Protein Intake and Distribution in Relation to Physical Functioning and Quality of Life in Community-Dwelling Elderly People: Acknowledging the Role of Physical Activity.

Increasing total protein intake and a spread protein intake distribution are potential strategies to attenuate sarcopenia related loss of physical function and quality of life. The aim of this cross-sectional study was to investigate whether protein intake and protein intake distribution are associated with muscle strength, physical function and quality of life in community-dwelling elderly people with a wide range of physical activity. Dietary and physical activity data were obtained from two studies (N = 140, age 81 ± 6, 64% male), with the following outcome measures: physical functioning (Short Physical Performance Battery (SPPB), comprising balance, gait speed and chair rise tests), handgrip strength and quality of life (EQ-5D-5L). Protein intake distribution was calculated for each participant as a coefficient of variance (CV = SD of grams of protein intake per main meal divided by the average total amount of proteins (grams) of the main meals). Based on the CV, participants were divided into tertiles and classified as spread, intermediate or pulse. The average total protein intake was 1.08 ± 0.29 g/kg/day. Total protein intake was not associated with outcome measures using multivariate regression analyses. Individuals with a spread protein diet during the main meals (CV < 0.43) had higher gait speed compared to those with an intermediate diet (CV 0.43⁻0.62) (β = -0.42, p = 0.035), whereas a spread and pulse protein diet were not associated with SPPB total score, chair rise, grip strength and Quality-Adjusted Life Year (QALY). The interaction of higher physical activity and higher total protein intake was significantly associated with higher quality of life (β = 0.71, p = 0.049). While this interaction was not associated with SPPB or grip strength, the association with quality of life emphasizes the need for a higher total protein intake together with an active lifestyle in the elderly

There Are No Nonresponders to Resistance-Type Exercise Training in Older Men and Women

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordOBJECTIVE: To assess the proposed prevalence of unresponsiveness of older men and women to augment lean body mass, muscle fiber size, muscle strength, and/or physical function following prolonged resistance-type exercise training. DESIGN/SETTING/PARTICIPANTS: A retrospective analysis of the adaptive response to 12 (n = 110) and 24 (n = 85) weeks of supervised resistance-type exercise training in older (>65 years) men and women. MEASUREMENTS: Lean body mass (DXA), type I and type II muscle fiber size (biopsy), leg strength (1-RM on leg press and leg extension), and physical function (chair-rise time) were assessed at baseline, and after 12 and 24 weeks of resistance-type exercise training. RESULTS: Lean body mass increased by 0.9 ± 0.1 kg (range: -3.3 to +5.4 kg; P < .001) from 0 to 12 weeks of training. From 0 to 24 weeks, lean body mass increased by 1.1 ± 0.2 kg (range: -1.8 to +9.2 kg; P < .001). Type I and II muscle fiber size increased by 324 ± 137 μm(2) (range: -4458 to +3386 μm(2); P = .021), and 701 ± 137 μm(2) (range: -4041 to +3904 μm(2); P < .001) from 0 to 12 weeks. From 0 to 24 weeks, type I and II muscle fiber size increased by 360 ± 157 μm(2) (range: -3531 to +3426 μm(2); P = .026) and 779 ± 161 μm(2) (range: -2728 to +3815 μm(2); P < .001). The 1-RM strength on the leg press and leg extension increased by 33 ± 2 kg (range: -36 to +87 kg; P < .001) and 20 ± 1 kg (range: -22 to +56 kg; P < .001) from 0 to 12 weeks. From 0 to 24 weeks, leg press and leg extension 1-RM increased by 50 ± 3 kg (range: -28 to +145 kg; P < .001) and 29 ± 2 kg (range: -19 to +60 kg; P < .001). Chair-rise time decreased by 1.3 ± 0.4 seconds (range: +21.6 to -12.5 seconds; P = .003) from 0 to 12 weeks. From 0 to 24 weeks, chair-rise time decreased by 2.3 ± 0.4 seconds (range: +10.5 to -23.0 seconds; P < .001). Nonresponsiveness was not apparent in any subject, as a positive adaptive response on at least one training outcome was apparent in every subject. CONCLUSIONS: A large heterogeneity was apparent in the adaptive response to prolonged resistance-type exercise training when changes in lean body mass, muscle fiber size, strength, and physical function were assessed in older men and women. The level of responsiveness was strongly affected by the duration of the exercise intervention, with more positive responses following more prolonged exercise training. We conclude that there are no nonresponders to the benefits of resistance-type exercise training on lean body mass, fiber size, strength, or function in the older population. Consequently, resistance-type exercise should be promoted without restriction to support healthy aging in the older population.This work was funded by TI Food and Nutrition, a public-private partnership on precompetitive research in food and nutrition

Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans

BACKGROUND: Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are largely determined by dietary protein digestion and amino acid absorption kinetics. OBJECTIVE: We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans. METHODS: We included data from 18 randomized controlled trials with a total of 602 participants [age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3] who consumed various quantities of intrinsically l-[1-13C]-phenylalanine-labeled whey (n = 137), casein (n = 393), or milk (n = 72) protein and received intravenous infusions of l-[ring-2H5]-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein-derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals. RESULTS: A total of 50% ± 14% of dietary protein-derived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary protein-derived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary protein-derived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein-derived phenylalanine appearing in the circulation, respectively (P = 0.001). CONCLUSIONS: Protein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans. These trials were registered at clinicaltrials.gov as NCT00557388, NCT00936039, NCT00991523, NCT01317511, NCT01473576, NCT01576848, NCT01578590, NCT01615276, NCT01680146, NCT01820975, NCT01986842, and NCT02596542, and at http://www.trialregister.nl as NTR3638, NTR3885, NTR4060, NTR4429, and NTR4492

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P &lt; 5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men &lt;= 50y, men &gt; 50y, women &lt;= 50y, women &gt; 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR&lt; 5%) age-specific effects, of which 11 had larger effects in younger (&lt; 50y) than in older adults (&gt;= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.</p

DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial

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

Attenuated strength gains during prolonged resistance exercise training in older adults with high inflammatory status

Attenuated strength gains during prolonged resistance exercise training in older adults with high inflammatory statu