The Role of Calorie Restriction in the Prevention of Cardiovascular Disease.

PURPOSE OF REVIEW: Calorie restriction (CR) has emerged as a non-pharmacological treatment to prevent cardiovascular disease (CVD). This article reviews recent progress regarding the role of CR in CVD prevention via reduction of cardiometabolic risk factors and promoting atherosclerotic stability. RECENT FINDINGS: Calorie restriction may be an approach to reduce the development of atherosclerosis. CR promotes eNOS activity and SIRT1 expression which in turn improves vasodilation resulting in greater regulation of blood pressure and blood flow. Modest CR in nonobese young and middle-aged adults results in improved cardiometabolic risk profile. The evidence for CR in CVD prevention has accumulated in the recent years. Most evidence, however, is from rodent or small human trials. Our understanding of the magnitude of calorie reduction that leads to the long-term therapeutic effects on cardiovascular health is limited. More well-designed controlled trials conducted in diverse populations with larger sample sizes and longer follow-ups are warranted.

Vitamin D Metabolism Varies among Women in Different Reproductive States Consuming the Same Intakes of Vitamin D and Related Nutrients.

BACKGROUND: The impact of the reproductive state on vitamin D metabolism and requirements is uncertain in part because of a lack of studies with controlled dietary intakes of vitamin D and related nutrients. OBJECTIVE: We aimed to quantify the impact of the reproductive state on a panel of vitamin D biomarkers among women of childbearing age consuming equivalent amounts of vitamin D and related nutrients. METHODS: Nested within a feeding study providing 2 doses of choline, healthy pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant/nonlactating; n = 21) women consumed a single amount of vitamin D (511 ± 48 IU/d: 311 ± 48 IU/d from diet and 200 IU/d as supplemental cholecalciferol) and related nutrients (1.6 ± 0.4 g Ca/d and 1.9 ± 0.3 g P/d) for 10 wk. Vitamin D biomarkers were measured in blood obtained at baseline and study end, and differences in biomarker response among the reproductive groups were assessed with linear mixed models adjusted for influential covariates (e.g., body mass index, season, race/ethnicity). RESULTS: At study end, pregnant women had higher (P < 0.01) circulating concentrations of 25-hydroxyvitamin D [25(OH)D; 30%], 1,25-dihydroxyvitamin D [1,25(OH)2D; 80%], vitamin D binding protein (67%), and C3 epimer of 25(OH)D3 (100%) than control women. Pregnant women also had higher (P ≤ 0.04) ratios of 25(OH)D to 24,25-dihydroxyvitamin D [24,25(OH)2D; 40%] and 1,25(OH)2D to 25(OH)D (50%) than control women. In contrast, no differences (P ≥ 0.15) in vitamin D biomarkers were detected between the lactating and control groups. Notably, the study vitamin D dose of 511 IU/d achieved vitamin D adequacy in most participants (95%) regardless of their reproductive state. CONCLUSIONS: The higher concentrations of vitamin D biomarkers among pregnant women than among control women suggest that metabolic adaptations, likely involving the placenta, transpire to enhance vitamin D supply during pregnancy. The study findings also support the adequacy of the current vitamin D RDA of 600 IU for achieving serum 25(OH)D concentrations ≥50 nmol/L among women differing in their reproductive state. This trial was registered at clinicaltrials.gov as NCT01127022.

Vitamin B-12 Status Differs among Pregnant, Lactating, and Control Women with Equivalent Nutrient Intakes.

BACKGROUND: Limited data are available from controlled studies on biomarkers of maternal vitamin B-12 status. OBJECTIVE: We sought to quantify the effects of pregnancy and lactation on the vitamin B-12 status response to a known and highly controlled vitamin B-12 intake. METHODS: As part of a 10-12 wk feeding trial, pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant, nonlactating; n = 21) women consumed vitamin B-12 amounts of ∼8.6 µg/d [mixed diet (∼6 µg/d) plus a prenatal multivitamin supplement (2.6 µg/d)]. Serum vitamin B-12, holotranscobalamin (bioactive form of vitamin B-12), methylmalonic acid (MMA), and homocysteine were measured at baseline and study-end. RESULTS: All participants achieved adequate vitamin B-12 status in response to the study dose. Compared with control women, pregnant women had lower serum vitamin B-12 (-21%; P = 0.02) at study-end, whereas lactating women had higher (P = 0.04) serum vitamin B-12 throughout the study (+26% at study-end). Consumption of the study vitamin B-12 dose increased serum holotranscobalamin in all reproductive groups (+16-42%; P ≤ 0.009). At study-end, pregnant (vs. control) women had a higher holotranscobalamin-to-vitamin B-12 ratio (P = 0.04) with ∼30% (vs. 20%) of total vitamin B-12 in the bioactive form. Serum MMA increased during pregnancy (+50%; P < 0.001) but did not differ by reproductive state at study-end. Serum homocysteine increased in pregnant women (+15%; P = 0.009) but decreased in control and lactating women (-16-17%; P < 0.001). Despite these changes, pregnant women had ∼20% lower serum homocysteine than the other 2 groups at study-end (P ≤ 0.02). CONCLUSION: Pregnancy and lactation alter vitamin B-12 status in a manner consistent with enhanced vitamin B-12 supply to the child. Consumption of the study vitamin B-12 dose (∼3 times the RDA) increased the bioactive form of vitamin B-12, suggesting that women in these reproductive states may benefit from vitamin B-12 intakes exceeding current recommendations. This trial was registered at clinicaltrials.gov as NCT01127022.

Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet.

BACKGROUND: Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 µg/d, whereas 35 µg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. OBJECTIVE: The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. METHODS: To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 µg of dietary biotin/d as part of a mixed diet. RESULTS: Over the course of the study, pregnant women excreted 69% more (vs. control; P < 0.001) 3-hydroxyisovaleric acid (3-HIA), a metabolite that accumulates during the catabolism of leucine when the activity of biotin-dependent methylcrotonyl-coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. CONCLUSIONS: Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and suggest that biotin intakes exceeding current recommendations are needed to meet the demands of these reproductive states. This trial was registered at clinicaltrials.gov as NCT01127022.

A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1).

This study investigated the influence of maternal choline intake on the human placental transcriptome, with a special interest in its role in modulating placental vascular function. Healthy pregnant women (n=26, wk 26-29 gestation) were randomized to 480 mg choline/d, an intake level approximating the adequate intake of 450 mg/d, or 930 mg/d for 12 wk. Maternal blood and placental samples were retrieved at delivery. Whole genome expression microarrays were used to identify placental genes and biological processes impacted by maternal choline intake. Maternal choline intake influenced a wide array of genes (n=166) and biological processes (n=197), including those related to vascular function. Of special interest was the 30% down-regulation (P=0.05) of the antiangiogenic factor and preeclampsia risk marker fms-like tyrosine kinase-1 (sFLT1) in the placenta tissues obtained from the 930 vs. 480 mg/d choline intake group. Similar decreases (P=0.04) were detected in maternal blood sFLT1 protein concentrations. The down-regulation of sFLT1 by choline treatment was confirmed in a human trophoblast cell culture model and may be related to enhanced acetylcholine signaling. These findings indicate that supplementing the maternal diet with extra choline may improve placental angiogenesis and mitigate some of the pathological antecedents of preeclampsia.

Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans.

The in utero availability of methyl donors, such as choline, may modify fetal epigenetic marks and lead to sustainable functional alterations throughout the life course. The hypothalamic-pituitary-adrenal (HPA) axis regulates cortisol production and is sensitive to perinatal epigenetic programming. As an extension of a 12-wk dose-response choline feeding study conducted in third-trimester pregnant women, we investigated the effect of maternal choline intake (930 vs. 480 mg/d) on the epigenetic state of cortisol-regulating genes, and their expression, in placenta and cord venous blood. The higher maternal choline intake yielded higher placental promoter methylation of the cortisol-regulating genes, corticotropin releasing hormone (CRH; P=0.05) and glucocorticoid receptor (NR3C1; P=0.002); lower placental CRH transcript abundance (P=0.04); lower cord blood leukocyte promoter methylation of CRH (P=0.05) and NR3C1 (P=0.04); and 33% lower (P=0.07) cord plasma cortisol. In addition, placental global DNA methylation and dimethylated histone H3 at lysine 9 (H3K9me2) were higher (P=0.02) in the 930 mg choline/d group, as was the expression of select placental methyltransferases. These data collectively suggest that maternal choline intake in humans modulates the epigenetic state of genes that regulate fetal HPA axis reactivity as well as the epigenomic status of fetal derived tissues.

Women's perspectives on human milk banking in Ghana: results from a cross-sectional study.

Background: Although political and academic interest exists in Ghana to include human milk banks (HMB) into current maternal and child health programs, efforts to establish a HMB have not yet been subjected to any real empirical inspection with the view toward implementation. Furthermore, views toward the establishment of a HMB in Ghana have not been assessed among Ghanaian women. The aims of the current study were to examine Ghanaian women's views about HMB, and to investigate women's willingness to donate to a HMB. Methods: Quantitative and qualitative responses were received from Ghanaian females (n = 1,270) aged 18+ years. Excluding outliers and missing data (n = 321), a final sample of 949 was retained for final analysis. Chi-square tests and logistic regression analysis were computed on quantitative data; Thematic analysis was performed on the qualitative responses. Results: In our sample, 64.7% of respondents indicated that Ghana is ready for a HMB. The majority (77.2%) were willing to donate milk, and 69.4% believed that donating to the HMB would favor their child. The main concerns for the unwillingness to donate excess milk included: (i) the idea of HMBs as strange/bizarre (n = 47), (ii) fear of infections (n = 15), (iii) religious beliefs (n = 9), and (iv) insufficient information (n = 24). This study serves as the first step toward the development of a HMB in Ghana. Conclusions: Overall, Ghanaian women support the building of a HMB to enhance infant nutrition and reduce childhood morbidity and mortality.

Changes in Choline Metabolites and Ceramides in Response to a DASH-Style Diet in Older Adults.

This feeding trial evaluated the impact of the Dietary Approaches to Stop Hypertension diet on changes in plasma choline, choline metabolites, and ceramides in obese older adults; 28 adults consumed 3oz (n = 15) or 6oz (n = 13) of beef within a standardized DASH diet for 12 weeks. Plasma choline, betaine, methionine, dimethylglycine (DMG), phosphatidylcholine (PC), lysophosphotidylcholine (LPC), sphingomyelin, trimethylamine-N-oxide (TMAO), L-carnitine, ceramide, and triglycerides were measured in fasted blood samples. Plasma LPC, sphingomyelin, and ceramide species were also quantified. In response to the study diet, with beef intake groups combined, plasma choline decreased by 9.6% (p = 0.012); DMG decreased by 10% (p = 0.042); PC decreased by 51% (p < 0.001); total LPC increased by 281% (p < 0.001); TMAO increased by 26.5% (p < 0.001); total ceramide decreased by 22.1% (p < 0.001); and triglycerides decreased by 18% (p = 0.021). All 20 LPC species measured increased (p < 0.01) with LPC 16:0 having the greatest response. Sphingomyelin 16:0, 18:0, and 18:1 increased (all p < 0.001) by 10.4%, 22.5%, and 24%, respectively. In contrast, we observed that sphingomyelin 24:0 significantly decreased by 10%. Ceramide 22:0 and 24:0 decreased by 27.6% and 10.9% (p < 0.001), respectively, and ceramide 24:1 increased by 36.8% (p = 0.013). Changes in choline and choline metabolites were in association with anthropometric and cardiometabolic outcomes. These findings show the impact of the DASH diet on choline metabolism in older adults and demonstrate the influence of diet to modify circulating LPC, sphingomyelin, and ceramide species.

Decreased myostatin in response to a controlled DASH diet is associated with improved body composition and cardiometabolic biomarkers in older adults: results from a controlled-feeding diet intervention study.

BACKGROUND: Elevated concentrations of myostatin inhibit muscle growth, function and strength. Myostatin is a mediator of sarcopenia and is associated with insulin resistance. For this study we tested the response of a calorie-restricted Dietary Approaches to Stop Hypertension (DASH) diet on changes in myostatin, follistatin, and mystatin:follistatin ratio levels after 12 weeks in comparison to basline in adults aged 65 years and older. Furthermore we evaluated correlations between changes in myostatin, body composition and cardiometabolic biomarkers in this cohort of older adults. METHODS: This was a controlled-feeding diet intervention study in which females (n = 17) and males (n = 11) aged 65 years and older consumed either 85 g (n = 15) or 170 g (n = 13) of fresh lean beef within a standardized DASH diet for 12-weeks. Myostatin and follistatin concentrations were measured from fasted blood samples collected at 5 timepoints throughout the 12-week feeding intervention period. Correlations were assessed between changes in myostatin and follistatin levels and measures of body composition and cardiometabolic biomarkers. RESULTS: There were no differences (p > 0.05) in circulating myostatin or follistatin levels between the beef intake groups. However, with beef groups combined myostatin decreased by 17.6% (p = 0.006) and the myostatin-to-follistatin ratio decreased by 16.5% (p < 0.001) in response to the study diet. Decreased myostatin was positively correlated with reductions in waist circumference (R2 = 0.163; p = 0.033) and fat mass (R2 = 0.233; p = 0.009). There was an inverse relationship between decreased myostatin and increased strength-to-weight ratio (R2 = 0.162; p = 0.034). The change in myostatin-to-follistatin ratio was associated with the change in skeletal muscle mass-to-fat mass ratio (R2 = 0.176; p = 0.026). Decreased myostatin was positively correlated with reductions in total cholesterol (R2 = 0.193; p = 0.012), LDL-C (R2 = 0.163; p = 0.031), insulin (R2 = 0.234; p = 0.009), and HOMA-IR (R2 = 0.248; P = 0.007). There was no change (p > 0.05) in circulating follistatin concentrations in response to the diet intervention. CONCLUSIONS: The outcomes from this study suggest that a calorie-restricted DASH diet has the potential to reduce myostatin concentrations in older adults. Furthermore these outcomes support interrelationships between myostatin, body composition and cardiometabolic health in adults aged 65 years and older. TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT04127240 ; Registration Date: 15/10/ 2019.

Plasma fatty acid responses to a calorie-restricted, DASH-style diet with lean beef.

BACKGROUND: Plasma fatty acid (FA) levels are used as biomarkers of health outcomes and nutritional intake. METHODS: This was an exploratory analysis of the plasma FA profile from a parallel-designed, controlled-feeding study in older, obese adults (females, n = 17; males, n = 11) consuming a DASH-based diet with two levels of lean beef (3oz and 6oz per day). Plasma FA levels (as percent composition) were measured by gas chromatography from five timepoints over the 12-week intervention. The primary plasma FA change patterns modeled were sustained (initial change to 'new normal') or homeostatic (initial change, then return toward original baseline). RESULTS: The study diet was low in fat (< 60 g/d), especially polyunsaturated FAs (PUFAs; < 5 g/d), compared to the average American diet of obese individuals as described by a nationally representative sample. Participants lost ∼6% of body mass and lowered plasma fasting triglyceride levels by ∼9% over the course of the study. With strong to very strong strength of evidence, the individual FAs displaying a sustained response were C16:1n7t, C18:1n9, C20:1n9, and C18:2n6, and homeostatic response, C18:0, 24:0, C24:1n9, C18:3n6, C20:4n6, and C22:6n3 (Ps < 0.0021, Bonferroni-adjusted). The data suggested that systematic changes in both the PUFA and de novo lipogenesis pathways occurred. CONCLUSIONS: Diet can affect plasma FA changes both due to nutritional composition and by affecting metabolic processes.

Human Milk for Vulnerable Infants: Breastfeeding and Milk Sharing Practice among Ghanaian Women.

Human milk has the best impact on childhood survival. In Ghana, it is estimated that 43% of women exclusively breastfeed for 0-5 months and only 42% of breastfeeding mothers continue through 20-23 months. Although the Ghanaian government has implemented policies to facilitate exclusive breastfeeding, substantial gaps to achieve optimal newborn health and wellbeing remain. The purpose of this study was to evaluate breastfeeding prevalence and human milk sharing practices among Ghanaian women. Qualitative responses were received from Ghanaian females (n = 1050). In our sample, 81% indicated they breastfed their children and 8% reported ever sharing breastmilk with another mother. Reasons for sharing milk included (i) insufficient breastmilk production of the recipient mother, and (ii) mother's unavailability prompting women to offer their milk to a crying baby. About 60% of our sample reported that they were not concerned about sharing their milk. Findings present a strong indicator for milk donation towards the establishment of a human milk bank in Ghana. Health promotion efforts should aim at increasing education about the risks involved in milk sharing as well as the benefits of human milk donation through formal and safer channels such as a Human Milk Bank.

Predisposition to late-onset obesity in GIRK4 knockout mice.

G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels mediate the inhibitory effects of many neurotransmitters on excitable cells. Four Girk genes have been identified (Girk1-4). Whereas GIRK4 is associated with the cardiac GIRK channel, Girk4 expression has been detected in a few neuron populations. Here, we used a transgenic mouse expressing enhanced green fluorescent protein (EGFP) under the control of the Girk4 gene promoter to clarify the expression pattern of Girk4 in the brain. Although small subsets of EGFP-positive neurons were evident in some areas, prominent labeling was seen in the hypothalamus. EGFP expression was most pronounced in the ventromedial, paraventricular, and arcuate nuclei, neuron populations implicated in energy homeostasis. Consistent with a contribution of GIRK4-containing channels to energy balance, Girk4 knockout -/- mice were predisposed to late-onset obesity. By 9 months, Girk4-/- mice were approximately 25% heavier than wild-type controls, a difference attributed to greater body fat. Before the development of overweight, Girk4-/- mice exhibited a tendency toward greater food intake and an increased propensity to work for food in an operant task. Girk4-/- mice also exhibited reduced net energy expenditure, despite displaying elevated resting heart rates and core body temperatures. These data implicate GIRK4-containing channels in signaling crucial to energy homeostasis and body weight.

Cardiometabolic Changes in Response to a Calorie-Restricted DASH Diet in Obese Older Adults.

Objective: To examine the response of a calorie-restricted Dietary Approaches to Stop Hypertension diet on indicators of cardiometabolic health in a cohort of sedentary obese older adults. Design: This was a controlled-feeding trial with a parallel design. Each participant consumed either 3 oz (85 g; n = 15) or 6 oz (170.1 g; n = 13) of lean fresh beef within a standardized calorie-restricted DASH-like diet for 12-weeks. Fasted blood samples were collected and used to measure conventional biomarkers of cardiovascular, metabolic and inflammatory health. Participants: Caucasian older (70.8 years), obese (BMI: 32 ± 6.9 kg/m2; WC: 101 ± 16.4 cm) females (n = 17) and males (n = 11) from the rural community of Brookings, South Dakota. Results: 28 participants completed the 12-week feeding trial, with no differences (p > 0.05) among the biomarkers of cardiometabolic health between the 3 and 6 oz beef intake groups. However, when the beef intake groups were combined, all biomarkers changed concentration in response to the intervention diet. Total cholesterol (p < 0.001), LDL-C (p = 0.004), HDL-C (p < 0.0001), insulin (p = 0.014), glucose (p = 0.008), HOMA-IR (p < 0.05), IL-12 (p < 0.001), and CRP (p = 0.006) all decreased in response to the study diet. IGF-1 (p < 0.001) and IL-8 (p = 0.005) increased in response to the intervention. Correlations among cardiometabolic biomarkers and body composition measures were observed. By study end, the decrease in insulin (R 2 = 0.22; P = 0.012) and HOMA-IR (R 2 = 0.22; P = 0.01) was positively correlated with the decrease in waist circumference. The increase in IGF-1 was significantly correlated with the decrease in waist circumference (R 2 = 0.21; p = 0.014). The increase in IGF-1 was significantly correlated with the increase in sit-to-stand (R 2 = 0.21; p = 0.016). The increase in IL-8 was significantly correlated with decreases in total cholesterol (R 2 = 0.24; P = 0.008), LDL-C (R 2 = 0.17; P = 0.031) and glucose (R 2 = 0.44; P = 0.0001). Conclusions: These findings suggest that a DASH-like diet with restricted calories may potentially improve biomarkers of cardiometabolic health in sedentary obese older adults. These results also point to interrelationships between body composition changes and changes in cardiometabolic biomarkers. Lastly, regardless of meat intake amount, positive impacts on cardiometabolic biomarkers were observed in this cohort of older adults with an obese phenotype.

Baseline red blood cell and breast milk DHA levels affect responses to standard dose of DHA in lactating women on a controlled feeding diet.

BACKGROUND: The importance of providing the newborn infant with docosahexaenoic acid (DHA) from breast milk is well established. However, women in the United States, on average, have breast milk DHA levels of 0.20%, which is below the worldwide average (and proposed target) of >0.32%. Additionally, the relationship between maternal red blood cell (RBC) and breast milk DHA levels may provide insight into the sufficiency of DHA recommendations during lactation. Whether the standard recommendation of at least 200 mg/day of supplemental DHA during lactation is sufficient for most women to achieve a desirable RBC and breast milk DHA status is unknown. METHODS: Lactating women (n = 27) at about 5 weeks postpartum were enrolled in a 10-12 week controlled feeding study that included randomization to 480 or 930 mg choline/d (diet plus supplementation). As part of the intervention, all participants were required to consume a 200 mg/d of microalgal DHA. RBC and breast milk DHA levels were measured by capillary gas chromatography in an exploratory analysis. RESULTS: Median RBC DHA was 5.0% (95% CI: 4.3, 5.5) at baseline and 5.1% (4.6, 5.4) after 10 weeks of supplementation (P = 0.6). DHA as a percent of breast milk fatty acids increased from 0.19% (0.18, 0.33) to 0.34% (0.27, 0.38) after supplementation (P<0.05). The proportion of women meeting the target RBC DHA level of >5% was unchanged (52% at baseline and week 10). The proportion of women achieving a breast milk DHA level of >0.32% approximately doubled from 30% to 56% (p = 0.06). Baseline RBC and breast milk DHA levels affected their responses to supplementation. Those with baseline RBC and breast milk DHA levels above the median (5% and 0.19%, respectively) experienced no change or a slight decrease in levels, while those below the median had a significant increase. Choline supplementation did not significantly influence final RBC or breast milk DHA levels. CONCLUSIONS: On average, the standard prenatal DHA dose of 200 mg/d did not increase RBC DHA but did increase breastmilk DHA over 10 weeks in a cohort of lactating women in a controlled-feeding study. Baseline DHA levels in RBC and breast milk affected the response to DHA supplementation, with lower levels being associated with a greater increase and higher levels with no change or a slight decrease. Additional larger, dose-response DHA trials accounting for usual intakes and baseline DHA status are needed to determine how to best achieve target breast milk DHA levels and to identify additional modifiers of the variable breast milk DHA response to maternal DHA supplementation.

Plasma Ceramides and Triglycerides Are Elevated during Pregnancy in Association with Markers of Insulin Resistance in Hutterite Women.

Changes in maternal insulin sensitivity and circulating lipids typically occur during the metabolic transitions of pregnancy and lactation. Although ceramides can cause insulin resistance in mammals, their potential roles during pregnancy and lactation are unknown. We hypothesized that changes in lipids like ceramide and triglycerides could occur across different reproductive states and relate to insulin resistance. Our objectives were to comprehensively characterize lipids in the plasma of pregnant, lactating, and nonpregnant and nonlactating (NPNL) women, and to evaluate the relationship between ceramides and the triglyceride index, a proxy of insulin resistance. Middle-aged Hutterite women from the South Dakota Rural Bone Health Study were classified by reproductive status as nonpregnant and nonlactating (NPNL; 19 observations), pregnant (14 observations), or lactating (31 observations). Several plasma lipids were elevated in pregnancy such as ceramides, triglycerides, and total- and high-density lipoprotein cholesterol. The triglyceride index was highest during pregnancy and was positively associated with long- and very long-chain ceramides. Lipidomics revealed lipid signatures specific to reproductive state, including triglycerides, phosphatidylcholines, sphingomyelins, and cholesteryl esters, which were also related to the triglyceride index. Our data support the possibility that ceramides contribute to the development of insulin resistance during pregnancy, and reveal distinct lipid signatures associated with pregnancy and lactation.

A Calorie-Restricted DASH Diet Reduces Body Fat and Maintains Muscle Strength in Obese Older Adults.

This study examined the effect of the Dietary Approaches to Stop Hypertension (DASH) diet containing lean red meat on measures of body composition and muscle strength in a cohort of obese adults 65 and older; 36 males (n = 15) and females (n = 21) consumed 1800 kcal/day for 12 weeks under controlled feeding conditions. The study diet included daily intakes of 126 g of meat. Measures of body composition and muscle strength were obtained at weeks 0, 3, 6, 9, and 12. Breakfast, lunch, and dinner were provided every day for 12 weeks, and equal portions of meat were distributed at each meal. Significant effects of the study diet were detected across time for total body weight, body mass index (BMI), waist circumference, hip circumference, body fat percentage, absolute fat mass (AFM), and blood pressure such that a decrease (p < 0.001) was observed over 12 weeks. Significant effects of the study diet were detected across time for sit/stand (p < 0.001) such that an increase was observed. From baseline to study end, total body weight decreased by 6.3% (p < 0.001), body fat percentage decreased by 2.5% (p < 0.001), and absolute fat mass (AFM) decreased by 4.4 kg (p < 0.001). By the study end, skeletal muscle mass (SMM) was positively correlated with handgrip strength (R2 = 0.75; p = 0.001) and resting energy expenditure (REE) (R2 = 0.29; p = 0.001). Handgrip strength, gait, balance, and resting energy expenditure (REE) were well maintained (p > 0.05) throughout the study. These findings suggest that the DASH diet has the potential to be a tool to preserve muscle strength while reducing fat mass in obese older adults.

Maternal vitamin D biomarkers are associated with maternal and fetal bone turnover among pregnant women consuming controlled amounts of vitamin D, calcium, and phosphorus.

Vitamin D plays a central role in calcium homeostasis; however, its relationship with bone turnover during pregnancy remains unclear due to a lack of studies that have rigorously controlled for vitamin D and other nutrients known to influence bone metabolism. Similarly, prior investigations of the effect of pregnancy on bone turnover relative to the nonpregnant state may have been confounded by varying intakes of these nutrients. Nested within a controlled intake study, the present investigation sought to quantify associations between maternal vitamin D biomarkers and biochemical markers of bone turnover among pregnant (versus nonpregnant) women and their fetuses under conditions of equivalent and adequate intakes of vitamin D and related nutrients. Changes in markers of bone turnover across the third trimester were also examined. Healthy pregnant (26-29 wk gestation; n=26) and nonpregnant (n=21) women consumed 511IU vitamin D/d, 1.6g calcium/d, and 1.9g phosphorus/d for 10weeks while participating in a controlled feeding study featuring two choline doses. Based on linear mixed models adjusted for influential covariates (e.g., BMI, ethnicity, and season), pregnant women had 50-150% higher (P<0.001) concentrations of bone resorption markers than nonpregnant women. Among pregnant women, increases in maternal 25(OH)D across the study period were associated (P<0.020) with lower osteocalcin and deoxypyridinoline at study-end, and higher fetal osteocalcin. In addition, maternal free 25(OH)D, 1,25(OH)2D and 24,25(OH)2D tended to be negatively associated (P≤0.063) with maternal NTx at study-end, and maternal free 25(OH)D and 24,25(OH)2D were positively associated (P≤0.021) with fetal CTx. Similarly, maternal 3-epi-25(OH)D3 was negatively related (P≤0.037) to maternal NTx and deoxypyridinoline at study-end. These declines in bone resorption markers resulting from higher vitamin D biomarker concentrations among pregnant women coincided with increases in their albumin-corrected serum calcium concentrations, indicating that calcium transfer to the fetus was uncompromised. Notably, none of these associations achieved statistical significance among nonpregnant women. Overall, our study findings suggest that achieving higher maternal concentrations of vitamin D biomarkers might attenuate third-trimester bone resorption while ensuring sufficient calcium delivery to the fetus.

Additional food folate derived exclusively from natural sources improves folate status in young women with the MTHFR 677 CC or TT genotype.

The effectiveness of additional food folate in improving folate status in humans is uncertain particularly in people with the common genetic variant (677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene. To examine the effect of a doubling of food folate consumption on folate status response variables, women (n=32; 18-46 years) with the MTHFR 677 CC or TT genotype consumed either 400 (n=15; 7 CC and 8 TT) or 800 (n=17; 8 CC and 9 TT) microg/day of dietary folate equivalents (DFE) derived exclusively from naturally occurring food folate for 12 weeks. A repeated measures two-factor ANOVA was used to examine the effect of the dietary treatment, the MTHFR C677T genotype and their interactions on serum folate, RBC folate and plasma total homocysteine (tHcy) during the last 3 weeks of the study. Consumption of 800 microg DFE/day resulted in serum folate concentrations that were 67% (P=.005) higher than consumption of 400 microg DFE/day (18.6+/-2.9 vs. 31.0+/-2.7 nmol/L, respectively) and RBC folate concentrations that were 33% (P=.001) higher (1172+/-75 vs. 1559+/-70 nmol/L, respectively). Serum folate (P=.065) and RBC folate (P=.022) concentrations were lower and plasma tHcy was higher (P=.039) in women with the MTHFR 677 TT genotype relative to the CC genotype. However, no genotype by dietary treatment interaction was detected. These data suggest that a doubling of food folate intake will lead to marked improvements in folate status in women with the MTHFR 677 CC or TT genotype.