Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly.

BACKGROUND: Dietary reference values for folate intake vary widely across Europe. METHODS: MEDLINE and Embase through November 2016 were searched for data on the association between folate intake and biomarkers (serum/plasma folate, red blood cell [RBC] folate, plasma homocysteine) from observational studies in healthy adults and elderly. The regression coefficient of biomarkers on intake (ß) was extracted from each study, and the overall and stratified pooled ß and SE (ß) were obtained by random effects meta-analysis on a double log scale. These dose-response estimates may be used to derive folate intake reference values. RESULTS: For every doubling in folate intake, the changes in serum/plasma folate, RBC folate and plasma homocysteine were +22, +21, and -16% respectively. The overall pooled regression coefficients were ß = 0.29 (95% CI 0.21-0.37) for serum/plasma folate (26 estimates from 17 studies), ß = 0.28 (95% CI 0.21-0.36) for RBC (13 estimates from 11 studies), and ß = -0.21 (95% CI -0.31 to -0.11) for plasma homocysteine (10 estimates from 6 studies). CONCLUSION: These estimates along with those from randomized controlled trials can be used for underpinning dietary recommendations for folate in adults and elderly.

Supplementation with calcium and short-chain fructo-oligosaccharides affects markers of bone turnover but not bone mineral density in postmenopausal women.

This 24-mo randomized, double-blind, controlled trial aimed to examine whether supplementation with a natural marine-derived multi-mineral supplement rich in calcium (Ca) taken alone and in conjunction with short-chain fructo-oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD) and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non-osteoporotic postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin. BMD was measured before and after intervention along with BTMs, which were also measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in the Ca and CaFOS groups did not differ from that in the maltodextrin group. Secondary analysis of changes to BTMs over time identified a greater decline in osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12 mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group compared with the maltodextrin group. In exploratory subanalyses of each treatment group against the maltodextrin group, women classified with osteopenia and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P = 0.03) BMD compared with the maltodextrin group, although this effect was restricted to those with higher total-body and mean spinal BMD at baseline, respectively. Although the change in BMD observed did not differ between the groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the maltodextrin group suggests a more favorable bone health profile after supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of total-body and spinal bone loss in postmenopausal women with osteopenia-an effect that warrants additional investigation. This trial was registered at www.controlled-trials.com as ISRCTN63118444.

Effects on obese women of the sugar sucrose added to the diet over 28 d: a quasi-randomised, single-blind, controlled trial.

To investigate whether obese women can compensate for sucrose added to the diet when it is given blind, rather than gaining weight or exhibiting dysfunctional regulation of intake, in the present study, forty-one healthy obese (BMI 30-35 kg/m²) women (age 20-50 years), not currently dieting, were randomly assigned to consume sucrose (n 20) or aspartame (n 21) drinks over 4 weeks in a parallel single-blind design. Over the 4 weeks, one group consumed 4 × 250 ml sucrose drinks (total 1800 kJ/d) and the other group consumed 4 × 250 ml aspartame drinks. During the baseline week and experimental weeks, body weight and other biometric data were measured and steps per day, food intake using 7 d unweighed food diaries, and mood using ten- or seven-point Likert scales four times a day were recorded. At the end of the experiment, the participants weighed 1·72 (SE 0·47) kg less than the value predicted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) model; the predicted body weight accounted for 94·3% of the variance in the observed body weight and experimental group accounted for a further 1·1% of the variance in the observed body weight, showing that women consuming sucrose drinks gained significantly less weight than predicted. The reported daily energy intake did not increase significantly, and sucrose supplements significantly reduced the reported voluntary sugar, starch and fat intake compared with aspartame. There were no effects on appetite or mood. Over 4 weeks, as part of everyday eating, sucrose given blind in soft drinks was partially compensated for by obese women, as in previous experiments with healthy and overweight participants.

Early-stage primary school children attending a school in the Malawian School Feeding Program (SFP) have better reversal learning and lean muscle mass growth than those attending a non-SFP school.

In developing countries, schoolchildren encounter a number of challenges, including failure to complete school, poor health and nutrition, and poor academic performance. Implementation of school feeding programs (SFPs) in less developed countries is increasing and yet there is mixed evidence regarding their positive effects on nutrition, education, and cognition at the population level. This study evaluated cognitive and anthropometric outcomes in entry-level primary school children in Malawi with the aim of generating evidence for the ongoing debate about SFPs in Malawi and other developing countries. A total of 226 schoolchildren aged 6-8 y in 2 rural Malawian public primary schools were followed for one school year. Children attending one school (SFP school) received a daily ration of corn-soy blend porridge, while those attending the other (non-SFP school) did not. Baseline and post-baseline outcomes included the Cambridge Neurological Test Automated Battery cognitive tests of paired associate learning, rapid visual information processing and intra-extra dimensional shift, and anthropometric measurements of weight, height, and mid-upper arm circumference (MUAC). At follow-up, the SFP subcohort had a greater reduction than the non-SFP subcohort in the number of intra-extra predimensional shift errors made (mean 18.5 and 24.9, respectively; P-interaction = 0.02) and also showed an increase in MUAC (from 16.3 to 17.0; P-interaction <0.0001). The results indicate that the SFP in Malawi is associated with an improvement in reversal learning and catch-up growth in lean muscle mass in children in the SFP school compared with children in the non-SFP school. These findings suggest that the Malawian SFP, if well managed and ration sizes are sustained, may have the potential to improve nutritional and cognitive indicators of the most disadvantaged children.

EURRECA-Estimating folate requirements for deriving dietary reference values.

In most countries, the dietary folate intake associated with adequate status of red cell folate and/or serum folate provides the basis for formulating reference values. One of the major challenges in setting dietary reference values for folate, however, is the need to account for the differences in bioavailability between the natural forms of the vitamin and the synthetic form, folic acid, albeit to date, few countries in Europe take bioavailability into consideration. A series of systematic reviews that included only those studies which used the most robust measures of both folate intake and folate status were carried out by the EURRECA Network of Excellence to examine the relationships between folate intake, status, and a number of health outcomes relevant to specific stages of the lifecycle. This review summarizes the available evidence and the issues to consider in the setting of dietary reference values for folate.

Factors influencing European consumer uptake of personalised nutrition. Results of a qualitative analysis.

The aim of this research was to explore consumer perceptions of personalised nutrition and to compare these across three different levels of "medicalization": lifestyle assessment (no blood sampling); phenotypic assessment (blood sampling); genomic assessment (blood and buccal sampling). The protocol was developed from two pilot focus groups conducted in the UK. Two focus groups (one comprising only "older" individuals between 30 and 60 years old, the other of adults 18-65 yrs of age) were run in the UK, Spain, the Netherlands, Poland, Portugal, Ireland, Greece and Germany (N=16). The analysis (guided using grounded theory) suggested that personalised nutrition was perceived in terms of benefit to health and fitness and that convenience was an important driver of uptake. Negative attitudes were associated with internet delivery but not with personalised nutrition per se. Barriers to uptake were linked to broader technological issues associated with data protection, trust in regulator and service providers. Services that required a fee were expected to be of better quality and more secure. An efficacious, transparent and trustworthy regulatory framework for personalised nutrition is required to alleviate consumer concern. In addition, developing trust in service providers is important if such services to be successful.

Nutritional and cognitive status of entry-level primary school children in Zomba, rural Malawi.

Entry-level Malawian children (n = 226) aged 6-8 years from two public primary schools, one a participant in a national school feeding programme (FP), the other not, were investigated for differences in nutritional and cognitive status. Stunted growth (42%) and underweight (25%) were prevalent, with no significant differences between the schools, although the school attended was a significant predictor of mid-upper arm circumference. Previous attendance at a community-based childcare centre was significantly associated with lower body weight and height. There were no significant differences in memory, reversal learning and attention outcomes between the schools. These findings report no major significant difference in nutrition or cognitive statuses between the schools, and on this basis suggest that both schools were equally in need of FP participation. More inclusive interventions and broadening/review of FP participation criteria are recommended.

Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women.

Choline is an essential nutrient and can also be obtained by de novo synthesis via an oestrogen responsive pathway. Choline can be oxidised to the methyl donor betaine, with short-term supplementation reported to lower plasma total homocysteine (tHcy); however, the effects of longer-term choline supplementation are less clear. We investigated the effect of choline supplementation on plasma concentrations of free choline, betaine and tHcy and B-vitamin status in postmenopausal women, a group more susceptible to low choline status. We also assessed whether supplementation altered plasma lipid profiles. In this randomised, double-blinded, placebo-controlled study, forty-two healthy postmenopausal women received 1 g choline per d (as choline bitartrate), or an identical placebo supplement with their habitual diet. Fasting blood samples were collected at baseline, week 6 and week 12. Administration of choline increased median choline and betaine concentrations in plasma, with significant effects evident after 6 weeks of supplementation (P<0·001) and remaining significant at 12 weeks (P<0·001); no effect was observed on folate status or on plasma lipids. Choline supplementation induced a median (25th, 75th percentile) change in plasma tHcy concentration at week 6 of -0·9 (-1·6, 0·2) µmol, a change which, when compared to that observed in the placebo group 0·6 (-0·4, 1·9) µmol, approached statistical significance (P=0·058). Choline supplementation at a dose of 1 g/d significantly increases the circulating concentration of free choline, and can also significantly increase the concentration of the methyl donor, betaine, thereby potentially enhancing the betaine-homocysteine methyltransferase-mediated remethylation of tHcy.

Associations between obesity (BMI and waist circumference) and socio-demographic factors, physical activity, dietary habits, life events, resilience, mood, perceived stress and hopelessness in healthy older Europeans.

BACKGROUND: It is important to understand the psycho-social context of obesity to inform prevention and treatment of obesity at both the individual and public health level. METHODS: Representative samples of middle-aged adults aged ≥43 years were recruited in Great Britain (GB) (n = 1182) and Portugal (n = 540) and interviewed to explore associations between body mass index (BMI), waist circumference (WC), demographic factors, physical activity, dietary habits (FFQ), life events (LES), Resilience (RS11), Mood (MS), Hopelessness (BDI) and Perceived Stress (PSS4). BMI (kg/m2) and WC (cm) were dependent variables in separate multiple linear regression models for which predictors were entered in 4 blocks: 1. demographic factors; 2. stressful life events; 3. diet/activity; and, 4. psychological measures. RESULTS: In the GB sample, BMI (kg/m2) was predicted by less education, illness in a close friend or relative, frequent alcohol consumption and sedentary behaviour. Among the Portuguese, higher BMI (kg/m2) was predicted by lower resilience. Being male and less education were independent predictors of having a larger WC (cm) in both countries. Within GB, not working, illness in a close friend or relative, sedentary lifestyle and lower resilience were also independent predictors of a larger WC (cm). CONCLUSIONS: These data suggest that intervention to treat and/or prevent obesity should target males, particularly those who have left education early and seek to promote resilience. In GB, targeting those with high alcohol consumption and encouraging physical activity, particularly among those who have experienced illness in a close friend or relative may also be effective in reducing obesity.

Effects of sucrose drinks on macronutrient intake, body weight, and mood state in overweight women over 4 weeks.

The long-term effects of sucrose on appetite and mood remain unclear. Normal weight subjects compensate for sucrose added blind to the diet (Reid et al., 2007). Overweight subjects, however, may differ. In a single-blind, between-subjects design, soft drinks (4x25cl per day; 1800kJ sucrose sweetened versus 67kJ aspartame sweetened) were added to the diet of overweight women (n=53, BMI 25-30, age 20-55) for 4 weeks. A 7-day food diary gave measures of total energy, carbohydrate, protein, fat, and micronutrients. Mood and hunger were measured by ten single Likert scales rated daily at 11.00, 14.00, 16.00, and 20.00. Activity levels were measured by diary and pedometer. Baseline energy intake did not differ between groups. During the first week of the intervention energy intake increased slightly in the sucrose group, but not in the aspartame group, then decreased again, so by the final week intake again did not differ from the aspartame group. Compensation was not large enough to produce significant changes in the composition of the voluntary diet. There were no effects on hunger or mood. It is concluded that overweight women do not respond adversely to sucrose added blind to the diet, but compensate for it by reducing voluntary energy intake. Alternative explanations for the correlation between sugary soft drink intake and weight gain are discussed.

The relationship between whole-blood serotonin and subjective mood in apparently healthy postmenopausal women.

The aim of this research has been to determine the degree to which biochemical indices of mood reflect subjective mood. Potential relationships between whole-blood (WB) serotonin (5-hydroxytryptamine, 5-HT) levels as determined by the positive and negative affect schedule (PANAS) have been explored in apparently healthy postmenopausal women (n=39). Partial correlations indicated that WB 5-HT was positively associated with positive affect (p=0.03). No association was apparent for negative affect. These findings indicate that WB 5-HT and positive affect are related in postmenopausal women.

Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials.

BACKGROUND: The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake. OBJECTIVE: We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake. DESIGN: Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged ≥18 y. For each biomarker response, the regression coefficient (ß) for individual studies and the overall pooled ß were calculated by using random-effects meta-analysis. RESULTS: Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 µg/d. Calculation of the overall pooled ß for studies in the range of 50 to 400 µg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I(2) = 13.5% compared with I(2) = 77.2%) and red blood cell (I(2) = 45.9% compared with I(2) = 70.2%) folate. CONCLUSIONS: Studies administering >400 µg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement.

A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy.

BACKGROUND: The lowest dose of folic acid required to achieve effective reductions in homocysteine is controversial but important for food fortification policy given recent concerns about the potential adverse effects of overexposure to this vitamin. OBJECTIVE: We compared the effectiveness of 0.2 mg folic acid/d with that of 0.4 and 0.8 mg/d at lowering homocysteine concentrations over a 6-mo period. DESIGN: A randomized dose-finding trial with folic acid was conducted. Of 203 participants screened, 101 patients with ischemic heart disease and 71 healthy volunteers completed the study. Participants were randomly assigned to receive placebo or folic acid at doses of 0.2, 0.4, or 0.8 mg/d for 26 wk; subsamples of patients with ischemic heart disease were also examined at 6 or 12 wk. RESULTS: Participants with higher baseline homocysteine concentrations had the greatest reductions in homocysteine in response to folic acid doses of 0.2 mg (-20.6%), 0.4 mg (-20.7%), and 0.8 mg (-27.8%); in those with lower baseline homocysteine concentrations, the responses were -8.2%, -8.9%, and -8.3%, respectively. No significant differences in homocysteine responses to the different doses were observed. In the patient group sampled at intervals during the intervention, the maximal homocysteine response appeared to be achieved by 6 wk in the 0.8-mg/d group and by 12 wk in the 0.4-mg/d group. However, the homocysteine response was suboptimal in the 0.2-mg/d group at both 6 and 12 wk compared with that at 26 wk. CONCLUSIONS: A folic acid dose as low as 0.2 mg/d can, if administered for 6 mo, effectively lower homocysteine concentrations. Higher doses may not be necessary because they result in no further significant lowering, whereas doses even lower than 0.2 mg/d may be effective in the longer term. Previous trials probably overestimated the folic acid dose required because of a treatment duration that was too short. This trial was registered at clinicaltrials.gov as ISRCTN45296887.