Andrea Darling

Dr Andrea Darling


My publications

Publications

REBECCA MICHALA VEARING, KATHRYN HAYLEY HART, Karen Charlton, Yasmine Probst, DAVID J BLACKBOURN, KOUROSH RASEKH AHMADI, SUSAN ALEXANDRA LANHAM-NEW, Andrea L. Darling (2021)Vitamin D Status of the British African-Caribbean Residents: Analysis of the UK Biobank Cohort, In: Nutrients13(11)4104 MDPI

The vitamin D status of the United Kingdom (UK) African-Caribbean (AC) population remains under-researched, despite an increased risk of vitamin D deficiency due to darker skin phenotypes and living at a high latitude. This cross-sectional study explored the vitamin D status and intake of AC individuals (n = 4046 with a valid serum 25(OH)D measurement) from the UK Biobank Cohort, aged ≥40 years at baseline (2006–2010). Over one third of the population were deficient (50 nmol/L). Median (IQR) 25(OH)D was 30.0 (20.9) nmol/L. Logistic regression showed that brown/black skin phenotype, winter blood draw, not consuming oily fish and not using vitamin D supplements predicted increased odds of vitamin D deficiency, whilst older age and a summer or autumn blood draw were significantly associated with reduced odds of vitamin D deficiency. Vitamin D deficiency and insufficiency were prevalent in this AC population and is of considerable concern given the individual and societal implications of increased morbidity. Public health messaging for this group should focus on year-round vitamin D supplementation and increasing intakes of culturally appropriate vitamin D-rich foods. These data also support the urgent requirement for a revised vitamin D RNI for ethnic groups.

Owen Cronin, Susan A. Lanham-New, Bernard M. Corfe, Celia L. Gregson, Andrea L. Darling, Kourosh R. Ahmadi, Philippa S. Gibson, Jon H. Tobias, Kate A. Ward, Maria H. Traka, Megan Rossi, Claire Williams, Nicholas C. Harvey, Cyrus Cooper, Kevin Whelan, Andre G. Uitterlinden, Paul W. O’Toole, Claes Ohlsson, Juliet E. Compston, Stuart H. Ralston (2021)Role of the microbiome in regulating bone metabolism and susceptibility to osteoporosis, In: Calcified Tissue International Springer

The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health; thus it is aligned closely with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. In this paper we summarize the presented content, discussion and conclusions at a recent workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. Here, we provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.

Marcela M. Mendes, Andrea L. Darling, Kathryn H. Hart, Stephen Morse, Richard Murphy, Susan A. Lanham-New (2019)Impact of high latitude, urban living and ethnicity on 25-hydroxyvitamin D status: A need for multidisciplinary action?, In: The Journal of Steroid Biochemistry and Molecular Biology188pp. pp 95-102 Elsevier

The effects of urban living on health are becoming increasingly important, due to an increasing global population residing in urban areas. Concomitantly, due to immigration, there is a growing number of ethnic minority individuals (African, Asian or Middle Eastern descent) living in westernised Higher Latitude Countries (HLC) (e.g. Europe, Canada, New Zealand). Of concern is the fact that there is already a clear vitamin D deficiency epidemic in HLC, a problem which is likely to grow as the ethnic minority population in these countries increases. This is because 25-hydroxyvitamin D (25(OH)D) status of ethnic groups is significantly lower compared to native populations. Environmental factors contribute to a high prevalence of vitamin D deficiency in HLC, particularly during the winter months when there is no sunlight of appropriate wavelength for vitamin D synthesis via the skin. Also, climatic factors such as cloud cover may reduce vitamin D status even in the summer. This may be further worsened by factors related to urban living, including air pollution, which reduces UVB exposure to the skin, and less occupational sun exposure (may vary by individual HLC). Tall building height may reduce sun exposure by making areas more shaded. In addition, there are ethnicity-specific factors which further worsen vitamin D status in HLC urban dwellers, such as low dietary intake of vitamin D from foods, lower production of vitamin D in the skin due to increased melanin and reduced skin exposure to UVB due to cultural dress style and sun avoidance. A multidisciplinary approach applying knowledge from engineering, skin photobiology, nutrition, town planning and social science is required to prevent vitamin D deficiency in urban areas. Such an approach could include reduction of air pollution, modification of sun exposure advice to emphasise spending time each day in non-shaded urban areas (e.g. parks, away from tall buildings), and advice to ethnic minority groups to increase sun exposure, take vitamin D supplements and/or increase consumption of vitamin D rich foods in a way that is safe and culturally acceptable. This review hopes to stimulate further research to assess the impact of high latitude, urban environment and ethnicity on the risk of vitamin D deficiency.

AL Darling, OA Hakim, K Horton, MA Gibbs, L Cui, JL Berry, SA Lanham-New, KH Hart (2013)Adaptations in tibial cortical thickness and total volumetric bone density in postmenopausal South Asian women with small bone size., In: Bone55(1)pp. 36-43

There is some evidence that South Asian women may have an increased risk of osteoporosis compared with Caucasian women, although whether South Asians are at increased risk of fracture is not clear. It is unknown whether older South Asian women differ from Caucasian women in bone geometry. This is the first study, to the authors' knowledge, to use peripheral Quantitative Computed Tomography (pQCT) to measure radial and tibial bone geometry in postmenopausal South Asian women. In comparison to Caucasian women, Asian women had smaller bone size at the 4% (-18% p

KATHRYN HAYLEY HART, REBECCA MICHALA VEARING, ANDREA L DARLING, Yasmine Probst, Aminat S Olayinka, JEEWAKA MENDIS, Helena Ribeiro, Siddhartha Thakur, MARCELA MORAES MENDES, Karen Charlton, SUSAN ALEXANDRA LANHAM-NEW (2021)Global Perspective of the Vitamin D Status of African-Caribbean Populations: A Systematic Review and Meta-analysis, In: European Journal of Clinical Nutrition Springer Nature

Objectives: Vitamin D deficiency remains a global public health issue, particularly in minority ethnic groups. This review investigates the vitamin D status (as measured by 25(OH)D and dietary intake) of the African-Caribbean population globally. Methods: A systematic review was conducted by searching key databases (PUBMED, Web of Science, Scopus) from inception until October 2019. Search terms included ‘Vitamin D status’ and ‘African-Caribbean’. A random effects and fixed effects meta-analysis was performed by combining means and standard error of the mean. Results: The search yielded 19 papers that included n=5,670 African-Caribbean participants from six countries. A meta-analysis found this population to have sufficient (>50 nmol/L) 25(OH)D levels at 67.8 nmol/L, 95% CI (57.9, 7.6) but poor dietary intake of vitamin D at only 3.0µg/day, 95% CI (1.67,4.31). For those living at low latitudes ‘insufficient’ (as defined by study authors) 25(OH)D levels were found only in participants with type 2 diabetes and in those undergoing haemodialysis. Suboptimal dietary vitamin D intake (according to the UK recommended nutrient intake of 10µg/day) was reported in all studies at high latitudes. Studies at lower latitudes, with lower recommended dietary intakes (Caribbean recommended dietary intake: 2.5µg/day) found ’sufficient’ intake in two out of three studies. Conclusions: 25(OH)D sufficiency was found in African-Caribbean populations at lower latitudes. However, at higher latitudes, 25(OH)D deficiency and low dietary vitamin D intake was prevalent. Trial registration: PROSPERO registration number: CRD42019158108.

J Wadsworth, AL Darling, M Shearer, MA Gibbs, J Adamson, D Torgerson, SA Lanham-New (2015)Vitamin K and Bone Health: An Updated Systematic Review and Meta-analysis, In: OSTEOPOROSIS INTERNATIONAL22 S1

Previous research suggests vitamin K may increase bone mass, prevent loss of bone mineral density (BMD), and possibly reduce fracture incidence. The purpose of this study was to update the systematic review and meta-analysis of the effect of both vitamin K1 and vitamin K2 (menaquinone-4 and menaquinone-7) on bone turnover, BMD and fracture risk that we published in 2007 in the light of key vitamin K supplementation studies completed in the last 30 months. The Cochrane Library (1994-2009) and EMBASE (1980-2009) databases were searched for relevant cross sectional, longitudinal and intervention studies. Thirty three studies were included in the systematic review and seven in the meta-analysis. Results from the systematic review for vitamin K1 suggested a significant negative correlation with undercarboxylated osteocalcin (ucOC), but mixed results for total OC, bone resorption markers and fracture, and no association with BMD. The meta analysis supported these results, showing a significant effect of vitamin K1 supplementation on reducing ucOC (p,0.00001, Z=15.59, weighted mean difference=-21.23 95% CI (-23.90 to-18.57)), but no significant effect on BMD at any site (P=0.78, Z=0.28, weighted mean difference=0.00, 95%CI (0.00 to 0.01)). There was insufficient data to analyse fracture incidence, bone resorption or OC in the K1 metaanalysis. Results from the systematic review of K2 studies showed a significant negative association of K2 on ucOC in intervention studies. The intervention studies, but not cross-sectional studies, independently associated vitamin K2 with fracture risk. No effect of vitamin K2 supplementation on bone resorption was found for any study type, but the intervention studies were associated with increased BMD. This was supported by results from the vitamin K2 meta-analysis for a reduction in ucOC (p,0.00001, Z=8.75, weighted mean difference=95% CI (-68.54 to-43.45)) and increased BMD from combined sites (p=0.004, Z=3.86, weighted mean difference= 95% CI (1.24-6.48)). These findings suggest vitamin K; especially K2, may be beneficial for bone health, as ucOC is an independent risk factor for osteoporotic fracture. In this analysis, K2, but not K1 supplementation, was associated with increased BMD. However, overall the results from the studies were too conflicting to recommend routine supplementation. Further, higher quality and more homogenous studies are needed before any clear conclusions can be made about vitamin K and bone health.

SA Lanham-New, JL Buttriss, LM Miles, M Ashwell, JL Berry, BJ Boucher, KD Cashman, C Cooper, AL Darling, RM Francis, WD Fraser, CPGM de Groot, E Hyppönen, K Kiely, C Lamberg-Allardt, HM Macdonald, AR Martineau, T Masud, A Mavroeidi, C Nowson, A Prentice, EM Stone, S Reddy, R Vieth, CM Williams (2011)Proceedings of the Rank Forum on Vitamin D, In: British Journal of Nutrition105(1)pp. 144-156 Cambridge University Press

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

H Lambert, V Boyd, A Darling, D Torgerson, P Burckhardt, L Frassetto, S Lanham-New (2011)Dietary potassium and bone health: A systematic review and meta-analysis, In: BONE48pp. S191-S191
Sonal R. Hattangdi-Haridas, Susan A. Lanham-New, Wilfred Hing Sang Wong, Marco Hok Kung Ho, Andrea L. Darling (2019)Vitamin D deficiency and effects of vitamin D supplementation on disease severity in patients with Atopic Dermatitis: a systematic review and meta-analysis in adults and children, In: Nutrients11(8)1854pp. 1-19 MDPI

Research has investigated 25-hydroxyvitamin D (25(OH)D) levels in the Atopic Dermatitis (AD) population, as well as changes in AD severity after vitamin D (VitD) supplementation. We performed an up-to-date systematic review and meta-analysis of these findings. Electronic searches of MEDLINE, EMBASE and COCHRANE up to February 2018 were performed. Observational studies comparing 25(OH)D between AD patients and controls, as well as trials documenting baseline serum 25(OH)D levels and clinical severity by either SCORAD/EASI scores, were included. Of 1085 articles retrieved, sixteen were included. A meta-analysis of eleven studies of AD patients vs. healthy controls (HC) found a mean difference of -14 nmol/L (95%CI -25 to -2) for all studies and -16 nmol/L (95% CI -31 to -1) for the paediatric studies alone. A meta-analysis of three VitD supplementation trials found lower SCORAD by -11 points (95% CI -13 to -9) (p ˂0·00001). This surpasses the Minimal Clinical Important Difference for AD of 9.0 points (by 22%). There were greater improvements in trials lasting three months and the mean weighted dose of all trials was 1500-1600U/day. Overall, the AD population, especially the paediatric subset, may be at high-risk for lower serum 25(OH)D. Supplementation with around 1600IU/d results in a clinically meaningful AD severity reduction.

OA Hakim, A Darling, K Hart, JL Berry, SA Lanham-New (2012)VOLUMETRIC BONE MINERAL DENSITY (VBMD) AT RADIUS SITE AND VITAMIN D STATUS IN PREMENOPAUSAL SOUTH ASIAN AND CAUCASIAN WOMEN, In: OSTEOPOROSIS INTERNATIONAL23pp. S336-S337
Andrea Darling, Margaret Rayman, Colin D. Steer, Jean Golding, Susan Lanham-New, Sarah Bath (2017)Association between maternal vitamin D status in pregnancy and neurodevelopmental outcomes in childhood; results from the Avon Longitudinal Study of Parents and Children, In: British Journal of Nutrition117(12)pp. 1682-1692 Cambridge University Press

Seafood intake in pregnancy has been positively associated with childhood cognitive outcomes which could potentially relate to the high vitamin-D content of oily fish. However, whether higher maternal vitamin D status [serum 25-hydroxy-vitamin D, 25(OH)D] in pregnancy is associated with a reduced risk of offspring suboptimal neurodevelopmental outcomes is unclear. A total of 7065 mother-child pairs were studied from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who had data for both serum total 25(OH)D concentration in pregnancy and at least one measure of offspring neurodevelopment (pre-school development at 6–42 months; “Strengths and Difficulties Questionnaire” scores at 7 years; IQ at 8 years; reading ability at 9 years). After adjustment for confounders, children of vitamin-D deficient mothers (< 50.0 nmol/L) were more likely to have scores in the lowest quartile for gross motor development at 30 months (OR 1.20 95% CI 1.03, 1.40), fine motor development at 30 months (OR 1.23 95% CI 1.05, 1.44), and social development at 42 months (OR 1.20 95% CI 1.01, 1.41) than vitamin-D sufficient mothers (≥ 50.0 nmol/L). No associations were found with neurodevelopmental outcomes, including IQ, measured at older ages. However, our results suggest that deficient maternal vitamin D status in pregnancy may have adverse effects on some measures of motor and social development in children under 4 years. Prevention of vitamin D deficiency may be important for preventing suboptimal development in the first 4 years of life.

T Kantermann, F Duboutay, D Haubruge, S Hampton, AL Darling, JL Berry, M Kerkhofs, KZ Boudjeltia, DJ Skene (2014)The direction of shift-work rotation impacts metabolic risk independent of chronotype and social jetlag - An exploratory pilot study., In: F Portaluppi (eds.), Chronobiology International: the journal of biological and medical rhythm researchpp. 1-7 Informa Healthcare

The aim of this pilot study was to explore the risk of metabolic abnormalities in steel workers employed in different shift-work rotations. Male workers in a steel factory [16 employed in a fast clockwise rotation (CW), 18 in slow counterclockwise rotation (CC), 9 day workers (DW); mean age 43.3 ± SD 6.8 years] with at least 5 years experience in their current work schedule participated. All workers provided fasting blood samples between 06:00 and 08:00 h for plasma glucose, insulin, apo-lipoproteins A and B (ApoA, ApoB), high- and low-density lipoproteins (HDL and LDL), total cholesterol (tCH), triglycerides (TG), minimally oxidized (mox) LDL, C-reactive protein (CRP), interleukin-8 (IL-8) and serum 25-hydroxyvitamin D (25(OH)D). HOMA index (homeostatic model assessment) was calculated to evaluate insulin resistance, beta cell function and risk of diabetes. Information on demographics, health, stimulants, sleep, social and work life, chronotype (phase of entrainment) and social jetlag (difference between mid-sleep on workdays and free days) as a surrogate for circadian disruption was collected by questionnaire. Neither chronotype nor social jetlag was associated with any of the metabolic risk blood markers. There were no significant differences in 25(OH)D, ApoA, ApoB, CRP, HDL, IL-8, insulin, LDL, mox-LDL, mox-LDL/ApoB ratio, tCH and TG levels between the three work groups. Although we did observe absolute differences in some of these markers, the small sample size of our study population might prevent these differences being statistically significant. Fasting glucose and HOMA index were significantly lower in CW compared to DW and CC, indicating lower metabolic risk. Reasons for the lower fasting glucose and HOMA index in CW workers remains to be clarified. Future studies of workers in different shift rotations are warranted to understand better the differential effects of shift-work on individual workers and their health indices.

AL Darling, SA Lanham-New (2010)Dietary protein and bone health: The urgent need for large scale supplementation studies, In: Nutritional Influences on Bone Health
AL Darling, F Gossiel, R Hannon, DJ Skene, JL Berry, R Eastell, SA Lanham-New (2015)Evidence for an Association Between Seasonal Fluctuation of 25(OH)D and Serum C-telopeptide (CTx): Preliminary Evidence from the D-FINES study., In: OSTEOPOROSIS INTERNATIONAL22

The purpose of this study was to assess whether there is a difference in bone resorption by degree of seasonal change in 25(OH)D and whether this varies by ethnicity. In the recent D-FINES study, (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England, 2006-2007), a subset of n=65 from the 293 participants (South Asian (n 30) and Caucasian (n 35)) had blood taken in four seasons for determination of 25(OH)D and serum c-telopeptide (sCTX). sCTX was measured using an electrochemiluminescent immunoassay (Roche cobas e411). Seasonal fluctuation of 25(OH)D was assessed by calculating differences between the winter (nadir) and summer (peak) 25(OH)D. For ease of interpretation these changes were expressed as positive values. This enabled investigation of the absolute change in 25(OH)D but not its direction. This variable was then split into quartiles within ethnicity. The dependent variables were absolute concentration of sCTX in each season as well as summer to winter change in sCTX. ANCOVA was run with absolute summer and winter 25(OH)D status, age, BMI, socioeconomic status, physical activity, and dietary calcium as covariates. In the Asian group there was no clear trend between degree of seasonal fluctuation and absolute sCTX. Indeed, only the autumn data was statistically significant (F=5.93; p= 0.01) and with no consistent pattern among the quartiles. No data were significant for change in summer to winter sCTX in Asians or Caucasians despite a trend in both ethnic groups for lower sCTX in the middle quartiles relative to the highest and lowest. Last, in Caucasians, there was a non-statistically significant (p.0.05) inverse trend between cycling of 25(OH)D and absolute serum C-telopeptide levels. These data suggest lower bone resorption in all seasons in Caucasians with increased cycling, and a reduction in sCTX between summer and winter in both ethnic groups in the middle quartile relative to the other quartiles. As the values were covariate adjusted, these findings are not likely to be due to other variables. However, it must be borne in mind that these results are only trends, which is likely due to the small numbers of subjects. Further research is required to analyse banked urine samples from the D-FINES study (n 293) which would enable us to see if these results are statistically significant with increased statistical power. The D-FINES study was funded by the UK Food Standards Agency. All views are those of the authors alone

AL Darling, F Gossiel, R Hannon, DJ Skene, JL Berry, R Eastell, SA Lanham-New (2015)ASSOCIATION BETWEEN DEGREE OF SEASONAL FLUCTUATION (‘CYCLING’) OF 25(OH)D, PTH AND BONE RESORPTION IN UK SOUTH ASIAN AND CAUCASIAN WOMEN LIVING AT 51ON (SURREY), In: Abstracts of the Osteoporosis Conference 201021 S3pp. 443-518

Introduction: It has been hypothesised that the U shaped association between 25(OH)D and some health outcomes may be due to large seasonal fluctuations of 25(OH)D1. It is unknown whether such fluctuation of 25(OH)D (‘cycling’) influences bone health. Methods: In the D-FINES study, n=373 women (South Asian/Caucasian) had repeated measurements in four seasons for serum 25(OH)D and PTH. A random sample (n=66) were measured for serum C-telopeptide (CTX). Seasonal cycling of 25(OH)D was assessed as the absolute difference between winter (nadir) and summer (peak) 25(OH)D and was split into quartiles within ethnicity. Summer to winter change in CTX and PTH were calculated. Results and Discussion: ANCOVA showed no statistically significant association between quartile of cycling of 25(OH)D and CTX or PTH. However, in Asians, there was a trend for increased cycling to be associated with reduced PTH but not CTX, and for an increase in PTH from summer to winter. In Caucasians, there was a trend for increased cycling in all seasons to be associated with reduced CTX. However, increased cycling was associated with increased PTH in summer and spring, but lower PTH in other seasons, as well as a reduction in PTH from summer to winter (p=0.06). Therefore increased cycling in Caucasians was associated with lower bone resorption and was differentially associated with PTH depending on season. Further analysis of banked samples for urine CTX (n=1500) will enable these novel results to be explored further.

Andrea L. Darling, David J. Blackbourn, Kourosh R. Ahmadi, Susan A. Lanham-New (2020)Very High Prevalence of 25-hydroxyvitamin D Deficiency in n 6433 UK South Asian adults: analysis of the UK Biobank Cohort, In: British Journal of Nutritionpp. 1-34 Cambridge University Press

Little research has assessed serum 25-hydroxyvitamin D (25(OH)D) concentration and its predictors in western dwelling South Asians in a relatively large sample size. This observational, cross-sectional analysis assessed baseline prevalence of 25(OH)D deficiency in UK dwelling South Asians (aged 40-69 years, 2006-2010) from the UK Biobank cohort. Serum 25(OH)D measurements were undertaken using the DiaSorin Liaison XL assay. Of n 6433 South Asians with a 25(OH)D measurement, using commonly used cut-off thresholds, 55% (n 3538) had 25(OH)D

AL Darling, KH Hart, DJ Skene, S Arber, SA Lanham-New (2014)Vitamin D status, functional ability and muscle strength in older South Asian and Caucasian women in the UK, In: PROCEEDINGS OF THE NUTRITION SOCIETY73(OCE1)pp. E23-E23
LE Chapman, AL Darling, JE Brown (2015)The association between the biguanide drug metformin and vitamin B-12 deficiency in diabetic patients: a systematic review, In: PROCEEDINGS OF THE NUTRITION SOCIETY74(OCE1)pp. E128-E128
A.L. Darling, K.H. Hart, S. Arber, J.L. Berry, P.L. Morgan, B.A. Middleton, S. Lanham-New, D.J. Skene (2019)25-Hydroxyvitamin D status, light exposure and sleep quality in UK dwelling South Asian and Caucasian postmenopausal women, In: The Journal of Steroid Biochemistry and Molecular Biology189pp. pp 265-273 Elsevier

There is a lack of research into 25-hydroxyvitamin D (25(OH)D) status, light exposure and sleep patterns in South Asian populations. In addition, results of research studies are conflicting as to whether there is an association between 25(OH)D status and sleep quality. We investigated 25(OH)D status, self-reported and actigraphic sleep quality in n = 35 UK dwelling postmenopausal women (n = 13 South Asians, n = 22 Caucasians), who kept daily sleep diaries and wore wrist-worn actiwatch (AWL-L) devices for 14 days. A subset of n = 27 women (n = 11 South Asian and n = 16 Caucasian) also wore a neck-worn AWL-L device to measure their light exposure. For 25(OH)D concentration, South Asians had a median ± IQR of 43.8 ± 28.2 nmol/L, which was significantly lower than Caucasians (68.7 ± 37.4 nmol/L)(P = 0.001). Similarly, there was a higher sleep fragmentation in the South Asians (mean ± SD 36.9 ± 8.9) compared with the Caucasians (24.7 ± 7.1)(P = 0.002). Non-parametric circadian rhythm analysis of rest/activity patterns showed a higher night-time activity (L5) (22.6 ± 14.0 vs. 10.5 ± 4.4; P = 0.0008) and lower relative amplitude (0.85 ± 0.07 vs. 0.94 ± 0.02; P ˂ 0.0001) in the South Asian compared with the Caucasian women. More South Asians (50%) met the criteria for sleep disorders (PSQI score ˃5) than did Caucasians (27%) (P = 0.001, Fishers Exact Test). However, there was no association between 25(OH)D concentration and any sleep parameter measured (P ˃ 0.05) in either ethnic group. South Asians spent significantly less time in illuminance levels over 200 lx (P = 0.009) than did Caucasians. Overall, our results show that postmenopausal South Asian women have lower 25(OH)D concentration than Caucasian women. They also have higher sleep fragmentation, as well as a lower light exposure across the day. This may have detrimental implications for their general health and further research into sleep quality and light exposure in the South Asian ethnic group is warranted.

AL Darling, DJ Torgerson, CE Hewitt, DJ Millward, SA Lanham-New (2009)(YOUNG INVESTIGATOR AWARD) DIETARY PROTEIN AND BONE HEALTH: A SYSTEMATIC REVIEW AND META-ANALYSIS, In: OSTEOPOROSIS INTERNATIONAL20pp. S262-S262
AL Darling, PA Lee, FK Hanjra, A Osborn, S Patel, A Duckworth, P Cardew, R Gray, JL Berry, SA Lanham-New (2015)POOR VITAMIN D STATUS IS ASSOCIATED WITH A DETRIMENTAL EFFECT ON MUSCULOSKELETAL HEALTH: RESULTS OF THE D-FINES STUDY
OA Hakim, A Darling, S Starkey, M Wong, F Shojaee-Moradie, K Hart, L Morgan, J Berry, A Umpleby, B Griffin, S Lanham-New (2010)POOR BONE HEALTH AND INCREASED CARDIOVASCULAR DISEASE RISK: EVIDENCE OF A LINK IN THE D-FINES STUDY POPULATION, In: OSTEOPOROSIS INTERNATIONAL21pp. 96-97
Andrea Darling (2020)Julie Wallace Award Lecture 2019: Vitamin D deficiency in western dwelling South Asian populations: an unrecognised epidemic, In: Proceedings of the Nutrition Society Cambridge University Press

Vitamin D deficiency (25-hydroxyvitamin D; (OH)D) is at epidemic proportions in western 20 dwelling South Asian populations, including severe deficiency (

HM Macdonald, A Mavroeidi, WD Fraser, AL Darling, AJ Black, L Aucott, F O'Neill, K Hart, JL Berry, SA Lanham-New, DM Reid (2011)Sunlight and dietary contributions to the seasonal vitamin D status of cohorts of healthy postmenopausal women living at northerly latitudes: a major cause for concern?, In: Osteoporos Int22(9)pp. 2461-2472

We assessed sunlight and dietary contributions to vitamin D status in British postmenopausal women. Our true longitudinal 25-hydroxyvitamin D (25(OH)D) measurements varied seasonally, being lower in the north compared to the south and lower in Asian women. Sunlight exposure in summer and spring provided 80% total annual intake of vitamin D.

AL Darling, F Gossiel, F Robertson, T Hill, R Eastell, SA Lanham-New (2014)PREMENOPAUSAL MIGRANT SOUTH ASIAN WOMEN HAVE HIGHER URINARY N-TELOPEPTIDE THAN WOULD BE EXPECTED FOR THEIR AGE, In: OSTEOPOROSIS INTERNATIONAL25pp. S680-S680
A. L. Darling, R. J. F. Manders, S. Sahni, K. Zhu, C. E. Hewitt, R. L. Prince, D. J. Millward, S. A. Lanham-New (2019)Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years, In: Osteoporosis International30(4)pp. 741-761 Springer London

We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0–4% of areal BMC and areal BMD variance in adults and 0–14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2 = 32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed) = 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD(fixed) = 0.04 g/cm2 (0.00 to 0.08, P = 0.07), I2 = 0%) or FNBMD (total n = 435, MD(random) = 0.01 g/cm2 (−0.03 to 0.05, P = 0.59), I2 = 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8–1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.

AL Darling, AR Kang'ombe, A Dragen, B Diffey, DP Lovell, DJ Torgerson, PA Lee, WTK Lee, JL Berry, SA Lanham-New (2015)INTERACTION BETWEEN DIET AND SUNLIGHT EXPOSURE ON VITAMIN D STATUS IN WOMEN LIVING IN SOUTHERN ENGLAND: MULTILEVEL MODELLING ANALYSIS OF THE D-FINES STUDY

A.L.Darling1, A.R.Kang’ombe2, A.Dragen1, B.Diffey3, D.P.Lovell1, D.J.Torgerson2, P.A. Lee1, W.T.K. Lee1, J.L. Berry4 and S.A. Lanham-New1

AL Darling, F Gossiel, R Hannon, R Eastell, SA Lanham-New (2015)PRELIMINARY EVIDENCE FOR MENOPAUSAL BUT NOT ETHNIC OR SEASONAL DIFFERENCES IN BONE RESORPTION AS MEASURED BY SERUM C-TELOPEPTIDE IN THE D-FINES STUDY, In: OSTEOPOROSIS INTERNATIONAL21pp. 84-84

This study aimed to establish if bone turnover shows significant seasonal variation, and if this varies by ethnicity. The D-FINES study investigated 373 Surrey Caucasian (C) and Asian (A) women every season over a 12 month period (2006-2007). A random sub-sample of premenopausal C (n 18) and postmenopausal C (n 17); premenopausal A (n 13) and postmenopausal A (n 17) with blood samples for all seasons were selected. Serum C-telopeptide (sCTX) was determined by electrochemiluminescent immunoassay (Roche Diagnostics). A mixed between-within subjects ANOVA showed there was no significant main effect of season on sCTX F(3,59.0)=1.467, p=0.233. However, there was a significant between subjects effect of group F(3,61)=3.099, p=0.033, with post hoc tests showing significant differences between the two C groups (p=0.007) and postmenopausal A and premenopausal C groups (p=0.042) but no significant differences between the other groups. Last, there was no significant interaction between season and group F(9,143.741)=0.540, p=0.843. It appears that it is menopausal status, not ethnicity which is likely the main reason for the group differences. Indeed, there was no significant difference between ethnic groups of the same menopausal status. Overall, no evidence for a seasonal variation in bone resorption was found here but there was evidence for a menopausal difference in bone resorption.

Andrea L. Darling, L Abar, T Norat (2015)WCRF-AICR continuous update project: Systematic literature review of prospective studies on circulating 25-hydroxyvitamin D and kidney cancer risk, In: The Journal of Steroid Biochemistry and Molecular Biology164pp. 85-89 Elsevier

As part of the World Cancer Research Fund/American Institute for Cancer Research (WCRF-AICR) Continuous Update project we performed a systematic review of prospective studies with data for both measured or predicted 25(OH)D concentration and kidney cancer risk. PubMed was searched from inception until 1st December 2014 using WCRF/AICR search criteria. The search identified 4 papers suitable for inclusion, reporting data from three prospective cohort studies, one nested case-control study and the Vitamin D Pooling Project of Rarer Cancers (8 nested case-control studies). Summary effect sizes could not be computed due to incompatibility between studies. All studies except the Pooling Project suggested a reduced risk of kidney cancer by 19-40% with higher or adequate vitamin D status,. However, these estimates only reached statistical significance in one cohort (Copenhagen City Heart Study; CCHS, HR=0.75 (0.58 to 0.96)). In the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a significant reduction in risk by 18% was seen when using combined matched and non-matched controls OR=0.82 (0.68, 0.99), but not when using only matched controls (OR=0.81 (0.65, 1.00). Pooled (but not single cohort) data for predicted 25(OH)D from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) showed a statistically significant reduction in risk by 37% (HR=0.63 (0.44, 0.91)). There is no clear explanation for the inconsistency of results between studies, but reasons may include prevalence of smoking or other study population characteristics. Methods for assessing circulating 25(OH)D levels and control for confounders including seasonality or hypertension do not seem explanatory.

LE Chapman, AL Darling, JE Brown (2016)Association between metformin and vitamin B12 deficiency in patients with Type 2 Diabetes: A systematic review and meta-analysis, In: Diabetes and Metabolism42(5)pp. 316-327 Elsevier

Aim Metformin is the most widely used oral hypoglycaemic drug, but it may lower B12 status, which could have important clinical implications. We undertook a systematic review and meta-analysis of the relationship between metformin use and vitamin B12 deficiency in persons with type 2 diabetes. Methods Electronic database searches were undertaken (1st January 1957–1st July 2013) using the Cochrane library, Scopus, CINAHL, Grey literature databases, Pub Med Central, NICE Clinical Guidelines UK, and ongoing clinical trials. Included studies were of any study design, with data from patients with type 2 diabetes of any age or gender, taking any dose or duration of metformin. Planned primary outcomes were serum vitamin B12 levels, % prevalence or incidence of vitamin B12 deficiency and risk of vitamin B12 deficiency. Results Twenty-six papers were included in the review. Ten out of 17 observational studies showed statistically significantly lower levels of vitamin B12 in patients on metformin than not on metformin. Meta-analysis performed on four trials demonstrated a statistically significant overall mean B12 reducing effect of metformin of 57 pmol/L [WMD (fixed) = –0.57 (95% CI: –35 to –79 pmol/L)] after 6 weeks to 3 months of use. Conclusion The evidence from this review demonstrates an association between metformin usage and lower levels of vitamin B12 by 57 pmol/L, which leads to frank deficiency or borderline status in some patients with type 2 diabetes. This suggests that it is prudent to monitor B12 levels in these patients who are at increased risk of deficiency.

MM Mendes, AL Darling, L Meira, SA Lanham-New (2014)Vitamin D status and body composition in UK Caucasian and South Asian postmenopausal women: results from the DFINES II study, In: PROCEEDINGS OF THE NUTRITION SOCIETY73(OCE1)pp. E40-E40
AL Darling, OA Hakim, KH Hart, JL Berry, SA Lanham-New (2012)POSTMENOPAUSAL SOUTH ASIAN WOMEN SHOW ADAPTATIONS IN TIBIAL CORTICAL THICKNESS AND VOLUMETRIC BONE MINERAL DENSITY TO COMPENSATE FOR SMALL OVERALL BONE SIZE, In: OSTEOPOROSIS INTERNATIONAL23pp. S584-S584
HM Macdonald, A Mavroeidi, WD Fraser, AL Darling, AJ Black, L Aucott, F O'Neill, K Hart, JL Berry, SA Lanham-New, DM Reid (2011)Erratum to: Sunlight and dietary contributions to the seasonal vitamin D status of cohorts of healthy postmenopausal women living at northerly latitudes: a major cause for concern?, In: Osteoporos Int
A Mavroeidi, F O'Neill, P Lee, A Darling, W Fraser, J Berry, W Lee, D Reid, S Lanham-New, H Macdonald (2009)NORTH VS. SOUTH, REGIONAL AND SEASONAL DIFFERENCES IN VITAMIN D STATUS OF UK POSTMENOPAUSAL WOMEN: CAUSE FOR CONCERN?, In: OSTEOPOROSIS INTERNATIONAL20pp. S260-S261
AL Darling, KH Hart, F Gossiel, R Eastell, JL Berry, SA Lanham-New (2015)Bone resorption levels are related to diet in UK dwelling South Asian but not Caucasian women, In: PROCEEDINGS OF THE NUTRITION SOCIETY74(OCE1)pp. E43-E43
H Lambert, V Boyd, A Darling, D Torgerson, P Burckhardt, L Frassetto, S Lanham-New (2011)Evidence for the role of potassium in bone health: results of a systematic review and meta-analysis, In: PROCEEDINGS OF THE NUTRITION SOCIETY70(OCE3)pp. E86-E86
O Hakim, A Darling, L Tripkovic, L Wilson, K Hart, J Berry, S Lanham-New (2015)DIFFERENCES IN VITAMIN D STATUS AND VOLUMETRIC BONE MINERAL DENSITY (VBMD) AT THE RADIUS AND TIBIA IN PREMENOPAUSAL CAUCASIAN, SOUTH ASIAN, AND ARAB FEMALES LIVING IN UK, In: OSTEOPOROSIS INTERNATIONAL26pp. S474-S474
Andrea Darling, Kathryn Hart, Susan Lanham-New, HM MacDonald, K Horton, AR Kang'Ombe, JL Berry (2013)Vitamin D deficiency in UK South Asian Women of childbearing age: A comparative longitudinal investigation with UK Caucasian women, In: Osteoporosis International24(2)pp. 477-488 Springer Verlag

This is the first 1-year longitudinal study which assesses vitamin D deficiency in young UK-dwelling South Asian women. The findings are that vitamin D deficiency is extremely common in this group of women and that it persists all year around, representing a significant public health concern. Introduction: There is a lack of longitudinal data assessing seasonal variation in vitamin D status in young South Asian women living in northern latitudes. Studies of postmenopausal South Asian women suggest a lack of seasonal change in 25-hydroxy vitamin D [25(OH)D], although it is unclear whether this is prevalent among premenopausal South Asians. We aimed to evaluate, longitudinally, seasonal changes in 25(OH)D and prevalence of vitamin D deficiency in young UK-dwelling South Asian women as compared with Caucasians. We also aimed to establish the relative contributions of dietary vitamin D and sun exposure in explaining serum 25(OH)D. Methods: This is a 1-year prospective cohort study assessing South Asian (n = 35) and Caucasian (n = 105) premenopausal women living in Surrey, UK (51 N), aged 20-55 years. The main outcome measured was serum 25(OH)D concentration. Secondary outcomes were serum parathyroid hormone, self-reported dietary vitamin D intake and UVB exposure by personal dosimetry. Results: Serum 25(OH)D

AL Darling, SA Lanham-New (2010)Dietary Protein and Bone Health: The Urgent Need for Large-Scale Supplementation Studies, In: P Burckhardt, B DawsonHughes, C Weaver (eds.), NUTRITIONAL INFLUENCES ON BONE HEALTHpp. 17-26
Andrea Darling, Kathryn Hart, F Gossiel, F Robertson, Julie Hunt, TR Hill, Sigurd Johnsen, JL Berry, R Eastell, R Vieth, Susan Lanham-New (2017)Higher bone resorption excretion in South Asian women vs White Caucasians and increased bone loss with higher seasonal cycling of vitamin D:  results from the D-FINES cohort study, In: Bone98pp. 47-53 Elsevier

Few data exist on bone turnover in South Asian women and it is not well elucidated as to whether Western dwelling South Asian women have different bone resorption levels to that of women from European ethnic backgrounds. This study assessed bone resorption levels in UK dwelling South Asian and Caucasian women as well as evaluating whether seasonal variation in 25-hydroxyvitamin D [25(OH)D] is associated with bone resorption in either ethnic group. Data for seasonal measures of urinary N-telopeptide of collagen (uNTX) and serum 25(OH)D were analysed from n=373 women (four groups; South Asian postmenopausal n=44, South Asian premenopausal n=50, Caucasian postmenopausal n=144, Caucasian premenopausal n =135) (mean (± SD) age 48 (14) years; age range 18-79 years) who participated in the longitudinal D-FINES (Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England) cohort study (2006-2007). A mixed between-within subjects ANOVA (n=192) showed a between subjects effect of the four groups (P

AL Darling, S Lanham-New (2014)Food Groups and Bone Health, In: M Holick, J Nieves (eds.), Nutrition and Bone Health(18)pp. 277-290 Humana Press

This newly revised edition contains updated versions of all of the topics that were in the first edition and has been substantially expanded with an additional 5 chapters.

A Darling, F Gossiel, R Hannon, D Skene, J Berry, R Eastell, S Lanham-New (2011)EVIDENCE FOR AN ASSOCIATION BETWEEN SEASONAL FLUCTUATION OF 25(OH)D AND SERUM C-TELOPEPTIDE (CTX): PRELIMINARY EVIDENCE FROM THE D-FINES STUDY, In: OSTEOPOROSIS INTERNATIONAL22pp. 326-326
Zahra Raisi-Estabragh, Adrian R. Martineau, Elizabeth M. Curtis, Rebecca J. Moon, ANDREA L DARLING, SUSAN ALEXANDRA LANHAM-NEW, Kate A. Ward, Cyrus Cooper, Patricia B. Munroe, Steffen E. Petersen, Nicholas C. Harvey (2021)Vitamin D and coronavirus disease 2019 (COVID-19): rapid evidence review, In: Aging Clinical and Experimental Research Springer

Background: The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the virus that causes coronavirus disease 2019 (COVID-19), has re-ignited interest in the possible role of vitamin D in modulation of host responses to respiratory pathogens. Indeed, vitamin D supplementation has been proposed as a potential preventative or therapeutic strategy. Recommendations for any intervention, particularly in the context of a potentially fatal pandemic infection, should be strictly based on clinically informed appraisal of the evidence base. In this narrative review, we examine current evidence relating to vitamin D and COVID-19 and consider the most appropriate practical recommendations. Observations: Although there are a growing number of studies investigating the links between vitamin D and COVID-19, they are mostly small and observational with high risk of bias, residual confounding, and reverse causality. Extrapolation of molecular actions of 1,25(OH)2-vitamin D to an effect of increased 25(OH)-vitamin D as a result of vitamin D supplementation is generally unfounded, as is the automatic conclusion of causal mechanisms from observational studies linking low 25(OH)-vitamin D to incident disease. Efficacy is ideally demonstrated in the context of adequately powered randomised intervention studies, although such approaches may not always be feasible. Conclusions: At present, evidence to support vitamin D supplementation for the prevention or treatment of COVID-19 is inconclusive. In the absence of any further compelling data, adherence to existing national guidance on vitamin D supplementation to prevent vitamin D deficiency, predicated principally on maintaining musculoskeletal health, appears appropriate.