Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults.

BACKGROUND: There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD. METHODS: Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65 years) were combined. Dietary intake was assessed with food records (2, 3 or 7 days) and BMD with dual-energy X-ray absorptiometry (DXA). Associations and effects were assessed by adjusted linear mixed models. RESULTS: A total of 1570 participants [57% women, median (inter-quartile range): age 71 (68-75) years] for which at least total protein intake and total body BMD were known were included in cross-sectional analyses. In fully adjusted models, total protein intake was associated with higher total body and spine BMD [beta (95% confidence interval): 0.0011 (0.0006-0.0015) and 0.0015 (0.0007-0.0023) g/cm2 , respectively]. Animal protein intake was associated with higher total body and spine BMD as well [0.0011 (0.0007-0.0016) and 0.0017 (0.0010-0.0024) g/cm2 , respectively]. Plant protein intake was associated with a lower total body and spine BMD [-0.0010 (-0.0020 to -0.0001) and -0.0019 (-0.0034 to -0.0004) g/cm2 , respectively]. Associations were similar between sexes. Participants with a high ratio of animal to plant protein intake had higher BMD. In participants with an adequate calcium intake and sufficient serum 25(OH)D concentrations, the association between total protein intake with total body and spine BMD became stronger. Likewise, the association between animal protein intake with total body BMD was stronger. In the longitudinal analyses, 340 participants [58% women, median (inter-quartile range): age 75 (70-81) years] were included. Interventions of 12 or 24 weeks with protein supplementation or protein supplementation combined with resistance exercise did not lead to significant improvements in BMD. CONCLUSIONS: An association between total and animal protein intake with higher BMD was found. In contrast, plant protein intake was associated with lower BMD. Research is warranted to further investigate the added value of dietary protein alongside calcium and vitamin D for BMD improvement, especially in osteopenic or osteoporotic individuals. Moreover, more research on the impact of a plant-based diet on bone health is needed.

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.

Impact of magnesium on bone health in older adults: A systematic review and meta-analysis.

BACKGROUND: Magnesium plays a key role in bone health and may, therefore, represent an interesting nutrient for the prevention of bone loss and osteoporosis. The aim of this systematic review and meta-analysis was to investigate the impact of magnesium intake from any source on bone mineral density (BMD), bone mineral content (BMC), bone turnover markers, and fracture risk in older adults. METHODS: A systematic search was conducted using Embase, Medline Ovid and Cochrane Central from database inception to October 2020. All studies that related magnesium intake with bone health outcomes among adults aged ≥60 years were included. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias assessments. Authors were contacted for missing data. RESULTS: Once 787 records were screened, six cohort studies, one case-control study and five cross-sectional studies were included. Qualitative evaluation demonstrated a positive trend between higher magnesium intake and higher hip and femoral neck BMD. Meta-analysis of four studies showed a significant positive association between magnesium intake and hip BMD (pooled beta: 0.03, 95% CI: 0.01-0.06, p < 0.05). CONCLUSIONS: This systematic review indicates that a higher magnesium intake may support an increase in hip and femoral neck BMD. Due to limited research no associations with BMD at other sites or fractures were found. There is a need for properly designed cohort studies to determine the association between magnesium intake and bone health in older adults. Next, large and long-term randomized controlled trials in older adults are needed to determine whether an increase in magnesium (supplementation) intake can improve bone health. The combination of several bone nutrients (calcium, vitamin D, protein, magnesium and potentially more) may be needed for the most optimal effect on bone health and to delay or prevent the development of osteoporosis.

The Effect of Protein Supplementation versus Carbohydrate Supplementation on Muscle Damage Markers and Soreness Following a 15-km Road Race: A Double-Blind Randomized Controlled Trial.

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

Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial.

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

Vitamin B-6 intake is related to physical performance in European older adults: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) study.

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 [ß: -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 (ß: 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 (ß: -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.

Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial.

BACKGROUND & AIMS: In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk. METHODS: Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 µg) and vitamin-B12 (500 µg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease. RESULTS: A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51-58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 µmol/l). No age-dependent effects were present. CONCLUSIONS: This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.

Design of the DYNAMO study: a multi-center randomized controlled trial to investigate the effect of pre-thickened oral nutritional supplements in nursing home residents with dysphagia and malnutrition (risk).

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

Beneficial Role of Replacing Dietary Saturated Fatty Acids with Polyunsaturated Fatty Acids in the Prevention of Sarcopenia: Findings from the NU-AGE Cohort.

Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65-79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.

A Combined Nutrition and Exercise Intervention Influences Serum Vitamin B-12 and 25-Hydroxyvitamin D and Bone Turnover of Healthy Chinese Middle-Aged and Older Adults.

BACKGROUND: Hong Kong faces several public health problems including malnutrition and osteoporosis. Considering the typical Chinese diet and overall low physical activity levels of Chinese adults, timely interventions to improve nutritional status and bone health are needed. OBJECTIVES: We examined the effects of a nutrition plus exercise intervention on serum vitamin B-12 and 25-hydroxyvitamin D [25(OH)D], bone turnover markers, and parathyroid hormone (PTH) concentrations in apparently healthy Chinese middle-aged and older adults. METHODS: In this 24-wk randomized controlled trial, 180 Chinese adults (85 women, mean ± SD age: 61 ± 6 y) were randomly assigned to receive a fortified milk supplement (2 × 30 g/d) and an exercise program (2 × 1 h/wk including resistance, balance, and aerobic training) or no intervention. The primary outcome was physical performance. In this article we analyzed the secondary outcomes serum vitamin B-12 and 25(OH)D concentrations, assessed at baseline, 12 wk, and 24 wk. Also, bone turnover markers and PTH concentrations were studied. Linear mixed models evaluated group differences over time. RESULTS: A significant time × group interaction (P < 0.001) was found for serum vitamin B-12 and 25(OH)D concentrations and the bone turnover markers, but not for serum PTH concentrations (P = 0.09). The intervention increased mean ± SD vitamin B-12 concentrations from baseline (345 ± 119 pmol/L) to 24 wk (484 ± 136 pmol/L), whereas concentrations remained stable within the control. For 25(OH)D concentrations, the intervention group had a greater increase from baseline (54.7 ± 14.2 nmol/L) to 24 wk (80.1 ± 19.2 nmol/L) than the control (60.6 ± 15.2 compared with 65.6 ± 14.6 nmol/L). The ratio of the net effect of bone formation and resorption was greater in the intervention group, suggesting less bone remodeling, irrespective of sex. CONCLUSIONS: A fortified milk supplement and exercise intervention successfully improved vitamin B-12 and 25(OH)D concentrations as well as the balance of bone turnover markers of Chinese middle-aged and older adults.This trial was registered at trialregister.nl as NTR6214.

Dietary Fibre May Mitigate Sarcopenia Risk: Findings from the NU-AGE Cohort of Older European Adults.

Sarcopenia is characterised by a progressive loss of skeletal muscle mass and physical function as well as related metabolic disturbances. While fibre-rich diets can influence metabolic health outcomes, the impact on skeletal muscle mass and function is yet to be determined, and the moderating effects by physical activity (PA) need to be considered. The aim of the present study was to examine links between fibre intake, skeletal muscle mass and physical function in a cohort of older adults from the NU-AGE study. In 981 older adults (71 ± 4 years, 58% female), physical function was assessed using the short-physical performance battery test and handgrip strength. Skeletal muscle mass index (SMI) was derived using dual-energy X-ray absorptiometry (DXA). Dietary fibre intake (FI) was assessed by 7-day food record and PA was objectively determined by accelerometery. General linear models accounting for covariates including PA level, protein intake and metabolic syndrome (MetS) were used. Women above the median FI had significantly higher SMI compared to those below, which remained in fully adjusted models (24.7 ± 0.2% vs. 24.2 ± 0.1%, p = 0.011, η2p = 0.012). In men, the same association was only evident in those without MetS (above median FI: 32.4 ± 0.3% vs. below median FI: 31.3 ± 0.3%, p = 0.005, η2p = 0.035). There was no significant impact of FI on physical function outcomes. The findings from this study suggest a beneficial impact of FI on skeletal muscle mass in older adults. Importantly, this impact is independent of adherence to guidelines for protein intake and PA, which further strengthens the potential role of dietary fibre in preventing sarcopenia. Further experimental work is warranted in order to elucidate the mechanisms underpinning the action of dietary fibre on the regulation of muscle mass.

B-vitamins and body composition: integrating observational and experimental evidence from the B-PROOF study.

PURPOSE: Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals. METHODS: A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA). RESULTS: Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per µgmol/L) was associated with a 1.108 kg/m2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention. CONCLUSIONS: Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.

Changing from a Western to a Mediterranean-style diet does not affect iron or selenium status: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) 1-year randomized clinical trial in elderly Europeans.

BACKGROUND: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. OBJECTIVES: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterranean-style diet on indices of inflammation and changes in nutritional status. METHODS: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65-79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. RESULTS: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. CONCLUSIONS: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

The Elderly-Nutrient Rich Food Score Is Associated With Biochemical Markers of Nutritional Status in European Older Adults.

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.

No effect of 25-hydroxyvitamin D supplementation on the skeletal muscle transcriptome in vitamin D deficient frail older adults.

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

Protein supplementation improves lean body mass in physically active older adults: a randomized placebo-controlled trial.

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

Efficacy of non-pharmacological interventions to treat malnutrition in older persons: A systematic review and meta-analysis. The SENATOR project ONTOP series and MaNuEL knowledge hub project.

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.

Effectiveness of nutritional interventions in older adults at risk of malnutrition across different health care settings: Pooled analyses of individual participant data from nine randomized controlled trials.

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.

Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial.

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.

Changes in Dietary Intake and Adherence to the NU-AGE Diet Following a One-Year Dietary Intervention among European Older Adults-Results of the NU-AGE Randomized Trial.

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 65⁻80 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 (0⁻160 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 < 0.05), with a significant increase in total NU-AGE index (difference in mean change = 21.3 ± 15.9 points, p < 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.