A Nutrient Formulation Affects Developmental Myelination in Term Infants: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Observational studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning. The study aims to investigate the efficacy of a blend of docosahexaenoic acid (DHA), arachidonic acid (ARA), iron, vitamin B12, folic acid, and sphingomyelin (SM) from a uniquely processed whey protein concentrate enriched in alpha-lactalbumin and phospholipids compared with a control formulation on myelination, cognitive, and behavioral development in the first 6 months of life. METHODS: These are 6-month results from an ongoing two-center, randomized controlled trial with a 12-month intervention period (completed for all participants). In this study, full term, neurotypical infants of both sexes (N = 81) were randomized into investigational (N = 42) or control groups (N = 39). In addition, non-randomized breast-fed children (N = 108) serve as a natural reference group. Main outcomes are myelination (MRI), cognitive (Bayley Scales of Infant and Toddler Development, 3rd edition [Bayley-III]), social-emotional development (Ages and Stages Questionnaires: Social-Emotional, 2nd edition [ASQ:SE-2]), sleep (Brief Infant Sleep Questionnaire [BISQ]), and safety (growth and adverse events [AEs]). RESULTS: The full analyses set comprises N = 66 infants. Significant differences in myelin structure, volume, and rate of myelination were observed in favor of the investigational myelin blend at 3 and 6 months of life. Effects were demonstrated for whole brain myelin and for cerebellar, parietal, occipital, and temporal regions, known to be functionally involved in sensory, motor, and language skills. No statistically significant differences were found for early behavior and cognition scores. CONCLUSIONS: This is the first study demonstrating the efficacy of a myelin nutrient blend in well-nourished, term infants on developmental myelination, which may be foundational for later cognitive and learning outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03111927.

Diet and nutrients in the modulation of infant sleep: A review of the literature.

OBJECTIVES: The establishment of organized sleep patterns is an important developmental process during infancy. Little is known about the role of nutrition in sleep maturation. This review focuses on exploring the link between infant sleep and nutrition with the aim to provide an overview of existing literature on the impact of diet and specific nutrients on sleep modulation in infants. METHODS: An exploratory literature search was performed on the topic in Medline, Scopus and Cochrane Library databases, with a focus on publications in English. RESULTS: Both the type of nutrients consumed and the timing at which they were consumed, relative to sleeping time, have been reported to influence infant sleep. Some nutrients have been shown to naturally fluctuate in maternal breast milk with circadian rhythm, and nutrients such as tryptophan, nucleotides, essential fatty acids and Omega-3 long-chain fatty acids have been suggested to impact infant sleep. DISCUSSION: In summary, little is known about the nutritional impact on infant sleep and sleep maturation, particularly with regard to specific nutrients. While nutrients like tryptophan and nucleotides seem to impact sleep at the level of brain activity, some fatty acids may affect sleep as a result of their role in supporting the maturity of the central nervous system. In our view, the existing literature indicates that the link between nutrition and infant sleep may be a promising concept to support this crucial phase of early development.

Stool fatty acid soaps, stool consistency and gastrointestinal tolerance in term infants fed infant formulas containing high sn-2 palmitate with or without oligofructose: a double-blind, randomized clinical trial.

BACKGROUND: Formula-fed (FF) infants often have harder stools and higher stool concentrations of fatty acid soaps compared to breastfed infants. Feeding high sn-2 palmitate or the prebiotic oligofructose (OF) may soften stools, reduce stool soaps, and decrease fecal calcium loss. METHODS: We investigated the effect of high sn-2 palmitate alone and in combination with OF on stool palmitate soap, total soap and calcium concentrations, stool consistency, gastrointestinal (GI) tolerance, anthropometrics, and hydration in FF infants. This double-blind trial randomized 165 healthy term infants 25-45 days old to receive Control formula (n = 54), formula containing high sn-2 palmitate (sn-2; n = 56), or formula containing high sn-2 palmitate plus 3 g/L OF (sn-2+OF; n = 55). A non-randomized human milk (HM)-fed group was also included (n = 55). The primary endpoint, stool composition, was determined after 28 days of feeding, and was assessed using ANOVA accompanied by pairwise comparisons. Stool consistency, GI tolerance and hydration were assessed at baseline, day 14 (GI tolerance only) and day 28. RESULTS: Infants fed sn-2 had lower stool palmitate soaps compared to Control (P = 0.0028); while those fed sn-2+OF had reduced stool palmitate soaps compared to both Control and sn-2 (both P < 0.0001). Stool total soaps and calcium were lower in the sn-2+OF group than either Control (P < 0.0001) or sn-2 (P < 0.0001). The HM-fed group had lower stool palmitate soaps, total soaps and calcium (P < 0.0001 for each comparison) than all FF groups. The stool consistency score of the sn-2+OF group was lower than Control and sn-2 (P < 0.0001), but higher than the HM-fed group (P < 0.0001). GI tolerance was similar and anthropometric z-scores were <0.2 SD from the WHO growth standards in all groups, while urinary hydration markers were within normal range for all FF infants. CONCLUSIONS: Increasing sn-2 palmitate in infant formula reduces stool palmitate soaps. A combination of high sn-2 palmitate and OF reduces stool palmitate soaps, total soaps and calcium, while promoting softer stools. TRIAL REGISTRATION: This study was registered on http://www.clinicaltrials.gov: number NCT02031003.

Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet.

We previously reported that carbohydrate restriction (CR) (10-15% en) during a weight loss intervention lowered plasma triglycerides (TG) by 45% in male subjects (P<.001). However, those subjects with a higher intake of cholesterol provided by eggs (640 mg additional cholesterol, EGG group) had higher concentrations of high-density lipoprotein (HDL) cholesterol (P<.0001) than the individuals consuming lower amounts (0 mg of additional cholesterol, SUB group). The objectives of the present study were to evaluate whether CR and egg intake (1) modulate circulating carotenoids and (2) affect the concentrations of plasma apolipoproteins (apo), lipoprotein size and subfraction distribution. CR decreased the number of large and medium very low-density lipoprotein cholesterol subclasses (P<.001), while small low-density lipoprotein (LDL) were reduced (P<.001). In agreement with these observations, a decrease in apo B (P<.01) was observed. In addition, CR resulted in a 133% increase in apo C-II and a 65% decrease in apo C-III (P<.0001). Although an increase of the larger LDL subclass was observed for all subjects, the EGG group had a greater increase (P<.05). The EGG group also presented a higher number of large HDL particles (P<.01) compared to the SUB group. Regarding carotenoids, CR resulted in no changes in dietary or plasma alpha- or beta-carotene and beta-cryptoxanthin, while there was a significant reduction in both dietary and plasma lycopene (P<.001). In contrast, dietary lutein and zeaxanthin were increased during the intervention (P<.05). However, only those subjects from the EGG group presented higher concentrations of these two carotenoids in plasma, which were correlated with the higher concentrations of large LDL observed in the EGG group. These results indicate that CR favorably alters VLDL metabolism and apolipoprotein concentrations, while the components of the egg yolk favor the formation of larger LDL and HDL leading to an increase in plasma lutein and zeaxanthin.

Carbohydrate restriction (with or without additional dietary cholesterol provided by eggs) reduces insulin resistance and plasma leptin without modifying appetite hormones in adult men.

Carbohydrate-restricted diets (CRDs) have been shown to reduce body weight, whereas whole egg intake has been associated with increased satiety. The purpose of this study was to evaluate the effects of additional dietary cholesterol and protein provided by whole eggs while following a CRD on insulin resistance and appetite hormones. Using a randomized blind parallel design, subjects were allocated to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) group for 12 weeks while following a CRD. There were significant reductions in fasting insulin (P < .025) and fasting leptin concentrations (P < .01) for both groups, which were correlated with the reductions in body weight and body fat (P < .05 and P < .01, respectively). Both groups reduced insulin resistance as measured by the homeostatic model assessment of insulin resistance (P < .025). There was a significant decrease in serum glucose levels observed after the intervention. We did not observe the expected increases in plasma ghrelin levels associated with weight loss, suggesting a mechanism by which subjects do not increase appetite with CRD. To confirm these results, the subjective measures of satiety using visual analog scale showed that both groups felt more "full" (P < .05), "satisfied" (P < .001), and "wanted to eat less" (P < .001) after the intervention. These results indicate that inclusion of eggs in the diet (additional dietary cholesterol) did not modify the multiple beneficial effects of CRD on insulin resistance and appetite hormones.

Raisins and walking alter appetite hormones and plasma lipids by modifications in lipoprotein metabolism and up-regulation of the low-density lipoprotein receptor.

The purpose of this study was to determine the effects of consuming raisins, increasing steps walked, or a combination of these interventions on lipoprotein metabolism and appetite hormones by assessing plasma apolipoprotein concentrations, cholesterol ester transfer protein activity, low-density lipoprotein (LDL) receptor messenger RNA (mRNA) abundance, and plasma ghrelin and leptin concentrations. Thirty-four subjects (17 men and 17 postmenopausal women) were matched for weight and sex and randomly assigned to consume 1 cup raisins per day (RAISIN), increase the amount of steps walked per day (WALK), or a combination of both interventions (RAISIN + WALK). The subjects completed a 2-week run-in period, followed by a 6-week intervention. Ribonucleic acid was extracted from mononuclear cells, and LDL receptor mRNA abundance was quantified by use of reverse transcriptase polymerase chain reaction. Plasma apolipoproteins were measured by Luminex (Austin, TX) technology. Apoproteins A-1, B, C-II, and E and cholesterol ester transfer protein activity were not altered for any of the groups. In contrast, apolipoprotein C-III was significantly decreased by 12.3% only in the WALK group (P < .05). Low-density lipoprotein receptor mRNA abundance was increased for all groups after the intervention (P < .001). There was a significant group effect for plasma leptin (P = .026). Plasma concentrations increased for RAISIN and RAISIN + WALK. Similarly, plasma ghrelin concentrations were elevated postintervention for both groups consuming raisins (P < .05). These data suggest that walking and raisin consumption decrease plasma LDL cholesterol by up-regulating the LDL receptor and that raisin consumption may reduce hunger and affect dietary intake by altering hormones influencing satiety.

Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men.

BACKGROUND: Carbohydrate restricted diets (CRD) consistently lower glucose and insulin levels and improve atherogenic dyslipidemia [decreasing triglycerides and increasing HDL cholesterol (HDL-C)]. We have previously shown that male subjects following a CRD experienced significant increases in HDL-C only if they were consuming a higher intake of cholesterol provided by eggs compared to those individuals who were taking lower concentrations of dietary cholesterol. Here, as a follow up of our previous study, we examined the effects of eggs (a source of both dietary cholesterol and lutein) on adiponectin, a marker of insulin sensitivity, and on inflammatory markers in the context of a CRD. METHODS: Twenty eight overweight men [body mass index (BMI) 26-37 kg/m2] aged 40-70 y consumed an ad libitum CRD (% energy from CHO:fat:protein = 17:57:26) for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume eggs (EGG, n = 15) (640 mg additional cholesterol/day provided by eggs) or placebo (SUB, n = 13) (no additional dietary cholesterol). Fasting blood samples were drawn before and after the intervention to assess plasma lipids, insulin, adiponectin and markers of inflammation including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1(VCAM-1). RESULTS: Body weight, percent total body fat and trunk fat were reduced for all subjects after 12 wk (P < 0.0001). Increases in adiponectin were also observed (P < 0.01). Subjects in the EGG group had a 21% increase in this adipokine compared to a 7% increase in the SUB group (P < 0.05). Plasma CRP was significantly decreased only in the EGG group (P < 0.05). MCP-1 levels were decreased for the SUB group (P < 0.001), but unchanged in the EGG group. VCAM-1, ICAM-1, TNF-alpha, and IL-8 were not modified by CRD or eggs. CONCLUSION: A CRD with daily intake of eggs decreased plasma CRP and increased plasma adiponectin compared to a CRD without eggs. These findings indicate that eggs make a significant contribution to the anti-inflammatory effects of CRD, possibly due to the presence of cholesterol, which increases HDL-C and to the antioxidant lutein which modulates certain inflammatory responses.

Dietary cholesterol from eggs increases plasma HDL cholesterol in overweight men consuming a carbohydrate-restricted diet.

Carbohydrate-restricted diets (CRD) significantly decrease body weight and independently improve plasma triglycerides (TG) and HDL cholesterol (HDL-C). Increasing intake of dietary cholesterol from eggs in the context of a low-fat diet maintains the LDL cholesterol (LDL-C)/HDL-C for both hyper- and hypo-responders to dietary cholesterol. In this study, 28 overweight/obese male subjects (BMI = 25-37 kg/m2) aged 40-70 y were recruited to evaluate the contribution of dietary cholesterol from eggs in a CRD. Subjects were counseled to consume a CRD (10-15% energy from carbohydrate) and they were randomly allocated to the EGG group [intake of 3 eggs per day (640 mg/d additional dietary cholesterol)] or SUB group [equivalent amount of egg substitute (0 dietary cholesterol) per day]. Energy intake decreased in both groups from 10,243 +/- 4040 to 7968 +/- 2401 kJ (P < 0.05) compared with baseline. All subjects irrespective of their assigned group had reduced body weight and waist circumference (P < 0.0001). Similarly, the plasma TG concentration was reduced from 1.34 +/- 0.66 to 0.83 +/- 0.30 mmol/L after 12 wk (P < 0.001) in all subjects. The plasma LDL-C concentration, as well as the LDL-C:HDL-C ratio, did not change during the intervention. In contrast, plasma HDL-C concentration increased in the EGG group from 1.23 +/- 0.39 to 1.47 +/- 0.38 mmol/L (P < 0.01), whereas HDL-C did not change in the SUB group. Plasma glucose concentrations in fasting subjects did not change. Eighteen subjects were classified as having the metabolic syndrome (MetS) at the beginning of the study, whereas 3 subjects had that classification at the end. These results suggest that including eggs in a CRD results in increased HDL-C while decreasing the risk factors associated with MetS.

Carbohydrate restriction and dietary cholesterol modulate the expression of HMG-CoA reductase and the LDL receptor in mononuclear cells from adult men.

The liver is responsible for controlling cholesterol homeostasis in the body. HMG-CoA reductase and the LDL receptor (LDL-r) are involved in this regulation and are also ubiquitously expressed in all major tissues. We have previously shown in guinea pigs that there is a correlation in gene expression of HMG-CoA reductase and the LDL-r between liver and mononuclear cells. The present study evaluated human mononuclear cells as a surrogate for hepatic expression of these genes. The purpose was to evaluate the effect of dietary carbohydrate restriction with low and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in mononuclear cells. All subjects were counseled to consume a carbohydrate restricted diet with 10-15% energy from carbohydrate, 30-35% energy from protein and 55-60% energy from fat. Subjects were randomly assigned to either EGG (640 mg/d additional dietary cholesterol) or SUB groups [equivalent amount of egg substitute (0 dietary cholesterol contributions) per day] for 12 weeks. At the end of the intervention, there were no changes in plasma total or LDL cholesterol (LDL-C) compared to baseline (P > 0.10) or differences in plasma total or LDL-C between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured in mononuclear cells using real time PCR. The EGG group showed a significant decrease in HMG-CoA reductase mRNA (1.98 +/- 1.26 to 1.32 +/- 0.92 arbitrary units P < 0.05) while an increase was observed for the SUB group (1.13 +/- 0.52 to 1.69 +/- 1.61 arbitrary units P < 0.05). Additionally, the LDL-r mRNA abundance was decreased in the EGG group (1.72 +/- 0.69 to 1.24 +/- 0.55 arbitrary units P < 0.05) and significantly increased in the SUB group (1.00 +/- 0.60 to 1.67 +/- 1.94 arbitrary units P < 0.05). The findings indicate that dietary cholesterol during a weight loss intervention alters the expression of genes regulating cholesterol homeostasis.