Infant Formula with Added Bovine Milk Fat Globule Membrane and Modified Iron Supports Growth and Normal Iron Status at One Year of Age: A Randomized Controlled Trial.

Inclusion of bovine-derived milk fat globule membrane (bMFGM) or bMFGM components in infant formulas (IFs) may support healthy brain development. This double-blind, prospective trial evaluated growth, tolerance, and iron status in infants receiving added bMFGM and modified protein, iron, and arachidonic acid (ARA) concentrations in IF. Healthy term infants were randomized to: control (marketed, routine cow's milk-based IF/100 kcal: 2.1 g protein, 1.8 mg iron, 34 mg ARA) or INV-MFGM (investigational cow's milk-based IF/100 kcal: 1.9 g protein, 1.2 mg iron, 25 mg ARA and whey protein-lipid concentrate, 5 g/L (source of bMFGM)). Anthropometrics, stool characteristics, fussiness, and gassiness through day 365 and blood markers of iron status at day 365 were evaluated. The primary outcome was rate of weight gain from 14-120 days of age. Of 373 infants enrolled (control: 191, INV-MFGM: 182), 275 completed the study (control: 141; INV-MFGM: 134). No group differences in growth rate (g/day) from day 14-120 or study discontinuation were detected. Few group differences in growth or parent-reported fussiness, gassiness, or stool characteristics were detected. No group differences were detected in hemoglobin, hematocrit, or incidence of anemia. In healthy term infants, bMFGM and modified protein, iron, and ARA concentrations in a cow's milk-based IF were well-tolerated, associated with adequate growth throughout the first year of life, and supported normal iron status at one year of age.

Nutrient Intake Adequacy from Food and Beverage Intake of US Children Aged 1-6 Years from NHANES 2001-2016.

The early years, between the ages of one and six, are a period of rapid physical, social and cognitive growth and a nutritionally adequate diet is an important factor for optimum development. We investigated the micronutrient adequacy and status of young US children aged 1-6 years (n = 9848) using 24-h dietary recall interviews completed by parents and caregivers participating in the National Health and Nutrition Examination Survey (NHANES) 2001-2016. data. The proportion of the sample not meeting the Dietary Reference Intakes (DRI) increased with increasing age and was most pronounced for calcium. Despite adequate iron intake, 7.4% and 2.5% had signs of iron deficiency and anemia based on serum ferritin and hemoglobin levels, with younger children and WIC participants at most risk and Non-Hispanic Black children the least. Vitamin B6 intake was adequate, but 6.4% had serum pyridoxal-5-phosphate deficiency. For vitamin E, 69% had intakes below the estimated average requirement (EAR), yet serum deficiency was only detected in 0.9%. Vitamin D intake was inadequate for 87%, but true deficiency may be overestimated. Mean DHA intake was 24 mg/d, well below expert recommendations of 70-100 mg/day. Iron and vitamin B6 deficiency and inadequate calcium, fiber, choline, potassium and DHA intakes are a concern for a significant percentage of young children. The discrepancy between nutrient intakes and serum deficiency levels needs to be further investigated.

Growth and tolerance of infants fed formula with a new algal source of docosahexaenoic acid: Double-blind, randomized, controlled trial.

Docosahexaenoic acid (DHA) in infant formula at concentrations based on worldwide human milk has resulted in circulating red blood cell (RBC) lipids related to visual and cognitive development. In this study, infants received study formula (17mg DHA/100kcal) with a commercially-available (Control: n=140; DHASCO®) or alternative (DHASCO®-B: n=127) DHA single cell oil from 14 to 120 days of age. No significant group differences were detected for growth rates by gender through 120 days of age. Blood fatty acids at 120 days of age were assessed by capillary column gas chromatography in a participant subset (Control: n=34; DHASCO-B: n=27). The 90% confidence interval (91-104%) for the group mean (geometric) total RBC DHA (µg/mL) ratio fell within the pre-specified equivalence limit (80-125%), establishing study formula equivalence with respect to DHA. This study demonstrated infant formula with DHASCO-B was safe, well-tolerated, and associated with normal growth. Furthermore, DHASCO and DHASCO-B represented equivalent sources of DHA as measured by circulating RBC DHA.

Omega-3 polyunsaturated fatty acid blood biomarkers increase linearly in men and women after tightly controlled intakes of 0.25, 0.5, and 1 g/d of EPA + DHA.

Blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been related to coronary heart disease risk. Understanding the response of EPA + DHA in blood to dietary intake of EPA + DHA would facilitate the use of blood measures as markers of adherence and enable the development of dietary recommendations. The objective of this study is examine the blood response to intakes of EPA + DHA ≤1 g/d with an intervention designed for dietary adherence. It was hypothesized this relationship would be linear and that intakes of EPA + DHA <1 g/d would result in blood levels below those associated with the highest level of protection for cardiovascular events. Background EPA + DHA intake of men and women (n = 20) was determined by food frequency questionnaire and adherence was monitored by weekly fingertip blood sampling for fatty acid determinations. Participants consumed nutraceuticals to achieve intakes of 0.25 g/d and 0.5 g/d EPA + DHA for successive four-week periods. A subgroup (n = 5) had intakes of 1.0 g/d EPA + DHA for an additional 4 weeks. Fatty acid composition of whole blood, erythrocytes, and plasma phospholipids were determined at each time point. Blood levels of EPA and DHA increased linearly in these pools. A comprehensive review of the literature was used to verify the blood-intake relationship. Blood levels of long chain omega-3 polyunsaturated fatty acids reached blood levels associated with the highest levels of primary cardiac arrest reduction and sudden cardiac death risk only with intakes of 1.0 g/d of EPA + DHA. The blood biomarker response to intakes of EPA + DHA ≤1 g/d is linear in a small but highly adherent study sample and this information can assist in determining adherence in clinical studies and help identify dietary intake targets from associations between blood and disease.

Microglial cell activation increases saturated and decreases monounsaturated fatty acid content, but both lipid species are proinflammatory.

Neuroinflammation is a component of age-related neurodegenerative diseases and cognitive decline. Saturated (SFA) and monounsaturated (MUFA) fatty acids are bioactive molecules that may play different extrinsic and intrinsic roles in neuroinflammation, serving as exogenous ligands for cellular receptors, or endogenous components of cell structural, energetic and signaling pathways. We determined the fatty acyl profile of BV2 microglial cells before and after acute activation with lipopolysaccharide (LPS). We also investigated the effect of SFA and MUFA pretreatment on the production of an invasive, neurotoxic phenotype in BV2 cells. Acute activation of BV2 microglia resulted in an increase in the relative content of SFA (12:0, 16:0, 18:0, 20:0, 22:0, and 24:0 increased significantly), and a relative decrease in the content of MUFA (16:1n7, 18:1n7, 18:1n9, 20:1n9, 24:1n9 decreased significantly). In agreement, the major stearoyl-CoA desaturase (SCD) isoform in BV2 cells, SCD2, was significantly down-regulated by LPS. We next treated cells with SFA (16:0 or 18:0) or MUFA (16:1n7 or 18:1n9), and found that levels of secreted IL6 were increased, as was secreted MMP9-mediated proteolytic activity. To test the functional significance, we treated SH-SY5Y neuronal cells with conditioned medium from BV2 cells pretreated with fatty acids, and found a small but significant induction of cell death. Our findings suggest differential intrinsic roles for SFA and MUFA in activated microglial cells, but similar extrinsic roles for these fatty acid species in inducing activation. Expansion of SFA is important during microglial cell activation, but either supplemental SFA or MUFA may contribute to chronic low-grade neuroinflammation.

The percentage of DHA in erythrocytes can detect non-adherence to advice to increase EPA and DHA intakes.

Characterisation of long-term adherence to EPA and DHA intakes through biomarkers and dietary assessments has implications for interpreting the findings of long-term intervention studies. Adherence to dietary advice targeting an EPA+DHA intake of 1 g/d was examined over 1 year. Men and women (n 45) received dietary advice to increase EPA and DHA intakes from seafood, nutraceutical (fish oil) or functional food sources, while a fourth group received combined advice. Blood biomarkers and dietary intakes of EPA and DHA were evaluated at baseline and post-intervention at weeks 4, 8, 12, 24 and 52. Assessment by 3 d diet records indicated that EPA+DHA intakes increased relative to baseline in weeks 4-52 following the seafood, nutraceutical and combined advice (advice group × time effect, P= 0·03). The percentage of DHA in plasma and whole blood and the percentage of EPA in erythrocytes, plasma and whole blood were higher in weeks 4-52 when compared with the corresponding baseline measurement. In contrast, the percentage of DHA in erythrocytes increased to a maximum at week 12 and returned to baseline levels in weeks 24 and 52 (time effect, P< 0·01). Measurement of the percentage of DHA in erythrocytes indicates that adherence was sustained during the first 12 weeks following the dietary advice, while other blood measurements of the percentage of EPA and DHA and dietary assessment suggest short-term increases in EPA+DHA intakes immediately before weeks 24 and 52. The percentage of DHA in erythrocytes characterises adherence to EPA and DHA intakes in long-term interventions.

Omega-3 polyunsaturated fatty acid profiling using fingertip-prick whole blood does not require overnight fasting before blood collection.

Fatty acid profiling through the rapid analysis of capillary blood collected by fingertip prick could enable economical screening for omega-3 polyunsaturated fatty acid (PUFA) status, although the typical requirement of fasting prior to sample collection may limit application. We hypothesize that moderate changes in omega-3 biomarkers determined from fingertip-prick blood will occur and correspond to omega-3 PUFA content of the meals. Eight participants consumed a single breakfast with high fat, high fat with omega-3 functional foods, and low fat and low fat with fish oil capsules in a cross-over design. The fatty acid composition of fingertip-prick blood total lipid and venous blood erythrocyte total lipid, plasma total lipid, plasma triacylglycerol, and plasma phospholipids were analyzed at baseline and 1, 2, 3 and 4 hours after each single breakfast consumption. Omega-3 blood biomarkers; % of omega-3 highly unsaturated fatty acid (HUFA) in total HUFA, weight % of eicosapentaenoic acid+docosahexaenoic acid, weight % of eicosapentaenoic acid+omega-3 docosapentaenoic acid+docosahexaenoic acid, and the ratio of total omega-6 PUFA to total omega-3 PUFA in fingertip-prick blood, did not change from baseline during the postprandial period (P > .05). However, meal type yielded lower (P < .05) % omega-3 HUFA in total HUFA in the low fat meal (22.8 ± 3.9) as compared with the low fat with omega-3 (24.2 ± 3.9) and, the high fat (23.8 ± 4) meals. The ratio of total omega-6 PUFA to total omega-3 PUFA was generally higher in meals without omega-3 compared with omega-3. In conclusion, determinations of omega-3 status by fingertip-prick blood sampling may not require prior overnight fasting.

Biomarker and dietary validation of a Canadian food frequency questionnaire to measure eicosapentaenoic and docosahexaenoic acid intakes from whole food, functional food, and nutraceutical sources.

BACKGROUND: Canadian dietary sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include marine and non-marine whole foods, functional foods, and nutraceuticals. OBJECTIVE/DESIGN: In the present study, these sources were incorporated into a nutrient-specific, semi-quantitative food frequency questionnaire (FFQ) and the ability to measure the EPA and DHA intakes of Canadian adults was assessed. Specifically, the EPA and DHA intakes estimated by FFQ of 78 men and women, 20 to 60 years of age, were compared with EPA and DHA measurements from 3-day food records and measures of EPA and DHA in fasting whole blood. RESULTS: Mean (±standard deviation) and median intakes of EPA+DHA were 0.34±0.34 and 0.21 g/day by FFQ and 0.47±0.71 and 0.13 g/day by food record, with no significant differences between mean intakes (P=0.93). The FFQ provided higher estimates than the food record at low intakes of EPA and DHA and lower estimates at high intakes based on Bland-Altman plots. The FFQ was moderately correlated with food record (r=0.31 to 0.49) and with blood biomarker measures of EPA and DHA (r=0.31 to 0.51). Agreement analysis revealed that 42% of participants were classified in the same and 77% into same or adjacent quartile when EPA and DHA intake was assessed by food record and by FFQ. Similar quartile agreement was found for EPA and DHA intakes by FFQ with blood biomarker EPA and DHA. The range of the validity coefficients, calculated using the method of triads, was 0.43 to 0.71 for FFQ measurement of EPA+DHA. CONCLUSIONS: The FFQ is an adequate tool for estimating usual EPA and DHA intakes and ranking Canadian adults by their intakes.

Direct quantitation of omega-3 fatty acid intake of Canadian residents of a long-term care facility.

An increased dietary intake of n-3 highly unsaturated fatty acids (HUFA; >or=20 carbons, >or=3 carbon-carbon double bonds), particularly eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), is associated with the decreased risk and incidence of several morbidities afflicting the elderly, including cognitive decline, dementia, rheumatoid arthritis, and macular degeneration. In this study, the dietary intake and blood levels of fatty acids were directly determined in residents of a retirement home or assisted living phase of a continuum of care facility for Canadian seniors. Finger-tip-prick blood samples, 3-day food duplicates, and 3-day food records were collected. The fatty acid composition of food duplicates and blood was determined by gas chromatography. Fifteen participants (7 male, 8 female; 87.1 +/- 4.8 years of age) completed the protocol. The daily intake of EPA and DHA combined, determined directly, was 70 mg (95% CI, 41-119) or 0.036% of total energy (95% CI, 0.022-0.058). In finger-tip-prick blood, the percent of n-3 HUFA in total HUFA of whole blood, a biomarker of n-3 polyunsaturated fatty acid status, was 28.8 +/- 5.2%. Correlations between daily n-3 HUFA intake and n-3 HUFA in blood were not significant (r = 0.14; n = 15), but became significant after the removal of 2 participants who appeared to consume fish irregularly (r = 0.59; n = 13). The n-3 HUFA intake and corresponding n-3 HUFA blood levels of Canadian long-term care residents are lower than levels estimated to prevent several morbidities associated with aging.

Direct determinations of the fatty acid composition of daily dietary intakes incorporating nutraceuticals and functional food strategies to increase n-3 highly unsaturated fatty acids.

OBJECTIVE: North American diets are low in eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA). This investigation aims to assess the ability to increase EPA and DHA in the Canadian diet using traditional whole food, functional food or nutraceutical strategies. METHODS: A typical Canadian diet (TC) was compared to four diets enriched with EPA and DHA but with similar caloric and macronutrient composition: a nutraceutical fish oil capsule diet (FO), an EPA + DHA-enriched functional foods diet (ED), a traditional whole foods (fish) diet (TW) and a comprehensive diet combining fish with functional foods (FF) containing EPA + DHA and alpha-linolenic acid. Direct biochemical quantitations were performed for energy, protein, carbohydrate (proximate analysis) and fat (gas chromatography). Costs of each diet and EPA + DHA source were assessed. RESULTS: The FO (1.03 +/- 0.01 g EPA + DHA), ED (0.59 +/- 0.02 g), TW (3.23 +/- 0.09 g) and FF (3.15 +/- 0.06 g) diets provided significantly higher amounts of EPA + DHA compared to the TC diet (0.08 +/- 0.01 g). Using the TC diet as a baseline, the daily cost increase for each revised diet was $0.53 (FO), $0.82 (TW), $0.93 (ED) and $1.62 (FF). The cost per gram of EPA + DHA was lowest for fish oil nutraceuticals ($0.53/g), followed by fish ( approximately $1.05/g). CONCLUSIONS: The EPA and DHA content of daily diets can be increased significantly and cost effectively using nutraceuticals, functional foods and whole foods. Several North American EPA + DHA recommendations for healthy individuals can be met using these strategies and American Heart Association recommendations for secondary coronary heart disease prevention can be met via traditional whole food, nutraceutical or combination approaches.