. Plasma leptin concentrations and gene expression have been related to n-3 fatty acids. OBJECTIVE: To investigate the relation between plasma leptin concentration and the docosahexaenoic acid (22:6n-3) content of plasma phospholipids during early pregnancy and the postpartum period. DESIGN: Leptin (radioimmunoassay) and the phospholipid fatty acid profile (capillary gas-liquid chromatography) were measured in plasma of women during two independent longitudinal observational studies. Dietary intake of n-3 fatty acids was also determined. RESULTS: Within the first 10 weeks after the last menstrual period, an almost parallel increase in leptin concentration and the 22:6n-3 content (mg/l and % wt/wt) of plasma phospholipids was seen (study 1, n = 21). During the postpartum period (study 2, n = 57), leptin levels decreased quickly, preceding the changes in 22:6n-3 concentrations. During both studies, leptin concentrations did not consistently relate to dietary intake of n-3 fatty acids or to 22:6n-3 concentrations in plasma phospholipids. Before and during early pregnancy (study 1), significant positive associations between leptin levels and the total amount of phospholipid-associated fatty acids were found. No such association was seen during late pregnancy or the postpartum period (study 2). The postpartum decrease in leptin levels did not differ between lactating and non-lactating women. CONCLUSIONS: Not the 22:6n-3 content, but the total amount of phospholipid-associated fatty acids was related to plasma leptin concentration, before and during early pregnancy but not during late pregnancy and the postpartum period.     

Effect of folic acid supplementation on plasma zinc concentrations of young women

OBJECTIVE: Women of reproductive age are advised to consume supplements or fortified foods containing at least 400 microg/d folic acid for the prevention of neural tubes defects. Concerns exist about the adverse effects of folic acid on zinc status. METHODS: Seventy-eight women (18 to 49 y) were assigned for 12-wk to receive either a placebo or a 400 microg/d folic acid supplement. RESULTS: At 12-wk mean (95% CI) red cell folate increased by 431 (350-511) nmol/L in the supplemented group relative to placebo (P < 0.001) but there was no change in plasma zinc in either group (P = 0.213). CONCLUSIONS: Folic acid supplementation does not reduce plasma zinc concentrations in women of childbearing age.     

孕妇补充牛奶对体内血清叶酸含量影响的研究

目的:观察汉族和蒙古族孕妇每日补充牛奶者及其新生儿脐带血清中叶酸含量变化。方法:采用群体对照的方法,以I125放射免疫法测定血清叶酸含量,分析比较孕前和孕早期3个月是否服用叶酸片的未孕、孕早期(5～7周)妇女,以及是否补充牛奶的孕16周、孕32周妇女及其分娩时脐带血中的血清叶酸含量。结果:在未孕和孕早期未服用叶酸片的汉族、蒙古族妇女的血清叶酸含量无差异(P﹥0.05),补充叶酸片妇女血清叶酸含量均明显增加(P﹤0.001)。孕前和孕早期3个月无论是否服用叶酸片的妇女,其孕16周、孕32周及其脐带血中的叶酸含量,补充牛奶者均高于未补充牛奶者(P﹤0.001)。孕妇血中叶酸含量随着孕期的延长逐渐下降,补充牛奶者体内叶酸含量明显增加,使其下降趋势明显改善(P﹤0.001),叶酸缺乏者明显减少(P﹤0.001)。结论:补充牛奶可使孕妇体内血清叶酸含量明显增加,汉族和蒙古族孕妇间未见差异(P﹥0.05)。饮用牛奶可有效提高叶酸的生物利用度。     

Kinetics of folate turnover in pregnant women (second trimester) and nonpregnant controls during folic acid supplementation: stable-isotopic labeling of plasma folate, urinary folate and folate catabolites shows subtle effects of pregnancy on turnover of folate pools.

To investigate the effects of pregnancy on folate metabolism, we conducted an 84-d study in second-trimester (gestational wk 14-25) pregnant women (n = 6) and nonpregnant controls (n = 6) with stable-isotopic tracer methods. All subjects were fed a diet containing approximately 272 nmol/d (120 microg/d) folate from food, along with supplemental folic acid that contained 15% [3',5'-(2)H(2)] folic acid ([(2)H(2)]folic acid) during d 1--41 and that was unlabeled during d 42--84 to yield a constant total folate intake of 1.02 or 1.93 micromol/d (450 or 850 microg/d). Isotopic enrichment of plasma folate, urinary folate and the urinary folate catabolites para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (ApABG) was determined at intervals throughout the study. The labeling of pABG and ApABG reflected that of tissue folate pools from which the catabolites originate. After the intake of labeled folic acid was terminated on d 41, labeling of urinary folate exhibited a biphasic exponential decline with distinct fast and slow components. In contrast, during d 42--84, the enrichment of urinary pABG and ApABG exhibited primarily monophasic exponential decline, and plasma folate underwent little decline of labeling during this period. Pregnant women and controls did not differ in estimates of body folate pool size and most aspects of the excretion of labeled urinary folate and catabolites, rates of decline of excretion, and areas under the curves for folate and catabolite excretion. Pregnant women, however, tended to have a slower rate of decline of pABG than ApABG and higher enrichment at d 42 of ApABG and pABG. These data support and extend our previous findings indicating that pregnancy (gestational wk 14--26) causes subtle changes in folate metabolism but does not elicit substantial increases in the rate or extent of folate turnover at these moderately high folate intakes.     

Effect of probiotic yoghurt on plasma glucose in overweight and obese pregnant women: a randomized controlled clinical trial

There is only some evidence about effectiveness of probiotics for preventing gestational hyperglycaemia. This trial examined the effects of probiotic yoghurts containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 on maternal plasma glucose (primary outcome) and on some maternal and infant complications (secondary outcomes) in overweight and obese women with no diabetes in pregnancy. Using stratified block randomization, women with pre- or early-pregnancy BMI ≥ 25 and fasting plasma glucose < 92 mg/dl at 22 weeks of gestation were assigned into probiotic or conventional yoghurt group, consuming 100 g/day from 24 weeks of gestation until delivery. The women and their infants were followed up until 1 month after birth. In each group, one out of 65 women had intra-uterine foetal death and were not analysed for other outcomes. The mean BMI was 29.2 (SD 3.3) in probiotic and 30.3 (SD 4.1) in conventional yoghurt group. Four weeks after initiation of the treatment, plasma glucose levels were significantly lower in the probiotic than in conventional yoghurt group at fasting (mean difference adjusted for the BMI category) and baseline FPG (− 4.0 mg/dl; 95% confidence interval − 6.9, − 1.1) and 2-h OGTT (− 13.9; − 22.8, − 5.0). At the 1-h OGTT, however, the difference was not statistically significant (− 9.8; − 20.6, 0.9). Further, there was a significantly lower infant bilirubin level in the probiotic group on days 3–5 after birth (− 2.2 mg/dl; − 3.3, − 1.2). There were not statistically significant differences between the groups regarding the risk of gestational diabetes (6 vs 11; odds ratio 0.5; 0.2, 1.5), preterm delivery (3 vs 8; 0.3; 0.1, 1.2), and other maternal and infant outcomes. The probiotics supplementation has some beneficial effects on glucose metabolism of overweight and obese pregnant women. Nevertheless, further studies are required to judge the clinical significance of such effects.     

Conversion of alpha-linolenic acid to eicosapentaenoic,docosapentaenoic and docosahexaenoic acids in young women

The extent to which women of reproductive age are able to convert the n-3 fatty acid alpha-linolenic acid (ALNA) to eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was investigated in vivo by measuring the concentrations of labelled fatty acids in plasma for 21 d following the ingestion of [U-13C]ALNA (700 mg). [13C]ALNA excursion was greatest in cholesteryl ester (CE) (224 (sem 70) micromol/l over 21 d) compared with triacylglycerol (9-fold), non-esterified fatty acids (37-fold) and phosphatidylcholine (PC, 7-fold). EPA excursion was similar in both PC (42 (sem 8) micromol/l) and CE (42 (sem 9) micromol/l) over 21 d. In contrast both [13C]DPA and [13C]DHA were detected predominately in PC (18 (sem 4) and 27 (sem 7) micromol/l over 21 d, respectively). Estimated net fractional ALNA inter-conversion was EPA 21 %, DPA 6 % and DHA 9 %. Approximately 22 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h of the study. These results suggest differential partitioning of ALNA, EPA and DHA between plasma lipid classes, which may facilitate targeting of individual n-3 fatty acids to specific tissues. Comparison with previous studies suggests that women may possess a greater capacity for ALNA conversion than men. Such metabolic capacity may be important for meeting the demands of the fetus and neonate for DHA during pregnancy and lactation. Differences in DHA status between women both in the non-pregnant state and in pregnancy may reflect variations in metabolic capacity for DHA synthesis.