Professor Susan Lanham-New

Optimal vitamin D status has commonly been defined as the level of 25-hydroxyvitamin D (25(OH)D) at which parathyroid hormone (PTH) concentrations would be maximally suppressed, represented by an observed minimum plateau. Previous findings indicate a large variation in this plateau, with values ranging from

We live in a world with an ever-increasing ageing population. Studying healthy ageing and reducing the socioeconomic impact of age-related diseases is a key research priority for the industrialised and developing countries, along with a better mechanistic understanding of the physiology and pathophysiology of ageing that occurs in a number of age-related musculoskeletal disorders. Arthritis and musculoskeletal disorders constitute a major cause of disability and morbidity globally and result in enormous costs for our health and social-care systems. By gaining a better understanding of healthy musculoskeletal ageing and the risk factors associated with premature ageing and senescence, we can provide better care and develop new and better-targeted therapies for common musculoskeletal disorders. This review is the outcome of a two-day multidisciplinary, international workshop sponsored by the Institute of Advanced Studies entitled “Musculoskeletal Health in the 21st Century” and held at the University of Surrey from 30th June-1st July 2015. The aim of this narrative review is to summarise current knowledge of musculoskeletal health, ageing and disease and highlight strategies for prevention and reducing the impact of common musculoskeletal diseases.

Background: Vitamin D deficiency has been associated with non-alcoholic fatty liver disease (NAFLD). However, the role of polymorphisms determining vitamin D status remains unknown. Objectives: To determine in UK children with biopsy-proven NAFLD: (i) vitamin D status throughout a 12-month period; (ii) interactions between key vitamin D-related genetic variants (NADSYN1/DHCR7, VDR, GC, CYP2R1) and disease severity. Methods: In 103 pediatric patients with NAFLD, serum 25-hydroxyvitamin D (25OHD) levels and genotypes were determined contemporaneously to liver biopsy and examined in relation to NAFLD activity score and fibrosis stage. Results: Only 19.2% of children had adequate vitamin D status; most had mean 25OHD levels considered deficient (

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.

Abstract Background and Objective There has been a resurgence of interest in the controversial relationship between dietary protein and bone health. This paper reports the first systematic review and meta-analysis of the relationship between protein and bone health in healthy human adults. Data sources/Methods The MEDLINE® (January 1966 to September 2007) and EMBASE (1974- July 2008) databases were electronically searched for all relevant studies of healthy adults, excluding studies examining calcium excretion or calcium balance. Results In cross sectional surveys, all pooled r values for the relationship between protein intake and BMD/BMC at the main clinically relevant sites were significant and positive, with protein intake explaining 1-2% of BMD. A meta-analysis of randomised, placebo controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD, but showed no association with relative risk (RR) of hip fractures. No significant effects were identified for soy protein or milk basic protein (MBP) on lumbar spine BMD. Conclusion A small positive effect of protein supplementation on lumbar spine BMD in randomised placebo controlled trials supports the positive association between protein intake and bone health found in cross sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were very small and had 95% confidence intervals which were close to zero. Therefore there is a small benefit of protein on bone health found here but any benefit may not necessarily translate into reduced fracture risk in the long term.

More data is urgently required examining the link between poor vitamin D status on bone health and muscle function in different UK ethnic groups. The D-FINES study examined a total of 373 Surrey-dwelling Caucasian (C) and Asian (A) women in four seasons of the year for diet, sunlight exposure, 25-hydroxyvitamin D (25(OH)D) and grip strength (GS). In the autumn season, lumbar spine bone mineral density (LSBMD) was also measured. The specific aim of this work was to examine differences in LSBMD and GS in A and C pre and postmenopausal women according to 25(OH)D. When women were grouped by 25(OH)D (

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.

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.

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

Aim: This study aimed to assess whether seasonal cycling of 25(OH)D (25-dihydroxy vitamin D) is associated with bone health. Method: A subgroup of 65 South Asian and Caucasian women who took part in the 2006-2007 D-FINES study was analysed. During this study they had blood drawn in four seasons for determination of 25(OH)D and serum c-telopeptide (sCTX)and in autumn and spring they had a DEXA scan (Hologic). Cycling of 25(OH)D was assessed by calculating the difference between the winter (nadir) and summer (peak) 25(OH)D and for ease of interpretation, expressing all change as positive values. Dependent variables analysed were absolute values for autumn femoral neck and lumbar spine BMD, BMC and bone area, and absolute sCTX in each season. Also, change in sCTX from summer to winter and change in the DEXA bone indices from autumn to spring were analysed. Results: ANCOVA, controlling for summer and winter 25(OH)D status, age, BMI, socioeconomic status, physical activity, and dietary calcium showed no statistically significant association (p>0.05) between quartile of cycling of 25(OH)D and any bone measurement in either ethnic group except in the Asians for absolute autumn CTX (F=5.925, p=0.01, fig 1) and change in FNBMC (F=3.111, p=0.05, see fig.3). Also, in Asians only, absolute autumn lumbar spine BMD approached significance (F =2.780, p=0.07, see fig 2). Conclusions: It has been suggested that some findings of increased risk of some cancers in countries with high 25(OH)D could be due to slow adaption of CYP27B1 and CYP24 to fluctuating 25(OH)D (1). This begs the question as to whether seasonal cycling of 25(OH)D could be detrimental to bone. Indeed, a recent review discussed a correlation between 25(OH)D and bone indices (2). The lack of an association between cycling and most bone indices found here does not support this view that 25(OH)D cycling is detrimental to bone. However, in Asians only, the loss of femoral neck BMC during the year in the top and bottom quartiles but gain in the 3rd quartile, and the increased autumn sCTX in the third quartile warrants further investigation.

The optimisation of skeletal health during the life cycle is critical, especially if we are to reduce the continuing rise in osteoporosis -1 in 2 women and 1 in 5 men over the age of 50 years will suffer an osteoporotic fracture. The foundations of adult bone health are laid down in the early years; therefore, optimisation of bone health in the young is fundamental. Although genetics play a major role, accounting for 70-75% of bone strength, other lifestyle and nutrition factors are known to be highly influential. Calcium (Ca) and vitamin D play critical roles in bone mineralisation as well as generally being key nutrients in health. All living cells require Ca to survive, with the majority (99%) of Ca being found in bones and teeth and the remainder in soft tissues and body fluids. Vitamin D is the generic term for two molecules: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). The former is derived by ultraviolet (UV) irradiation of ergosterol, which is distributed in plants and fungi. The latter is formed from the effect of UV irradiation on the skin. The principal role of vitamin D is to support the serum Ca concentration within narrow limits. Vitamin D is crucial for maximising gut absorption of calcium via vitamin D dependent Ca receptors. It is estimated that adequate vitamin D status increases Ca absorption to 30-40% of intake compared with only 10-15% absorption without adequate vitamin D. Intakes of Ca are a concern among certain groups of the population, for example a high proportion (>12%) of teenage boys and girls fail to meet the lower reference nutrient intake for Ca. For vitamin D, there are no dietary reference values for the age group 4-64 years as it is considered that UV exposure provides sufficient quantities of vitamin D, but there is now mounting evidence of widespread vitamin D insufficiency in the population. Weight-bearing physical activity is beneficial to the skeleton but clarification is needed of the exact type, intensity and duration required for optimal bone mass. The role of othermicronutrients on bone metabolism remains to be fully quantified. This review investigates the current evidence of the impact of dietary and lifestyle factors on bone health, with specific reference to children and adolescents and with a focus on vitamin D, Ca and weight-bearing exercise. © 2007 The Authors; Journal compilation © 2007 British Nutrition Foundation.

Vitamin D is essential for bone development during adolescence and low vitamin D status during this critical period of growth may impact bone mineralization, potentially reducing peak bone mass and consequently increasing the risk of osteoporosis in adulthood. Therefore, the high prevalence of vitamin D inadequacy and deficiency in adolescent populations is of great concern. However, there is currently a lack of consensus on the 25-hydroxyvitamin D [25(OH)D] concentration, the widely accepted biomarker of vitamin D status, that defines adequacy, and the vitamin D intake requirements to maintain various 25(OH)D thresholds are not well established. While the current intake recommendations of 10–15 μg/day may be sufficient to prevent vitamin D deficiency (25(OH)D < 25–30 nmol/l), greater intakes may be needed to achieve the higher threshold levels proposed to represent adequacy (25(OH)D > 50 nmol/l). This review will address these concerns and consider if the current dietary recommendations for vitamin D in adolescents are sufficient.

It is known that skin pigmentation reduces the penetration of ultraviolet radiation (UVR) and thus photosynthesis of 25-hydroxvitamin D (25(OH)D). However ethnic differences in 25(OH)D production remain to be elucidated.The aim of this study was to investigate differences in vitamin D production between UK South Asian and Caucasian postmenopausal women, in response to a defined and controlled exposure to UVR.Seventeen women; 9 white Caucasian (skin phototype II and III), 8 South Asian women (skin phototype IV and V) participated in the study, acting as their own controls. Three blood samples were taken for the measurement of vitamin D status during the run in period (9 days, no sunbed exposure) after which, all subjects underwent an identical UVR exposure protocol irrespective of skin colour (9 days, 3 sun bed sessions, 6, 8 and 8minutes respectively with approximately 80% body surface exposed). Skin tone was measured four times during the study.Despite consistently lower 25(OH)D levels in South Asian women, they were shown to synthesise vitamin D as efficiently as Caucasians when exposed to the same dose of UVR. Interestingly, the baseline level of vitamin D rather than ethnicity and skin tone influenced the amount of vitamin D synthesised.This study have found no ethnic differences in the synthesis of 25(OH)D, possibly due to the baseline differences in 25(OH)D concentration or due to the small population size used in this study. Applying mixed linear model, findings indicated no effect of ethnicity and skin tone on the production of vitamin D; baseline level and length of exposure were the critical factors. To confirm that ethnicity and skin tone has no effect on 25(OH)D production, a larger sample size study is required that considers other ethnic groups with highly pigmented skin. Initial vitamin D status influences the amount of UVB needed to reach equal serum concentrations.

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 

Background: Low serum 25-hydroxyvitamin D [25(OH)D] has been associated with unfavorable cardiometabolic risk profiles in many observational studies in children, but very few randomized controlled trials have investigated this. Objective: We explored the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in young, white, 4- to 8-y-old healthy Danish children (55°N) as part of the pan-European ODIN project. Methods: In the ODIN Junior double-blind, placebo-controlled, dose-response trial, 119 children (mean ± SD age: 6.7 ± 1.5 y; 36% male; 82% normal weight) were randomly allocated to 0, 10 or 20 μg/d of vitamin D3 for 20 wk (October–March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, serum triglycerides and cholesterol (total, LDL, HDL, and total:HDL), plasma glucose and insulin, and whole-blood glycated hemoglobin were measured at baseline and endpoint as secondary outcomes together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint adjusted for baseline value of the outcome, and additionally for age, sex, baseline serum 25(OH)D, BMIz, time since breakfast, and breakfast content. Results: Mean ± SD serum 25(OH)D was 56.7 ± 12.3 nmol/L at baseline and differed between groups at endpoint with concentrations of 31.1 ± 7.5, 61.8 ± 10.6, and 75.8 ± 11.5 nmol/L in the 0-, 10-, and 20 μg/d groups, respectively (P < 0.0001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers in analyses adjusted for baseline value of the outcome (all P ≥ 0.05), and additional covariate adjustment did not change the results notably. Conclusions: Preventing the winter decline in serum 25(OH)D with daily vitamin D3 supplementation of 10 or 20 μg had no cardiometabolic effects in healthy 4- to 8-y-old Danish children. This trial was registered at www.clinicaltrials.gov as NCT02145195.

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

This analysis assessed whether seasonal change in 25-hydroxyvitamin D concentration was associated with bone resorption, as evidenced by serum parathyroid hormone and C-terminal telopeptide concentrations. The main finding was that increased seasonal fluctuation in 25-hydroxyvitamin D was associated with increased levels of parathyroid hormone and C-terminal telopeptide. Introduction: It is established that adequate 25-hydroxyvitamin D (25(OH)D, vitamin D) concentration is required for healthy bone mineralisation. It is unknown whether seasonal fluctuations in 25(OH)D also impact on bone health. If large seasonal fluctuations in 25(OH)D were associated with increased bone resorption, this would suggest a detriment to bone health. Therefore, this analysis assessed whether there is an association between seasonal variation in 25(OH)D and bone resorption. Methods: The participants were (n = 279) Caucasian and (n = 88) South Asian women (mean (±SD); age 48.2 years (14.4)) who participated in the longitudinal Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England study (2006-2007). The main outcomes were serum 25(OH)D, serum parathyroid hormone (sPTH) and serum C-terminal telopeptide of collagen (sCTX), sampled once per season for each participant. Results: Non-linear mixed modelling showed the (amplitude/mesor) ratio for seasonal change in log 25(OH)D to be predictive of log sPTH (estimate = 0.057, 95 % CI (0.051, 0.063), p < 0.0001). Therefore, individuals with a higher seasonal change in log 25(OH)D, adjusted for overall log 25(OH)D concentration, showed increased levels of log sPTH. There was a corresponding significant ability to predict the range of seasonal change in log 25(OH)D through the level of sCTX. Here, the corresponding parameter statistics were estimate = 0.528, 95 % CI (0.418, 0.638) and p ≤ 0.0001. Conclusions: These findings suggest a possible detriment to bone health via increased levels of sPTH and sCTX in individuals with a larger seasonal change in 25(OH)D concentration. Further larger cohort studies are required to further investigate these preliminary findings. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.

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.

Tuberculosis (TB) is a chronic disease affecting humans and other mammal species. Severity of TB caused by Mycobacterium tuberculosis in humans seems to be influenced by nutritional factors like vitamin D3 intake. However, this relationship has been scarcely studied in cattle and other mammals infected with Mycobacterium bovis. The aim of this work was to assess if wildlife reservoirs of M. bovis show different levels of TB severity depending on the level of vitamin D found in serum after supplementation with vitamin D3. Forty hunted wildlife mammals were included in this study: 20 wild boar and 20 red deer. Ten wild boar and ten red deer had been supplemented with a vitamin D3-enriched food, whereas the remaining animals had received no supplementation. TB diagnosis was carried out in each animal based on microbiological isolation of M. bovis. Animals infected with M. bovis were then classified as animals with localized or generalized TB depending on the location and dissemination of the lesions. Furthermore, serum levels of vitamin D2 and D3 were determined in each animal to evaluate differences not only between supplemented and non-supplemented animals but also between those with localized and generalized TB. Levels of vitamin D3 found in both, supplemented wild boar and red deer, were significantly higher than those found in the non-supplemented animals. Interestingly, higher levels of vitamin D3 were observed in animals suffering localized TB when compared to animals with generalized TB suggesting that vitamin D3 concentration correlates negatively with TB severity in these wildlife reservoirs.

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

Background Group-specific component (GC) and cytochrome P450 Family 2 Subfamily R Member 1 (CYP2R1) genes are one of the vital genes involved in the vitamin D (vitD) metabolic pathway. Association of genetic polymorphisms in these two genes with 25-hyroxyvitamin D (25(OH)D) level has been reported in several studies. However, this association has been reported to be discrepant among populations from different ethnicities. Therefore, we aimed in this study to investigate association of the two major single nucleotide polymorphisms (SNP) in GC (rs4588 and rs7014) and a SNP (rs12794714) in CYP2R1 in postmenopausal women in Saudi Arabia. Methods This study randomly selected 459 postmenopausal women (aged ≥ 50 years) of multiple ethnicities in Jeddah, Saudi Arabia. Blood samples were collected from all participating women for DNA extraction and for assessment of serum levels of total 25(OH)D, directly measured free 25(OH)D and other biochemical parameters. SNPs in selected vitD related genes (rs4588 in GC, c.1364G>T with transcript ID: NM_001204307.1 and rs7041 in GC, c.1353A>C with transcript ID NM_001204307.1 and rs12794714 in CYP2R1, c.177G>A with transcript ID NM_024514.4) were determined in DNA samples using Sanger DNA sequencing. Results Minor allele frequency for rs4588, rs7041 and rs12794714 were 0.25, 0.44 and 0.42 respectively. Genotypes of rs7041 showed significant difference in total 25(OH)D level but not in free 25(O)D level (P=0.023). In comparison, genotypes of rs4588 and rs12794714 did not show any significant difference neither in total nor in free 25(OH)D level. Post hoc test revealed that total 25(OH)D was lower in the rs7041 TT allele compared to the GG allele (P=0.022). Chi-square test showed that vitD status was associated with rs7041 genotypes (P=0.035). In addition, rs7041 minor alleles were found to have an association with vitD deficiency with a statistical significant odds ratio (>1) of 2.24 and 3.51 with P=0.006 and P=0.007 for TG and GG genotypes respectively. Conclusion The rs7041 SNP in GC was associated with total 25(OH)D level in postmenopausal women in Saudi Arabia, while rs4588 in GC and rs12794714 in CYP2R1 did not show association with total 25(OH)D. Further studies exploring additional variants in vitD related genes are needed to understand genetic factors underlying vitD deficiency in Saudi population.

Background: Numerous research have found an association between vitamin D (vitD) status and single nucleotide polymorphisms (SNPs) in genes involved in vitD metabolism. It is notable that the influence of these SNPs on 25-hydroxyvitamin D (25(OH)D) levels might vary in different populations. We aimed in this study to explore for genetic variants in genes related to vitD metabolism in families with vitD deficiency in Saudi Arabia using whole exome sequencing (WES). Methods: This family-based WES study was conducted for 21 families with vitD deficiency (n=39) from Saudi Arabia. WES was performed for DNA samples, then obtained WES data was filtered and a number of variants were prioritized and validated by Sanger DNA sequencing. Results: Several missense variants in vitD related genes were detected in families. We determined two variants in Low-density lipoprotein 2 gene (LRP2) with one variant (rs2075252) observed in six individuals, while the other LRP2 variant (rs4667591) was detected in 13 subjects. Single variant in 7-dehydrocholesterol reductase (DHCR7) (rs143587828) and melanocortin 1 receptor (MC1R) (rs1805005) gene were observed in 2 subjects of 2 different families. Other variants in group-specific component (GC), cubilin (CUBN) and calcium-sensing receptor (CASR) gene were seen in index cases and controls. Polymorphisms in GC (rs9016) and CASR (rs1801726) were seen in majority of family cases (94% and 88%) respectively. Conclusion: In vitD deficient families in Saudi Arabia, we were able to detect a number of missense exonic variants including variants in GC (rs9016), CUBN (rs1801222), CASR (rs1801726) and LRP2 (rs4667591). However, the existence of these variants was not different between affected family members and non-affected controls. Additionally, we were able to find a mutation in DHCR7 (rs143587828) and a polymorphism in LRP2 (rs2075252) which may affect vitD levels and influence vitD status. However, further studies are required to confirm the association of these variants with vitD deficiency.

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. This is an important issue, because if ‘cycling’ is detrimental for bone, then winter only rather than year round vitamin D supplementation may be useful for bone health to ‘blunt’ the rhythm. In the D-FINES study, n = 373 women (South Asian/Caucasian) had repeated measurements in four seasons for serum 25(OH)D and PTH, as well as a DXA scan in autumn and spring. Serum C-telopeptide (sCTX) was also measured in a random subset (n = 66). Cosinor regression analysis was used to identify individuals showing a significant rhythm (p < 0.10) (‘cyclers’) and those not showing a significant seasonal rhythm (‘non-cyclers’). Potential differences in bone indices between the two groups were assessed within ethnicity. Dependent variables analysed were absolute values for autumn femoral neck and lumbar spine BMD, BMC and bone area, and absolute sCTX and sPTH in each season. Also, change in sCTX and sPTH from summer to winter and change in DXA bone indices from autumn to spring were analysed. ANCOVA was run, adjusting for summer and winter 25(OH)D status, age, socioeconomic status, physical activity, and dietary calcium. BMI was also controlled for in the analysis due to its negative correlation with seasonal change in 25(OH)D. There was no statistically significant difference (p>0.05) between ‘cyclers’ and ‘non-cyclers’ for any of the bone indices in either ethnic group. However, there were trends for a higher CTX and PTH in ‘cyclers’ versus ‘non-cyclers’ in both ethnic groups in every season, but no differences for BMD or BMC (Figs. 1–4). This suggests tentatively that ‘cycling’ could be associated with changes in bone metabolism but may not translate into structural changes. In summary, there is no clear evidence here to suggest that ‘cycling’ is detrimental to bone health, although there are trends in PTH and CTX that warrant further investigation with a larger sample.

Background: Children in northern latitudes are at high risk of vitamin D deficiency during winter because of negligible dermal vitamin D3 production. However, to our knowledge, the dietary requirement for maintaining the nutritional adequacy of vitamin D in young children has not been investigated. Objective: We aimed to establish the distribution of vitamin D intakes required to maintain winter serum 25-hydroxyvitamin D [25(OH)D] concentrations above the proposed cutoffs (25, 30, 40, and 50 nmol/L) in white Danish children aged 4–8 y living at 55°N. Design: In a double-blind, randomized, controlled trial 119 children (mean age: 6.7 y) were assigned to 0 (placebo), 10, or 20 μg vitamin D3/d supplementation for 20 wk. We measured anthropometry, dietary vitamin D, and serum 25(OH)D with liquid chromatography–tandem mass spectrometry at baseline and endpoint. Results: The mean ± SD baseline serum 25(OH)D was 56.7 ± 12.3 nmol/L (range: 28.7–101.4 nmol/L). Serum 25(OH)D increased by a mean ± SE of 4.9 ± 1.3 and 17.7 ± 1.8 nmol/L in the groups receiving 10 and 20 μg vitamin D3/d, respectively, and decreased by 24.1 ± 1.2 nmol/L in the placebo group (P < 0.001). A nonlinear model of serum 25(OH)D as a function of total vitamin D intake (diet and supplements) was fit to the data. The estimated vitamin D intakes required to maintain winter serum 25(OH)D >30 (avoiding deficiency) and >50 nmol/L (ensuring adequacy) in 97.5% of participants were 8.3 and 19.5 μg/d, respectively, and 4.4 μg/d was required to maintain serum 25(OH)D >40 nmol/L in 50% of participants. Conclusions: Vitamin D intakes between 8 and 20 μg/d are required by white 4- to 8-y-olds during winter in northern latitudes to maintain serum 25(OH)D >30–50 nmol/L depending on chosen serum 25(OH)D threshold. This trial was registered at clinicaltrials.gov as NCT02145195.

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.

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.

Few data exist looking at vitamin D status and bone health in school-aged boys and girls from Saudi Arabia. The present study aimed to determine the extent of poor vitamin D status in school boys and girls aged 6-18 years and to examine if there was any difference in status with age, physical activity and veiling and concomitant effects on bone.

Background: Measurement of free 25-hydroyvitamin D [25(OH)D] status has been suggested as a more representative marker of vitamin D status than that of total 25(OH) D. Previously, free 25(OH)D could only be calculated indirectly; however, a newly developed direct assay for the measurement of free 25(OH)D is now available. The aim of this study therefore was to investigate directly measured total and free vitamin D levels association with metabolic health in postmenopausal healthy women living in Saudi Arabia. Methods: A sample of 302 postmenopausal women aged ≥ 50 years (n=302) living in Saudi Arabia were recruited in a cross-section study design. Blood samples were collected from subjects for measurement of serum levels of total 25(OH)D, directly measured free 25(OH)D, metabolic bone parameters, lipid profile, and other biochemical tests. Results: A positive correlation was found between directly measured free and total 25(OH)D (r=0.64, P

The role of vitamin D in supporting the growth and maintenance of the skeleton is robust; with recent research also suggesting a beneficial link between vitamin D and other nonskeletal health outcomes, including immune function, cardiovascular health and cancer. Despite this, vitamin D deficiency remains a global public health issue, with a renewed focus in the UK following the publication of Public Health England’s new Dietary Vitamin D Requirements. Natural sources of vitamin D (dietary and UVB exposure) are limited, and thus mechanisms are needed to allow individuals to achieve the new dietary recommendations. Mandatory or voluntary vitamin D food fortification may be one of the mechanisms to increase dietary vitamin D intakes and subsequently improve vitamin D status. However, for the food industry and public to make informed decisions, clarity is needed as to whether vitamins D2 and D3 are equally effective at raising total 25-hydroxyvitamin D (25(OH)D) concentrations as the evidence thus far is inconsistent. This review summarises the evidence to date behind the comparative efficacy of vitamins D2 and D3 at raising 25(OH)D concentrations, and the potential role of vitamin D food fortification as a public health policy to support attainment of dietary recommendations in the UK. The comparative efficacy of vitamins D2 and D3 has been investigated in several intervention trials, with most indicating that vitamin D3 is more effective at raising 25(OH)D concentrations. However, flaws in study designs (predominantly under powering) mean there remains a need for a large, robust randomised-controlled trial to provide conclusive evidence, which the future publication of the D2–D3 Study should provide (BBSRC DRINC funded: BB/ I006192/1). This review also highlights outstanding questions and gaps in the research that need to be addressed to ensure the most efficacious and safe vitamin D food fortification practices are put in place. This further research, alongside cost, availability and ethical considerations (vitamin D3 is not suitable for vegans), will be instrumental in supporting government, decision-makers, industry and consumers in making informed choices about potential future vitamin D policy and practice.

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

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

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.

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

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.

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.

The present paper reviews published literature on the relationship between dietary protein and bone health. It will include arguments both for and against the anabolic and catabolic effects of dietary protein on bone health. Adequate protein intake provides the amino acids used in building and maintaining bone tissue, as well as stimulating the action of insulin-like growth factor 1, which in turn promotes bone growth and increases calcium absorption. However, the metabolism of dietary sulphur amino acids, mainly from animal protein, can lead to increased physiological acidity, which may be detrimental for bone health in the long term. Similarly, cereal foods contain dietary phytate, which in turn contains phosphate. It is known that phosphate consumption can also lead to increased physiological acidity. Therefore, cereal products may produce as much acid as do animal proteins that contain sulphur amino acids. The overall effect of dietary protein on physiological acidity, and its consequent impact on bone health, is extremely complex and somewhat controversial. The consensus is now moving towards a synthesised approach. Particularly, how anabolic and catabolic mechanisms interact; as well as how the context of the whole diet and the type of protein consumed is important.

Objective: Vitamin D deficiency (serum 25-hydroxyvitamin D˂25nmol/L) is extremely common in western-dwelling South Asians but evidence regarding vitamin D supplement usage in this group is very limited. This work identifies demographic, dietary and lifestyle predictors associated with vitamin D supplement use. Design: Cross-sectional analysis of baseline vitamin D supplement use data. Setting: UK Biobank cohort. Subjects: In total, n 8024 South Asians (Bangladeshi, Indian, Pakistani), aged 40-69 years. Results: Twenty-three % of men and 39% of women (P˂0.001) [22% of Bangladeshis, 32% of Indians, 25% of Pakistanis (P˂0.001)] took a vitamin D containing supplement. Median vitamin D intakes from diet were low at 1.0-3.0 micrograms per day, being highest in Bangladeshis and lowest in Indians (P˂0.001). Logistic regression modelling showed that females had a higher odds of vitamin D supplement use than males (odds ratio (OR) = 2.02; 95% confidence interval (CI) 1.79 to 2.28). A lower supplement usage was seen in younger persons (40-60 years) (OR=0.75; 95% CI 0.65 to 0.86 reference= ˃60 years), and those living outside of Greater London (OR=0.53 to 0.77), with borderline trends for a lower body mass index, higher oily fish intake and higher household income associated with increased odds of vitamin D supplement use. Conclusions: Vitamin D supplements were not used by most South Asians and intakes from diet alone are likely to be insufficient to maintain adequate vitamin D status. Public health strategies are now urgently required to promote the use of vitamin D supplements in these specific UK South Asian sub-groups.

The principal objectives of the D-FINES study are to compare vitamin D status, food intake, bone health indices and sunlight exposure in Caucasian and Asian women living in Southern England. It is known that in women both muscle and fat mass influence whole-body BMD(1) and the aim of the present subsidiary study was to examine for differences in body composition and compare the relationship between body composition components in Asian and Caucasian women. Measurements of body composition were undertaken in seventy-two Asian and 227 Caucasian women in autumn–winter (A/W) with a follow-up assessment in spring–summer (S/S) by dual X-ray absorptiometry (QDR-4500; Hologic Inc., Bedford, MA, USA). Measures of whole-body bone mineral density (BMD), whole-body bone mineral content (BMC), fat mass and lean mass were undertaken. Regional as well as total measurements were available.

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.

Background Adolescents are a population group at high risk of low vitamin D status, yet the evidence base for establishing dietary vitamin D requirements to ensure adequacy remains weak. Objective To establish the distribution of vitamin D intakes required to maintain serum 25- hydroxyvitamin D [25(OH)D] concentrations above proposed cut-offs (25, 30, 40 and 50 nmol/L) during the winter-time in white males and females (14-18 years) in the UK (51o 9 N). Design In a dose-response trial, 110 adolescents (age 15.9 ± 1.4 years; 43% male) were randomizedto receive daily 0, 10 or 20 µg vitamin D3 supplements for 20 weeks during the winter-time. A non-linear regression model was fit to the total vitamin D intake (diet plus supplemental) and post-intervention serum 25(OH)D concentrations, and regression predicted values were used to estimate the vitamin D intakes required to maintain serum 25(OH)D concentrations above specific cut-offs. Results Mean (± SD) serum 25(OH)D concentrations increased from 49.2 ± 12.0 to 56.6 ± 12.4 nmol/L and from 51.7 ± 13.4 to 63.9 ± 10.6 nmol/L in the 10 and 20 µg/day groups respectively, and decreased in the placebo group from 46.8 ± 11.4 to 30.7 ± 8.6 nmol/L (all p ≤ 0.001). Vitamin D intakes required to maintain post-intervention 25(OH)D concentrations > 25 and > 30 nmol/L in 97.5% of adolescents were estimated as 10.1 and 13.1 µg/day respectively, and 6.6 µg/day to maintain 50% of adolescents > 40 nmol/L. As the response of 25(OH)D plateaued at 46 nmol/L, there is uncertainty in estimating the vitamin D intake required to maintain 25(OH)D > 50 nmol/L in 97.5% of adolescents, but it did exceed 30 µg/day Conclusions Vitamin D intakes of between 10 and ~30 µg/day are required by white adolescents during the winter-time in order to maintain serum 25(OH)D concentrations > 25 – 50 nmol/L, depending on the serum 25(OH)D threshold chosen.

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.

There is still limited data on the association between 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and bone health in healthy younger adults, particularly in Latin America. This cross-sectional analysis aimed to investigate the associations of 25(OH)D and plasma PTH concentrations with bone parameters, and potential confounders, in women living in a high (England) or low (Brazil) latitude country. Bone was assessed by either peripheral quantitative computed tomography (pQCT) (England) or dual-energy x-ray absorptiometry (DXA) scan (Brazil), serum 25(OH)D concentrations by high performance liquid chromatography tandem mass spectrometry (HPLC-MS) and PTH by the chemiluminescent method. In participants living in England, total volumetric bone mineral density (vBMD) was significantly higher in women

Now widely adopted on courses throughout the world, the prestigious Nutrition Society Textbook series provides students with the scientific basics in nutrition in the context of a systems and disease approach rather than on a nutrient by nutrient basis. In addition books provide a means to enable teachers and students to explore the core principles of nutrition and to apply these throughout their training to foster critical thinking at all times. This NS Textbook on Sport and Exercise Nutrition has been written to cover the latest information on the science and practice of sport and exercise nutrition. A key concept behind this textbook is that it aims to combine the viewpoints of world leading nutrition experts from both academia/research and a practical stand point. Plus where necessary there are additional practitioner based authors to ensure theory is translated into practice for each chapter in the form of either 'practice tips' or 'information sheets' at the end of relevant chapters. The textbook in essence can be divided into three distinct but integrated parts: Part 1: covers the key components of the science that supports the practice of sport and exercise nutrition including comprehensive reviews on: nutrients both in general and as exercise fuels; exercise physiology; hydration, micronutrients; and supplements. Part 2: moves into focusing on specific nutrition strategies to support different types of training including: resistance; power/sprint; middle distance/speed endurance; endurance; technical/skill, team; and specific competition nutrition needs. The unique format of this textbook is that it breaks down nutrition support into training specific as opposed to the traditional sport specific support. This reflects the majority of current sport and exercise requirements of the need to undertake concurrent training and therefore facilitating targeted nutrition support to the different training components through the various macro and micro training cycles. Part 3: explores some of the practical issues encountered in working in the sport and exercise nutrition field and includes key sport related topics such as: disability sport; weight management; eating disorders; bone and gut health; immunity; injury; travel; and special populations and situations. READERSHIP: Students of nutrition and dietetics at both undergraduate and postgraduate level. All those working in the field of nutrition and related health sciences. © 2011 The Nutrition Society.

Background: The relationship between Vitamin D (VitD) and insulin sensitivity and secretion in Type-2 diabetes (T2D) has been shown to be different amongst different ethnic populations. In Saudi Arabia, where both T2D and VitD deficiency are highly prevalent health concerns, little is known about the relationship between VitD, insulin sensitivity, resistance and the relative importance of ethnicity. Our primary aim in this study was to investigate influence of ethnicity on VitD association with glycaemic profile and to measures of obesity as a secondary outcome, among multiethnic postmenopausal women with T2D in Saudi Arabia. Methods: A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Postmenopausal females (n = 173, age ≥ 50 years) with T2D were randomly selected in this study. Anthropometric measures and fasting blood samples were obtained for all study participants. Several biochemical parameters were measured including 25-hydroxyvitamin D (25(OH)D), glycosylated hemoglobin (HbA1c), insulin, glucose and c-peptide. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment 2 for insulin resistance and beta cell activity (HOMA2-IR, HOMA2-β). Results: Overall, 25(OH)D was inversely associated with fasting glucose (r=-0.165, P=0.037), insulin (r=-0.184, P=0.02), C-peptide (r=-0.19, P=0.015) and HOMA2- IR C-peptide (r=-0.23,P=0.004). Additionally, serum 25 (OH)D showed a negative correlation with body weight (r=-0.173 P=0.028), waist and hip circumferences (r=-0.167, P=0.033; r=-0.22, P=0.004 respectively) but not with body mass index (BMI) or waist hip ratio (WHR). In the white ethnic group but not in black or Asian population groups, 25(OH)D level was also associated with only serum fasting C-peptide and HOMA2-IR C-peptide and BMI (P

Background: There are conflicting views in the literature as to whether vitamin D2 and vitamin D3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D2 or vitamin D3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20–64 y (n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D2, biscuit supplemented with 15 μg vitamin D2, juice supplemented with 15 μg vitamin D3, or biscuit supplemented with 15 μg vitamin D3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography–tandem mass spectrometry at baseline and at weeks 6 and 12 of the study. Results: Postintervention in the 2 ethnic groups combined, both the vitamin D3 biscuit and the vitamin D3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) (P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) (P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) (P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) (P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) (P < 0.0002)]. Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D3 was more effective than vitamin D2 in increasing serum 25(OH)D in the wintertime. Vitamin D3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591.

The aim of this presentation was to assess the impact of a 'vegetarian diet' on indices of skeletal integrity. Analyses of existing literature were assessed in relation to bone health for: lacto-ovo-vegetarian and vegan diets vs. omnivorous; predominantly meat diets; consumption of animal vs. vegetable protein; fruit and vegetable consumption. The key findings include: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone, with high and low protein intake being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. © 2007 Elsevier B.V. All rights reserved.

Few data exist on the effect of dietary and lifestyle factors on indices of bone health in women living in Middle Eastern countries. As part of our on-going bone health study in 212 Saudi Arabian women, a total of 100 premenopausal and 112 postmenopausal women living in the city of Jeddah were studied. They were aged 20-30 years and 45-60 years, respectively. Measurements were made on weight and height as well as spine, hip and calcaneal bone mass. All subjects were interviewed concerning their habitual dietary intake, physical activity levels and general lifestyle. Prevalence of osteopenia and osteoporosis was common amongst postmenopausal women. Vitamin D deficiency was extensive in both the pre- and postmenopausal women Saudi women. Further analysis of the dataset are required to examine extensively the effect of diet on bone health in Middle Eastern women, but these data are a cause for concern regarding the extent of vitamin D deficiency. © 2007 Elsevier B.V. All rights reserved.

Background: Epidemiological studies have supported inverse associations between low serum 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk markers, but few randomized trials have investigated the effect of vitamin D supplementation on these markers in adolescents. Objective: The objective of this study was to investigate the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in white, healthy 14-18 year-old adolescents in the UK (51°N) as part of the ODIN Project. Methods: In a dose-response trial, 110 adolescents (15.9±1.4 years; 43% male; 81% normal weight) were randomly assigned to receive 0, 10 or 20 μg/day vitamin D3 for 20 weeks (October-March). Cardiometabolic risk markers including BMI-for-age z-score (BMIz), waist circumference, systolic and diastolic blood pressure, fasting plasma triglycerides, cholesterol (total, HDL, LDL and total:HDL) and glucose were measured at baseline and endpoint as secondary outcomes, together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint, adjusted for the baseline value of the outcome variable and additionally for age, sex, Tanner stage, BMIz and baseline serum 25(OH)D. Results: Mean±SD baseline serum 25(OH)D was 49.1±12.3 nmol/L and differed between groups at endpoint with concentrations of 30.7±8.6, 56.6±12.4 and 63.9±10.6 nmol/L in the 0, 10 and 20 μg/day groups respectively (P≤0.001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers (all P>0.05), except for lower HDL (-0.12 mmol/L, 95% CI -0.21, 0.04, P=0.003) and total cholesterol (-0.21 mmol/L, 95% CI -0.42, 0.00, P=0.05) in the 20 compared to the 10 μg/day group, which disappeared in the fully adjusted analysis (P=0.27 and P=0.30 respectively). Conclusions: Supplementation with vitamin D3 at 10 and 20 μg/25 day, which increased serum 25(OH)D concentrations during the winter-time, had no effect on markers of cardiometabolic risk in healthy 14-18 year-old adolescents. This trial was registered at clinicaltrials.gov as NCT02150122.

The link between vitamin D and bone health is well established. However, little is known about the bone health, vitamin D status, and lifestyle characteristics of women living in Saudi Arabia. To characterize: i) bone health indices; ii) vitamin D status; iii) potential influential of sunlight exposure and physical activity level. A total of 100 premenopausal aged 20-30 years and 112 postmenopausal aged 45-60 years were included. Bone mineral density was determined at the lumbar spine and femoral neck. Serum levels of 25-hydroxyvitamin D, intact parathyroid hormone, and ionized calcium and phosphorus were measured. The subjects interviewed about their physical activity levels and lifestyle. Using the WHO criteria, 37% of the premenopausal and 52% of the postmenopausal were osteopenic at the lumbar spine. Vitamin D deficiency was highly prevalent in Saudi women, with 98% of women being below the IOM recommended level of 50nmol/L. There was a significant correlation between duration of sunlight exposure (min/day) and axial BMD and calcaneal bone mass in partly veiled women. These data indicate that younger and older Saudi Arabian women had poor bone health and that their vitamin D status and lifestyle factors do not promote skeletal integrity. © 2013. Marsland Press, Zhengzhou University.

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.

Aim: Bone turnover is a well studied phenomenon, however it is still unclear as to whether bone shows a season driven rhythm over the course of the year, particularly in ethnic groups. Some studies have found a significant seasonal variation in bone resorption markers but others have not. This study aimed to establish if bone turnover shows significant seasonal variation as this has practical implications in terms of the use of bone markers in diagnostics. Method: The D-FINES study (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) 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 on a cobas e411 automated analyser (Roche Diagnostics). Results: As shown in the Figure above, a mixed between-within subjects ANOVA showed there was no significant main effect of season 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 between the 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. The lower sCTX in the younger premenopausal groups is as would be expected. However, unexpectedly, there was a non-significant trend in the postmenopausal groups for the A women to have a lower mean sCTX than the C women. In contrast, in the premenopausal women, the sCTX was lower in the C group. Therefore 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. Conclusions: Overall, no evidence for a seasonal variation in bone resorption was found here but there was evidence for a menopausal difference in bone resorption. However, numbers of participants in this preliminary analysis was small, and the trend for an ethnic difference in the postmenopausal women might be statistically significant with higher subject numbers. Further analysis with a larger sample is planned.

Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D(2) and D(3) in the raising of serum 25-hydroxyvitamin D [25(OH)D].

The relative contribution of UVB sunlight exposure and dietary vitamin D intake to 25-hydroxyvitamin D (25(OH)D) remains to be fully determined. The aim of this study was to examine these factors in combination using a repeated measures multilevel modelling approach. The D-FINES study investigated 373 Surrey Caucasian and Asian women in four seasons of the year for 25(0H)D, dietary vitamin D and UVB exposure. To capitalise on the clustered nature of the repeated seasonal measurements within individuals, multilevel modelling was undertaken using MLwiN v.2.1software. Thus seasonal data (dietary vitamin D (DietaryVitD), UV exposure (UVdosi), vitamin D status (VitDstatus)) were included at level one (ij) and individual level data (ethnicity, menopausal status (0=Caucasian, 1=Asian; 0=Premenopausal, 1=Postmenopausal)) at level two (j). Using a random intercept model, the following equation was constructed, which was significantly different from an intercept only model (Log likelihood test- Chi square X2= 2216.51, df=5, p

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.

Vitamin D is a unique nutrient. Firstly, it acts as a pro-hormone and secondly, the requirement for vitamin D can be met by both endogenous synthesis from sunlight and by dietary sources. This complicates the determination of dietary requirements for vitamin D, which along with the definition of optimal vitamin D status, have been highly controversial and much debated over recent years. Adolescents are a population group at high risk of low vitamin D status, which is concerning given the important role of vitamin D, and calcium, in promoting normal bone mineralisation and attainment of peak bone mass during this rapid growth phase. Dietary vitamin D recommendations are important from a public health perspective in helping to avoid deficiency and optimise vitamin D status for health. However limited experimental data from winter-based dose-response randomised trials in adolescents has hindered the development of evidence-based dietary requirements for vitamin D in this population group. This review will highlight how specifically designed randomised trials and the approach adopted for estimating such requirements can lead to improved recommendations. Such data indicates that vitamin D intakes of between 10 and ~30 µg/day may be required to avoid deficiency and ensure adequacy in adolescents, considerably greater than the current recommendations of 10-15 µg/day. Finally this review will consider the implications of this on public health policy, in terms of future refinements of vitamin D requirement recommendations and prioritisation of public health strategies to help prevent vitamin D deficiency

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.

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.