The importance of maternal dietary choline for fetal neural development and later cognitive function has been well-documented in experimental studies. Although choline is an essential dietary ...nutrient for humans, evidence that low maternal choline in pregnancy impacts neurodevelopment in human infants is lacking. We determined potential associations between maternal plasma free choline and its metabolites betaine and dimethylglycine in pregnancy and infant neurodevelopment at 18 months of age.
This was a prospective study of healthy pregnant women and their full-term, single birth infants. Maternal blood was collected at 16 and 36 weeks of gestation and infant neurodevelopment was assessed at 18 months of age for 154 mother-infant pairs. Maternal plasma choline, betaine, dimethylglycine, methionine, homocysteine, cysteine, total B12, holotranscobalamin and folate were quantified. Infant neurodevelopment was evaluated using the Bayley Scales of Infant Development-III. Multivariate regression, adjusting for covariates that impact development, was used to determine the associations between maternal plasma choline, betaine and dimethylglycine and infant neurodevelopment.
The maternal plasma free choline at 16 and 36 weeks gestation was median (interquartile range) 6.70 (5.78-8.03) and 9.40 (8.10-11.3) µmol/L, respectively. Estimated choline intakes were (mean ± SD) 383 ± 98.6 mg/day, and lower than the recommended 450 mg/day. Betaine intakes were 142 ± 70.2 mg/day. Significant positive associations were found between infant cognitive test scores and maternal plasma free choline (B=6.054, SE=2.283, p=0.009) and betaine (B=7.350, SE=1.933, p=0.0002) at 16 weeks of gestation. Maternal folate, total B12, or holotranscobalamin were not related to infant development.
We show that choline status in the first half of pregnancy is associated with cognitive development among healthy term gestation infants. More work is needed on the potential limitation of choline or betaine in the diets of pregnant women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Osteoporosis: A Review of Treatment Options Tu, Kristie N; Lie, Janette D; Wan, Chew King Victoria ...
P&T (Lawrenceville, N.J.),
02/2018, Letnik:
43, Številka:
2
Journal Article
Recenzirano
Approximately 10 million men and women in the U.S. have osteoporosis,1 a metabolic bone disease characterized by low bone density and deterioration of bone architecture that increase the risk of ...fractures.2 Osteoporosis-related fractures can increase pain, disability, nursing home placement, total health care costs, and mortality.3 The diagnosis of osteoporosis is primarily determined by measuring bone mineral density (BMD) using noninvasive dual-energy x-ray absorptiometry. Osteoporosis medications include bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, estrogen agonists/antagonists, parathyroid hormone analogues, and calcitonin.3-6 Emerging therapies utilizing novel mechanisms include a cathepsin K inhibitor and a monoclonal antibody against sclerostin.7,8 While professional organizations have compiled recommendations for the management of osteoporosis in various populations, a consensus has yet to develop as to which is the gold standard; therefore, economic evaluations have been increasingly important to help guide decision-makers. A review of cost-effectiveness literature on the efficacy of oral bisphosphonates has shown alendronate and risedronate to be most cost-effective in women with low BMD without previous fractures.9 Guidelines are inconsistent as to the place in therapy of denosumab (Prolia, Amgen). In economic analyses evaluating treatment of postmenopausal women, denosumab outperformed risedronate and ibandronate; its efficacy was comparable to generic alendronate, but it cost more.10 With regard to older men with osteoporosis, denosumab was also found to be cost-effective when compared with bisphosphonates and teriparatide (Forteo, Lilly).11.
High linoleic acid (LA) intakes have been suggested to reduce α-linolenic acid ALA, 18:3(n-3) metabolism to eicosapentaenoic acid EPA, 20:5(n-3) and docosahexaenoic acid DHA, 22:6(n-3), and favor ...high arachidonic acid ARA, 20:4(n-6). We used a randomized cross-over study with men (n = 22) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods, while maintaining constant ALA, for 4 wk each, on plasma (n-3) fatty acids. Nonvegetable sources of fat, except fish and seafoods, were unrestricted. We determined plasma phospholipid fatty acids at wk 0, 2, 4, 6, and 8, and triglycerides, cholesterol, serum CRP, and IL-6, and platelet aggregation at wk 0, 4, and 8. LA and ALA intakes were 3.8 ± 0.12% and 1.0 ± 0.05%, and 10.5 ± 0.53% and 1.1 ± 0.06% energy with LA:ALA ratios of 4:0 and 10:1 during the low and high LA diets, respectively. The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period (P < 0.001), but DHA declined over the 8-wk period (r = -0.425, P < 0.001). The plasma phospholipid ARA:EPA ratios were (mean ± SEM) 20.7 ± 1.52 and 12.9 ± 1.01 after 4 wk consuming the high or low LA diets, respectively (P < 0.001); LA was inversely associated with EPA (r = -0.729, P < 0.001) but positively associated with ARA:EPA (r = 0.432, P < 0.001). LA intake did not influence ALA, ARA, DPA, DHA, or total, LDL or HDL cholesterol, CRP or IL-6, or platelet aggregation. In conclusion, high LA intakes decrease plasma phospholipid EPA and increase the ARA:EPA ratio, but do not favor higher ARA.
DHA is accumulated in the central nervous system (CNS) before birth and is involved in early developmental processes, such as neurite outgrowth and gene expression.
To determine whether fetal DHA ...insufficiency occurs and constrains CNS development in term gestation infants.
A risk reduction model using a randomized prospective study of term gestation single birth healthy infants born to women (n = 270) given a placebo or 400 mg/day DHA from 16 wk gestation to delivery. Fetal DHA deficiency sufficient to constrain CNS development was assessed based on increased risk that infants in the placebo group would not achieve neurodevelopment scores in the top quartile of all infants in the study.
Infants in the placebo group were at increased risk of lower language development assessed as words understood (OR 3.22, CL 1.49-6.94, P = 0.002) and produced (OR 2.61, CL 1.22-5.58, P = 0.01) at 14 mo, and words understood (OR 2.77, CL 1.23-6.28, P = 0.03) and sentences produced (OR 2.60, CL 1.15-5.89, P = 0.02) at 18 mo using the McArthur Communicative Developmental Inventory; receptive (OR 2.23, CL 1.08-4.60, P = 0.02) and expressive language (OR 1.89, CL 0.94-3.83, P = 0.05) at 18 mo using the Bayley Scales of Infant Development III; and visual acuity (OR 2.69, CL 1.10-6.54, P = 0.03) at 2 mo.
ClinicalTrials.gov NCT00620672.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dietary methyl donors (e.g., choline) support the activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, which generates phosphatidylcholine (PC) molecules enriched in DHA that ...are exported from the liver and made available to extrahepatic tissues.
This study investigated the effect of prenatal choline supplementation on biomarkers of DHA status among pregnant participants consuming supplemental DHA.
Pregnant participants (n = 30) were randomly assigned to receive supplemental choline intakes of 550 mg/d 500 mg/d d0-choline + 50 mg/d deuterium-labeled choline (d9-choline); intervention or 25 mg/d (25 mg/d d9-choline; control) from gestational week (GW) 12–16 until delivery. All participants received a daily 200-mg DHA supplement and consumed self-selected diets. Fasting blood samples were obtained at baseline, GW 20–24, and GW 28–32; maternal/cord blood was obtained at delivery. Mixed-effects linear models were used to assess the impact of prenatal choline supplementation on maternal and newborn DHA status.
Choline supplementation (550 vs. 25 mg/d) did not achieve a statistically significant intervention × time interaction for RBC PC-DHA (P = 0.11); a significant interaction was observed for plasma PC-DHA and RBC total DHA, with choline supplementation yielding higher levels (+32–38% and +8–11%, respectively) at GW 28–32 (P < 0.05) and delivery (P < 0.005). A main effect of choline supplementation on plasma total DHA was also observed (P = 0.018); its interaction with time was not significant (P = 0.068). Compared with controls, the intervention group exhibited higher (P = 0.007; main effect) plasma enrichment of d3-PC (d3-PC/total PC). Moreover, the ratio of d3-PC to d9-PC was higher (+50–67%; P < 0.001) in the choline intervention arm (vs. control) at GW 20–24, GW 28–32, and delivery.
Prenatal choline supplementation improves hepatic DHA export and biomarkers of DHA status by bolstering methyl group supply for PEMT activity among pregnant participants consuming supplemental DHA. This trial is registered at www.clinicaltrials.gov as NCT03194659.
Background: Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. ...Vitamin B-12 deficiency increases choline use for homocysteine methylation.Objectives: We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants.Design: Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference.Results: The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148–220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient.Conclusion: This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.
Several studies have investigated the potential health benefits, including those associated with neurological function, of the n-3 fatty acid DHA. This has arisen in part because of the association ...between higher intakes of fish, which is a major dietary source of DHA, and reduced disease risk. In addition to DHA, fish also provides choline and vitamin D. The objective of the present study was to assess whether women in the first half of pregnancy with low fish intake also had low blood concentrations of vitamin D, choline and DHA. A total of 222 pregnant women at 16 weeks of gestation were examined for dietary intake, erythrocyte (phosphatidylethanolamine PE) DHA, plasma free choline and 25-hydroxyvitamin D (25(OH)D). Women who consumed ≤ 75 g fish/week (n 56) compared to ≥ 150 g fish/week (n 116) had lower dietary intake of DHA, total choline and vitamin D (P< 0·001), and lower erythrocyte PE DHA (5·25 (sd 1·27), 6·83 (sd 1·62) g/100 g total fatty acid, respectively, P< 0·01), plasma free choline (6·59 (sd 1·65), 7·40 (sd 2·05) μmol/l, respectively, P= 0·023) and 25(OH)D (50·3 (sd 20·0), 62·5 (sd 29·8) nmol/l, respectively, P< 0·01). DHA intake was positively related to the intake of vitamin D from foods (ρ 0·47, P< 0·001) and total choline (ρ 0·32, P< 0·001). Dietary intakes and biomarkers of DHA, choline and vitamin D status were assessed to be linked. This raises the possibility that unidentified concurrent nutrient inadequacies might have an impact on the results of studies addressing the benefits of supplemental DHA.
Background: The n-3 fatty acid docosahexaenoic acid (DHA; 22:6n-3) is important for neural and visual functional development. In animals, 22:6n-3 deficiency is accompanied by increased ...docosapentaenoic acid (DPA; 22:5n-6), which suggests that the ratio of 22:6n-3 to 22:5n-6 could be a useful biochemical marker of low n-3 fatty acid status. The n-3 fatty acid status of preschool children has not been described, and data are lacking on whether low 22:6n-3 is accompanied by high 22:5n-6 in humans. Objective: We determined n-3 fatty acid status and investigated the relation between 22:6n-3 and 22:5n-6 in children. Design: In Canadian children aged 18-60 mo (n = 84), the n-3 and n-6 fatty acid status of erythrocyte phosphatidylethanolamine was measured, and dietary fat intake was estimated by using a food-frequency questionnaire. Results: The mean (± SEM) 22:6n-3 concentration in erythrocyte phosphatidylethanolamine among children was 3.06 ± 0.13 g/100 g fatty acids (5th-95th percentiles: 1.43-5.79 g/100 g fatty acids). Concentrations of 22:5n-6 increased with increasing 22:6n-3 concentrations in erythrocyte phosphatidylethanolamine (P < 0.01). Mean intakes of linoleic acid (18:2n-6), linolenic acid (18:3n-3), and trans fatty acids were 3.6 ± 0.2%, 0.7 ± 0.5%, and 2.0 ± 1.3%, respectively. Phosphatidylethanolamine 22:6n-3 and 22:5n-3 concentrations were inversely related to the intakes of 18:2n-6 and trans fatty acids, but not to those of total fat or n-3 fatty acids. Conclusions: The concentration of 22:5n-6 is not a useful biochemical marker of low n-3 fatty acid intake or status in the membrane phosphatidylethanolamine of preschool children. High intakes of 18:2n-6 and trans fatty acids could compromise the incorporation of 22:6n-3 into membrane phospholipids.
Background: Human milk fatty acids vary with maternal dietary fat composition. Hydrogenated dietary oils with trans fatty acids may displace cis n-6 and n-3 unsaturated fatty acids or have adverse ...effects on their metabolism. The effects of milk trans, n-6, and n-3 fatty acids in breast-fed infants are unclear, although n-6 and n-3 fatty acids are important in infant growth and development. Objective: We sought to determine the relations between trans and cis unsaturated fatty acids in milk and plasma phospholipids and triacylglycerols of breast-fed infants, and to identify the major maternal dietary sources of trans fatty acids. Design: We collected milk from 103 mothers with exclusively breast-fed 2-mo-old infants, blood from 62 infants, and 3-d dietary records from 21 mothers. Results: Mean (+/- SEM) percentages of trans fatty acids were as follows: milk, 7.1 +/- 0.32%; infants' triacylglycerols, 6.5 +/- 0.33%; and infants' phospholipids, 3.7 +/- 0.16%. Milk trans fatty acids, alpha-linolenic acid (18:3n-3), arachidonic acid (20:4n-6), docosahexaenoic acid (22:6n-3) (P < 0.001), and linoleic acid (18:2n- 6) (P = 0.007) were each related to the same fatty acid in infant plasma phospholipids. Milk trans fatty acids were inversely related to milk 18:2n-6 and 18:3n-3, but not to milk or infant plasma 20:4n-6 or 22:6n-3. trans Fatty acids represented 7.7% of maternal total fat intake (2.5% of total energy); the major dietary sources were bakery products and breads (32%), snacks (14%), fast foods (11%), and margarines and shortenings (11%). Conclusions: There were comparable concentrations of trans fatty acids in the maternal diet, breast milk, and plasma triacylglycerols of breast-fed infants. Prepared foods were the major dietary source of trans fatty acids.
Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. Vitamin B-12 ...deficiency increases choline use for homocysteine methylation.
We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants.
Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference.
The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148–220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient.
This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.
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