Dynamic Metabolic Signatures of Choline and Carnitine across Healthy Pregnancy and in Cord Blood: Association with Maternal Dietary Protein.

BACKGROUND: In pregnancy, choline is deemed an essential nutrient and carnitine needs are increased, but amounts remain undefined. OBJECTIVES: We aimed to measure choline and total dietary protein and dairy protein intake from food and supplements across pregnancy and the response to intake by profiling choline and carnitine metabolites across pregnancy and in cord blood. METHODS: An exploratory analysis of choline and protein intake from 3-d diet records and measures of 36 serum choline and carnitine metabolites in early (12-17 wk) and late (36-38 wk) pregnancy was conducted in participants from the Be Healthy in Pregnancy study randomized to high dairy protein+walking exercise or usual care. Metabolites were measured in fasted maternal and cord serum using multisegment injection-capillary electrophoresis-mass spectrometry. Mixed ANOVA adjusted for body mass index was performed for comparison of metabolites across pregnancy and between intervention and control. RESULTS: In 104 participants, the median (Q1, Q3) total choline intake was 347 (263, 427) mg/d in early and 322 (270, 437) mg/d in late pregnancy. Only ∼20% of participants achieved the recommended adequate intake (450 mg/d) and ∼10% consumed supplemental choline (8-200 mg/d). Serum-free choline (µmol/L) was higher in late compared with early pregnancy [12.9 (11.4, 15.1) compared with 9.68 (8.25, 10.61), P < 0.001], but choline downstream metabolites were similar across pregnancy. Serum carnitine [10.3 (9.01, 12.2) compared with 15.9 (14.1, 17.9) µmol/L, P < 0.001] and acetylcarnitine [2.35 (1.92, 2.68) compared with 3.0 (2.56, 3.59), P < 0.001] were significantly lower in late pregnancy. High cord:maternal serum metabolite ratios were found in most measured metabolites. CONCLUSIONS: Despite inadequate choline intake, serum-free choline was elevated in late pregnancy and enriched in cord blood compared with maternal serum. Serum carnitine declined in late pregnancy despite a high protein diet. The higher cord:maternal concentrations in choline and carnitine metabolites suggest active uptake in late pregnancy, reflecting the importance of these circulating metabolites in fetal development. This trial was registered at clinicaltrials.gov as NCT01689961.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Evidence gaps and research needs in current guidance on feeding children from birth to 24 months.

A United States National Academies report summarized recommendations on what and how to feed infants and young children in high-income countries from 43 eligible guideline documents. Consistency existed across many recommendations, but some differences occurred in topic areas, age groupings, and methodological approaches. Future development of guidelines on feeding of infants and young children requires new research and a rigorous evidence-based review process that is harmonized within and across countries and incorporates dissemination and implementation guidance. Novelty: New research and rigorous methods are recommended to develop future harmonized guidance on feeding of infants and young children that incorporates dissemination and implementation methods.

Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis.

In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50-125 nmol/L, requiring 600-4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50-125 nmol/L (600-4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.

Diet in Early Pregnancy: Focus on Folate, Vitamin B12, Vitamin D, and Choline.

Purpose: Prenatal multivitamins are recommended in pregnancy. This study assessed food and supplement intakes of folate, vitamin B12 (B12), vitamin D, and choline in pregnant women living in Southern Ontario in comparison with current recommendations. Methods: Women recruited to the Be Healthy in Pregnancy RCT (NCT01693510) completed 3-day diet/supplement records at 12-17 weeks gestation. Intakes of folate, B12, vitamin D, and choline were quantified and compared with recommendations for pregnant women. Results: Folate intake (median (min, max)) was 1963 µg/day dietary folate equivalents (153, 10 846); 90% of women met the Estimated Average Requirement (EAR) but 77% exceeded the Tolerable Upper Intake Level (UL) (n = 232). B12 intake was 12.1 µg/day (0.3, 2336); 96% of women met the EAR with 7% exceeding the EAR 100-fold (n = 232). Vitamin D intake was 564 IU/day (0.0, 11 062); 83% met the EAR, whereas 1.7% exceeded the UL (n = 232). Choline intake was 338 mg/day (120, 1016); only 18% met the Adequate Intake and none exceeded the UL (n = 158). Conclusion: To meet the nutrient requirements of pregnancy many women rely on prenatal vitamins. Reformulating prenatal multivitamin supplements to provide doses of vitamins within recommendations to complement a balanced healthy diet would ensure appropriate micronutrient intakes for pregnant women.

Summer Season and Recommended Vitamin D Intake Support Adequate Vitamin D Status throughout Pregnancy in Healthy Canadian Women and Their Newborns.

BACKGROUND: Vitamin D deficiency in pregnancy is reported as a prevalent public health problem. OBJECTIVES: We aimed to evaluate, in pregnant Canadian women, 1) vitamin D intake, 2) maternal and cord serum 25-hydroxycholecalciferol [25(OH)D] and maternal 1,25-dihydroxycholecalciferol [1,25(OH)2D], and 3) factors associated with maternal serum 25(OH)D. METHODS: Women (n = 187; mean prepregnancy BMI 24.4 kg/m2, mean age 31 y) recruited to the Be Healthy in Pregnancy study provided fasting blood samples and nutrient intake at 12-17 (early) and 36-38 (late) weeks of gestation, and cord blood. Vitamin D intakes (Nutritionist Pro™) and serum 25(OH)D and 1,25(OH)2D concentrations (LC-tandem MS) were measured. RESULTS: Vitamin D intake was comparable in early and late pregnancy [median (IQR) = 586 (459, 859) compared with 689 (544, 974) IU/d; P = 0.83], with 71% consumed as supplements. Serum 25(OH)D was significantly higher in late pregnancy (mean ± SD: 103.1 ± 29.3 nmol/L) than in early pregnancy (82.5 ± 22.5 nmol/L; P < 0.001) and no vitamin D deficiency (<30 nmol/L) occurred. Serum 1,25(OH)2D concentrations were significantly higher in late pregnancy (101.1 ± 26.9 pmol/L) than in early pregnancy (82.2 ± 19.2 pmol/L, P < 0.001, n = 84). Cord serum 25(OH)D concentrations averaged 55% of maternal concentrations. In adjusted multivariate analyses, maternal vitamin D status in early pregnancy was positively associated with summer season (est.ß: 13.07; 95% CI: 5.46, 20.69; P < 0.001) and supplement intake (est.ß: 0.01; 95% CI: 0.00, 0.01; P < 0.001); and in late pregnancy with summer season (est.ß: 24.4; 95% CI: 15.6, 33.2; P < 0.001), nonmilk dairy intake (est.ß: 0.17; 95% CI: 0.02, 0.32; P = 0.029), and supplement intake (est.ß: 0.01; 95% CI: 0.00, 0.01; P = 0.04). CONCLUSIONS: Summer season and recommended vitamin D intakes supported adequate vitamin D status throughout pregnancy and in cord blood at >50 nmol/L in healthy Canadian pregnant women. This trial was registered at clinicaltrials.gov as NCT01693510.

Factors Associated with Serum 25-Hydroxyvitamin D Concentration in Two Cohorts of Pregnant Women in Southern Ontario, Canada.

Vitamin D deficiency in pregnancy is widely reported, but whether this applies in North America is unclear since no population-based surveys of vitamin D status in pregnancy exist in Canada or the United States. The objectives were to assess (i) the intake and sources of vitamin D, (ii) vitamin D status, and (iii) factors associated with serum 25-hydroxyvitamin D (25-OHD) concentration in two cohorts of pregnant women from Southern Ontario, Canada, studied over a span of 14 years. Maternal characteristics, physical measurements, fasting blood samples and nutrient intake were obtained at enrolment in 332 pregnant women from the Family Atherosclerosis Monitoring In early Life (FAMILY) study and 191 from the Be Healthy in Pregnancy (BHIP) study. Serum 25-OHD was measured by LC/MS-MS. The median (Q1, Q3) total vitamin D intake was 383 IU/day (327, 551) in the FAMILY study and 554 IU/day (437, 796) in the BHIP study. Supplemental vitamin D represented 64% of total intake in participants in FAMILY and 78% in BHIP. The mean (SD) serum 25-OHD was 76.5 (32.9) nmol/L in FAMILY and 79.7 (22.3) nmol/L in BHIP. Being of European descent and blood sampling in the summer season were significantly associated with a higher maternal serum 25-OHD concentration. In summary, health care practitioners should be aware that vitamin D status is sufficient in the majority of pregnant Canadian women of European ancestry, likely due to sun exposure.

Validation of a Food Frequency Questionnaire for Bone Nutrients in Pregnant Women.

PURPOSE: The aim was to validate a food frequency questionnaire (FFQ) against a 3-day food record (3DFR) for pregnant women with a focus on nutrients important for bone health from food and supplements. METHODS: The FFQ and 3DFR were administered to pregnant women (n = 42) aged 18-45 years in their third trimester of pregnancy in Hamilton, Ontario. Nutrient analysis of intakes was conducted using an FFQ calculator and Nutritionist-Pro software. The average daily serving consumption of Milk and alternatives group and Vegetable subgroup from Canada's Food Guide were also compared. RESULTS: There was a high positive correlation between methods for total dietary vitamin D (r = 0.83). Low positive associations were observed for total protein (r = 0.37), calcium (r = 0.36), vitamin K (r = 0.41), and servings of Milk and alternatives (r = 0.36). A cross-classification analysis using participants' intake quartiles revealed no major misclassifications. Bland-Altman analysis showed that the FFQ mildly underestimated the intake for protein, whereas it grossly overestimated the intake of vitamin K, and daily servings of Milk and alternatives and Vegetable. CONCLUSIONS: This FFQ can serve as a useful tool in clinical and research settings to assess key bone nutrients from foods and supplement sources in pregnant women.

The Role of Avocados in Maternal Diets during the Periconceptional Period, Pregnancy, and Lactation.

Maternal nutrition plays a crucial role in influencing fertility, fetal development, birth outcomes, and breast milk composition. During the critical window of time from conception through the initiation of complementary feeding, the nutrition of the mother is the nutrition of the offspring-and a mother's dietary choices can affect both the early health status and lifelong disease risk of the offspring. Most health expert recommendations and government-sponsored dietary guidelines agree that a healthy diet for children and adults (including those who are pregnant and/or lactating) should include an abundance of nutrient-rich foods such as fruits and vegetables. These foods should contain a variety of essential nutrients as well as other compounds that are associated with lower disease risk such as fiber and bioactives. However, the number and amounts of nutrients varies considerably among fruits and vegetables, and not all fruit and vegetable options are considered "nutrient-rich". Avocados are unique among fruits and vegetables in that, by weight, they contain much higher amounts of the key nutrients folate and potassium, which are normally under-consumed in maternal diets. Avocados also contain higher amounts of several non-essential compounds, such as fiber, monounsaturated fats, and lipid-soluble antioxidants, which have all been linked to improvements in maternal health, birth outcomes and/or breast milk quality. The objective of this report is to review the evidence that avocados may be a unique nutrition source for pregnant and lactating women and, thus, should be considered for inclusion in future dietary recommendations for expecting and new mothers.

Influences of nutrition and adiposity on bone mineral density in individuals with chronic spinal cord injury: A cross-sectional, observational study.

BACKGROUND: Dietary inadequacy and adiposity, both prevalent in the chronic spinal cord injury (SCI) population, are known to influence bone turnover and may be potential modifiable risk factors for the development of sublesional osteoporosis following SCI. This pilot study in an SCI cohort aimed to assess measures of nutrition and obesity, to determine if these measures were associated with bone mineral density (BMD), and to compare these measures to a non-SCI control cohort. METHODS: In a cross-sectional observational study, volunteers with chronic SCI (> 1 year post-injury, lesions from C1 to T12 and severity category A-D by the American Spinal Injury Association Impairment Scale) were assessed, and 8 non-SCI individuals were recruited as a comparison group. BMD at the femoral neck (FN) and lumbar spine (LS), and an estimate of visceral adipose tissue (VAT) from lumbar vertebrae 1 through 4 were measured using dual energy X-ray absorptiometry (DXA); nutrient intake of calcium, vitamins D & K, and protein were estimated using a food frequency questionnaire; plasma 25-hydroxyvitamin D (25(OH)D) was analyzed using ultra-high performance liquid chromatography/tandem mass spectroscopy; and serum leptin, adiponectin and insulin were analyzed using a multiplex assay. RESULTS: A total of 34 individuals with SCI (n = 22 tetraplegic; n = 12 paraplegic; 94% male) who averaged 12.7 (9.0) years post-injury, age 40.0 (10.9) years and % body fat of 28.4 (7.3) were assessed. Multiple linear regression analyses in the SCI cohort showed significant associations between BMD at the FN and LS with leptin (FN: r = 0.529, p = 0.005; LS: r = 0.392, p = 0.05), insulin (FN: r = 0.544, p = 0.003; LS: r = 0.388, p = 0.05), and VAT percent (FN: r = 0.444, p = 0.02; LS: r = 0.381, p = 0.05). Adiponectin was only correlated with LS BMD (r = 0.429, p = 0.03). No significant relationships were found between BMD and serum 25(OH)D, or intakes of calcium, vitamins D & K, and protein. Intake of vitamin D was adequate in 69% of participants with SCI, where 91% of those persons consumed either vitamin D and/or multivitamin supplements. Vitamin D status was similar between SCI and non-SCI groups as was sub-optimal status (25(OH)D < 75 nmol/L) (60% of SCI compared to 50% of non-SCI). Participants with SCI had significantly lower FN BMD in comparison to non-SCI controls (p = 0.001). CONCLUSIONS: Compromised BMD among individuals with SCI was not associated with a deficiency of vitamin D or other bone nutrients. The observed positive associations between BMD and leptin, insulin, adiponectin and VAT provide a framework to evaluate links between adiposity and bone health in a larger SCI cohort.

Exploring the benefits and challenges of establishing a DRI-like process for bioactives.

Bioactives can be defined as: "Constituents in foods or dietary supplements, other than those needed to meet basic human nutritional needs, which are responsible for changes in health status" (Office of Disease Prevention and Health Promotion, Office of Public Health and Science, Department of Health and Human Services in Fed Reg 69:55821-55822, 2004). Although traditional nutrients, such as vitamins, minerals, protein, essential fatty acids and essential amino acids, have dietary reference intake (DRI) values, there is no such evaluative process for bioactives. For certain classes of bioactives, substantial scientific evidence exists to validate a relationship between their intake and enhanced health conditions or reduced risk of disease. In addition, the study of bioactives and their relationship to disease risk is a growing area of research supported by government, academic institutions, and food and supplement manufacturers. Importantly, consumers are purchasing foods containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects. This conference, Bioactives: Qualitative Nutrient Reference Values for Life-stage Groups?, explored why it is important to have a DRI-like process for bioactives and challenges for establishing such a process.

A food frequency questionnaire for the assessment of calcium, vitamin D and vitamin K: a pilot validation study.

The study objective was to validate a food frequency questionnaire (FFQ) to assess calcium, vitamin D and vitamin K intakes in overweight and obese postmenopausal community-dwelling women. The FFQ was validated against intakes derived from a 5-day diet record (5DDR) that also included assessment of supplement intake. Strong correlations between methods were observed for all nutrients (r = 0.63, 0.89, 0.54 for calcium, vitamin D and vitamin K, respectively) and cross-classification analyses demonstrated no major misclassification of participants into intake quartiles. Bland-Altman analysis showed that the FFQ overestimated intakes for calcium, by 576 mg/day (95% CI, -668 to 1,821 mg/day), for vitamin D by 75 IU/day (95% CI, -359 to 510 IU/day), and for vitamin K by 167 mcg/day (95% CI, -233 to 568 mcg/day). This pilot study showed promising validation evidence for the use of this FFQ, which focuses on calcium, vitamin D and vitamin K intakes in postmenopausal women, as a screening tool in clinical and research settings.

Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review.

BACKGROUND: Many residents of the United States and Canada depend on dietary sources of vitamin D to help maintain vitamin D status. Because few natural food sources contain vitamin D, fortified foods may be required. OBJECTIVE: We aimed to determine the effects of vitamin D-fortified foods on serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN: We searched MEDLINE (1966 to June Week 3 2006), Embase, CINAHL, AMED, Biological Abstracts, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing vitamin D-fortified foods with a control and reporting serum 25(OH)D concentrations. Two reviewers independently determined study eligibility, assessed trial quality, and extracted relevant data. Disagreements were resolved by consensus. Meta-analyses of absolute mean change in 25(OH)D were conducted by using a random-effects model, with evaluation of heterogeneity. RESULTS: Nine RCTs (n = 889 subjects) were included, of which 8 consistently showed a significant beneficial effect of food fortification on 25(OH)D concentrations. Although 7 RCTs (n = 585 subjects) potentially were meta-analyzable, we were unable to combine the overall results because of significant heterogeneity. The individual treatment effects ranged from 14.5 (95% CIs: 10.6, 18.4) nmol/L to 34.5 (17.64, 51.36) nmol/L (3.4-25 microg vitamin D/d). Subgroup analyses showed a reduction in heterogeneity and significant treatment effect when 4 trials that used milk as the fortified food source were combined. CONCLUSION: Most trials were small in size and inadequately reported allocation concealment, but results showed that vitamin D-fortified foods improved vitamin D status in adults.

Calcium, magnesium, phosphorus and vitamin D fortification of complementary foods.

Provision of the bone minerals and vitamin D as fortificants in food or as dietary supplements designed for older infants and toddlers in Latin America is likely to be beneficial and safe. Currently available data are inadequate to establish the precise amounts of these nutrients that would be required for such a supplement. These amounts would vary according to the local base diet. However, reasonable estimates can be made on the basis of current dietary recommendations as well as existing data on bioavailability and customary intake. The strongest case can be made for calcium and vitamin D supplementation. Because excessive dietary calcium can reduce zinc absorption as a result of interactive effects within the intestine, an appropriate ratio of calcium to zinc should be used, even if this means adding zinc as a fortificant or supplement. Magnesium supplementation may be appropriate in some circumstances but it cannot be routinely advocated at present. It is unlikely that phosphorus supplementation is needed for most population groups because of the relatively high usual dietary phosphorus intakes, primarily from phosphate salts added to carbonated beverages and as food preservatives.