Selenium status and its determinants in very old adults: insights from the Newcastle 85+ Study.

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP.

Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study.

BACKGROUND: The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia. METHODS: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested. RESULTS: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia. CONCLUSIONS: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

Implementation strategies for improving vitamin D status and increasing vitamin D intake in the UK: current controversies and future perspectives: proceedings of the 2nd Rank Prize Funds Forum on vitamin D.

A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose-response and dietary modelling studies indicate dairy products, bread, hens' eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for 'real-world' cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D's importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.

Contribution of protein intake and its interaction with physical activity to transitions between disability states and to death in very old adults: the Newcastle 85+ Study.

INTRODUCTION: Growth in the number of very old (≥ 85 years) adults will likely lead to increased prevalence of disability. Our aim was to determine the contribution of protein intake, and the interaction between protein intake and physical activity (PA), to the transition between disability states and to death in the very old using the Newcastle 85+ Study. METHODS: The analytic sample comprised of 717 older adults aged 85 years at baseline and living in the community. Protein intake was estimated with 2 × 24-h multiple pass recalls (24 h-MPR) at baseline. Disability was measured as difficulty performing 17 activities of daily living (ADL) at baseline, at 18, 36, and 60 months, and defined as having difficulties in one or more ADL. The contribution of protein intake [g/kg adjusted body weight/day (g/kg aBW/d)] to transition probabilities to and from disability, and to death over 5 years was examined by multi-state models adjusted for key health covariates. RESULTS: Participants were expected to spend 0.8 years (95% CI 0.6-1.0) disability-free and 2.8 years (95% CI 2.6-2.9) with disability between the ages 85 and 90 years. One unit increase in protein intake (g/kg aBW/d) halved the likelihood of incident disability (HR 0.44, 95% CI 0.24-0.83) but not for other transitions. Similar reductions in disability incidence were also found in individuals with protein intake ≥ 0.8 (HR 0.50, 95% CI 0.31-0.80) and ≥ 1 g/kg aBW/d (HR 0.49, 95% CI 0.33-0.73). Participants with high PA and protein intake ≥ 1 g/kg aBW/d were less likely to transition from disability-free to disability than those within the same PA level but with protein intake < 1 g/kg aBW/d (HR 0.45, 95% CI 0.28-0.72). CONCLUSION: Higher protein intake, especially in combination with higher physical activity, may delay the incidence of disability in very old adults.

Osteoporosis and the Ageing Skeleton.

Osteoporosis is a "skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture" which, in light of demographic change, is becoming an increasing burden on health care worldwide. Increasing age and female gender are associated with the condition, although a wider range of clinical risk factors are being used increasingly to identify those at risk of osteoporosis and its most important sequelae, fracture.While osteoporosis and fracture have long been associated with women in the post-menopausal age, fracture incidence increases because of the ageing of our population. Interventions to abate the progression of osteoporosis and to prevent fractures must focus on the old and the very old. Evidence associating nutritional factors, particularly calcium and vitamin D are reviewed as are the association of falls risk with fracture and the potential for interventions to prevent falls. Finally, the assessment of frailty in the oldest old, associated sarcopenia and multi-morbidity are considered in the evaluation of fall and fracture risk and the management of osteoporosis in the ninth decade of life and beyond.

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study.

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

Dairy foods and bone health throughout the lifespan: a critical appraisal of the evidence.

The consumption of high-Ca, high-protein dairy foods (i.e. milk, cheese, yogurt) is advocated for bone health across the lifespan to reduce the risk of low-trauma fractures. However, to date, the anti-fracture efficacy of dairy food consumption has not been demonstrated in randomised controlled trials but inferred from cross-sectional and prospective studies. The anti-fracture efficacy of dairy food consumption is plausible, but testing this requires a robust study design to ensure outcomes are suitably answering this important public health question. The evidence of skeletal benefits of dairy food consumption is equivocal, not because it may not be efficacious but because the study design and execution are often inadequate. The key issues are compliance with dietary intervention, dropouts, sample sizes and most importantly lack of deficiency before intervention. Without careful appraisal of the design and execution of available studies, precarious interpretations of outcomes may be made from these poorly designed or executed studies, without consideration of how study design may be improved. Dairy food interventions in children are further hampered by heterogeneity in growth: in particular sex and maturity-related differences in the magnitude, timing, location and surface-specific site of bone accrual. Outcomes of studies combining children of different sexes and maturity status may be masked or exaggerated by these differences in growth, so inaccurate conclusions are drawn from results. Until these critical issues in study design are considered in future dairy food interventions, the anti-fracture efficacy of dairy food consumption may remain unknown and continue to be based on conjecture.

Vitamin D and Ageing.

One hundred years has passed since the discovery of vitamin D as the active component of cod-liver oil which cured the bone disease rickets. Since then our knowledge of vitamin D has expanded tremendously and has included recognition of the importance of UV radiation as a source of the vitamin as well as the discovery of the vitamin as a nutrient, a pro-hormone and a potent steroid hormone with a major role in calcium and bone metabolism. In the last 25 years or so, the discovery of the vitamin D receptor in over 30 different body tissues together with the existence of the alpha-1-hydroxylase enzyme in these tissues provided evidence of a pleiotropic role of vitamin D outside its classical role in the skeleton. These important discoveries have provided the basis for the increasing interest in vitamin D in the context of nutritional requirements for health including the prevention of chronic diseases of ageing. The recent publication of the Dietary Reference Intake report on vitamin D and calcium by the North American Institute of Medicine (IOM) is the most comprehensive report to date on the basis for setting nutritional requirements for vitamin D. This chapter will summarize the nutritional aspects of vitamin D and discuss the changes in vitamin D metabolism and requirements with ageing. It will summarize key evidence on the relationship between vitamin D status and some of the main ageing related health outcomes including bone, muscle and cognitive health as well as survival focusing on the published literature in very-old adults (those >= 85 years of age).

Prevalence and determinants of low protein intake in very old adults: insights from the Newcastle 85+ Study.

PURPOSE: The very old (aged ≥ 85 years), fastest growing age group in most western societies, are at especially high risk of muscle mass and strength loss. The amount, sources and timing of protein intake may play important roles in the aetiology and management of sarcopenia. This study investigated the prevalence and determinants of low protein intake in 722 very old adults participating in the Newcastle 85+ Study. METHODS: Protein intake was estimated with 2 × 24-h multiple pass recalls (24 h-MPR) and contribution (%) of food groups to protein intake was calculated. Low protein intake was defined as intake < 0.8 g of protein per adjusted body weight per day. A backward stepwise multivariate linear regression model was used to explore socioeconomic, health and lifestyle predictors of protein intake. RESULTS: Twenty-eight percent (n = 199) of the community-living very old in the Newcastle 85+ Study had low protein intake. Low protein intake was less likely when participants had a higher percent contribution of meat and meat products to total protein intake (OR 0.97, 95% CI 0.95, 1.00) but more likely with a higher percent contribution of cereal and cereal products and non-alcoholic beverages. Morning eating occasions contributed more to total protein intake in the low than in the adequate protein intake group (p < 0.001). Being a woman (p < 0.001), having higher energy intake (p < 0.001) and higher tooth count (p = 0.047) was associated with higher protein intake in adjusted models. CONCLUSION: This study provides novel evidence on the prevalence of low protein intake, diurnal protein intake patterns and food group contributors to protein intake in the very old.

Dietary Patterns High in Red Meat, Potato, Gravy, and Butter Are Associated with Poor Cognitive Functioning but Not with Rate of Cognitive Decline in Very Old Adults.

BACKGROUND: Healthy dietary patterns (DPs) have been linked to better cognition and reduced risk of dementia in older adults, but their role in cognitive functioning and decline in the very old (aged ≥85 y) is unknown. OBJECTIVE: We investigated the association between previously established DPs from the Newcastle 85+ Study and global and attention-specific cognition over 5 y. METHODS: We followed up with 302 men and 489 women (1921 birth cohort from Northeast United Kingdom) for change in global cognition [measured by the Standardized Mini-Mental State Examination (SMMSE)] over 5 y and attention (assessed by the cognitive drug research attention battery) over 3 y. We used 2-step clustering to derive DPs and mixed models to determine the relation between DPs and cognition in the presence of the dementia susceptibility gene. RESULTS: Previously, we characterized 3 DPs that differed in intake of red meat, potato, gravy, and butter and varied with key health measures. When compared with participants in DP1 (high red meat) and DP3 (high butter), participants in DP2 (low meat) had higher SMMSE scores at baseline (P < 0.001) and follow-ups, and better initial attention (P < 0.05). Membership in DP1 and DP3 was associated with overall worse SMMSE scores (ß = 0.09, P = 0.01 and ß = 0.08, P = 0.02, respectively) than membership in DP2 after adjustment for sociodemographic factors, lifestyle, multimorbidity, and body mass index (BMI). Additional adjustment for apolipoprotein (apoE) ε4 genotype attenuated the association to nonsignificant in women but not in men in DP1 (ß = 0.13, P = 0.02). Participants in DP1 and DP3 also had overall worse concentration (ß = 0.04, P = 0.002 and ß = 0.028, P = 0.03, respectively) and focused attention (ß = 0.02, P = 0.01 and ß = 0.02, P = 0.03, respectively), irrespective of apoE ε4 genotype, but similar rate of decline in all cognitive measures over time. CONCLUSION: DPs high in red meat, potato, gravy (DP1), or butter (DP3) were associated with poor cognition but not with the rate of cognitive decline in very old adults.

Micronutrient intake and food sources in the very old: analysis of the Newcastle 85+ Study.

A number of socio-economic, biological and lifestyle characteristics change with advancing age and place very old adults at increased risk of micronutrient deficiencies. The aim of this study was to assess vitamin and mineral intakes and respective food sources in 793 75-year-olds (302 men and 491 women) in the North-East of England, participating in the Newcastle 85+ Study. Micronutrient intakes were estimated using a multiple-pass recall tool (2×24 h recalls). Determinants of micronutrient intake were assessed with multinomial logistic regression. Median vitamin D, Ca and Mg intakes were 2·0 (interquartile range (IQR) 1·2-6·5) µg/d, 731 (IQR 554-916) mg/d and 215 (IQR 166-266) mg/d, respectively. Fe intake was 8·7 (IQR 6·7-11·6) mg/d, and Se intake was 39·0 (IQR 27·3-55·5) µg/d. Cereals and cereal products were the top contributors to intakes of folate (31·5 %), Fe (49·2 %) and Se (46·7 %) and the second highest contributors to intakes of vitamin D (23·8 %), Ca (27·5 %) and K (15·8 %). More than 95 % (n 756) of the participants had vitamin D intakes below the UK's Reference Nutrient Intake (10 µg/d). In all, >20 % of the participants were below the Lower Reference Nutrient Intake for Mg (n 175), K (n 238) and Se (n 418) (comparisons with dietary reference values (DRV) do not include supplements). As most DRV are not age specific and have been extrapolated from younger populations, results should be interpreted with caution. Participants with higher education, from higher social class and who were more physically active had more nutrient-dense diets. More studies are needed to inform the development of age-specific DRV for micronutrients for the very old.

Macronutrient intake and food sources in the very old: analysis of the Newcastle 85+ Study.

Food and nutrient intake data are scarce in very old adults (85 years and older) - one of the fastest growing age segments of Western societies, including the UK. Our primary objective was to assess energy and macronutrient intakes and respective food sources in 793 85-year-olds (302 men and 491 women) living in North-East England and participating in the Newcastle 85+ cohort Study. Dietary information was collected using a repeated multiple-pass recall (2×24 h recalls). Energy, macronutrient and NSP intakes were estimated, and the contribution (%) of food groups to nutrient intake was calculated. The median energy intake was 6·65 (interquartile ranges (IQR) 5·49-8·16) MJ/d - 46·8 % was from carbohydrates, 36·8 % from fats and 15·7 % from proteins. NSP intake was 10·2 g/d (IQR 7·3-13·7). NSP intake was higher in non-institutionalised, more educated, from higher social class and more physically active 85-year-olds. Cereals and cereal products were the top contributors to intakes of energy and most macronutrients (carbohydrates, non-milk extrinsic sugars, NSP and fat), followed by meat and meat products. The median intakes of energy and NSP were much lower than the estimated average requirement for energy (9·6 MJ/d for men and 7·7 MJ/d for women) and the dietary reference value (DRV) for NSP (≥18 g/d). The median SFA intake was higher than the DRV (≤11 % of dietary energy). This study highlights the paucity of data on dietary intake and the uncertainties about DRV for this age group.

Incremental cholecalciferol supplementation up to 15 µg/d throughout winter at 51-55° N has no effect on biomarkers of cardiovascular risk in healthy young and older adults.

Two separate, identical, double-blind, randomized, placebo-controlled intervention studies were carried out in the south and north of Ireland (51-55°N). Men and women aged 20-40 y (n = 202) and ≥64 y (n = 192) received cholecalciferol at doses of 0 (P), 5 (D3-5), 10 (D3-10), or 15 (D3-15) µg/d (0-600 IU) during wintertime. Serum 25-hydroxyvitamin D [s25(OH)D], intact parathyroid hormone, systolic and diastolic blood pressure, fasting lipids, glucose and insulin, HOMA-IR, high-sensitivity CRP, matrix metalloproteinase-9, and its inhibitor (tissue inhibitor metalloproteinase-1) were measured at baseline (October) and 22 wk later at endpoint (March). Vitamin D receptor Fok I and Taq I genotypes were analyzed and dietary intakes of vitamin D and calcium were assessed. In young adults, s25(OH)D decreased from baseline to endpoint (P < 0.001), except in the D3-15 group, who maintained the baseline concentration of ~70 nmol/L. Older adults had lower s25(OH)D at baseline (median, 54.2 nmol/L) and concentrations increased in the D3-10 and D3-15 groups (P < 0.001). There were no significant effects of supplementation on cardiovascular disease (CVD) risk biomarkers in either age group. Fasting glucose and total and HDL cholesterol were lower (P < 0.05) in older adults with the Fok 1 ff genotype than in those with FF or Ff. Putative effects of vitamin D on cardio-metabolic health will only be evident at higher intakes than the current RDA and possibly in individuals at particular risk of low s25(OH)D and/or CVD risk.

Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults.

There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity. Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation, results have been equivocal. The aim of this randomised, placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol (25(OH)D) response to 15 µg cholecalciferol per d in healthy young and older Irish adults. A total of 110 young adults (20-40 years) and 102 older adults ( ≥ 64 years) completed the 22-week intervention with >85 % compliance. The change in 25(OH)D from baseline was calculated. Anthropometric measures of adiposity taken at baseline included height, weight and waist circumference (WC), along with skinfold thickness measurements to estimate fat mass (FM). FM was subsequently expressed as FM (kg), FM (%), FM index (FMI (FM kg/height m2)) and as a percentage ratio to fat-free mass (FFM). In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r - 0·33, - 0·36, - 0·33, - 0·30, - 0·33 and - 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (ß - 1·27, CI - 2·37, - 0·16, P = 0·026); however, no such associations were apparent in younger adults. Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes.

Long-Term Selenium-Yeast Supplementation Does Not Affect Bone Turnover Markers: A Randomized Placebo-Controlled Trial.

Higher selenium status has been associated with lower bone turnover markers (BTM) in epidemiological studies. However, the long-term impact of selenium supplementation on BTMs has not been studied. We investigated the effects of selenium supplementation on BTMs including osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), collagen type I cross-linked C-telopeptide (CTX), and bone alkaline phosphatase (BALP) in the short (6 months) and long term (5 years). A total of 481 Danish men and women (60-74 years) were randomized to receive placebo-yeast versus 100, 200, or 300 µg selenium as selenium-enriched yeast daily for 5 years. Plasma selenium concentration was measured using inductively coupled plasma mass spectrometry, and BTMs were measured in nonfasted samples at baseline, 6 months, and 5 years. Data were analyzed by ANCOVA to investigate the shape of the dose-response relationships. Covariates included age, body mass index, baseline selenium status, baseline BTM, smoking, alcohol, supplement use, and medication. Plasma selenium concentration (mean 86.5 µg/d at baseline) increased significantly with increasing selenium supplementation to 152.6, 209.1, and 253.7 µg/L after 6 months and remained elevated at 5 years (158.4, 222.4, and 275.9 µg/L for 100, 200, and 300 µg supplemental selenium/d, respectively (p < 0.001)). There was no change in plasma selenium concentration in the placebo-treated group. There was no significant effect of selenium supplementation on OC (6 months p = 0.37; 5 years p = 0.63), PINP (6 months p = 0.37; 5 years p = 0.79), CTX (6 months p = 0.91; 5 years p = 0.58) or BALP (6 months p = 0.17; 5 years p = 0.53). The relatively replete baseline selenium status in the study participants may explain this lack of effect. Testing in more deficient populations may provide further insights into the impact of selenium supplementation on bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Maintenance of wintertime vitamin D status with cholecalciferol supplementation is not associated with alterations in serum cytokine concentrations among apparently healthy younger or older adults.

Epidemiological studies have shown that low vitamin D status results in impaired immune function and is associated with the prevalence of autoimmune and inflammatory conditions. Vitamin D supplementation has been shown to reduce circulating concentrations of inflammatory markers in such conditions. However, the possible beneficial effect of vitamin D supplementation in the general population, particularly for those individuals living at high latitudes where hypovitaminosis D is common during wintertime, remains unclear. The aim of this study was to assess the effect of vitamin D supplementation using doses of 5, 10, and 15 µg/d cholecalciferol (D3) compared with placebo on cytokine concentrations throughout winter in apparently healthy younger (aged 20-40 y) and older (aged ≥64 y) adults. A total of 211 younger and 202 older adults completed the 22-wk intervention (from October to March) with >85% compliance. Serum concentrations of 25-hydroxycholecalciferol [25(OH)D3], high sensitivity C-reactive protein, IL-6, IL-10, soluble CD40 ligand, TGFß, TNFα, and fibrinogen were measured using ELISA. 25(OH)D3 concentrations significantly decreased in the placebo and 5 and 10/d µg D3 groups in the younger cohort and in the placebo group in the older cohort. Whereas 15 µg/d D3 supplementation maintained 25(OH)D3 concentrations in the younger cohort (baseline, 75.9 nmol/L; postintervention, 69.0 nmol/L) and significantly increased concentrations in the older cohort (baseline, 55.1 nmol/L; postintervention, 73.9 nmol/L), it had no significant effect on cytokine concentrations (ANCOVA, P > 0.05). The long-term effects of low vitamin D status remain to be elucidated and optimization of vitamin D status in otherwise healthy individuals may potentially have lasting beneficial effects on the immune system.

Vitamin d status and indices of bone turnover in older European adults.

An increased rate of bone turnover increases risk of osteoporotic fracture later in life. The concentration of 25-hydroxyvitamin D that contributes to an elevated rate of bone turnover in older adults is unclear. The objective of this study was to investigate the associations between 25-hydroxyvitamin D and biochemical markers of bone turnover in an older, pan-European cohort. 25-hydroxyvitamin D and serum markers of bone-formation (osteocalcin and bone-specific alkaline phosphatase) were assessed by ELISA, while urinary markers of bone-resorption (pyridinoline and deoxypyridinoline) were assessed by HPLC. Six percent, 36 %, and 64 % of subjects had 25-hydroxyvitamin D concentrations < 25, < 50, and < 80 nmol/L throughout the year, respectively. 25-hydroxyvitamin D was significantly and inversely correlated with serum bone-specific alkaline phosphatase (r = 0.119; p = 0.022) and urinary pyridinoline (r = 0.207; p < 0.0001) and deoxypyridinoline (r = 0.230; p < 0.0001). Stratification on the basis of tertiles [T] of 25-hydroxyvitamin D (< 47.6 [T(1)]; 47.6 - 85.8 [T2]; > 85.8 [T3] nmol/L), showed that urinary pyridinoline and deoxypyridinoline were significantly lower in subjects in the 2(nd) and 3(rd) compared to the 1(st) tertile (p < 0.015). Low vitamin D status (< 50 nmol/L) was associated with an increased rate of bone turnover in this older pan-European cohort.

Effect of selenium supplementation on musculoskeletal health in older women: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Observational and preclinical studies show associations between selenium status, bone health, and physical function. Most adults in Europe have serum selenium below the optimum range. We hypothesised that selenium supplementation could reduce pro-resorptive actions of reactive oxygen species on osteoclasts and improve physical function. METHODS: We completed a 6-month randomised, double-blind, placebo-controlled trial. We recruited postmenopausal women older than 55 years with osteopenia or osteoporosis at the Northern General Hospital, Sheffield, UK. Participants were randomly assigned 1:1:1 to receive selenite 200 µg, 50 µg, or placebo orally once per day. Medication was supplied to the site blinded and numbered by a block randomisation sequence with a block size of 18, and participants were allocated medication in numerical order. All participants and study team were masked to treatment allocation. The primary endpoint was urine N-terminal cross-linking telopeptide of type I collagen (NTx, expressed as ratio to creatinine) at 26 weeks. Analysis included all randomly assigned participants who completed follow-up. Groups were compared with analysis of covariance with Hochberg testing. Secondary endpoints were other biochemical markers of bone turnover, bone mineral density, short physical performance battery, and grip strength. Mechanistic endpoints were glutathione peroxidase, highly sensitive C-reactive protein, and interleukin-6. This trial is registered with EU clinical trials, EudraCT 2016-002964-15, and ClinicalTrials.gov, NCT02832648, and is complete. FINDINGS: 120 participants were recruited between Jan 23, 2017, and April 11, 2018, and randomly assigned to selenite 200 µg, 50 µg, or placebo (n=40 per group). 115 (96%) of 120 participants completed follow-up and were included in the primary analysis (200 µg [n=39], 50 µg [n=39], placebo [n=37]). Median follow-up was 25·0 weeks (IQR 24·7-26·0). In the 200 µg group, mean serum selenium increased from 78·8 (95% CI 73·5-84·2) to 105·7 µg/L (99·5-111·9). Urine NTx to creatinine ratio (nmol bone collagen equivalent:mmol creatinine) did not differ significantly between treatment groups at 26 weeks: 40·5 (95% CI 34·9-47·0) for placebo, 43·4 (37·4-50·5) for 50 µg, and 42·2 (37·5-47·6) for 200 µg. None of the secondary or mechanistic endpoint measurements differed between treatment groups at 26 weeks. Seven (6%) of 120 participants were withdrawn from treatment at week 13 due to abnormal thyroid-stimulating hormone concentrations (one in the 200 µg group, three in the 50 µg group, and three in the placebo group) and abnormal blood glucose (one in the 50 µg group). There were three serious adverse events: a non-ST elevation myocardial infarction at week 18 (in the 50 µg group), a diagnosis of bowel cancer after routine population screening at week 2 (in the placebo group), and a pulmonary embolus due to metastatic bowel cancer at week 4 (in the 200 µg group). All severe adverse events were judged by the principal investigator as unrelated to trial medication. INTERPRETATION: Selenium supplementation at these doses does not affect musculoskeletal health in postmenopausal women. FUNDING: UK National Institute for Health Research Efficacy and Mechanism Evaluation programme.