Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Falsely elevated parathyroid hormone in a patient with osteoporosis: a case report and review.

BACKGROUND: Parathyroid hormone (PTH) measurements can be falsely elevated due to the hormone binding to other molecules (macro-PTH) or immunoassay interference with heterophile, human anti-animal or other antibodies. This is rare but could lead to incorrect diagnosis, unnecessary investigations or avoidance of teriparatide treatment. We report a case of falsely high PTH levels due to assay interference and review the literature on cases of spuriously elevated PTH. CASE REPORT: An 87-year-old woman attending our bone health clinic with osteoporosis had persistently elevated PTH (383-784 pg/ml) using the Roche Cobas e801 immunoassay despite having normal serum calcium, phosphate, 25 hydroxyvitamin D (> 50 nmol/l) and eGFR (> 60 ml/min). To rule out falsely elevated PTH, a polyethylene glycol precipitation (PEG) test was performed which recovered less than 10% of the hormone resulting in a normal level. PTH was also tested on a different assay (Atellica Siemens) that identified a result of 27 pg/ml. The findings were consistent with immunoassay interference likely due to heterophile antibodies giving rise to a spuriously high PTH. DISCUSSION: The presence of unexpectedly high PTH levels should alert physicians to the possibility of false results due to assay interference or macro-PTH. This highlights the importance of clinically correlating results and of good communication with the testing laboratory. Here, we present the case of an 87-year-old woman with spuriously elevated PTH levels due to immunoassay interference likely mediated by heterophile antibodies. The presence of unexpectedly high PTH levels should prompt consideration of the possibility of false results due to assay interference or macro-PTH.

Vitamin D: determinants of status, indications for testing and knowledge in a convenience sample of Irish adults.

Vitamin D deficiency is common in Irish adults, though there is limited research on its determinants, knowledge of vitamin D or indications for testing. We aimed to explore the determinants of vitamin D status in adults and examine knowledge and reasons for testing. The study population comprised adults who had serum 25-hydroxyvitamin D tested by general practitioners request at a Dublin Hospital in 2020. Questionnaires detailing dietary intake, sun exposure, ethnicity, biophysical factors and vitamin D knowledge were sent to a sample stratified by age, sex and vitamin D status. In total, there were 383 participants, mean age 56·0 (sd 16·6) years. Wintertime deficiency disproportionally affected non-white v. white (60 % v. 24 %, P < 0·001). The greatest predictors of deficiency were low vitamin D intake (< 10 µg/d) (P < 0·001) and non-white ethnicity (P = 0·006), followed by sun avoidance (P = 0·022). It was also more prevalent in those with lower body exposure when outdoors. The majority (86 %) identified vitamin D as important for bone health. However, 40 % were tested for non-clinical indications and half were not aware of the recommended daily allowance (RDA). Low vitamin D intake was the most important determinant of deficiency, but ethnicity and sun exposure habits were also significant predictors. The majority had no clear indication for testing and were not aware of the RDA. Public health policies to improve knowledge and vitamin D intake, especially for those of non-white ethnicity and with reduced sun exposure, should be considered.

Vitamin D intake and status in Ireland: a narrative review.

Vitamin D is crucial for musculoskeletal health, with evidence suggesting non-skeletal benefits. Cutaneous vitamin D synthesis is limited in Ireland due to its northern latitude (52-55°N) and the population is dependent on dietary sources, yet intakes are inadequate. No study to-date has comprehensively examined vitamin D intakes and status in Ireland (Northern Ireland and the Republic). We aimed to review the evidence since 2010 and summarise the results in subgroups of the Irish population. We found that in the largest studies prevalence of deficiency [25-hydroxyvitamin D (25(OH)D) < 30 nm/l] was 15-17% in pregnancy, 15-23% in children and 13% in adults. Approximately half the population had 25(OH)D < 50 nm/l. There were only four small studies in an ethnic population with the largest in Southeast Asians finding that 67% were deficient. All studies found higher rates of deficiency and levels <50 nm/l in winter v. summer. Vitamin D intake was lowest in children (mean 2⋅3-4⋅2 µg/d) and pregnant women (mean 1⋅9-5⋅1 µg/d) and highest in older adults (6⋅9 µg/d), with over 90% of the population not meeting the recommended daily allowance. This review indicates that low vitamin D status and dietary vitamin D intake are widespread with children, adolescents, younger adults, pregnant women and ethnic minorities most at-risk. However, data are sparse in at-risk groups including the Travelling community, non-Europeans and institutionalised adults. Given the significant prevalence of deficiency, public health policies to promote better awareness of recommended vitamin D intakes and explore the options of food fortification are needed to address this issue.

Vitamin D status & associations with inflammation in older adults.

Research studies have observed associations of vitamin D with inflammation but data in representative older adult studies is lacking. We aimed to investigate the association of C-reactive protein (CRP) with vitamin D status in a representative sample of the older Irish population. The concentrations of 25-hydroxyvitamin D (25(OH)D) and CRP was measured in 5,381 community dwelling Irish adults aged ≥50 years from the Irish Longitudinal Study on Ageing (TILDA). Demographic, health and lifestyle variables were assessed by questionnaire and categorical proportions of CRP were generated by vitamin D status and age. Multi-nominal logistic regression was used to investigate the association of 25(OH)D and CRP status. The prevalence (mean; 95% confidence interval (95% CI)) of normal CRP status (0-5 mg/dL) was 83.9% (82.6-85.0%), elevated status (5-10 mg/dL) 11.0% (9.9-12.0%) and high status (>10 mg/dL) was 5.1% (4.5-5.8%). Mean (95% CI) CRP concentrations were lower in those with normal vs. deficient 25(OH)D status (2.02 mg/dL (1.95-2.08) vs. 2.60 mg/dL (2.41-2.82); p<0.0001). In a logistic regression analysis, those with insufficient or sufficient 25(OH)D status were less likely to have a high CRP status compared to those with deficient 25(OH)D status (insufficient: coefficient (CE) -0.732, 95% CI -1.12-0.33, p<0.0001; sufficient: CE -0.599, 95% CI -0.95-0.24, p = 0.001). In conclusion older adults with deficient vitamin D status had higher levels of inflammation as measured by CRP. Given that inflammation is an important pathological driver of chronic diseases of ageing, and that emerging evidence suggests that vitamin D therapy can reduce inflammation in some disease settings, optimising vitamin D status could represent an effective low risk/low-cost pathway to modulate inflammation in community dwelling older adults.

On-campus mental health services for Australian university students: A retrospective analysis of service utilisation.

OBJECTIVE: To investigate on-campus mental health service utilisation by Australian university students. METHOD: Retrospective analysis of clinical data from two on-campus health services (general practice and psychology and counselling service). Descriptive statistics include total consults, demographic factors, diagnoses, presenting concerns and rates of suicidal ideation. RESULTS: Mental health conditions account for the largest proportion of ongoing illness in on-campus health service users, representing 46% of all ongoing health conditions. Depression and anxiety were the most common diagnoses, and stress, anxiety and low mood were the most common presenting concerns. Females utilise mental health services more frequently than males, accounting for 65.3% and 60.1% of patients for the respective services. International students present for specific mental health consults less frequently than domestic students. Rates of suicidal ideation at presentation were high (37%). CONCLUSIONS: This retrospective analysis provides important information regarding the proportion and distribution of mental health conditions and service utilisation amongst Australian university students. There is clear scope for increased access to specialist care, renewed efforts to decrease stigma and increase rates of presentation (particularly amongst international students and males), greater support for general practitioners and more rigorous routine data collection and reporting, both within and across universities nationally.

Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: a 4-year longitudinal study.

This was a longitudinal study utilising the Irish Longitudinal Study on Ageing (n 3849 aged ≥ 50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). A score ≥ 9 on the Center for Epidemiological Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. B12 status profiles (pmol/l) were defined as < 185, deficient low; 185 to < 258, low normal; > 258-601, normal and > 601 high. Folate status profiles (nmol/l) were defined as ≤ 10·0, deficient low; > 10-23·0, low normal; > 23·0-45·0, normal; >45·0, high. Logistic regression models were used to analyse the longitudinal associations. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms v. non-depressed (folate: 21·4 v. 25·1 nmol/l; P = 0·0003; B12:315·7 v. 335·9 pmol/l; P = 0·0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression 4 years later (OR 1·51, 95 % CI 1·01, 2·27, P = 0·043). This finding remained robust after controlling for relevant covariates. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51 % increased likelihood of developing depressive symptoms over 4 years. The findings highlight the need to further explore the low-cost benefits of optimising vitamin B12 status for depression in older adults.

Association between vitamin D deficiency and the risk of prevalent type 2 diabetes and incident prediabetes: A prospective cohort study using data from The Irish Longitudinal Study on Ageing (TILDA).

Background: It is hypothesized that vitamin D contributes to the aetiology of type 2 diabetes mellitus (diabetes). This study's objective was to examine the relationships between baseline vitamin D status (as measured by plasma 25-hydroxyvitamin D concentration) and both prevalent diabetes and prospective risk of developing diabetes, including prediabetes, in a population with historically low levels of vitamin D. Methods: In this prospective cohort study, data from The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort of adults aged ≥50 years residing in Ireland were analysed, including wave 1 (October 2009-June 2011) (n = 5272) and wave 3 (March 2014-October 2015) (n = 3828). Those aged <50 years at baseline or who did not complete the health assessment were excluded. Logistic regression models examined the associations between baseline vitamin D concentration (nmol/L) with prevalent diabetes status and incident diabetes/prediabetes collected at a 4-year follow-up. Models were adjusted for age, sex, education, body mass index, smoking history, physical activity, use of statins, and the season in which the vitamin D concentration was sampled. Findings: Deficient baseline vitamin D concentration was cross-sectionally associated with an increased likelihood of having prevalent diabetes (Relative Risk Ratio [RRR] 1·5, 95% CI: 1·03, 2·18; p = 0·037). In longitudinal analyses evaluating diabetes status 4 years later, there was a 62% increased likelihood (RRR: 1·62, 95% CI: 1·12, 2·35; p = 0·011) of developing prediabetes for those with vitamin D <30 nmol/L compared to those with ≥75 nmol/L. The rate of progression from prediabetes to diabetes between wave 1 and 3 was observed to be 32·5%. Interpretation: Those with lower concentrations of vitamin D, as measured by 25-hydroxyvitamin D, may have different risk profiles with regards to their glycaemic status. Our study had limited power due to the low incidence of diabetes but showed strong associations with incident prediabetes, so further research is required. Optimising vitamin D status at a population level may significantly reduce diabetes. Funding: TILDA is funded by Atlantic Philanthropies, the Irish Department of Health, and Irish Life, while additional funding was provided by the Irish Department of Agriculture, Food and the Marine (13F492) to cover the cost of 25-hydroxyvitamin D analysis.

Low socioeconomic status predicts vitamin D status in a cross-section of Irish children.

Vitamin D is essential for bone and muscle health with adequate status in childhood crucial for normal skeletal development. We aimed to investigate vitamin D status in a convenience sample (n = 1226) of Irish children (aged 1-17 years) who had serum 25-hydroxyvitamin D (25(OH)D) tested by request of their GP at a Dublin Hospital between 2014 and 2020. We examined predictors including age, sex, season and socioeconomic status (SES). Vitamin D deficiency (<30 nmol/l) was prevalent affecting 23 % and was more common in disadvantaged areas (34 %) and in those aged >12 v. ≤12 years (24 % v. 16 %, P = 0⋅033). The greatest predictor was SES (disadvantaged v. affluent, OR 2⋅18, CI 1⋅34, 3⋅53, P = 0⋅002), followed by female sex (OR 1⋅57, CI 1⋅15, 2⋅14, P = 0⋅005) and winter season (October to February, OR 1⋅40, CI 1⋅07, 1⋅84, P = 0⋅015). A quarter of our sample of children were deficient, rising to one-third in those in disadvantaged areas. Females and those aged over 12 years had a higher prevalence of deficiency. Public health strategies to improve vitamin D status in Irish children, including systematic food fortification may need to be considered to address this issue.

Title: Understanding a Low Vitamin D State in the Context of COVID-19.

While a low vitamin D state has been associated with an increased risk of infection by SARS-CoV-2 in addition to an increased severity of COVID-19 disease, a causal role is not yet established. Here, we review the evidence relating to i) vitamin D and its role in SARS-CoV-2 infection and COVID-19 disease ii) the vitamin D status in the Irish adult population iii) the use of supplemental vitamin D to treat a deficient status and iv) the application of the Bradford-Hill causation criteria. We conclude that reverse causality probably makes a minimal contribution to the presence of low vitamin D states in the setting of COVID-19. Applying the Bradford-Hill criteria, however, the collective literature supports a causal association between low vitamin D status, SARS-CoV-2 infection, and severe COVID-19 (respiratory failure, requirement for ventilation and mortality). A biologically plausible rationale exists for these findings, given vitamin D's role in immune regulation. The thresholds which define low, deficient, and replete vitamin D states vary according to the disease studied, underscoring the complexities for determining the goals for supplementation. All are currently unknown in the setting of COVID-19. The design of vitamin D randomised controlled trials is notoriously problematic and these trials commonly fail for a number of behavioural and methodological reasons. In Ireland, as in most other countries, low vitamin D status is common in older adults, adults in institutions, and with obesity, dark skin, low UVB exposure, diabetes and low socio-economic status. Physiological vitamin D levels for optimal immune function are considerably higher than those that can be achieved from food and sunlight exposure alone in Ireland. A window exists in which a significant number of adults could benefit from vitamin D supplementation, not least because of recent data demonstrating an association between vitamin D status and COVID-19. During the COVID pandemic, we believe that supplementation with 20-25ug (800-1000 IU)/day or more may be required for adults with apparently normal immune systems to improve immunity against SARS-CoV-2. We expect that higher monitored doses of 37.5-50 ug (1,500-2,000)/day may be needed for vulnerable groups (e.g., those with obesity, darker skin, diabetes mellitus and older adults). Such doses are within the safe daily intakes cited by international advisory agencies.

Vitamin D retesting by general practitioners: a factor and cost analysis.

OBJECTIVES: Vitamin D testing by Primary Care doctors is increasing, placing greater workloads on healthcare systems. There is little data though on vitamin D retesting in Ireland. This study aims to investigate the factors associated with vitamin D retesting by Irish General Practitioners (GPs) and examine the resulting costs. METHODS: This is a retrospective analysis over 5 years (2014-2018) of GP requested 25-hydroxyvitamin D (25(OH)D) results in 36,458 patients at a major city hospital in Dublin, Ireland. Those with one test were compared with individuals who were retested and samples categorised to determine changes in status between tests. RESULTS: Nearly one in four patients (n=8,305) were retested. Positive predictors of retesting were female (p<0.001), age (60-69 years, p<0.001), location (Co. Kildare, p<0.001) and initial deficiency (<30 nmol/L, p<0.001) or insufficiency (30-49.9 nmol/L, p<0.001). Vitamin D status improved on retesting, with deficiency halving on first retest (9 vs. 18%, p<0.001) and dropping to 6% on further retests. About 12.2% of retests were done within 3 months and 29% had ≥2 retests within 1 year. 57% of retests were in those initially vitamin D replete (>50 nmol/L). The annual cost of inappropriate testing was €61,976. CONCLUSIONS: One in four patients were retested and this varied by age, gender and patient location. Over 10% of retests were inappropriately early (<3 months), a third too frequent and over half were in replete individuals incurring significant costs. Clear guidance for GPs on minimum retesting intervals is needed, as well as laboratory ordering systems to limit requests using pre-defined criteria.

Maternal obesity and baseline vitamin D insufficiency alter the response to vitamin D supplementation: a double-blind, randomized trial in pregnant women.

BACKGROUND: The achievement of target 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy may be altered by maternal obesity. OBJECTIVE: The authors examined the effects of maternal supplementation of 10 µg compared with 20 µg vitamin D3/d on maternal and umbilical cord 25(OH)D. The secondary aim was to investigate the influence of maternal BMI (in kg/m2) on the response of the primary outcomes. METHODS: The authors performed a 2-arm parallel double-blind randomized trial with 240 pregnant women recruited throughout the year in Northern Ireland. Women were stratified by BMI to receive 10 or 20 µg vitamin D3/d from 12 gestational wk (GW) until delivery. Maternal blood samples collected at 12, 28, and 36 GW and from the umbilical cord were analyzed for total serum 25(OH)D. A total of 166 women completed the study. RESULTS: Mean ± SD 25(OH)D at 36 GW was 80.8 ± 28.2 compared with 94.4 ± 33.2 nmol/L (P < 0.001) (10 compared with 20 µg vitamin D3/d, respectively). In those classified with 25(OH)D <50 nmol/L at baseline and assigned 10 µg vitamin D3/d, mean 25(OH)D concentrations remained <50 nmol/L at 36 GW, whereas those <50 nmol/L at baseline and assigned 20 µg vitamin D3/d, had mean 25(OH)D concentrations ≥50 nmol/L at 28 and 36 GW. In women with obesity and 25(OH)D <50 nmol/L at baseline, the related mean umbilical cord 25(OH)D was deficient (<25 nmol/L) in both treatment groups, whereas those with obesity and 25(OH)D ≥50 nmol/L at baseline had an average umbilical cord 25(OH)D between 25 and 50 nmol/L in both treatment groups. CONCLUSIONS: Supplementation of 20 µg vitamin D3/d is needed to attain maternal and umbilical cord 25(OH)D concentrations ≥50 nmol/L on average, in those who start pregnancy with low 25(OH)D concentrations (<50 nmol/L). Under current recommendations, women with obesity and low 25(OH)D in early pregnancy are particularly vulnerable to maintaining a low 25(OH)D concentration throughout pregnancy and having an infant born with deficient 25(OH)D concentrations. This trial was registered at ClinicalTrials.gov as NCT02713009.

Vitamin D and Hospital Admission in Older Adults: A Prospective Association.

The health effects of vitamin D are well documented, with increasing evidence of its roles beyond bone. There is, however, little evidence of the effects of vitamin D on hospitalisation among older adults. This study aimed to prospectively determine the relationship of vitamin D status in older adults with hospital admission and emergency department (ED) attendance. Trinity University of Ulster Department of Agriculture (TUDA) is a large cross-sectional study of older adults with a community population from three disease-defined cohorts (cognitive dysfunction, hypertension, and osteoporosis). Participants included in this analysis were recruited between 2008 and 2012. ED and hospital admission data were gathered from the date of TUDA participation until June 2013, with a mean follow up of 3.6 years. Of the 3093 participants, 1577 (50.9%) attended the ED during the period of follow-up. Attendees had lower mean serum 25(OH)D concentrations than non-attendees (59.1 vs. 70.6 nmol/L). Fully adjusted models showed an inverse association between vitamin D and ED attendance (Hazard Ratio (HR) 0.996; 95% Confidence Interval (CI) 0.995-0.998; p < 0.001). A total of 1269 participants (41%) were admitted to hospital during the follow-up. Those admitted had lower mean vitamin D concentrations (58.4 vs. 69.3 nmol/L, p < 0.001). In fully adjusted models, higher vitamin D was inversely associated with hospital admission (HR 0.996; 95% CI 0.994-0.998; p < 0.001) and length of stay (LOS) (ß = -0.95, p = 0.006). This study showed independent prospective associations between vitamin D deficiency and increased hospitalisation by older adults. The need for further evaluation of current recommendations in relation to vitamin D supplementation, with consideration beyond bone health, is warranted and should focus on randomised controlled trials.

A High Prevalence of Vitamin D Deficiency Observed in an Irish South East Asian Population: A Cross-Sectional Observation Study.

At northern latitudes, non-ethnic population groups can be at an increased risk of vitamin D deficiency (defined as a 25-hydroxyvitamin D [25(OH)D] status ≤30 nmol/L). The vitamin D status of ethnic minority groups has been examined both in UK and European populations, but not in the Irish context. The aim of this study is to assess the vitamin D status from a selection of the Dublin population of South East Asian descent. A search was conducted, using the laboratory information system of St James's Hospital, Dublin, for vitamin D requests by General practitioners. From 2013 to 2016, 186 participants were identified and 25(OH)D analysis was quantified using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Overall, the median age was 32 years, 51% were male, and the 25(OH)D concentration ranged from 10 to 154 nmol/L. In total, 66.7% of the total sample were vitamin D deficient and 6.7% had a 25(OH)D status greater than 50 nmol/L (the 25(OH)D concentration defined by the EU as 'sufficient'). Females had a significantly higher 25(OH)D concentration than males (25.0 vs. 18.0 nmol/L; p = 0.001) but both groups had a significant proportion with deficient status (56% and 76.8%, respectively). Seasonal variation of 25(OH)D was not evident while high rates of deficiency were also observed in those aged <18 years and >50 years. Given the importance of vitamin D for health, this sub-population could be at a significantly increased risk of rickets, impaired bone metabolism, and osteoporosis. In addition, vitamin D deficiency has been associated with several non-bone related conditions, including cardiovascular disease and diabetes. Currently, there is no unique vitamin D intake or vitamin D status maintenance guidelines recommended for adults of non-Irish descent; this needs to be considered by the relevant public health bodies in Ireland.

Geomapping Vitamin D Status in a Large City and Surrounding Population-Exploring the Impact of Location and Demographics.

Vitamin D status was assessed in a large urban area to compare differences in deficiency and to geomap the results. In total, 36,466 participants from 28 geographical areas were identified in this cross-sectional, retrospective analysis of general practitioner (GP)-requested 25(OH)D tests at St James's Hospital, Dublin between 2014 and 2018. The population were community-dwelling adults, median age 50.7 (18-109 years) with 15% of participants deficient (<30 nmol/L), rising to 23% in the winter. Deficiency was greatest in younger (18-39 years) and oldest (80+ years) adults, and in males versus females (18% vs. 11%, p < 0.001). Season was the biggest predictor of deficiency (OR 4.44, winter versus summer, p < 0.001), followed by location (west Dublin OR 2.17, north Dublin 1.54, south Dublin 1.42 versus rest of Ireland, p < 0.001) where several urban areas with an increased prevalence of deficiency were identified. There was no improvement in 25(OH)D over the 5-year period despite increased levels of testing. One in four adults were vitamin D deficient in the winter, with significant variations across locations and demographics. Overall this study identifies key groups at risk of 25(OH)D deficiency and insufficiency, thus providing important public health information for the targeting of interventions to optimise 25(OH)D. Mandatory fortification may be necessary to address this widespread inadequacy.

Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing.

OBJECTIVES: To examine the associations between 3 frailty instruments and circulating micronutrients in a large representative sample of older adults. DESIGN: Cross-sectional data from a nationally representative cohort study conducted between October 2009 and July 2011. PARTICIPANTS AND SETTING: Adults age ≥50 years (n = 4068) living in the community in Ireland. MEASUREMENTS: Circulating micronutrients (lutein, zeaxanthin, folate, vitamin B-12, and vitamin D) were measured, transformed, and standardized. Frailty was assessed using the Frailty Phenotype, the Frailty Index, and the FRAIL Scale (fatigue, resistance, ambulation, illnesses, and loss of weight), instruments. Multinomial logistic regression determined associations between micronutrients and prefrailty or frailty. Models were adjusted for sociodemographic, lifestyle, health, and seasonal factors. RESULTS: Adjusting for age, sex, and educational attainment, all 3 measures of frailty were associated with lower levels of lutein [relative risk ratios (RRRs): 0.43‒0.63], zeaxanthin (RRRs: 0.49‒0.63), and vitamin D (RRRs: 0.51‒0.75), and with the accumulation of micronutrient insufficiencies (RRRs: 1.42‒1.90). Attenuated but significant associations were also observed with all measures of prefrailty for lutein, vitamin D, and number of micronutrient insufficiencies. The associations with frailty persisted following additional adjustment for social, lifestyle, and health and seasonal factors, and following multiple test correction. CONCLUSIONS AND IMPLICATIONS: We have presented the most consistent evidence in the largest study to date that micronutrient concentrations are associated with prefrailty and frailty in older adults. Our data suggest that low micronutrient status has potential as an easily modifiable marker and intervention target for frailty and supports further investigation into micronutrient supplementation and fortification to prevent frailty and disability among older adults.

Vitamin D Deficiency Is Associated With Impaired Muscle Strength And Physical Performance In Community-Dwelling Older Adults: Findings From The English Longitudinal Study Of Ageing.

PURPOSE: Maintaining skeletal muscle function throughout life is a crucial component of successful ageing. Adequate vitamin D status may be important in preserving muscle function. We aimed to determine the association between impaired muscle function and serum vitamin D status in community-dwelling older adults. Falls were explored as a secondary aim. METHODS: Data were analyzed from adults aged ≥60 years, from Wave 6 of the English Longitudinal Study of Aging (ELSA). Handgrip strength (HGS) and the short physical performance battery (SPPB) were employed as measures of muscle strength and physical function, respectively. Serum 25-hydroxyvitamin D [25(OH)D] was assessed with concentration <30 nmol/L classed as vitamin D deficient. RESULTS: The study comprised 4157 community-dwelling adults with a mean age of 69.8 (SD 6.9). Overall, 30.6% had low HGS and 12.7% had low SPPB (≤6). Participants with the lowest serum 25(OH)D (<30 nmol/L) had the highest prevalence of impaired muscle strength and performance (40.4% and 25.2%) compared with participants with levels ≥50 nmol/L (21.6% and 7.9%). Consistent with this, vitamin D deficiency (<30 nmol/L) was a significant determinant of low HGS (OR 1.44 [1.22, 1.71], p<0.001) and poor physical performance (OR 1.65 [1.31, 2.09], p<0.001) in the logistic regression models. Older adults partaking in regular moderate physical activity had significantly lower odds of impaired muscle strength (OR 0.65 [0.58, 0.79]) and physical function (OR 0.30 [0.24, 0.38]), p <0.001, respectively. Single or multiple falls (15.8% and 10.5% in past year) were not associated with vitamin D status. CONCLUSION: Vitamin D deficiency was associated with impaired muscle strength and performance in a large study of community-dwelling older people. It is generally accepted that vitamin D deficiency at the <30 nmol/L cut-off should be reversed to prevent bone disease, a strategy that may also protect skeletal muscle function in ageing.

Vitamin D Status Is Not Associated With Orthostatic Hypotension in Older Adults.

There has been much interest in investigating vitamin D status with orthostatic hypotension. However, studies have been small, inconsistent, and with a lack of standardization. The aim of this study was to investigate the association with vitamin D status in a large, nationally representative older adult population using a traceable standard of measurement and an accurate assessment of beat-to-beat blood pressure (BP). This study used participants aged >50 years from The Irish Longitudinal Study on Ageing. Impaired stabilization of BP on standing was defined as a sustained drop of ≥20 mm Hg systolic BP or ≥10 mm Hg diastolic BP up to 40 seconds post stand (impaired stabilization of BP on standing). We also analyzed participants who sustained a drop of ≥20 mm Hg systolic BP or ≥10 mm Hg diastolic BP throughout the 110 seconds stand (OH110). Vitamin D was categorized into sufficient (≥50 nmol/L), insufficient (30-50 nmol/L), and deficient (<30 nmol/L) status. After exclusion criteria 4209 participants were included. Those with deficiency were more likely to be smokers, take antihypertensive medications and had higher levels of cardiovascular disorders compared with those with sufficient status. In a univariate logistic regression those with deficient (odds ratio, 1.18; 95% CI, 0.86-1.61; P=0.303) or insufficient (odds ratio, 1.13; 95% CI, 0.91; P=0.272) status were no more likely to have evidence of impaired stabilization of BP on standing on active stand compared with sufficiency. Similar findings were found for OH110: deficient (odds ratio, 0.85; 95% CI, 0.52-1.40; P=0.528) or insufficient (odds ratio, 0.86; 95% CI, 0.61-1.21; P=0.384) versus sufficiency. In conclusion, vitamin D is not significantly associated with orthostatic hypotension in older adults.

The Prevalence and Determinants of Vitamin D Status in Community-Dwelling Older Adults: Results from the English Longitudinal Study of Ageing (ELSA).

Vitamin D deficiency is often associated with adverse health outcomes in older adults. The circulating 25-hydroxyvitamin D (25(OH)D) status predominately relies on UV exposure. However, the extent of which northerly latitude exasperates deficiency is less explored in ageing. We aimed to investigate vitamin D deficiency in community-dwelling, older adults, residing at latitudes 50-55° north. This study was comprised of 6004 adults, aged >50 years from wave 6 (2012-2013) of the English Longitudinal Study of Ageing (ELSA). Deficiency was categorised by two criteria: Institute of Medicine (IOM) (<30 nmol/L) and Endocrine Society (ES) (<50 nmol/L). The overall prevalence of Institute of Medicine (IOM) and Endocrine Society (ES) definitions of deficiency were 26.4% and 58.7%, respectively. Females (odds ratio (OR) 1.23; CI: 1.04-1.44), those aged 80+ (OR: 1.42; CI: 1.01-1.93), smoking (OR: 1.88; CI: 1.51-2.34); of non-white ethnicity (OR: 3.8; CI:2.39-6.05); being obese (OR: 1.32; CI:1.09-1.58), and of poor self-reported health (OR:1.99; CI:1.33, 2.96), were more likely to be vitamin D deficient (by IOM). Residents in the south of England had a reduced risk of deficiency (OR: 0.78; CI:0.64-0.95), even after adjustment for socioeconomic and traditional predictors (obesity, age, lifestyle, etc.) of vitamin D status. Other factors, such as being retired, having a normal BMI, engaging in regular vigorous physical activity, vitamin D supplement use, sun travel, and summer season were also significantly positive correlates of deficiency. Similar results were observed for the ES cut-off definition. Importantly, more than half of adults aged >50 years had 25(OH)D concentrations <50 nmol/L. These findings demonstrate that low vitamin D status is highly prevalent in older English adults and the crucial importance of public health strategies throughout midlife and older age to achieve optimal vitamin D status.