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.

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).

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.

The Association between 25-Hydroxyvitamin D Concentration and Telomere Length in the Very-Old: The Newcastle 85+ Study.

(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from cross-sectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as <25 nmol/L (low), 25-50 nmol/L (moderate) and >50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0-110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = -59.9--7.5, B = -33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.

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.

The Association between 25-Hydroxyvitamin D Concentration and Disability Trajectories in Very Old Adults: The Newcastle 85+ Study.

Background: Low vitamin D status is common in very old adults which may have adverse consequences for muscle function, a major predictor of disability. Aims: To explore the association between 25-hydroxyvitamin D [25(OH)D] concentrations and disability trajectories in very old adults and to determine whether there is an 'adequate' 25(OH)D concentration which might protect against a faster disability trajectory. Methodology: A total of 775 participants from the Newcastle 85+ Study for who 25(OH)D concentration at baseline was available. Serum 25(OH)D concentrations of <25 nmol/L, 25-50 nmol/L and >50 nmol/L were used as cut-offs to define low, moderate and high vitamin D status, respectively. Disability was defined as difficulty in performing 17 activities of daily living, at baseline, after 18, 36 and 60 months. Results: A three-trajectory model was derived (low-to-mild, mild-to-moderate and moderate-to-severe). In partially adjusted models, participants with 25(OH)D concentrations <25 nmol/L were more likely to have moderate and severe disability trajectories, even after adjusting for sex, living in an institution, season, cognitive status, BMI and vitamin D supplement use. However, this association disappeared after further adjustment for physical activity. Conclusions: Vitamin D status does not appear to influence the trajectories of disability in very old adults.

Dietary Selenium Intakes and Musculoskeletal Function in Very Old Adults: Analysis of the Newcastle 85+ Study.

Background: Selenium is a trace element essential for health. Severe selenium deficiencies are associated with poor musculoskeletal (MSK) function. However, the effects of moderate deficiency on MSK function, especially in older adults, is unclear. Objectives: To determine the associations between selenium intake and MSK function in very old adults. Methods: Selenium intake at baseline and, hand-grip strength (HGS) and timed-up-and-go (TUG) at four phases over 5 years, were available in 791 participants in the Newcastle 85+ Study, a community-based, longitudinal cohort of ≥85 year old individuals. We investigated relationships between selenium intake and HGS and TUG in cross-sectional analyses at baseline using multivariate analyses and, prospectively using linear mixed models to explore HGS and TUG changes over 5 years in association with baseline selenium intake. Results: At baseline, 53% of participants had selenium intakes that were classified as low. These individuals had 2.80 kg lower HGS and were 2.30 s slower performing the TUG, cross-sectionally. In multivariate, baseline analyses, selenium intake had no significant impact on HGS or TUG. Selenium intake had no significant effect on MSK function, prospectively. Conclusion: Low selenium intake is common among very old adults and, in cross-sectional analyses, is associated with poorer MSK function.

Effects of dietary patterns and low protein intake on sarcopenia risk in the very old: The Newcastle 85+ study.

BACKGROUND: Sarcopenia, a progressive age-related loss of skeletal muscle mass and strength, leads to disability, falls, and hospitalisation. Individual variation in sarcopenia onset may be partly explained by lifestyle factors such as physical activity and diet. Healthy dietary patterns (DPs) have been linked to better physical functioning in older adults, but their role in sarcopenia in the very old (aged ≥85) is unknown. AIMS: To investigate the association between DPs and the risk of sarcopenia over 3 years, and to determine whether protein intake influences this relationship in community-dwelling older adults from the Newcastle 85 + Study. METHODS: The analytic sample consisted of 757 participants (61.2% women) who had dietary assessment at baseline. After two-step clustering with 30 food groups to derive DPs, we used logistic regression to determine the risk of prevalent and incident sarcopenia across DPs in all participants, and in those with low (<1 g/kg adjusted body weight/day [g/kg aBW/d]) and good protein intake (≥1 g/kg aBW/d). RESULTS: We identified three DPs (DP1: 'Low Red Meat', DP2: 'Traditional British' and DP3: 'Low Butter') that varied by unsaturated fat spreads/oils, butter, red meat, gravy and potato consumption. Compared with participants in DP3, those in DP2 had an increased risk of prevalent (OR = 2.42, 95% CI: 1.15-5.09, p = 0.02) but not 3-year incident sarcopenia (OR = 1.67, 0.59-4.67, p = 0.33) adjusted for socio-demographic, anthropometry, health and lifestyle factors. Furthermore, DP2 was associated with an increased risk of prevalent sarcopenia at baseline (OR = 2.14, 1.01-4.53, p = 0.05) and 3-year follow-up (OR = 5.45, 1.81-16.39, p = 0.003) after adjustment for key covariates in participants with good protein intake. CONCLUSION: A DP high in foods characteristic of a traditional British diet (butter, red meat, gravy and potato) was associated with an increased risk of sarcopenia even when overall protein intake was good. The results need to be replicated in other cohorts of the very old to understand the role of DPs in sarcopenia onset and management.

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.

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.

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.

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.

Protein Intake and Disability Trajectories in Very Old Adults: The Newcastle 85+ Study.

OBJECTIVES: To determine whether protein intake is associated with better disability trajectories in the oldest adults (≥85) and whether muscle mass and muscle strength would partially mediate this. DESIGN: Prospective cohort study. SETTING: Newcastle-upon-Tyne and North Tyneside, United Kingdom. PARTICIPANTS: Community-dwelling older adults aged 85 at baseline (N=722). METHODS: Protein intake was estimated using two 24-hour multiple-pass recalls at baseline. Disability was measured as difficulty performing 17 activities of daily living at baseline and 18, 36, and 60 months. Trajectories were derived using mortality-adjusted group-based trajectory modelling. The effect of protein intake (g/kg of adjusted body weight (aBW)/d) on disability trajectories was examined using multinomial logistic regression. RESULTS: Participants had 4 distinct disability trajectories (between the ages of 85 and 90: constant very low (AT1), mild (AT2), moderate (AT3), and severe (AT4). Each unit increase in protein (g) per kg of aBW/d was associated with greater odds of AT1 (odds ratio (OR=7.97, 95% confidence interval (CI)=1.96-32.43, p = .004) and AT2 (OR=3.28, 95% CI=1.09-9.87, p = .03) than of AT4 over 5 years in models adjusted for selected covariates. Participants with protein intake of 1.0 g/kg aBW/d or more were more likely to belong to AT1 (OR=3.65, 95% CI=1.59-8.38, p = .009) and AT2 (OR=2.12, 95% CI=1.16-3.90, p = .01) than to AT4. CONCLUSION: Higher protein intake, especially 1.0 g/kg aBW/d or more, was associated with better disability trajectories in the oldest adults. These findings will inform new dietary strategies to support active, healthy ageing. J Am Geriatr Soc 67:50-56, 2019.

Nutrition in the Very Old.

The population of older adults aged 85 years and over (the very old) is growing rapidly in many societies because of increases in life expectancy and reduced mortality at older ages. In 2016, 27.3 million very old adults were living in the European Union, and in the UK, 2.4% of the population (1.6 million) were aged 85 and over. Very old age is associated with increased risks of malnutrition, multimorbidity, and disability. Diet (nutrition) is a modifiable risk factor for multiple age-related conditions, including sarcopenia and functional decline. Dietary characteristics and nutrient intakes of the very old have been investigated in several European studies of ageing to better understand their nutritional requirements, which may differ from those in the young-old. However, there is a major gap in regard to evidence for the role of dietary patterns, protein, vitamin D and other nutrients for the maintenance of physical and cognitive functioning in later life. The Newcastle 85+ Study, UK and the Life and Living in Advanced Age, New Zealand are unique studies involving single birth cohorts which aim to assess health trajectories in very old adults and their biological, social and environmental influences, including nutrition. In this review, we have updated the latest findings in nutritional epidemiology with results from these studies, concentrating on the diet-physical functioning relationship.

Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study.

Background: Folate and vitamin B12 are keys to the correct functioning of one-carbon (1-C) metabolism. The current evidence on associations between 1-C metabolism biomarkers and mortality is inconclusive and generally based on younger or institutionalized populations. This study aimed to determine the associations between biomarkers of 1-C metabolism and all-cause and cardiovascular (CVD) mortality in the very old. Methods: The Newcastle 85+ Study is a prospective longitudinal study of participants aged 85 at recruitment living in Northeast England. Baseline red blood cell folate (RBC folate), plasma vitamin B12, and total homocysteine (tHcy) concentrations were available for 752-766 participants. Associations between biomarkers of 1-C metabolism and all-cause and CVD mortality for up to 9 years were assessed by Cox proportional hazard models and confirmed by restricted cubic splines. Results: Participants with higher tHcy concentrations had higher risk of death from any cause (hazard ratio [HR] [×10 µmol/L]: 1.24, 95% confidence interval [CI]: 1.10-1.41) and cardiovascular diseases (HR [×10 µmol/L]: 1.23, 95% CI: 1.04-1.45) than those with lower concentrations; and women with higher plasma vitamin B12 concentrations had increased risk of all-cause and cardiovascular mortality (HR [×100 pmol/L]: 1.10, 95% CI: 1.04-1.16) after adjustment for key sociodemographic, lifestyle, and health confounders. Conclusion: Higher concentrations of tHcy in all participants and plasma vitamin B12 in women were associated with increased risk of all-cause and CVD mortality in the very old. This confirms findings for tHcy in younger populations but the adverse relationships between elevated plasma vitamin B12 concentrations and mortality in this setting are novel and require further investigation.