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Background: Although epidemiological studies suggest a protective role of B vitamins and omega-3 (ω-3) fatty acids in cognitive decline, findings from intervention studies are conflicting. Mechanistic studies suggest that the ω-3 (n-3) fatty acid status can modulate the effects of B vitamins on cognitive decline., Objectives: We investigated the interaction between baseline ω-3 fatty acid statuses and folic acid treatment on cognitive decline in a placebo-controlled trial [FACIT (Folic Acid and Carotid Intima-media Thickness)]., Methods: This post hoc analysis included 791 older adults aged 50-70 y with plasma total homocysteine ≥13 µmol/L and ≤26 µmol/L and serum vitamin B12 ≥200 pmol/L. Participants received 800 µg folic acid or placebo daily for 3 y. Global cognitive functioning and domain-specific functioning (episodic memory, information processing speed, executive functioning) were assessed at baseline and after 3 y. The effect of the folic acid supplementation was analyzed according to tertiles of baseline ω-3 fatty acid concentrations using linear multiple regression., Results: The mean ± SD age of the study population was 60.2 ± 5.6 y, and the mean ± SD Mini-Mental State Examination score was 28.6 ± 1.5. The treatment effect of folic acid was significantly larger in participants in the low compared to high ω-3 fatty acid tertile for global cognition (difference in z-score: mean ± SE = 0.16 ± 0.059; P < 0.01). Regarding domain-specific functioning, similar results were observed for information processing speed (mean ± SE = 0.167 ± 0.068; P = 0.01). There were no overall interactions between folic acid treatment and ω-3 fatty acid tertiles for episodic memory (P = 0.14) and executive functioning (P = 0.21)., Conclusions: This post hoc analysis revealed that the efficacy of folic acid treatment on cognitive functioning is dependent on the ω-3 fatty acid status. Individuals with a lower ω-3 fatty acid status at baseline benefited from folic acid treatment, while individuals with a higher ω-3 fatty acid status did not. The results potentially explain the inconsistency in outcomes of B-vitamin supplementation trials and emphasize the importance of a personalized approach. This trial was registered at clinicaltrials.gov as NCT00110604., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

We assessed whether a protein supplementation protocol could attenuate running-induced muscle soreness and other muscle damage markers compared to iso-caloric placebo supplementation. A double-blind randomized controlled trial was performed among 323 recreational runners (age 44 ± 11 years, 56% men) participating in a 15-km road race. Participants received milk protein or carbohydrate supplementation, for three consecutive days post-race. Habitual protein intake was assessed using 24 h recalls. Race characteristics were determined and muscle soreness was assessed with the Brief Pain Inventory at baseline and 1-3 days post-race. In a subgroup ( n = 149) muscle soreness was measured with a strain gauge algometer and creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured. At baseline, no group-differences were observed for habitual protein intake (protein group: 79.9 ± 26.5 g/d versus placebo group: 82.0 ± 26.8 g/d, p = 0.49) and muscle soreness (protein: 0.45 ± 1.08 versus placebo: 0.44 ± 1.14, p = 0.96). Subjects completed the race with a running speed of 12 ± 2 km/h. With the Intention-to-Treat analysis no between-group differences were observed in reported muscle soreness. With the per-protocol analysis, however, the protein group reported higher muscle soreness 24 h post-race compared to the placebo group (2.96 ± 2.27 versus 2.46 ± 2.38, p = 0.039) and a lower pressure muscle pain threshold in the protein group compared to the placebo group (71.8 ± 30.0 N versus 83.9 ± 27.9 N, p = 0.019). No differences were found in concentrations of CK and LDH post-race between groups. Post-exercise protein supplementation is not more preferable than carbohydrate supplementation to reduce muscle soreness or other damage markers in recreational athletes with mostly a sufficient baseline protein intake running a 15-km road race.

Sarcopenia is characterised by a progressive loss of skeletal muscle mass and physical function as well as related metabolic disturbances. While fibre-rich diets can influence metabolic health outcomes, the impact on skeletal muscle mass and function is yet to be determined, and the moderating effects by physical activity (PA) need to be considered. The aim of the present study was to examine links between fibre intake, skeletal muscle mass and physical function in a cohort of older adults from the NU-AGE study. In 981 older adults (71 ± 4 years, 58% female), physical function was assessed using the short-physical performance battery test and handgrip strength. Skeletal muscle mass index (SMI) was derived using dual-energy X-ray absorptiometry (DXA). Dietary fibre intake (FI) was assessed by 7-day food record and PA was objectively determined by accelerometery. General linear models accounting for covariates including PA level, protein intake and metabolic syndrome (MetS) were used. Women above the median FI had significantly higher SMI compared to those below, which remained in fully adjusted models (24.7 ± 0.2% vs. 24.2 ± 0.1%, p = 0.011, η 2 p = 0.012). In men, the same association was only evident in those without MetS (above median FI: 32.4 ± 0.3% vs. below median FI: 31.3 ± 0.3%, p = 0.005, η 2 p = 0.035). There was no significant impact of FI on physical function outcomes. The findings from this study suggest a beneficial impact of FI on skeletal muscle mass in older adults. Importantly, this impact is independent of adherence to guidelines for protein intake and PA, which further strengthens the potential role of dietary fibre in preventing sarcopenia. Further experimental work is warranted in order to elucidate the mechanisms underpinning the action of dietary fibre on the regulation of muscle mass.

Purpose: Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals., Methods: A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA)., Results: Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m 2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m 2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m 2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention., Conclusions: Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.

Objective: Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults., Methods: A double-blind placebo-controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group and the calcifediol group (10 μg per day). Muscle biopsies were obtained before and after 6 months of calcifediol (n = 10) or placebo (n = 12) supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays., Results: Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies, with Ct values exceeding 30. Blood 25-hydroxycholecalciferol levels were significantly higher after calcifediol supplementation (87.3 ± 20.6 nmol/L) than after placebo (43.8 ± 14.1 nmol/L). No significant difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak, as indicated by the fact that correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any reasonable cut-offs (all q-values ~ 1). P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups., Conclusion: Calcifediol supplementation did not significantly affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults., Trial Registration: This study was registered at clinicaltrials.gov as NCT02349282 on January 28, 2015.

Background: An inadequate protein intake may offset the muscle protein synthetic response after physical activity, reducing the possible benefits of an active lifestyle for muscle mass. We examined the effects of 12 weeks of daily protein supplementation on lean body mass, muscle strength, and physical performance in physically active older adults with a low habitual protein intake (<1.0 g/kg/day)., Methods: A randomized double-blinded controlled trial was performed among 116 physically active older adults [age 69 (interquartile range: 67-73) years, 82% male] who were training for a 4 day walking event of 30, 40, or 50 km/day. Participants were randomly allocated to either 31 g of milk protein or iso-caloric placebo supplementation for 12 weeks. Body composition (dual-energy X-ray absorptiometry), strength (isometric leg extension and grip strength), quadriceps contractile function, and physical performance [Short Physical Performance Battery, Timed Up-and-Go test, and cardiorespiratory fitness (Åstrand-Rhyming submaximal exercise test)] were measured at baseline and after 12 weeks. We assessed vitamin D status and markers of muscle damage and renal function in blood and urine samples before and after intervention., Results: A larger increase in relative lean body mass was observed in the protein vs. placebo group (∆0.93 ± 1.22% vs. ∆0.44 ± 1.40%, P Interaction  = 0.046). Absolute and relative fat mass decreased more in the protein group than in the placebo group (∆-0.90 ± 1.22 kg vs. ∆-0.31 ± 1.28 kg, P Interaction  = 0.013 and ∆-0.92 ± 1.19% vs. ∆-0.39 ± 1.36%, P Interaction  = 0.029, respectively). Strength and contractile function did not change in both groups. Gait speed, chair-rise ability, Timed Up-and-Go, and cardiorespiratory fitness improved in both groups (P < 0.001), but no between-group differences were observed. Serum urea increased in the protein group, whereas no changes were observed in the placebo group (P Interaction  < 0.001). No between-group differences were observed for vitamin D status, muscle damage, and renal function markers., Conclusions: In physically active older adults with relatively low habitual dietary protein consumption, an improvement in physical performance, an increase in lean body mass, and a decrease in fat mass were observed after walking exercise training. A larger increase in relative lean body mass and larger reduction in fat mass were observed in participants receiving 12 weeks of daily protein supplementation compared with controls, whereas this was not accompanied by differences in improvements between groups in muscle strength and physical performance., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial., Methods: Long-term follow-up of B-PROOF trial participants ( N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 μg) and vitamin B12 (500 μg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for colorectal cancer., Results: Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08-2.90, P = 0.02]., Conclusions: Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer., Impact: Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency., (©2018 American Association for Cancer Research.)

Introduction: We aimed to perform a review of SRs of non-pharmacological interventions in older patients with well-defined malnutrition using relevant outcomes agreed by a broad panel of experts., Methods: PubMed, Cochrane, EMBASE, and CINHAL databases were searched for SRs. Primary studies from those SRs were included. Quality assessment was undertaken using Cochrane and GRADE criteria., Results: Eighteen primary studies from seventeen SRs were included. Eleven RCTs compared oral nutritional supplementation (ONS) with usual care. No beneficial effects of ONS treatment, after performing two meta-analysis in body weight changes (six studies), mean difference: 0.59 (95%CI -0.08, 1.96) kg, and in body mass index changes (two studies), mean difference: 0.31 (95%CI -0.17, 0.79) kg/m2 were found. Neither in MNA scores, muscle strength, activities of daily living, timed Up&Go, quality of life and mortality. Results of other intervention studies (dietary counselling and ONS, ONS combined with exercise, nutrition delivery systems) were inconsistent. The overall quality of the evidence was very low due to risk of bias and small sample size., Conclusions: This review has highlighted the lack of high quality evidence to indicate which interventions are effective in treating malnutrition in older people. High quality research studies are urgently needed in this area., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: A short period of leg immobilization leads to rapid loss of muscle mass and strength. Creatine supplementation has been shown to increase lean body mass in active individuals and can be used to augment gains in muscle mass and strength during prolonged resistance-type exercise training., Objective: Our objective was to investigate whether creatine loading can attenuate the loss of muscle mass and strength during short-term leg immobilization., Methods: Healthy young men (n = 30; aged 23 ± 1 years; body mass index [BMI] 23.3 ± 0.5 kg/m -2 ) were randomly assigned to either a creatine or a placebo group. Subjects received placebo or creatine supplements (20 g/d) for 5 days before one leg was immobilized by means of a full-leg cast for 7 days. Muscle biopsies were taken before creatine loading, prior to and immediately after leg immobilization, and after 7 days of subsequent recovery. Quadriceps cross-sectional area (CSA) (computed tomography [CT] scan) and leg muscle strength (one-repetition maximum [1-RM] knee extension) were assessed before and immediately after immobilization and after 1 week of recovery. Data were analyzed using repeated measures analysis of variance (ANOVA). Data are presented consistently as mean ± standard error of the mean (SEM)., Results: There was a significant overall increase in muscle total creatine content following the 5-day loading phase (p = 0.049), which appeared driven by an increase in the creatine group (from 90 ± 9 to 107 ± 4 mmol/kg -1 dry muscle) with no apparent change in the placebo group (from 88 ± 4 to 90 ± 3 mmol/kg -1 ; p = 0.066 for time × treatment interaction). Quadriceps muscle CSA had declined by 465 ± 59 and 425 ± 69 mm 2 (p < 0.01) in the creatine and placebo group, respectively, with no differences between groups (p = 0.76). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the creatine and from 59 ± 3 to 53 ± 3 kg in the placebo group, with no differences between groups (p = 0.20). Muscle fiber size did not change significantly over time in either group (p > 0.05). When non-responders to creatine loading were excluded (n = 6), responders (n = 8; total creatine content increasing from 70 to 106 mmol/kg -1 ) showed similar findings, with no signs of preservation of muscle mass or strength during immobilization. During the subsequent recovery phase, no differences in muscle mass or strength were found between the two groups (p > 0.05)., Conclusion: Creatine supplementation prior to and during leg immobilization does not prevent or attenuate the loss of muscle mass or strength during short-term muscle disuse. NIH Clinical Trial Registration Number: NCT01894737 ( http://www.clinicaltrials.gov/ ).

Objective: Protein supplementation increases gains in lean body mass following prolonged resistance-type exercise training in frail older adults. We assessed whether the greater increase in lean body mass can be attributed to muscle fiber type specific hypertrophy with concomitant changes in satellite cell (SC) content., Design: A total of 34 frail elderly individuals (77 ± 1 years, n = 12 male adults) participated in this randomized, double-blind, placebo-controlled trial with 2 arms in parallel., Intervention: Participants performed 24 weeks of progressive resistance-type exercise training (2 sessions per week) during which they were supplemented twice-daily with milk protein (2 × 15 g) or a placebo., Methods: Muscle biopsies were taken at baseline, and after 12 and 24 weeks of intervention, to determine type I and type II muscle fiber specific cross-sectional area (CSA), SC content, and myocellular characteristics., Results: In the placebo group, a trend for a 20% ± 11% increase in muscle fiber CSA was observed in type II fibers only (P = .051), with no increase in type I muscle fiber CSA. In the protein group, type I and II muscle fiber CSA increased by 23% ± 7% and 34% ± 10% following 6 months of training, respectively (P < .01). Myonuclear domain size increased over time in both groups and fiber types (P < .001), with no significant differences between groups (P > .05). No changes in myonuclear content and SC contents were observed over time in either group (both P > .05). Regression analysis showed that changes in myonuclear content and domain size are predictive of muscle fiber hypertrophy., Conclusions: Protein supplementation augments muscle fiber hypertrophy following prolonged resistance-type exercise training in frail older people, without changes in myonuclear and SC content., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B 12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants ( N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B 12 and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D₃. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. -0.02, p = 0.004). In conclusion, two-year supplementation with vitamin B 12 and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL., Competing Interests: The authors declare no conflict of interest. The funding sources had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

With aging, energy needs decrease, necessitating a more nutrient-dense diet to meet nutritional needs. To bridge this gap, the use of nutrient-dense foods, fortified foods, and dietary supplements can be important. This observational study aims to describe current micronutrient intakes of Dutch elderly and to identify the contribution of nutrient-dense foods, fortified foods, and dietary supplements to the intake of micronutrients that are often inadequately consumed in Dutch elderly. Data of 245 Dutch volunteers from the NU-AGE study aged 65 to 80 years were used. Dietary intake was assessed by means of 7-day food records, and dietary supplement use was recorded with an additional questionnaire. Information on fortified foods was obtained from the Dutch Food Composition Table 2011. Nutrient density of foods was evaluated using the Nutrient Rich Food 9.3 score. The percentages of participants not meeting their average requirement were high for vitamin D (99%), selenium (41%), and vitamin B6 (54%) based on conventional foods and also when taking into account fortified foods (98%, 41%, and 27%, respectively) and vitamin and mineral supplements (87%, 36%, and 20%, respectively). Conventional foods were the main source of vitamin D, vitamin B6, and selenium intake (42%, 45%, and 82%, respectively), followed by vitamin and mineral supplements (41%, 44%, and 18%) and fortified foods (17%, 11%, and 1%). Foods with the highest nutrient density contributed most to total vitamin B6 intake only. To optimize nutrient intakes of elderly, combinations of natural food sources, fortified foods, and dietary supplements should be considered., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514., (© The Author(s) 2016.)

Introduction: Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients., Methods: The B-PROOF study is a double-blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50  μmol/l), treated with B-vitamins (500  μg vitamin B12 and 400  μg folic acid) or placebo for 2 years. In a subgroup (n = 569), the effect of B-vitamins on pulse wave velocity (PWV) was investigated as a measurement of arterial stiffness. To measure atherosclerosis, carotid intima-media thickness (IMT) measures had been used. Incidents of cardiovascular and cerebrovascular events were determined via structured questionnaires, and blood pressure was also measured., Results: Compared to placebo, B-vitamin supplementation lowered serum homocysteine by 3.6  μmol/l (P < 0.001). Analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline. Furthermore, no effect on carotid IMT was observed., Discussion: Vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly patients have no effect on PWV or carotid IMT. Further research will still be necessary to unravel the effects and pathways of homocysteine-lowering treatment on cardiovascular outcomes.

Background: Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk., Objective: This study [B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF)] aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals., Design: This was a double-blind, randomized, placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations (12-50 μmol/L). Participants were assigned to receive daily 500 μg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3. The primary endpoint was time to first osteoporotic fracture. Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per-protocol principles., Results: Osteoporotic fractures occurred in 61 persons (4.2%) in the intervention group and 75 persons (5.1%) in the placebo group. Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21). For persons aged >80 y, in per-protocol analyses, osteoporotic fracture risk was lower in the intervention group than in the placebo group (HR: 0.27; 95% CI: 0.10, 0.74). The total number of adverse events (including mortality) did not differ between groups. However, 63 and 42 participants in the intervention and placebo groups, respectively, reported incident cancer (HR: 1.56; 95% CI: 1.04, 2.31)., Conclusions: These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population. Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged >80 y. However, treatment was also associated with increased incidence of cancer, although the study was not designed for assessing cancer outcomes. Therefore, vitamin B-12 plus folic acid supplementation cannot be recommended at present for fracture prevention in elderly people. The B-PROOF study was registered with the Netherlands Trial Register (trialregister.nl) as NTR1333 and at clinicaltrials.gov as NCT00696414., (© 2014 American Society for Nutrition.)

Physical activity has been proposed as one of the most effective strategies to prevent cognitive decline. Protein supplementation may exert an additive effect. The effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly people was assessed in a secondary analysis. Two 24-week, double-blind, randomized, placebo-controlled intervention studies were carried out in parallel. Subjects performed a resistance-type exercise program of two sessions per week (n=62) or no exercise program (n=65). In both studies, subjects were randomly allocated to either a protein (2×15 g daily) or a placebo drink. Cognitive functioning was assessed with a neuropsychological test battery focusing on the cognitive domains episodic memory, attention and working memory, information processing speed, and executive functioning. In frail and pre-frail elderly, resistance-type exercise training in combination with protein supplementation improved information processing speed (changes in domain score 0.08±0.51 versus -0.23±0.19 in the non-exercise group, p=0.04). Exercise training without protein supplementation was beneficial for attention and working memory (changes in domain scores 0.35±0.70 versus -0.12±0.69 in the non-exercise group, p=0.02). There were no significant differences among the intervention groups on the other cognitive tests or domain scores., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery. Consequently, it is generally accepted that protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolonged resistance-type exercise training. However, there is much discrepancy in the literature regarding the proposed benefits of protein supplementation during prolonged resistance-type exercise training in younger and older populations., Objective: The objective of the study was to define the efficacy of protein supplementation to augment the adaptive response of the skeletal muscle to prolonged resistance-type exercise training in younger and older populations., Design: A systematic review of interventional evidence was performed through the use of a random-effects meta-analysis model. Data from the outcome variables fat-free mass (FFM), fat mass, type I and II muscle fiber cross-sectional area, and 1 repetition maximum (1-RM) leg press strength were collected from randomized controlled trials (RCTs) investigating the effect of dietary protein supplementation during prolonged (>6 wk) resistance-type exercise training., Results: Data were included from 22 RCTs that included 680 subjects. Protein supplementation showed a positive effect for FFM (weighted mean difference: 0.69 kg; 95% CI: 0.47, 0.91 kg; P < 0.00001) and 1-RM leg press strength (weighted mean difference: 13.5 kg; 95% CI: 6.4, 20.7 kg; P < 0.005) compared with a placebo after prolonged resistance-type exercise training in younger and older subjects., Conclusion: Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects.

Objectives: Protein supplementation has been proposed as an effective dietary strategy to increase skeletal muscle mass and improve physical performance in frail elderly people. Our objective was to assess the impact of 24 weeks of dietary protein supplementation on muscle mass, strength, and physical performance in frail elderly people., Design/setting/participants: A total of 65 frail elderly subjects were included and randomly allocated to either daily protein or placebo supplementation (15 g protein at breakfast and lunch)., Measurements: Skeletal muscle mass (DXA), muscle fiber size (muscle biopsy), strength (1-RM), and physical performance (SPPB) were assessed at baseline, and after 12 and 24 weeks of dietary intervention., Results: Skeletal muscle mass did not change in the protein- (from 45.8 ± 1.7 to 45.8 ± 1.7 kg) or placebo-supplemented group (from 46.7 ± 1.7 to 46.6 ± 1.7 kg) following 24 weeks of intervention (P > .05). In accordance, type I and II muscle fiber size did not change over time (P > .05). Muscle strength increased significantly in both groups (P < .01), with leg extension strength tending to increase to a greater extent in the protein (57 ± 5 to 68 ± 5 kg) compared with the placebo group (57 ± 5 to 63 ± 5 kg) (treatment × time interaction effect: P = .059). Physical performance improved significantly from 8.9 ± 0.6 to 10.0 ± 0.6 points in the protein group and did not change in the placebo group (from 7.8 ± 0.6 to 7.9 ± 0.6 points) (treatment × time interaction effect: P = .02)., Conclusion: Dietary protein supplementation improves physical performance, but does not increase skeletal muscle mass in frail elderly people., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Protein supplementation has been proposed as an effective dietary strategy to augment the skeletal muscle adaptive response to prolonged resistance-type exercise training in elderly people. Our objective was to assess the impact of protein supplementation on muscle mass, strength, and physical performance during prolonged resistance-type exercise training in frail elderly men and women., Design/setting/participants: A randomized, double-blind, placebo-controlled trial with 2 arms in parallel among 62 frail elderly subjects (78 ± 1 year). These elderly subjects participated in a progressive resistance-type exercise training program (2 sessions per week for 24 weeks) during which they were supplemented twice daily with either protein (2 * 15 g) or a placebo., Measurements: Lean body mass (DXA), strength (1-RM), and physical performance (SPPB) were assessed at baseline, and after 12 and 24 weeks of intervention., Results: Lean body mass increased from 47.2 kg (95% CI, 43.5-50.9) to 48.5 kg (95% CI, 44.8-52.1) in the protein group and did not change in the placebo group (from 45.7 kg, 95% CI, 42.1-49.2 to 45.4 kg, 95% CI, 41.8-48.9) following the intervention (P value for treatment × time interaction = .006). Strength and physical performance improved significantly in both groups (P = .000) with no interaction effect of dietary protein supplementation., Conclusions: Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance in frail elderly people. Dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people., Trial Registration: clinicaltrials.gov identifier: NCT01110369., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Nutrition is one of many factors that affect brain development and functioning, and in recent years the role of certain nutrients has been investigated. B vitamins and n-3 polyunsaturated fatty acids (PUFA) are two of the most promising and widely studied nutritional factors., Methods: In this review, we provide an overview of human studies published before August 2011 on how vitamin B(6), folate, vitamin B(12) and n-3 PUFA may affect the brain, their nutrient status and the existing evidence for an association between these nutrients and brain development, brain functioning and depression during different stages of the life cycle., Results: No recommendation can be given regarding a role of B vitamins, either because the number of studies on B vitamins is too limited (pregnant and lactating women and children) or the studies are not consistent (adults and elderly). For n-3 PUFA, observational evidence may be suggestive of a beneficial effect; however, this has not yet been sufficiently replicated in randomized controlled trials (RCTs)., Conclusions: We found that the existing evidence from observational studies as well as RCTs is generally too limited and contradictory to draw firm conclusions. More research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs., (Copyright © 2012 S. Karger AG, Basel.)

Background: Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk. As vitamin B12 and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration., Methods/design: The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration (≥ 12 μmol/L). One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet. In both tablets 15 μg (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers, physical performance and physical activity including falls, nutritional intake and status, cognitive function, depression, genetics and quality of life. This large multi-center project is carried out by a consortium from the Erasmus MC (Rotterdam, the Netherlands), VUmc (Amsterdam, the Netherlands) and Wageningen University, (Wageningen, the Netherlands), the latter acting as coordinator., Discussion: To our best knowledge, the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population. We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013. The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures., Trial Registration: The B-PROOF study is registered with the Netherlands Trial (NTR NTR1333) and with ClinicalTrials.gov (NCT00696514).

Background: It is hypothesis that in relatively healthy older people supplement usage can be consider as healthy life style habit and as such can positively influence longevity., Aim of the Study: To determine whether supplement use was associated with all-cause mortality in the participants of the SENECA study., Methods: Baseline measurements were carried out in 1988/1989 among 75 to 80-year-old people living in 15 European small towns. All-cause mortality was followed up to April 30, 1999. Data from 920 men and 980 women who were ischemic heart diseases-, stroke- and cancer-free at baseline were included. The multivariate adjusted (for sex, age, years of education, physical activity, BMI, chronic diseases, Mediterranean Diet Score, alcohol use and the place of living) hazard ratio (HRs) and 95% confidence intervals (CIs) of mortality by use of any type of nutrient supplement and by particular nutrient supplement use were estimated by Cox proportional hazards regression models., Results: At baseline, 13% of participants used nutritional supplements, 19% of subjects were smokers. During 10 years of follow-up 445 men and 252 women died. Among non-smokers no significant associations between total supplement use and particular nutrient supplement use were observed. Among smokers use of any type of supplements (Multivariate HR: 1.52; 95%CI: 1.02-2.28), use of vitamin B(1) (Multivariate HR: 1.57; 95%CI: 1.00-2.48) and vitamin B(2) supplements (Multivariate HR: 1.60; 95%CI: 1.00-2.56) were associated with a significantly higher risk of all-cause mortality. The similar tendencies were observed among vitamin B(6) and vitamin C supplement users who were smokers., Conclusions: Among smokers, participants of the SENECA study, supplement use increased all-cause mortality risk.

Background and Aims: Many elderly people with Alzheimer's disease experience weight loss. Illness and inadequate regain after a period of illness are considered as contributory causes of progressive weight loss in psychogeriatric patients. We studied whether early use of a liquid nutrition supplement immediately after onset of acute illness from infection can prevent weight loss in elderly psychogeriatric nursing home residents., Methods: Randomised controlled trial of 5 weeks after the onset of illness. Thirty-four psychogeriatric nursing home residents (aged > or =65 yrs) completed the study period. A liquid nutrition supplement (200 ml) once daily immediately after diagnosis of infection or standard treatment (enriched food after referral to a dietician) were provided. Body weight, mid-upper arm circumference, calf circumference, triceps skin fold thickness, dietary energy intake, and need for care were measured., Results: Weight change during the study period was significantly different between the standard (-0.4 kg) and supplement (+0.8 kg) groups (p = 0.040). No significant differences were observed in changes of mid-upper arm circumference, triceps skin fold thickness, calf circumference or energy intake between groups., Conclusions: Early provision of a liquid nutrition supplement immediately after onset of acute illness from infection leads to weight gain in elderly psychogeriatric nursing home residents.

Background: Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B(12) deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain., Methods: We conducted a randomized, parallel-group, double-blind, dose-finding trial to determine the lowest oral dose of cyanocobalamin required to normalize biochemical markers of vitamin B(12) deficiency in older people with mild vitamin B(12) deficiency, defined as a serum vitamin B(12) level of 100 to 300 pmol/L (135-406 pg/mL) and a methylmalonic acid level of 0.26 mumol/L or greater. We assessed the effects of daily oral doses of 2.5, 100, 250, 500, and 1000 mug of cyanocobalamin administered for 16 weeks on biochemical markers of vitamin B(12) deficiency in 120 people. The main outcome measure was the dose of oral cyanocobalamin that produced 80% to 90% of the estimated maximal reduction in the plasma methylmalonic acid concentration., Results: Supplementation with cyanocobalamin in daily oral doses of 2.5, 100, 250, 500, and 1000 mug was associated with mean reductions in plasma methylmalonic acid concentrations of 16%, 16%, 23%, 33%, and 33%, respectively. Daily doses of 647 to 1032 mug of cyanocobalamin were associated with 80% to 90% of the estimated maximum reduction in the plasma methylmalonic acid concentration., Conclusion: The lowest dose of oral cyanocobalamin required to normalize mild vitamin B(12) deficiency is more than 200 times greater than the recommended dietary allowance, which is approximately 3 mug daily.

Severe hyperhomocysteinemia is typically caused by rare enzymatic defects or by renal failure. In contrast, mild to moderate hyperhomocysteinemia chiefly results from suboptimal status of nutritional factors involved in homocysteine metabolism. Low dietary intake of folate is the most important nutritional cause of elevated homocysteine (tHcy) concentrations. Folic acid is more effective than dietary folate in lowering tHcy concentrations, and a daily dose of 400 mug of folic acid is the minimum daily dose associated with the maximum tHcy-lowering effect ( approximately 20-25% reduction). Mean fasting tHcy concentrations have dropped substantially in populations with mandatory folic acid fortification, and other B-vitamins, such as vitamin B (12), are important determinants of tHcy levels in this setting. Vitamins B (2) and B (6) have little influence on fasting tHcy concentrations, although the former may be relevant in individuals with the MTHFR 677 TT-genotype, and the latter may improve tHcy catabolism in elderly individuals. Betaine and choline can lower fasting tHcy concentrations to a similar extent as folic acid, particularly in the setting of a high intake of methionine. Consumption of tea and coffee increase tHcy concentrations by up to 20%. A high-protein meal also increases tHcy, but these changes are transient, and levels return to normal after an overnight fast. Serine and cystine also influence the methionine-induced postprandial rise in tHcy concentrations. In conclusion, alteration in dietary intake or use of folic acid supplements can substantially lower tHcy concentrations. However, it is not known whether lowering tHcy levels can reduce the risk of cardiovascular disease or cognitive decline or prevent pregnancy complications or osteoporosis.

Background: The effectiveness of nutritional supplementation in improving cognitive functioning is evaluated in elderly people., Methods: The authors systematically reviewed randomized controlled trials that compared nutritional supplementation with a placebo treatment. Trials were identified from a MEDLINE search and from reference lists of identified studies and review articles. From each trial, information was gathered on the number and age of persons studied; the type, dosage, and duration of the intervention; and the assessed outcome measures., Results: From 1086 titles, 571 articles were excluded based on their titles. Of the remaining 467 articles, the abstracts were read and 422 articles were excluded based on information found there. The remaining articles were screened for quality aspects of the study design, leaving 21 proper randomized, controlled trials. These trials are discussed in three groups according to the type of supplementation: multinutrient intervention or single components with or without a putative mechanism. Twelve studies, which were evenly distributed among the three supplement groups, found significantly positive effects of nutritional intervention on cognitive functioning, whereas nine studies did not. None of the studies found a significantly negative effect of nutritional intervention., Conclusions: Shortcomings in methodology varying from the duration of intervention to outcome measures partly explain discrepancies in findings. Despite the heterogeneity in trial design, the results of this review suggest that nutritional supplements may improve the cognitive functioning of elderly persons and do no harm. Further well-designed studies are needed to support these findings.

Objective: To investigate whether a drink enriched with essential vitamins and minerals can improve biochemical status of enzymatic and non-enzymatic antioxidants in frail elderly people., Methods: A six-month randomized, double blind, placebo controlled intervention study. Frail elderly people 65 years of age or older, with a body mass index (BMI) below 25 kg/m(2) and residing in a home for the elderly or in sheltered housing. Enriched (with essential vitamins and minerals in 30% to 150% of RDA and higher levels of antioxidants) drink (n = 28) or placebo (n = 27) to be taken twice a day in addition to the normal food consumed. Plasma levels of vitamin C, vitamin E, antioxidant capacity (TEAC), cysteine, uric acid and whole blood levels of total thiol and glutathione peroxidase (GSH-Px), dietary intake., Results: Changes in vitamin E (16 +/- 2 vs. 2 +/- 1 mmol/L), vitamin C (37 +/- 5 vs. 1 +/- 5 mmol/L), TEAC (38 +/- 15 vs. -10 +/- 11 mmol/L Trolox eq) and cysteine (17 +/- 10 vs. 0.4 +/- 6 mmol/L) were significantly different between groups (p < 0.05). There was a trend towards significant changes in erythrocyte glutathione peroxidase (-0.2 +/- 3 vs. -10 +/- 7 U/mg Hb, p = 0.097). Baseline dietary intake of antioxidant vitamins was below 2/3 RDA for a substantial proportion (43% to 76%) of subjects., Conclusions: Supplementation with an enriched drink can raise plasma levels of enzymatic and non-enzymatic antioxidants in frail elderly people.

Purpose: Trials aiming to lower homocysteine by B-vitamin supplementation have reported mixed results on slowing cognitive decline. We investigated if efficacy of B-vitamin supplementation is affected by baseline plasma omega-3 fatty acid levels. Methods: This post-hoc analysis of the B-proof trial included 191 adults aged 65 years or older with baseline plasma total homocysteine ≥ 12 μmol/L, randomly assigned to 400 µg folic acid and 500 µg vitamin B12 or placebo daily for 2 years. Global and domain-specific cognitive functioning were assessed at baseline and after 2 years. The effect of B-vitamin supplementation was analyzed according to tertiles of baseline plasma omega-3 fatty acids concentrations combined, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) individually using multiple linear regression analyses. Results: The mean ± SD age of the participants was 71.6 ± 5.9 years and median [IQR] Mini-Mental State Examination was 29 [28–30]. The treatment effect of B-vitamins on global cognition was larger in participants in the high compared to the middle DHA tertile (difference in z-score, mean ± SE 0.22 ± 0.10, p = 0.03). There was no significant interaction between B-vitamin supplementation and combined omega-3 fatty acid (p = 0.49) and EPA (p = 0.99) tertiles. Similarly, the efficacy of B-vitamin treatment on domain-specific cognitive functioning did not link to omega-3 fatty acid, DHA, or EPA plasma levels. Conclusion: This post-hoc analysis indicated that efficacy of B-vitamin supplementation in slowing cognitive decline relates to DHA status, with individuals with higher plasma DHA levels benefitting more from vitamin B12 and folic acid use. The results support earlier observations that positive effects of B-vitamins in cognitive ageing may be subgroup-specific. Trial registration: Registered at clinicaltrials.gov (NCT00696514) on June 12, 2008. [ABSTRACT FROM AUTHOR]

Background Maintenance of high physical performance during aging might be supported by an adequate dietary intake of niacin, vitamins B-6 and B-12, and folate because these B vitamins are involved in multiple processes related to muscle functioning. However, not much is known about the association between dietary intake of these B vitamins and physical performance. Objectives The objectives of this study were to investigate the association between dietary intake of niacin, vitamins B-6 and B-12, and folate and physical performance in older adults and to explore mediation by niacin status and homocysteine concentrations. Methods We used baseline data from the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) trial, which included n  = 1249 healthy older adults (aged 65–79 y) with complete data on dietary intake measured with 7-d food records and questionnaires on vitamin supplement use and physical performance measured with the short physical performance battery and handgrip dynamometry. Associations were assessed by adjusted linear mixed models. Results Intake of vitamin B-6 was related to lower chair rise test time [β: –0.033 ± 0.016 s (log); P  = 0.043]. Vitamin B-6 intake was also significantly associated with handgrip strength, but for this association, a significant interaction effect between vitamin B-6 intake and physical activity level was found. In participants with the lowest level of physical activity, higher intake of vitamin B-6 tended to be associated with greater handgrip strength (β: 1.5 ± 0.8 kg; P  = 0.051), whereas in participants in the highest quartile of physical activity, higher intake was associated with lower handgrip strength (β: –1.4 ± 0.7 kg; P  = 0.041). No evidence was found for an association between intake of niacin, vitamin B-12, or folate and physical performance or for mediation by niacin status or homocysteine concentrations. Conclusions Vitamin B-6 intake was associated with better chair rise test time in a population of European healthy older adults and also with greater handgrip strength in participants with low physical activity only. Homocysteine concentrations did not mediate these associations. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal Dysphagia (OD) and malnutrition are frequently reported conditions in nursing home residents, and are often interrelated. Best care for dysphagic residents with, or at risk of, malnutrition should target adequate nutritional intake and the safety and efficacy of swallowing. The effect of oral nutritional supplements (ONS) suitable for nursing home residents with concurrent OD and malnutrition (risk) on nutritional status has not been investigated before. The current study aims to investigate the effect of daily use of a range of pre-thickened ONS on the body weight of nursing home residents with OD and malnutrition (risk) compared to standard OD and nutritional care.Methods/ Design: The DYNAMO study is a randomized, controlled, multi-center, open label trial with two parallel groups. Study participants will be recruited in nursing homes of several care organizations in the south of the Netherlands. Study duration is 12 weeks. Residents in the control group will receive standard OD and nutritional care, and residents in the test group will receive standard OD and nutritional care with extra daily supplementation of pre-thickened ONS. The main outcome parameter is the difference in body weight change between the control and test groups. An a priori estimation of the required sample size per group (control / test) totals 78. Other outcome parameters are differences in: nutritional intake, health-related quality of life, OD-specific quality of life, activities of daily living, vital signs, and blood nutrient and metabolite levels.Discussion: Regular ONS could address the nutritional needs of nursing home residents with malnutrition (risk), but might be too thin and unsafe for residents with OD. Pre-thickened ONS is suitable for residents with OD. It offers the advantage of being a ready-to-use amylase-resistant product available in several consistencies which are able to increase swallowing efficacy and safety. The DYNAMO study is the first to investigate the effects of pre-thickened ONS on nutritional status in nursing home residents with concurrent OD and malnutrition (risk).Trial Registration: Netherlands Trial Register (NTR): NTR NL7898. Registered 24 July 2019, https://www.trialregister.nl/trial/7898. [ABSTRACT FROM AUTHOR]

In this work we present a novel statistical approach to improve the assessment of the adherence to a 1-year nutritional intervention within the framework of the NU-AGE project. This was measured with a single adherence score based on 7-days food records, under limitations on the number of observations per subject and time frame of intervention. The results of the NU-AGE dietary intervention were summarized by variations of the NU-AGE index as described in the NU-AGE protocol. Food and nutrient intake of all participants was assessed by means of 7-days food records at recruitment and after 10 to 14 months of intervention (depending on the subject availability). Sixteen food groups and supplementations covering the dietary goals of the NU-AGE diet have been used to estimate the NU-AGE index before and after the intervention. The 7-days food record is a reliable tool to register food intakes, however, as with other tools used to assess lifestyle dietary compliance, it is affected by uncertainty in this estimation due to the possibility that the observed week is not fully representative of the entire intervention period. Also, due to logistic limitations, the effects of seasonality can never be completely removed. These variabilities, if not accounted for in the index estimation, will reduce the statistical power of the analyses. In this work we discuss a method to assess these uncertainties and thus improve the resulting NU-AGE index. The proposed method is based on Hierarchical Bayesian Models. This model explicitly includes country-specific averages of the NU-AGE index, index variation induced by the dietary intervention, and country based seasonality. This information is used to evaluate the NU-AGE index uncertainty and thus to estimate the "real" NU-AGE index for each subject, both before and after the intervention. These corrections reduce the possibility of misinterpreting measurement variability as real information, improving the power of the statistical tests that are performed with the resulting index. The results suggest that this method is able to reduce the short term and seasonal variability of the measured index in the context of multicenter dietary intervention trials. Using this method to estimate seasonality and variability would allow one to obtain better measurements from the subjects of a study, and be able to simplify the scheduling of diet assessments. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01754012. [ABSTRACT FROM AUTHOR]

Introduction: The differential associations of beer, wine, and spirit consumption on cardiovascular risk found in observational studies may be confounded by diet. We described and compared dietary intake and diet quality according to alcoholic beverage preference in European elderly. Methods: From the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES), seven European cohorts were included, i.e. four sub-cohorts from EPIC-Elderly, the SENECA Study, the Zutphen Elderly Study, and the Rotterdam Study. Harmonized data of 29,423 elderly participants from 14 European countries were analyzed. Baseline data on consumption of beer, wine, and spirits, and dietary intake were collected with questionnaires. Diet quality was assessed using the Healthy Diet Indicator (HDI). Intakes and scores across categories of alcoholic beverage preference (beer, wine, spirit, no preference, non-consumers) were adjusted for age, sex, socio-economic status, self-reported prevalent diseases, and lifestyle factors. Cohort-specific mean intakes and scores were calculated as well as weighted means combining all cohorts. Results: In 5 of 7 cohorts, persons with a wine preference formed the largest group. After multivariate adjustment, persons with a wine preference tended to have a higher HDI score and intake of healthy foods in most cohorts, but differences were small. The weighted estimates of all cohorts combined revealed that non-consumers had the highest fruit and vegetable intake, followed by wine consumers. Non-consumers and persons with no specific preference had a higher HDI score, spirit consumers the lowest. However, overall diet quality as measured by HDI did not differ greatly across alcoholic beverage preference categories. Discussion: This study using harmonized data from ~30,000 elderly from 14 European countries showed that, after multivariate adjustment, dietary habits and diet quality did not differ greatly according to alcoholic beverage preference. [ABSTRACT FROM AUTHOR]

Background Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B12 deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain. Methods We conducted a randomized, parallel-group, double-blind, dose-finding trial to determine the lowest oral dose of cyanocobalamin required to normalize biochemical markers of vitamin B12 deficiency in older people with mild vitamin B12 deficiency, defined as a serum vitamin B12 level of 100 to 300 pmol/L (135-406 pg/mL) and a methylmalonic acid level of 0.26 μmol/L or greater. We assessed the effects of daily oral doses of 2.5, 100, 250, 500, and 1000 μg of cyanocobalamin administered for 16 weeks on biochemical markers of vitamin B12 deficiency in 120 people. The main outcome measure was the dose of oral cyanocobalamin that produced 80% to 90% of the estimated maximal reduction in the plasma methylmalonic acid concentration. Results Supplementation with cyanocobalamin in daily oral doses of 2.5, 100, 250, 500, and 1000 μg was associated with mean reductions in plasma methylmalonic acid concentrations of 16%, 16%, 23%, 33%, and 33%, respectively. Daily doses of 647 to 1032 μg of cyanocobalamin were associated with 80% to 90% of the estimated maximum reduction in the plasma methylmalonic acid concentration. Conclusion The lowest dose of oral cyanocobalamin required to normalize mild vitamin B12 deficiency is more than 200 times greater than the recommended dietary allowance, which is approximately 3 μg daily. [ABSTRACT FROM AUTHOR]

Deals with a study which determined the effects of enriched foods and all-around physical exercise on bone and body composition in frail elderly persons. Methodology; Results; Discussion. [ABSTRACT FROM AUTHOR]

Energy metabolism was measured in 24 women before pregnancy and during lactation (2 mo postparturn). Resting metabolic rate (RMR) increased by 0.17 ± 0.38 kJ/min and postprandial metabolic rate (PPMR) showed a similar increase (0.17 ± 0.45 kJ/min). Thus, the thermic effect of the meal (PPMR minus RMR) was not affected by lactation. Between subjects, the lactation-induced increase in RMR appeared to be positively related to body weight. During lactation gross metabolic rates during cycling (CMR) were slightly reduced and net metabolic rates during cycling (CMR minus RMR) tended to decrease by 0.6 kJ/min at all workloads; however, the decrease was statistically significant only at the lowest workload. Changes in metabolic rate during the recovery period after exercise were not significant, but resembled changes in RMR rather than changes in CMR. We conclude that no major changes in metabolic efficiency occurred during lactation. [ABSTRACT FROM AUTHOR]