Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function.

BACKGROUND: Aging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak. OBJECTIVES: Two independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2). METHODS: In Study 1, 40 young (20-49 y) and older (50-75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined. RESULTS: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 µmol·h-1·kg-1 compared with 0.39 ± 0.10 µmol·h-1·kg-1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = -0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = -0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = -0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = -0.31, P = 0.004). CONCLUSIONS: Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

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).

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.

Novel atypical Aeromonas salmonicida bath challenge model for juvenile ballan wrasse (Labrus bergylta, Ascanius).

Atypical Aeromonas salmonicida (aAs) is currently one of the most routinely recovered bacterial pathogens isolated during disease outbreaks in farmed cleaner fish, ballan wrasse (Labrus bergylta, Ascanius). Vibrionaceae family bacteria have also been isolated from ballan wrasse in Scotland. This study determined the infectivity, pathogenicity and virulence of aAs and Vibrionaceae isolates in juvenile farmed ballan wrasse (n = 50; approx. 2 g) using a bath challenge, and fish were monitored for a period of 16 days. Atypical As caused significant mortalities in contrast to Vibrionaceae isolates. Notably, differential virulence was observed between two aAs vapA type V strains at similar challenge doses. Diseased fish exhibited a systemic infection where aAs was detected in all analysed tissues (liver, spleen and kidney) by PCR and qPCR. Macroscopically, moribund and survivor fish exhibited hepatomegaly and splenomegaly. In moribund and surviving fish, histopathology showed granulomatous hepatitis with eosinophilic granular cells surrounding bacterial colonies and endocarditis along with splenic histiocytosis. This is the first report of a successful aAs bath challenge model for juvenile ballan wrasse which provides an important tool for future studies on vaccine efficacy and immunocompetence.

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.

What do we know about the nutritional status of the very old? Insights from three cohorts of advanced age from the UK and New Zealand.

Very old people (referred to as those aged 85 years and over) are the fastest growing age segment of many Western societies owing to the steady rise of life expectancy and decrease in later life mortality. In the UK, there are now more than 1·5 million very old people (2·5 % of total population) and the number is projected to rise to 3·3 million or 5 % over the next 20 years. Reduced mobility and independence, financial constraints, higher rates of hospitalisation, chronic diseases and disabilities, changes in body composition, taste perception, digestion and absorption of food all potentially influence either nutrient intake or needs at this stage of life. The nutritional needs of the very old have been identified as a research priority by the British Nutrition Foundation's Task Force report, Healthy Ageing: The Role of Nutrition and Lifestyle. However, very little is known about the dietary habits and nutritional status of the very old. The Newcastle 85+ study, a cohort of more than 1000 85-year olds from the North East of England and the Life and Living in Advanced Age study (New Zealand), a bicultural cohort study of advanced ageing of more than 900 participants from the Bay of Plenty and Rotorua regions of New Zealand are two unique cohort studies of ageing, which aim to assess the spectrum of health in the very old as well as examine the associations of health trajectories and outcomes with biological, clinical and social factors as each cohort ages. The nutrition domain included in both studies will help to fill the evidence gap by identifying eating patterns, and measures of nutritional status associated with better, or worse, health and wellbeing. This review will explore some of this ongoing work.

Vitamin D and bone health outcomes in older age.

The aim of this review is to summarise the evidence linking vitamin D to bone health outcomes in older adults. A plethora of scientific evidence globally suggests that large proportions of people have vitamin D deficiency and are not meeting recommended intakes. Older adults are at particular risk of the consequences of vitamin D deficiency owing to a combination of physiological and behavioural factors. Epidemiological studies show that low vitamin D status is associated with a variety of negative skeletal consequences in older adults including osteomalacia, reduced bone mineral density, impaired Ca absorption and secondary hyperparathyroidism. There seems to be inconsistent evidence for a protective role of vitamin D supplementation alone on bone mass. However, it is generally accepted that vitamin D (17·5 µg/d) in combination with Ca (1200 mg/d) reduces bone loss among older white subjects. Evidence for a benefit of vitamin D supplementation alone on reducing fracture risk is varied. According to a recent Agency for Healthcare Research and Quality review in the USA the evidence base shows mixed results for a beneficial effect of vitamin D on decreasing overall fracture risk. Limitations such as poor compliance with treatment, incomplete assessment of vitamin D status and large drop-out rates however, have been highlighted within some studies. In conclusion, it is generally accepted that vitamin D in combination with Ca reduces the risk of non-vertebral fractures particularly those in institutional care. The lack of data on vitamin D and bone health outcomes in certain population groups such as diverse racial groups warrants attention.

Low vitamin D status adversely affects bone health parameters in adolescents.

BACKGROUND: The effects of subclinical vitamin D deficiency on bone mineral density (BMD) and bone turnover in adolescents, especially in boys, are unclear. OBJECTIVE: We aimed to investigate the relations of different stages of vitamin D status and BMD and bone turnover in a representative sample of adolescent boys and girls. DESIGN: BMD was measured by dual-energy X-ray absorptiometry at the nondominant forearm and dominant heel in a random sample of 12- (n = 260) and 15-y-old (n = 239) boys and 12- (n = 266) and 15-y-old (n = 250) girls. Serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and type I collagen cross-linked C-telopeptide were assessed by using enzyme-linked immunoassays. Relations between vitamin D status and bone health indexes were assessed by using regression modeling. RESULTS: Using multivariate regression to adjust for potential physical, lifestyle, and dietary confounding factors, we observed that 12- and 15-y-old girls with high vitamin D status (>/=74.1 nmol/L) had significantly greater forearm (but not heel) BMD (beta = 0.018; SE = 0.008; P < 0.05 for each age group) and lower serum parathyroid hormone concentrations and bone turnover markers than did those with low vitamin D status. These associations were evident in subjects sampled throughout the year and in winter only. There was no significant relation between vitamin D status and BMD in boys. CONCLUSIONS: Maintaining serum 25-hydroxyvitamin D concentrations above approximately 50 nmol/L throughout the year may be a cost-effective means of improving bone health. Increased emphasis on exploring strategies for improving vitamin D status in adolescents is needed.

Vitamin D status of 51-75-year-old Irish women: its determinants and impact on biochemical indices of bone turnover.

OBJECTIVES: To assess the vitamin D status of Irish postmenopausal women during wintertime, and to examine its relationship with serum parathyroid hormone (PTH) and biochemical markers of bone turnover. In addition, the determinants of wintertime serum 25-hydroxyvitamin D (25OH-D) levels in these women were investigated. DESIGN: A cross-sectional observational study. SETTING: Cork City, Ireland (52 degrees N). SUBJECTS: Ninety-five apparently healthy, free-living postmenopausal women (aged 51-75 years), not taking any medication and free from any condition likely to affect vitamin D status or calcium/bone metabolism. RESULTS: Forty-eight per cent and 7% of women had serum 25OH-D levels <50 nmol l(-1) and <25 nmol l(-1), respectively. 25OH-D levels in these women were positively associated with dietary calcium intake (P = 0.0002) and use of vitamin D-containing supplements (P = 0.031), and negatively associated with cigarette smoking (P = 0.027) and body mass index (BMI) (P = 0.030). Low serum 25OH-D levels (<50 nmol l(-1)) were associated (P < 0.01) with elevated serum PTH levels. There were no significant differences in urinary pyridinium crosslinks or serum osteocalcin, biochemical indices of bone turnover, between subjects with serum 25OH-D levels above or below 50 nmol l(-1). CONCLUSION: A high proportion of Irish postmenopausal women had low vitamin D status (<50 nmol l(-1)) during late wintertime, which appeared to lead to elevated levels of serum PTH but not of bone turnover markers. Use of regular low-dose supplemental vitamin D, meeting daily calcium recommendations, cessation of smoking and maintaining BMI in the normal range are important factors that could help maintain adequate vitamin D levels during wintertime in these women.