Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting—an important finding considering the essential roles of DHA and vitamin D.

In industrialized countries, fertility has declined in recent years to the lowest recorded levels. Identifying modifiable factors that influence human fertility, such as diet, is therefore of major clinical and public health relevance. Micronutrient status is a modifiable risk factor that may have an impact on female fertility, as essential vitamins and minerals have important roles in the physiological processes that are involved. Adequate levels are important for oocyte quality, maturation, fertilization, and implantation, whereas antioxidants are vital to reduce oxidative stress, a process known to impair fertility. In women who are diagnosed as infertile, lower than recommended levels of certain micronutrients have been reported. A similar scenario has been found in a proportion of women of childbearing age in general, some of whom may be struggling to conceive. Supplementation studies with multiple micronutrients are still scarce, but the literature suggests that supplementation before conception can help restore micronutrient status to recommended levels and reduce oxidative stress when antioxidants are included. Overall, supplementation has a small but beneficial effect on fertility in healthy and infertile women, including a shorter time to pregnancy and an increased chance of becoming pregnant. Nevertheless, many studies are small or observational, and adequately powered randomized controlled trials of supplementation with multiple micronutrients are necessary to confirm any definite effects on fertility. This review substantiates the potential benefits of micronutrient supplementation beyond the prevention of neural tube defects, the traditionally viewed value of prenatal vitamin use.

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Breastfed infants require an adequate supply of critical nutrients for growth, tissue functions, and health. Recommended intakes for several nutrients are considerably higher in lactating than non-lactating women but are not always met with habitual diets. We report a randomized, double-blind clinical trial in 70 healthy lactating women in Germany evaluating the effects of supplementation with multiple micronutrients, lutein, and docosahexaenoic acid (DHA) compared to placebo on maternal nutrient status and milk composition. The primary endpoint was the effect on the change of human milk DHA content (as a proportion of total milk fatty acids) during 12 weeks of supplementation. Maternal blood and milk biomarkers were measured as secondary endpoints. Supplementation increased maternal milk DHA by 30% compared to a decline in the placebo group. Supplementation also increased maternal blood DHA (17%), eicosapentaenoic acid (4%), 25-OH-vitamin D (24%), vitamin B12 (12%), lutein (4%), and beta carotene (49%), while homocysteine decreased. No significant difference in the number of adverse events was observed between supplementation and placebo groups. In conclusion, multi-micronutrient supplementation was safe and increased maternal blood and milk concentrations of selected nutrients in healthy women.

To examine the validity of the deuterium (D) incorporation technique for measurement of human cholesterol synthesis rates, D uptake from D 2 O into cholesterol was compared to sterol balance in 13 subjects each under three controlled diet settings. Subjects (age 62 ؎ 3.6 yr, body weight 74 ؎ 4.0 kg, BMI 27 ؎ 1.4) consumed weight maintenance diets enriched in either corn oil, beef tallow, or stick corn oil margarine over a 5-week period. During the final week of the study period, subjects were given 1.2 g/ D 2 O per kg body water. D enrichment was measured in plasma water and total cholesterol over 24 h. Also, during the final week, dietary intake and fecal elimination rates of cholesterol were assessed over one 6-day period to calculate sterol balance. There was no significant difference (t ‫؍‬ 0.858, P ‫؍‬ 0.397) between D incorporation into cholesterol (1,183 ؎ 92 mg/day) and sterol balance (1,316 ؎ 125 mg/ day). Among diets, net cholesterol biosynthesis measured by D incorporation agreed ( r ‫؍‬ 0.745, P ‫؍‬ 0.0001) with values derived from sterol balance. The degree of association between methods was not influenced by the wide range of fatty acid composition of the diet fat. These data demonstrate the utility of the simple, non-restrictive deuterium incorporation method as a reliable means of determining cholesterol biosynthesis in free-living humans.-Jones, P.

Background: Nutritional quality during pregnancy is crucial for mother and child health and their short/long-term outcomes. The aim of this study is to evaluate the adherence to nutritional recommendations in Italy during the three pregnancy trimesters in Normal Weight (NW) and Over Weight (OW) women. Methods: Data from a multicenter randomized controlled trial included 176 women (NW = 133; OW = 43) with healthy singleton pregnancies enrolled within 13 + 6 weeks of gestation. Dietary intake was assessed every trimester by a Food Frequency Questionnaire. Results: OW and NW had similar gestational weight gain. However, as Institute of Medicine (IOM) recommend lower gestational weight gain (GWG) for OW, they exceeded the suggested range. In both groups, caloric intake during the three trimesters never met recommendations. Protein intake in first and second trimester was higher than recommendations, as was sugars percentage. Dietary fiber intake was lower in OW. Polyunsaturated fatty acids, calcium, iron and folic acid requirements were never satisfied, while sodium intake exceeded recommendations. Conclusions: NW and OW women in Italy do not adhere to nutritional recommendations during pregnancy, with lower caloric intake, protein and sugars excess and inadequacies in micronutrients intake. Pregnant women in Italy should be provided with an adequate counseling and educational intervention as well as supplementation when indicated.

Objective: To evaluate the efficacy of a multi-vitamin/mineral preparation (MMP) in achieving erythrocyte folate levels (Fol-E) considered preventive of neural tube defects (NTDs). Methods:In this single-center, double-blind, randomized, placebo (PBO)-controlled trial, healthy women of childbearing potential (WCBP) took either an oral MMP containing 400 µg folic acid and 451 µg L-5-methyltetrahydrofolate (MTHF) or PBO once daily for 16 weeks. Primary endpoints were achievement of Fol-E ≥ 906 nmol/L at Week 4 and maintenance of this level once achieved. Secondary efficacy variables were plasma concentrations of folate, homocysteine, and vitamins B2, B6, and B12 at Week 4, 8, 12, and 16. Results:Of the 40 women enrolled, 20 were randomized to each study arm. All but one PBO-subject completed the study as planned. Baseline characteristics in both groups were comparable with mean Fol-E around 500 nmol/L. In contrast to only one PBO-subject, all MMP subjects achieved and maintained the target Fol-E (MMP: 100% vs PBO: 5%, p<0.001), 14 (70%) MMP subjects already by Week 4 (means ± SD: 976 ± 186 vs 629 ± 215 nmol/L, p<0.001). In plasma, the only change under PBO was a 10% decrease of vitamin B12 whereas under MMP folate and vitamin B6 significantly increased and homocysteine significantly decreased. There was no serious and only one severe adverse event (AE); most common AEs were gastrointestinal with greater incidence in the MMP group (30% versus 5%). Conclusion:Supplementation with folic acid and MTHF at equimolar amounts was efficacious in replenishing Fol-E of WCBP within 4 weeks to levels considered protective of NTDs.