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Background: Handheld dynamometry (HHD) is a practical alternative to traditional testing of lower extremity strength. However, its reliability and validity across different populations and settings are not clear. Hypothesis: We hypothesize that HHD is a valid and reliable device to assess lower extremity strength in a population of older adults. Study Design: Cross-sectional/cohort. Level of Evidence: Level 3. Methods: This study included 258 older adults (≥65 years). Isometric knee extension and flexion force were measured by 1 examiner, using an HHD (n = 222), including 3 repetitions to calculate within-day intrarater reliability. These measurements were repeated by the examiner in a subgroup (n = 23) to analyze intrarater reliability over a test-retest period of on average 8 weeks. In addition, HHD force measures were performed by a second examiner (n = 29) to analyze interrater reliability. In another subgroup (n = 77), isometric knee extension and flexion torque were measured by 1 examiner using both the HHD and Biodex System 4 to assess relative validity. Results: HHD and Biodex measurements were highly correlated and showed excellent concurrent validity. HHD systematically overestimated torque as compared with Biodex by 8 N·m on average. Same-day intrarater intraclass correlation coefficients (ICCs) ranged from 0.97 to 0.98. Interrater reliability ICCs ranged from 0.83 to 0.95. Conclusion: HHD represents a reliable and valid alternative to Biodex to rank individuals on leg strength, or to assess within-person changes in leg strength over time, because of the high validity and reliability. The HHD is less suited for absolute strength assessment because of significant systematic overestimations. Clinical Relevance: Clinicians are encouraged to use HHD to rank older adults on leg strength, or to assess within-person changes in leg strength over time, but not to compare readings with cut-offs or normative values.

Objective: Approximately 50 % of Dutch community-dwelling older adults does not meet protein recommendations. This study assesses the effect of replacing low protein foods with protein-rich alternatives on the protein intake of Dutch community-dwelling older adults. Design: The Dutch National Food Consumption Survey—Older Adults 2010–2012 (DNFCS-OA) was used for scenario modelling. Dietary intake was estimated based on two 24-h recalls. Commonly consumed products were replaced by comparable products rich in protein (scenario 1), foods enriched in protein (scenario 2) and a combination of both (scenario 3). Replacement scenarios were confined to participants whose dietary protein intake was < 1·0 g/kg BW/d (n 391). Habitual protein intake of all older adults was estimated, adjusting for effects of within-person variation in the 2-d intake data. Setting: A simulation study based on the DNFCS-OA. Participants: 727 Dutch community-dwelling older adults aged 70+. Results: Mean protein intake of the total population increased from 1·0 to 1·2 g/kg BW/d (scenarios 1 and 2) and to 1·3 g/kg BW/d (scenario 3). The percentage of participants with intakes of ≥ 1·0 g/kg BW/d increased from 47·1 % to 91·4 %, 90·2 % and 94·6 %, respectively, in scenarios 1, 2 and 3. The largest increases in protein intake were due to replacements in food groups: yoghurt, cream desserts and pudding, potatoes, vegetables and legumes and non-alcoholic beverages and milk in scenario 1 and bread; yoghurt, cream desserts and pudding and soups in scenario 2. Conclusions: This simulation model shows that replacing low protein foods with comparable alternatives rich in protein can increase the protein intake of Dutch community-dwelling older adults considerably. Results can be used as a basis for nutritional counselling.

An adequate protein intake is important for healthy ageing, yet nearly 50% of Dutch community-dwelling older adults do not meet protein recommendations. This study explores protein intake in relation to eight behavioral determinants (I-Change model) among Dutch community-dwelling older adults. Data were collected through an online questionnaire from October 2019–October 2020. Protein intake was assessed by the Protein Screener 55+, indicating a high/low chance of a low protein intake (

Background & aims: Protein-energy malnutrition is a health concern among older adults. Improving nutritional status by increasing energy and protein intake likely benefits health. We therefore aimed to investigate effects of nutritional interventions in older adults (at risk of malnutrition) on change in energy intake and body weight, and explore if the intervention effect was modified by study or participants’ characteristics, analysing pooled individual participant data. Methods: We searched for RCTs investigating the effect of dietary counseling, oral nutritional supplements (ONS) or both on energy intake and weight. Principle investigators of eligible studies provided individual participant data. We investigated the effect of nutritional intervention on meaningful increase in energy intake (>250 kcal/day) and meaningful weight gain (>1.0 kg). Logistic generalized estimating equations were performed and ORs with 95% CIs presented. Results: We included data of nine studies with a total of 990 participants, aged 79.2 ± 8.2 years, 64.5% women and mean baseline BMI 23.9 ± 4.7 kg/m2. An non-significant intervention effect was observed for increase in energy intake (OR:1.59; 95% CI 0.95, 2.66) and a significant intervention effect for weight gain (OR:1.58; 95% CI 1.16, 2.17). Stratifying by type of intervention, an intervention effect on increase in energy intake was only observed for dietary counseling in combination with ONS (OR:2.28; 95% CI 1.90, 2.73). The intervention effect on increase in energy intake was greater for women, older participants, and those with lower BMI. Regarding weight gain, an intervention effect was observed for dietary counseling (OR:1.40; 95% CI 1.14, 1.73) and dietary counseling in combination with ONS (OR:2.48; 95% CI 1.92, 3.31). The intervention effect on weight gain was not influenced by participants’ characteristics. Conclusions: Based on pooled data of older adults (at risk of malnutrition), nutritional interventions have a positive effect on energy intake and body weight. Dietary counseling combined with ONS is the most effective intervention.

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. 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. 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. 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. This study was registered at clinicaltrials.gov as NCT02349282 on January 28, 2015.

Purpose: Sufficient 25-hydroxyvitamin D (25(OH)D) concentrations might prevent a decline in physical performance, and are considered important for the prevention of frailty. This study investigates the association of serum 25(OH)D concentration with physical performance and frailty status in Dutch older adults. Methods: This cross-sectional study included 756 men and women, aged ≥ 65 years. Serum 25(OH)D concentration and frailty status (Fried criteria) were assessed in the total population. Screening for frailty status included functional tests of gait speed and hand grip strength. In a subgroup (n = 494), the Timed Up and Go test (TUG) and knee-extension strength were measured. Associations of serum 25(OH)D status with physical performance were examined by multiple linear regression. Prevalence ratios (PR) were used to quantify associations between serum 25(OH)D deficiency (< 50 nmol/L) and frailty. Results: In total, 45% of the participants were vitamin D deficient. Participants with vitamin D status < 50 and 50–75 nmol/L had significantly lower scores on the TUG and gait speed test, compared to participants with vitamin D status > 75 nmol/L. No significant associations with serum 25(OH)D concentrations were observed for handgrip strength or knee-extension strength. Participants with serum 25(OH)D status < 50 nmol/L were about two times more likely to be frail compared to participants with serum 25(OH)D status ≥ 50 nmol/L. No significant associations were observed between the pre-frail state and serum 25(OH)D status. Conclusion: In this study, serum 25(OH)D concentrations were significantly associated with frailty status and measures of physical performance, including gait speed and TUG, but not with strength-related outcomes.

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.

Objectives The aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. Methods A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65–79 years) women and men from five European countries of the “New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe” project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-β1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. Results BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2. Conclusions The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice. Key Points • Body composition markers concordantly associated positively or negatively with adipose-related and inflammatory markers, with the exception of skeletal muscle mass index. • No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, gp130, TNF-α-R1, and TNF-α-R2. • Skeletal muscle mass index (SMI) shows a good correlation with inflammatory profile in age-related sarcopenia. Electronic supplementary material The online version of this article (10.1007/s00330-018-5973-2) contains supplementary material, which is available to authorized users.

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.

Summary: Vitamin D is proposed as an antihypertensive agent, but current evidence is inconclusive. Calcifediol is more potent in raising vitamin D status. It might, therefore, be more effective in lowering pulse pressure than cholecalciferol especially in patients with low vitamin D status and high levels of parathyroid hormone (PTH). This study investigated the efficacy of calcifediol on pulse pressure in older adults with vitamin D deficiency and elevated PTH levels. Supplementation with 15 μg calcifediol resulted in lower pulse pressure (Δ 35.4 mm Hg, 95%CI: 4.8, 66.1 mm Hg, P = 0.021) and PTH levels (Δ 1.83 pmol/l, 95%CI: −0.1, 3.7 pmol/l, P = 0.065) compared to 5 μg calcifediol. These effects were observed in a limited sample size of 16 older adults and therefore need confirmation in a larger trial.In conclusion, supplementation with 15 μg calcifediol might be an effective way to reduce pulse pressure in elderly with vitamin D deficiency and elevated PTH levels. Keywords: Vitamin D, Pulse pressure, Parathyroid hormone, Randomized clinical trial, Older adults

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10(−9), OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10(−9), OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

ObjectiveThe present study aimed to conduct a process evaluation of a multicomponent nutritional telemonitoring intervention implemented among Dutch community-dwelling older adults.DesignA mixed-methods approach was employed, guided by the process evaluation framework of the Medical Research Council and the Unified Theory of Acceptance and Use of Technology. The process indicators reach, dose, fidelity and acceptability were measured at several time points within the 6-month intervention among participants and/or nurses.SettingThe intervention was implemented in the context of two care organisations in the Netherlands.SubjectsIn total, ninety-seven participants (average age 78 years) participated in the intervention and eight nurses were involved in implementation.ResultsAbout 80 % of participants completed the intervention. Dropouts were significantly older, had worse cognitive and physical functioning, and were more care-dependent. The intervention was largely implemented as intended and received well by participants (satisfaction score 4·1, scale 1–5), but less well by nurses (satisfaction score 3·5, scale 1–5). Participants adhered better to weight telemonitoring than to telemonitoring by means of questionnaires, for which half the participants needed help. Intention to use the intervention was predicted by performance expectancy (β=0·40; 95 % CI 0·13, 0·67) and social influence (β=0·17; 95 % CI 0·00, 0·34). No association between process indicators and intervention outcomes was found.ConclusionsThis process evaluation showed that nutritional telemonitoring among older adults is feasible and accepted by older adults, but nurses’ satisfaction should be improved. The study provided relevant insights for future development and implementation of eHealth interventions among older adults.

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

International audience; ABSTRACT 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.

ObjectiveAgeing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty.DesignWe profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet).ResultsAdherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks.ConclusionCollectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.

Background In nutritional epidemiology, dealing with confounding and complex internutrient relations are major challenges. An often-used approach is dietary pattern analyses, such as principal component analysis, to deal with internutrient correlations, and to more closely resemble the true way nutrients are consumed. However, despite these improvements, these approaches still require subjective decisions in the preselection of food groups. Moreover, they do not make efficient use of multivariate dietary data, because they detect only marginal associations. We propose the use of copula graphical models (CGMs) to model and make statistical inferences regarding complex associations among variables in multivariate data, where associations between all variables can be learned simultaneously. Objective We aimed to reconstruct nutritional intake and physical functioning networks in Dutch older adults by applying a CGM. Methods We addressed this issue by uncovering the pairwise associations between variables while correcting for the effect of remaining variables. More specifically, we used a CGM to infer the precision matrix, which contains all the conditional independence relations between nodes in the graph. The nonzero elements of the precision matrix indicate the presence of a direct association. We applied this method to reconstruct nutrient–physical functioning networks from the combined data of 4 studies (Nu-Age, ProMuscle, ProMO, and V-Fit, total n = 662, mean ± SD age = 75 ± 7 y). The method was implemented in the R package nutriNetwork which is freely available at https://cran.r-project.org/web/packages/nutriNetwork. Results Greater intakes of vegetable protein and vitamin B-6 were partially correlated with higher scores on the total Short Physical Performance Battery (SPPB) and the chair rise test. Greater intakes of vitamin B-12 and folate were partially correlated with higher scores on the chair rise test and the total SPPB, respectively. Conclusions We determined that vegetable protein, vitamin B-6, folate, and vitamin B-12 intakes are partially correlated with improved functional outcome measurements in Dutch older adults.

Background: Vitamin D supplementation is proposed as a potential treatment strategy to counteract functional decline in older adults. However, data from randomized trials are either limited or inconsistent. Objective: This study investigated the effect of daily supplementation with 25-hydroxycholecalciferol [25(OH)D3] or cholecalciferol (vitamin D3) on muscle strength and physical performance in older adults. Methods: This was a randomized, double-blind, placebo-controlled trial of 6 mo including 78 prefrail or frail (according to the Fried criteria), community-dwelling older adults (n = 43 men) aged ≥65 y, with a baseline 25-hydroxyvitamin D [25(OH)D] concentration between 20 and 50 nmol/L. Participants were supplemented daily with 10 µg 25(OH)D3, 20 µg vitamin D3, or a placebo capsule. Serum 25(OH)D was measured by liquid chromatography–tandem mass spectrometry. The primary outcome was maximal isometric knee-extension strength (Biodex System 4); secondary outcomes included knee-flexion and hand grip strength, Short-Physical Performance Battery score, Timed Up and Go score, postural sway, muscle mass (dual-energy X-ray absorptiometry), and muscle fiber type and size. Results: The mean baseline serum 25(OH)D concentration was 37.7 nmol/L (95% CI: 35.4, 39.9 nmol/L). After 6 mo of supplementation, concentrations increased to 98.7 nmol/L (95% CI: 93.1, 104.4 nmol/L) in the 25(OH)D3 group and to 72.0 nmol/L (95% CI: 66.1, 77.8 nmol/L) in the vitamin D3 group, compared with 47.5 nmol/L (95% CI: 41.8, 53.3 nmol/L) in the placebo group (P-interaction < 0.01). Knee-extension strength did not significantly change in the 25(OH)D3group (5.9 Nm; 95% CI: −6.2, 18.0 Nm), in the vitamin D3 group (5.5 Nm; 95% CI: −6.8, 17.8 Nm), or in the placebo group (1.8 Nm; 95% CI: −10.7, 14.4 Nm) (P-interaction = 0.74). Furthermore, mean changes in physical performance tests, muscle mass, and muscle fiber type and size did not differ between the groups. Conclusion: Increasing the serum 25(OH)D concentration over a period of 6 mo did not significantly change muscle strength and physical performance in prefrail and frail older adults. This trial was registered at www.clinicaltrials.gov as NCT02349282.

Adequate protein intake is important in preventing and treating undernutrition. Hospitalized older patients are recommended to consume 1.2-1.5 g of protein per kg body weight per day (g/kg/d) but most of them fail to do so. Therefore, we investigated whether a range of newly developed protein-enriched familiar foods and drinks were effective in increasing protein intake of hospitalized older patients.This randomized controlled trial involved 147 patients of ≥65 years (mean age: 78.5 ± 7.4 years). The control group (n = 80) received the standard energy and protein rich hospital menu. The intervention group (n = 67) received the same menu with various protein-enriched intervention products replacing regular products or added to the menu. Macronutrient intake on the fourth day of hospitalization, based on food ordering data, was compared between the two groups by using Independent T-tests and Mann Whitney U-tests.In the intervention group 30% of total protein was provided by the intervention products. The intervention group consumed 105.7 ± 34.2 g protein compared to 88.2 ± 24.4 g in the control group (p 0.01); corresponding with 1.5 vs 1.2 g/kg/d (p 0.01). More patients in the intervention group than in the control group reached a protein intake of 1.2 g/kg/d (79.1% vs 47.5%). Protein intake was significantly higher in the intervention group at breakfast, during the morning between breakfast and lunch, and at dinner.This study shows that providing protein-enriched familiar foods and drinks, as replacement of regular products or as additions to the hospital menu, better enables hospitalized older patients to reach protein intake recommendations. This trial is registered on ClinicalTrials.gov, Identifier: NCT02213393.

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 (β) was extracted from each study, and the overall and stratified pooled β and SE (β) 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 β = 0.29 (95% CI 0.21–0.37) for serum/plasma folate (26 estimates from 17 studies), β = 0.28 (95% CI 0.21–0.36) for RBC (13 estimates from 11 studies), and β = –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.

Context Glucose is the main energy source for the brain, and as such, manipulation of glucose supply may affect brain function. It has been suggested that a change in blood glucose may influence mood. Objective The aim of this review was to investigate the potential effects of glucose and sucrose, compared with placebo, on mood. Data sources The electronic databases PubMed and Scopus were searched. Reference lists of selected articles were checked manually. Data extraction Randomized controlled trials or crossover trials comparing the effects of glucose or sucrose on mood that were published up to May 2017 were eligible. Potentially eligible articles were selected independently by 2 reviewers. Results In total, 19 studies were found. Thirteen studies investigated the effects of glucose consumption compared with placebo on mood. Seven of these 13 studies found no effect of glucose on mood. The other 6 studies found small and partial effects that may also be due to other factors like palatability and expectation. Seven of the 19 studies investigated the effects of sucrose ingestion versus placebo on mood. None of these studies found a positive effect on mood, and 1 study observed an adverse effect. One of the studies investigated the effects of both glucose and sucrose. Conclusions The results from this review show limited effects of glucose ingestion on mood and no effect of sucrose on mood.

Objective To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk. Design Three prospective studies; the Rotterdam Study, B-PROOF, and LASA. Setting Community-dwelling individuals living in or near five Dutch cities. Participants There were 11,485 participants aged ≥55 years. Measurements Fall incidents were recorded prospectively. Benzodiazepine use was determined using pharmacy dispensing records or interviews. Cox proportional hazard models adjusted for age and sex were applied to determine the association between benzodiazepine use and fall risk stratified for CYP2C9 genotype and comparing benzodiazepine users to nonusers. The results of the three studies were combined applying meta-analysis. Within benzodiazepine users, the association between genotypes and fall risk was also assessed. Results Three thousand seven hundred five participants (32%) encountered a fall during 91,996 follow-up years, and 4% to 15% (depending on the study population) used benzodiazepines. CYP2C9 variants had frequencies of 13% for the *2 allele and 6% for the *3 allele. Compared to nonusers, current benzodiazepine use was associated with an 18% to 36% increased fall risk across studies with a combined hazard ratio (HR) = 1.26 (95% confidence interval [CI], 1.13; 1.40). CYP2C9*2 or *3 allele variants modified benzodiazepine-related fall risk. Compared to nonusers, those carrying a CYP2C9*2 or *3 allele and using benzodiazepines had a 45% increased fall risk (HR, 1.45 95% CI, 1.21; 1.73), whereas CYP2C9*1 homozygotes using benzodiazepines had no increased fall risk (HR, 1.14; 95% CI, 0.90; 1.45). Within benzodiazepine users, having a CYP2C9*2 or *3 allele was associated with an increased fall risk (HR, 1.35; 95% CI, 1.06; 1.72). Additionally, we observed an allele dose effect; heterozygous allele carriers had a fall risk of (HR = 1.30; 95% CI, 1.05; 1.61), and homozygous allele carriers of (HR = 1.91 95% CI, 1.23; 2.96). Conclusions CYP2C9*2 and *3 allele variants modify benzodiazepine-related fall risk. Those using benzodiazepines and having reduced CYP2C9 enzyme activity based on their genotype are at increased fall risk. In clinical practice, genotyping might be considered for elderly patients with an indication for benzodiazepine use. However, because the exact role of CYP2C9 in benzodiazepine metabolism is still unclear, additional research is warranted.

Background: In order to prevent age-related degenerative diseases in the aging population, their diets should be nutrient dense. For this purpose, the Elderly-Nutrient rich food (E-NRF7.3) score has been developed to assess nutrient density of diets by capturing dietary reference values for older adults. To demonstrate its practical importance such score should be validated against markers of nutritional status and health. Objective: The objective of this study was to examine the association between the E-NRF7.3 score and markers of nutritional status and inflammation. Design: This study was carried out in a sample of the NU-AGE study including 242 Dutch and 210 Polish men and women, aged 65–79 years. Dietary intake was assessed by means of 7-day food records and structured questionnaires collected data on supplement use, lifestyle, and socio-economic information. Baseline measurements included anthropometrics, physical and cognitive function tests, and a fasting venipuncture. E-NRF7.3 scores were calculated to estimate nutrient density of foods and the diet. Associations between the E-NRF7.3 scores and micronutrient status of vitamin D, folate, vitamin B12, homocysteine, and c-reactive protein (CRP) were examined using linear regression analysis while adjusting for confounders. Results: Each one unit increase in E-NRF7.3 score was associated with a 2.2% increase in serum folate in Dutch and 1.6% increase in Polish participants in the fully adjusted models (both p < 0.01). Each one unit increase in E-NRF7.3 was significantly associated with a 1.5% decrease in homocysteine levels in Dutch participants (p < 0.01), whereas, a 0.9% increase in vitamin B12 levels was observed in Polish participants only (p < 0.01). Higher E-NRF7.3 scores were not associated with vitamin D or CRP levels. Adjustment for potential confounders did not substantially alter these results. Discussion: The E-NRF7.3 was developed to reflect dietary intake of relevant nutrients for older adults. Its association with markers of nutritional status could be confirmed for folate (both populations), vitamin B12 (Poland only), and homocysteine (the Netherlands only). There was no association with vitamin D and CRP. To further demonstrate its validity and practical implication, future studies should include a wider range of nutritional status makers, health outcomes, and inflammation markers.

Objective: To develop a nutrient-rich food (NRF) score that captures dietary reference values for older adults and to validate this against a diet index that was specifically designed to assess adherence to dietary guidelines for the older population. Design: A cross-sectional study within the Dutch National Food Consumption Survey (DNFCS, n = 735 men and women aged 70–94 years, enrolled between October 2010 and February 2012) and within the NU-AGE study (n = 250 men and women aged 65–79 years, enrolled between April 2012 and March 2013). Dietary intake was assessed by means of two non-consecutive dietary record assisted 24-h recalls and 7-day food records, respectively. Structured questionnaires collected data on lifestyle and socio-economic information. Anthropometrics were measured by trained dieticians or research assistants. We evaluated Elderly NRF (E-NRF) scores against the NU-AGE index, a measure of adherence to European dietary guidelines for the aging population. The E-NRF scores were composed of nutrients that: (1) have been shown to be of inadequate intake in the aging population (>20%), (2) were defined as nutrients of public health relevance, and (3) were associated with relevant health outcomes. Results: The E-NRF score that best predicted the NU-AGE index included seven nutrients to encourage (protein, dietary fiber, folate, vitamin D, calcium, magnesium, potassium) and three nutrients to limit (saturated fat, sodium and mono- and disaccharides) on a 100-kcal basis, the E-NRF7.3 score (model R2 0.27 in DNFCS and 0.41 in NU-AGE). Food groups contributing the most to the individual E-NRF7.3 scores were vegetables, bread, potatoes and milk and milk products. Conclusion: The E-NRF7.3 score is a useful tool for assessing nutrient density of diets within the older population. No index has previously been developed with the aim of evaluating nutrient density of diets and foods specifically capturing dietary reference values for older adults.

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.

Background and Objectives: Undernutrition has unfavorable consequences for health and quality of life. This pilot study aimed to evaluate the feasibility of a telemonitoring intervention to improve the nutritional status of community-dwelling older adults. Research Design and Methods: The study involved a one-group pretest post-test design, complemented by a qualitative study. The 3-month intervention included 20 Dutch home care clients aged >65 years and consisted of nutritional telemonitoring, television messages, and dietary advice. A process evaluation provided insight into intervention delivery and acceptability. Changes in behavioral determinants, diet quality, appetite, nutritional status, physical functioning, and quality of life were assessed. Results: Researchers and health care professionals implemented the intervention as intended and health care professionals accepted the intervention well. However, 9 participants dropped out, and participants’ acceptance was low, mainly due to the low usability of the telemonitoring television channel. Adherence to the telemonitoring measurements was good, although participants needed more help from nurses than anticipated. Participants increased compliance to several Dutch dietary guidelines and no effects on nutritional status, physical functioning, and quality of life were found. Discussion and Implications: Successful telemonitoring of nutritional parameters in community-dwelling older adults starts with optimal usability and acceptability by older adults and their health care professionals. This pilot study provides insight into how to optimize telemonitoring interventions for older adults for maximum impact on behavior and health.

While revising this Analysis article (BMJ 2019;366:l4137, doi:10.1136/bmj.l4137) the authors mistakenly included a section on the reanalysis of the Minnesota Coronary Experiment. The authors had originally agreed among themselves not to include the section in the final manuscript for two reasons. First, the key message of the article is to move from recommendations of single nutrients into food based recommendations because saturated fat is a heterogeneous group of fatty acids with divergent health effects, and the effect is furthermore dependent on the food matrix they exist in. For that reason, the authors felt the section was redundant. Second, for a discussion of the health effects of polyunsaturated fat, the authors did not feel that the section provided a balanced and complete analysis of the issue. Soon after publication the authors contacted The BMJ to notify the journal of the mistake and request correction of the article by removing the following paragraphs, which does not substantially change the message or argument of the Analysis: “Reanalysis of the Minnesota Coronary Experiment (a double blind randomised controlled trial that tested whether replacing saturated fat with polyunsaturated fat reduced coronary heart disease and death) also supports the claim that serum cholesterol is not a valid surrogate biomarker for cardiovascular disease risk when making dietary changes.10 Despite the finding that the polyunsaturated fat diet produced a 13% greater reduction in serum cholesterol than the saturated fat diet, there was no reduction in cardiovascular disease endpoints.10 “The reanalysis found a 22% higher mortality for each 0.78 mmol/L reduction in serum cholesterol caused by the polyunsaturated diet.10 A meta-analysis found that cholesterol lowering using polyunsaturated fat diets did not show any evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27).10” These paragraphs have been removed from the article online.

BackgroundA few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan.ObjectiveTo assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans.Design, setting and participantsThirty healthy (22 +/- 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg).MeasuresBefore and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area.ResultsQuadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 +/- 1% and -6 +/- 1%, respectively; main effect of time PConclusionsThis is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.

Objectives Ageing is associated with a decline in functioning and a loss of independence, which will lead to increased health care costs in the future. The ProMuscle in Practice intervention was found to be effective in improving muscle strength, muscle mass, and functioning of older adults. The current study assesses the cost-effectiveness and perceived benefits of the intervention. Design Trial-based cost-effectiveness analysis complemented by interviews. Setting and participants A total of 168 community-dwelling older adults were included. Intervention participants started with a 12-week intensive support program, comprising resistance exercise guided by physiotherapists and consultations with a dietitian to increase protein intake. To maintain the adapted lifestyle pattern, they continued with a 12-week moderate support intervention. The control group received usual care. Methods Costs and outcomes were measured at baseline, after 12 and 24 weeks. Costs were assessed from a societal perspective. Health care use, out-of-pocket costs, and productivity losses were measured using questionnaires. Intervention costs were quantified according to bottom-up micro-costing. Outcomes included quality of life (EQ-5D-5L) and physical functioning (Short Physical Performance Battery [SPPB]). Bootstrap analyses were used to generate cost-effectiveness planes and acceptability curves. Interviews with participants and professionals were conducted after 24 weeks to measure perceived benefits. Results An Incremental Cost-Effectiveness Ratio of €2988 ($3385)/point increase in SPPB was found. The intervention has an 82.4% probability of being cost-effective at a willingness to pay (WTP) of €12.000 ($13.559)/point increase in SPPB. No change in quality of life was found according to EQ-5D-5L. Interviews, however, revealed a wide range of function-related perceived benefits. Conclusions and Implications At a WTP of €12.000 ($13.559)/point increase in SPPB, the intervention was found to have an 82.4% probability of being cost-effective. Because generic quality of life questionnaires seem unable to detect subtle changes in public health interventions, future studies are advised to include targeted and specific questionnaires.

Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference If thisgroup. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies.

The ageing process is influenced by a variety of factors, including extrinsic, malleable lifestyle variables. The present paper deals with the epidemiological evidence for the role of dietary patterns and key nutritional concerns in relation to survival and ageing-related disorders that present themselves in later life. Healthful dietary patterns appear to be most relevant in old age. Specific nutritional concerns are related to vitamin D, vitamin B12 and protein malnutrition. An important challenge to further expand the knowledge base is currently addressed by the NuAge project, acknowledging the complexity of the ageing process and integrating different dimensions of research into human healthy ageing. In the meantime, reversing poor adherence to existing guidelines for a healthy diet remains a first challenge in public health nutritional practices.

The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50–84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95 % confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults. © 2015, Springer Science+Business Media Dordrecht.

Undernutrition risk among community-dwelling older adults is partly caused by inadequate protein intake. Enriching readymade meals with protein could be beneficial in increasing protein intake. Moreover, reduced-size meals could suit older adults with diminished appetite. In this single-blind randomized crossover study with 120 participants (age: 70.5 ± 4.5 y, BMI: 27.2 ± 4.4 kg/m(2)), 60 participants consumed four beef meals and another 60 consumed four chicken meals on four different days, once per week. These meals were produced according to a 2 × 2 factorial design: the protein content was either ∼25 g (lower) or ∼30 g (enriched), and the portion size was either 450 g (normal) or of 400 g (reduced). Palatability evaluation, meal intake, and subsequent satiety ratings after 120 min were measured. No significant differences in palatability among meals were found. While absolute intake (g) of the normal-size meals was significantly higher than that of the reduced-size meals, the relative intake (%) of the served meals did not differ between the four meals. Both protein and energy intakes were significantly higher for the enriched meals, regardless of portion size. Protein intakes were 5.4 g and 5.1 g higher in the normal-size and reduced-size enriched beef meals, respectively, and 6.1 g and 7.1 g higher in the enriched chicken meals, respectively. The normal-size enriched beef meal and reduced-size enriched chicken meal led to slightly but significantly higher ratings of satiety than the non-enriched meals. Due to these mixed satiety findings, separate effects of meal-size reduction and protein enrichment could not be distinguished in this study. The intake findings show that palatable protein-enriched meals support higher protein and energy intakes in vital community-dwelling older adults during a single meal.

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged a parts per thousand yen65 years with elevated plasma homocysteine concentrations [12-50 A mu mol/L (n = 2919)] were randomly assigned to daily supplementation of 500 A mu g vitamin B12, 400 A mu g folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95 % CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95 % CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons > 80 years. These effects should be further tested in future studies.

The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults. Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530). Serum 25(OH)D concentrations

Various dairy nutrients have been associated with cognitive performance. Several observational studies have explored associations between the intake of total dairy or some dairy subgroups and cognitive performance. However, studies on the potential impact of a broad variety of dairy subclasses are scarce. We examined cross-sectional associations between a wide assortment of dairy products and cognitive performance. A total of 619 Dutch community-dwelling adults aged &ge, 65 years completed a semi-quantitative Food Frequency Questionnaire. Cognitive performance was assessed with an extensive neuropsychological test battery, the tests were clustered into cognitive domains using z-scores. Linear and logistic regression analyses, adjusted for age, sex, BMI, education, smoking, alcohol consumption, habitual physical activity, total energy intake, and dietary factors, were performed to quantify the associations. The Benjamini&ndash, Hochberg method was used to correct for multiple testing. After full adjustment, higher skimmed dairy (&beta, &plusmn, SD: 0.05 &plusmn, 0.02, p = 0.06), fermented dairy (0.04 &plusmn, 0.02, p = 0.09), and buttermilk (0.08 &plusmn, 0.03, p = 0.19) consumption were associated with better executive functioning. Logistic regression analyses indicated that a 30 g increase in Dutch cheese intake was associated with a 33% lower probability of poor information processing speed (PR = 0.67, 95% CI 0.47&ndash, 0.97). No associations were observed between dairy consumption and attention and working memory or episodic memory.

This report on vitamin B-12 (B12) is part of the Biomarkers of Nutrition for Development (BOND) Project, which provides state-of-the art information and advice on the selection, use, and interpretation of biomarkers of nutrient exposure, status, and function. As with the other 5 reports in this series, which focused on iodine, folate, zinc, iron, and vitamin A, this B12 report was developed with the assistance of an expert panel (BOND B12 EP) and other experts who provided information during a consultation. The experts reviewed the existing literature in depth in order to consolidate existing relevant information on the biology of B12, including known and possible effects of insufficiency, and available and potential biomarkers of status. Unlike the situation for the other 5 nutrients reviewed during the BOND project, there has been relatively little previous attention paid to B12 status and its biomarkers, so this report is a landmark in terms of the consolidation and interpretation of the available information on B12 nutrition. Historically, most focus has been on diagnosis and treatment of clinical symptoms of B12 deficiency, which result primarily from pernicious anemia or strict vegetarianism. More recently, we have become aware of the high prevalence of B12 insufficiency in populations consuming low amounts of animal-source foods, which can be detected with ≥1 serum biomarker but presents the new challenge of identifying functional consequences that may require public health interventions.

Body composition (BC) is an emerging important factor for the characterization of metabolic status. The assessment of BC has been studied in various populations and diseases such as obesity, diabetes, endocrine diseases as well as physiological and paraphysiological conditions such as growth and aging processes, and physical training. A gold standard technique for the assessment of human BC at molecular level is represented by dual-energy X-ray absorptiometry (DXA), which is able to precisely assess the body mass (and areal bone mineral density-aBMD) on a regional and whole-body basis. For the first time, within the framework of the NU-AGE project, BC has been assessed by means of a whole-body DXA scan in 1121 sex-balanced free-living, apparently healthy older adults aged 65-79 years enrolled in 5 European countries (Italy, France, United Kingdom, Netherlands, and Poland). The aim of this analysis is to provide a complete profile of BC in healthy elderly participants from five European countries and to investigate country- and sex-related differences by state-of-the-art DXA technology. To compare BC data collected in different centers, specific indexes and ratios have been used. Non-parametric statistical tests showed sex-specific significant differences in certain BC parameters. In particular, women have higher fat mass (FM) (Fat/Lean mass ratio: by 67%, p < 2.2e-16) and lower lean mass (Lean Mass index: by -18%, p < 2.2e-16) than men. On the other hand, men have higher android FM than women (Android/gynoid FM ratio: by 56%, p < 2.2e-16). Interesting differences also emerged among countries. Polish elderly have higher FM (Fat/Lean mass ratio: by 52%, p < 2.2e-16) and lower lean mass (Skeletal Mass index: by -23%, p < 2.2e-16) than elderly from the other four countries. At variance, French elderly show lower FM (Fat/Lean mass ratio: by -34%, p < 2.2e-16) and higher lean mass (Skeletal Mass index: by 18%, p < 2.2e-16). Moreover, five BC profiles in women and six in men have been identified by a cluster analysis based on BC parameters. Finally, these data can serve as reference for normative average and variability of BC in the elderly populations across Europe.

Methods for measuring diet composition and quantifying nutrient intake with sufficient validity are essential to study the association between nutrition and health outcomes and risk of diseases. 7-day food records provides a quantification of food actually and currently consumed and is interesting for its use in intervention studies to monitor diet in a short-term period and to guide participants toward changing their intakes. The objective of this study is to analyze the correlation/association between the daily intake of selected nutrients (collected by a 7-day food records plus a mineral/vitamin supplementation questionnaire) and estimates of energy expenditure as well as blood and urine biomarkers of dietary intakes in 1,140 healthy elderly subjects (65–79 years) at baseline of the NU-AGE intervention study (NCT01754012, clinicaltrials.gov). The results show that: the daily intake of energy correlated significantly with predicted total energy expenditure (pTEE) (ρ = 0.459, p < 0.001, and q < 0.001); protein intake correlated significantly with the ratio of 24 h urinary urea to creatinine excretion (ρ = 0.143 for total protein intake, ρ = 0.296 for animal protein intake, and ρ = 0.359 for protein intake/body weight, p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes correlated significantly with their serum concentrations (ρ = 0.151 and ρ = 0.363, respectively; p < 0.001 and q < 0.001 for each correlation); sodium and potassium intakes correlated significantly with their 24 h urinary excretion (ρ = 0.298 and ρ = 0.123, respectively; p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes were negatively associated with plasma homocysteine measure (p = 0.001 and p = 0.004, respectively); stratifying subjects by gender, the correlations between energy intake and pTEE and between potassium intake and its 24 h urinary excretion lost their significance in women. Even if the plasma and urinary levels of these nutrients depend on several factors, the significant correlations between daily reported intake of nutrients (protein, vitamin B12, folate, and sodium) and their blood/urinary markers confirmed that the 7-day food records (plus a supplementation questionnaire) provides reliable data to evaluate short-term current dietary intake in European elderly subjects and it can be exploited to guide and monitor NU-AGE participants through the shift of their diet according NU-AGE recommendations.

Background Exercise and nutrition are important for older adults to maintain or to regain their muscle mass, function, strength, and ultimately quality of life. The effectiveness of combined resistance exercise and diet interventions is commonly evaluated in controlled clinical studies, but evidence from real-life settings is lacking. This article describes the effectiveness, process, and economic evaluation design of a combined nutrition and exercise intervention for community-dwelling older adults in a Dutch real-life setting. Methods The ProMuscle in Practice study is a randomised controlled multicentre intervention study, conducted in five municipalities in the Netherlands. Two hundred community-dwelling older adults (≥65 years) who are frail or pre-frail based on Fried frailty criteria or who experience strength loss are randomised over an intervention and control group by municipality. In the first 12-week intensive support intervention, participants in the intervention group perform resistance exercise training guided by a physiotherapist twice a week and increase protein intake by consuming protein-rich products under the supervision of a dietitian. Afterwards, they continue with a 12-week moderate support intervention. The control group receives only regular care during the two 12-week periods. Effect outcomes are measured at all locations at baseline, 12 weeks, 24 weeks, 36 weeks and only at three locations at 52 weeks. The primary outcome is physical functioning (Short Physical Performance Battery). Secondary outcomes include leg muscle strength, lean body mass, activities of daily living, social participation, food intake, and quality of life. Qualitative and quantitative implementation process data are collected during the intervention. Healthcare use and intervention costs are registered for the economic evaluation. Discussion Evaluating the effects, implementation, and costs of this combined intervention provides valuable insight into the feasibility of this intervention for community-dwelling older adults and into the intervention’s ability to improve or to maintain physical functioning and quality of life. Trial registration Netherlands Trial Register (NTR6038) since 30 August 2016. Electronic supplementary material The online version of this article (10.1186/s12889-018-5788-8) contains supplementary material, which is available to authorized users.

Background: Nutrition-related knowledge (NRK) and nutrition-related attitudes (NRAs) are necessary for dietary changes toward healthier dietary patterns. In turn, healthier dietary patterns can be beneficial in maintaining health of older adults. Therefore, the aim of this cross-sectional study was to investigate whether NRK and NRAs were associated with lifestyle and health features among older adults (65+ years) from five European countries (France, Italy, Poland, the Netherlands and United Kingdom). Methods: Within the European project NU-AGE, 1,144 healthy elderly volunteers (65–79 years) were randomly assigned to two groups: intervention (NU-AGE diet) or control. After 1-year of follow-up, both NRK and NRAs were assessed during exit interviews, in combination with a number of lifestyle and health variables (e.g., physical activity, smoking, alcohol use, BMI, self-assessed health status). Multivariable linear regression models were used in data analysis. Results: In the NU-AGE study sample, good NRK was associated with lower BMI and higher physical activity. More positive NRAs were related to lower BMI and self-reported very good or good appetite. Moreover, both NRK and NRAs were associated with some socio-economic determinants, like financial situation, age, education, living area (for NRK), and country (for NRAs). Participants in the intervention group showed a better NRK (β = 0.367 [95% CI: 0.117; 0.617], p = 0.004) and more positive NRAs (β = 0.838 [95% CI: 0.318; 1.358], p = 0.002) than those in the control group. Higher self-evaluated knowledge was also significantly related to more positive NRAs (p < 0.001). The most popular sources of nutrition information were food labels, books and magazines on health, the dietitian and the doctor's office, although their importance varied significantly among countries, and, to a lesser extent, between women and men and between intervention and control group. Conclusion: Higher NRK and NRA scores were associated with lower BMI and higher physical activity level. Therefore, a good nutrition-related knowledge and positive nutrition-related attitudes can strongly and positively influence the health status and quality of life among the older population. These results offer a great opportunity for policy makers to implement educational programs in order to counteract the epidemic of obesity and to improve the health span of European population.

ObjectivesChronic systemic low grade inflammation is associated with the age-related loss of muscle mass. Resistance exercise has been suggested to reduce or lower chronic systemic low grade inflammation. However, systemic chronic low-grade inflammation may adversely affect the adaptive response to exercise training. We investigated the effect of resistance exercise training on systemic chronic low-grade inflammation in older adults. In addition, we studied the association between systemic chronic low-grade inflammation and the adaptive response to exercise training.Design/setting/participantsFrail and pre-frail older adults (61 subjects) performed 24 weeks of progressive resistance exercise training. Frailty was assessed using the Fried frailty criteria.MeasurementsLean body mass (DXA), strength (1RM), circulating levels of IL-1β, IL-6, IL-8 and TNF-α were measured prior to exercise training, after 12 weeks of training, and after 24 weeks of training.ResultsProlonged progressive resistance exercise training did not affect circulating levels of IL-6, IL-8 and TNF-α. However, exercise training led to a small but significant increase of 0.052 pg/mL in IL-1β. Higher circulating levels of TNF-α, IL-8 and IL-6 during the training period were negatively associated with strength gains for the leg press. A doubling of plasma TNF-α, IL-8 or IL-6 resulted in reduced strength gains for leg press with coefficients of −3.52, −3.42 and −1.54 respectively. High levels of circulating TNF-α were also associated with decreased strength gains for the leg extension (coefficient −1.50). Inflammatory cytokines did not appear to have an effect on gains in lean mass.ConclusionOur findings suggest that increased levels of plasma cytokines (TNF-α, IL-6 and IL-8) are associated with lower strength gains during resistance exercise training.

Background: Short successive periods of physical inactivity occur throughout life and contribute considerably to the age-related loss of skeletal muscle mass. The maintenance of muscle mass during brief periods of disuse is required to prevent functional decline and maintain metabolic health. Objective: To assess whether daily leucine supplementation during a short period of disuse can attenuate subsequent muscle loss in vivo in humans. Methods: Thirty healthy (22 ± 1 y) young males were exposed to a 7-day unilateral knee immobilization intervention by means of a full leg cast with (LEU, n = 15) or without (CON, n = 15) daily leucine supplementation (2.5 g leucine, three times daily). Prior to and directly after immobilization, quadriceps muscle cross-sectional area (computed tomography (CT) scan) and leg strength (one-repetition maximum (1-RM)) were assessed. Furthermore, muscle biopsies were taken in both groups before and after immobilization to assess changes in type I and type II muscle fiber CSA. Results: Quadriceps muscle cross-sectional area (CSA) declined in the CON and LEU groups (p < 0.01), with no differences between the two groups (from 7712 ± 324 to 7287 ± 305 mm2 and from 7643 ± 317 to 7164 ± 328 mm2; p = 0.61, respectively). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the CON group and from 63 ± 3 to 55 ± 2 kg in the LEU group (main effect of time p < 0.01), with no differences between the groups (p = 0.052). Type I and II muscle fiber size did not change significantly over time, in both groups (p > 0.05). Conclusions: Free leucine supplementation with each of the three main meals (7.5 g/d) does not attenuate the decline of muscle mass and strength during a 7-day limb immobilization intervention.

OBJECTIVE: Although it has been established that sufficient protein is required to maintain good nutritional status and support healthy aging, it is not clear if the pattern of protein consumption may also influence nutritional status, especially in institutionalized elderly who are at risk of malnutrition. Therefore, we aim to determine the association between protein intake distribution and nutritional status in institutionalized elderly people.DESIGN: Cross-sectional study among 481 institutionalized older adults.METHODS: Dietary data from 481 ambulant elderly people (68.8% female, mean age 87.5 ± 6.3 years) residing in 52 aged-care facilities in Victoria, Australia, were assessed over 2 days using plate waste analysis. Nutritional status was determined using the Mini-Nutritional Assessment tool and serum (n = 208) analyzed for albumin, hemoglobin, and IGF-1. Protein intake distribution was classified as: spread (even distribution across 3 meals, n = 65), pulse (most protein consumed in one meal, n = 72) or intermediate (n = 344). Regression analysis was used to investigate associations.RESULTS: Mean protein intakes were higher in the spread (60.5 ± 2.0 g/d) than intermediate group (56.0 ± 0.8 g/d, P = .037), and tended to be higher than those in the pulse group (55.9 ± 1.9 g/d, P = .097). Residents with an even distribution of protein intake achieved a higher level of the recommended daily intake for protein (96.2 ± 30.0%) than the intermediate (86.3 ± 26.2%, P = .008) and pulse (87.4 ± 30.5%, P = .06) groups, and also achieved a greater level of their estimated energy requirements (intermediate; P = .039, pulse; P = .001). Nutritional status (Mini-Nutritional Assessment score) did not differ between groups (pulse; 20.5 ± 4.5, intermediate; 21.0 ± 2.5, spread; 20.5 ± 3.5), nor did any other indices of nutritional status.CONCLUSIONS: Meeting protein requirements is required before protein distribution may influence nutritional status in institutionalized elderly. Achieving adequate protein and energy intakes is more likely when protein is distributed evenly throughout the day. Provision of high protein foods especially at breakfast, and in the evening, may support protein adequacy and healthy aging, especially for institutionalized elderly.

Background & aims: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D-2 or D-3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose response effects of supplementation with calcifediol compared to vitamin D-3 and assessed the dose which results in mean serum 25(OH)D-3 concentrations between 75 and 100 nmol/L.Methods: This randomized, double-blind intervention study included men and women aged >= 65 years (n = 59). Participants received either 5, 10 or 15 mu g calcifediol or 20 mu g vitamin D-3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D-3, 25(OH)D-3, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and 24,25-dihydroxyvitamin D-3 (24,25(OH)(2)D-3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated.Results: Supplementation with 20 jig vitamin 03 increased 25(OH)D-3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 mu g calcifediol increased 25(OH)D-3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D-3 levels stabilizing between 84 and 89 nmol/L in the 10 mu g calcifediol group. A significant association was observed between the changes in 25(OH)D-3 and 24,25(OH)(2)D-3 (R-2 = 0.83, P Conclusions: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D-3 concentrations to improve vitamin D status in older adults. A daily dose of 10 mu g calcifediol allows serum 25(OH)D-3 concentrations to be maintained between 75 and 100 nmol/L.Trial registration number: NCT01868945. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background: The Mediterranean Diet has been proposed as an effective strategy to reduce inflammaging, a chronic low grade inflammatory status, and thus, to slow down the aging process. We evaluated whether a Mediterranean-like dietary pattern specifically targeting dietary recommendations of people aged over 65 years (NU-AGE diet) could be effective to shift dietary intake of older adults towards a healthful diet. Methods: Adults aged 65&ndash, 80 years across five EU-centers were randomly assigned to a NU-AGE diet group or control group. The diet group followed one year of NU-AGE dietary intervention specifying consumption of 15 food groups plus the use of a vitamin D supplement. Participants in the diet group received counselling and individually tailored dietary advice, food products and a vitamin D supplement. Dietary intake was assessed by means of seven-day food records at baseline and one-year follow-up. A continuous NU-AGE index (0&ndash, 160 points) was developed to assess NU-AGE diet adherence. Results: In total 1296 participants were randomized and 1141 participants completed the intervention (571 intervention, 570 control). After one year, the diet group improved mean intake of 13 out of 16 NU-AGE dietary components (p &lt, 0.05), with a significant increase in total NU-AGE index (difference in mean change = 21.3 &plusmn, 15.9 points, p &lt, 0.01). Conclusions: The NU-AGE dietary intervention, based on dietary recommendations for older adults, consisting of individual dietary counselling, free healthy foods and a vitamin D supplement, may be a feasible strategy to improve dietary intake in an aging European population.

Background: Findings from animal and epidemiological research support the potential neuroprotective benefits from healthy diets. However, to establish diet-neuroprotective causal relations, evidence from dietary intervention studies is needed. NU-AGE is the first multicenter intervention assessing whether a diet targeting health in aging can counteract the age-related physiological changes in different organs, including the brain. In this study, we specifically investigated the effects of NU-AGE's dietary intervention on age-related cognitive decline. Materials and Methods: NU-AGE randomized trial (NCT01754012, clinicaltrials.gov) included 1279 relatively healthy older-adults, aged 65–79 years, from five European centers. Participants were randomly allocated into two groups: “control” (n = 638), following a habitual diet; and, “intervention” (n = 641), given individually tailored dietary advice (NU-AGE diet). Adherence to the NU-AGE diet was measured over follow-up, and categorized into tertiles (low, moderate, high). Cognitive function was ascertained at baseline and at 1-year follow-up with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Neuropsychological Battery and five additional domain-specific single cognitive tests. The raw scores from the CERAD subtests [excluding the Mini-Mental State Examination (MMSE)] and the single tests were standardized into Z-scores. Global cognition (measured with MMSE and CERAD-total score), and five cognitive domains (perceptual speed, executive function, episodic memory, verbal abilities, and constructional praxis) were created. Cognitive changes as a function of the intervention were analyzed with multivariable mixed-effects models. Results: After the 1-year follow-up, 571 (89.1%) controls and 573 (89.8%) from the intervention group participated in the post-intervention assessment. Both control and intervention groups showed improvements in global cognition and in all cognitive domains after 1 year, but differences in cognitive changes between the two groups were not statistically significant. However, participants with higher adherence to the NU-AGE diet showed statistically significant improvements in global cognition [β 0.20 (95%CI 0.004, 0.39), p-value = 0.046] and episodic memory [β 0.15 (95%CI 0.02, 0.28), p-value = 0.025] after 1 year, compared to those adults with lower adherence. Discussion: High adherence to the culturally adapted, individually tailored, NU-AGE diet could slow down age-related cognitive decline, helping to prevent cognitive impairment and dementia.

This study aimed to evaluate the effects of an intervention including nutritional telemonitoring, nutrition education, and follow-up by a nurse on nutritional status, diet quality, appetite, physical functioning and quality of life of Dutch community-dwelling elderly. We used a parallel arm pre-test post-test design with 214 older adults (average age 80 years) who were allocated to the intervention group (n97) or control group (n107), based on the municipality. The intervention group received a 6-month intervention including telemonitoring measurements, nutrition education and follow-up by a nurse. Effect measurements took place at baseline, after 4·5 months, and at the end of the study. The intervention improved nutritional status of participants at risk of undernutrition (β(T1)=2·55; 95 % CI 1·41, 3·68;β(T2)=1·77; 95 % CI 0·60, 2·94) and scores for compliance with Dutch guidelines for the intake of vegetables (β=1·27; 95 % CI 0·49, 2·05), fruit (β=1·24; 95 % CI 0·60, 1·88), dietary fibre (β=1·13; 95 % CI 0·70, 1·57), protein (β=1·20; 95 % CI 0·15, 2·24) and physical activity (β=2·13; 95 % CI 0·98, 3·29). The intervention did not have an effect on body weight, appetite, physical functioning and quality of life. In conclusion, this intervention leads to improved nutritional status in older adults at risk of undernutrition, and to improved diet quality and physical activity levels of community-dwelling elderly. Future studies with a longer duration should focus on older adults at higher risk of undernutrition than this study population to investigate whether the impact of the intervention on nutritional and functional outcomes can be improved.

A protein intake of ≥1.2 grams per kg body weight (g/kg) is recommended for ill older adults. In a cross-sectional study, we investigated if this recommendation was met by 62 hospitalized adults of 65 years and older in a Dutch hospital. We compared protein intake between two subgroups based on the risk of malnutrition and the prescribed diet: a low risk group (n = 31) receiving a standard hospital diet and a medium/high risk group (n = 31) receiving a protein-enriched diet. A 24h-recall was performed to calculate protein intake per patient. Protein intake was on average 1.2 g/kg in the medium/high risk group and 0.9 g/kg in the low-risk group. Seventeen patients reached a protein intake of ≥1.2 g/kg. Fifteen patients had a protein intake below 0.8 g/kg. It seems sensible to consider providing a protein-enriched diet to all older hospitalized adults, regardless of their risk of malnutrition.

Background: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking. Objective: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans. Design: An RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country. Results: A total of 1294 participants (mean ± SD age: 70.9 ±4.0 y; 44% male) were recruited to the study and 1142 completed the 1-y trial. The Mediterranean-like dietary pattern had no effect on BMD (site-specific or whole-body); the inclusion of compliance to the intervention in the statistical model did not change the findings. There was also no effect of the intervention on the urinary biomarkers free pyridinoline or free deoxypyridinoline. Serum 25-hydroxyvitamin D significantly increased and parathyroid hormone decreased (P < 0.001) in the MD compared with the control group. Subgroup analysis of individuals with osteoporosis at baseline (site-specific BMD T-score ≤ −2.5 SDs) showed that the MD attenuated the expected decline in femoral neck BMD (n = 24 and 30 in MD and control groups, respectively; P = 0.04) but had no effect on lumbar spine or whole-body BMD. Conclusions: A 1-y intervention of the Mediterranean-like diet together with vitamin D3 supplements (10 µg/d) had no effect on BMD in the normal age-related range, but it significantly reduced the rate of loss of bone at the femoral neck in individuals with osteoporosis. The NU-AGE trial is registered at clinicaltrials.gov as NCT01754012.