Dr Andrea Darling

Vitamin D can be sourced from food and produced from skin exposure to sunlight.(1) In Australia and worldwide, vitamin D deficiency is highly prevalent. Data shows that 23% of the Australian population are considered to be vitamin D insufficient (25(OH)D < 50 nmol/L), increasing to 36% during the winter.(2) Current estimated average intakes do not meet dietary recommendations.(3) A lack of vitamin D, and thus reduced absorption of calcium, results in leaching of calcium stored in the bones leading to poor musculoskeletal health.(1) The aim of this study is to determine the impact that latitude, skin type, diet and sun exposure have on vitamin D status of healthy Australian women and to explore the rates and potential causes of deficiency. This cross-sectional study was conducted in Wollongong, Australia (34.42°S) during winter 2020 and spring 2021 with 100 women (> 18 years, pre- or post-menopausal). Skin types were self-defined. Serum 25(OH)D was measured through liquid chromatography mass spectrometry, dietary intake through a 4-day food record analysed using FoodWorks 10, bone density through dual energy x-ray absorptiometry and sun exposure through a polysulphone film badge worn for 4 days. Participants were aged 41.4 ± 15.5 years and 98 women had valid serum 25(OH)D measurements. Of these, n = 1 (1.0%) was deficient (< 25 nmol/L), n = 14 (14.3%) were insufficient (25–50 nmol/L) and n = 41 (41.8%) were sufficient (> 50 nmol/L), while n = 42 (42.9%) had an optimal status (> 75 nmol/L) of vitamin D. The mean 25(OH)D was significantly different across skin type groups (white compared to moderate brown skin types) (F(4,93) = 2.6, p = 0.04), whilst average sun exposure (SED) of 1.1 ± 1.0 was on the borderline of significantly predicting 25(OH)D levels (F(1, 92) = 3.74, p = 0.06). A significant positive correlation existed between 25(OH)D and total bone mineral density (r(96) = 0.27, p < 0.001). Mean vitamin D intake (n = 94) was 3.1 ± 3.0 μg/day, with the majority of participants (86.2%) having intakes below.(3) Logistic regression, controlling for age, showed that an increase in reported calcium intake (OR = 1.0, 95% CI [1.0, 1.0], p = 0.01), average SED (OR = 0.0, 95% CI [0.0, 1.3], p < 0.001) and having a lighter skin type (OR = 7.0, 95% CI [1.1, 43.3], p = 0.04) were significantly associated with reduced odds of deficiency/insufficiency. Serum 25(OH)D was found to be higher than reported in previous Australian data,(2) which is favourable given the essential role vitamin D plays in calcium homeostasis and musculoskeletal health. However, reported dietary vitamin D intakes were low. Given the increased risk of melanoma from excessive sun exposure, targeted advice towards vitamin D-rich food sources may be helpful for those individuals with poorer vitamin D status.

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.

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.

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.

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

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

There is an urgent need to assess risk factors affecting individual likelihood of contracting the novel SARS-CoV-2 virus, and development of COVID-19. One potential risk factor is vitamin D deficiency(Reference Lanham-New1). Vitamin D is important for immune defence against pathogens as it promotes macrophage antimicrobial responses and the regulation of antigen-presenting dendritic cells and suppressor T-cells(Reference Hewison2). However, it is unclear whether 25(OH)D concentration is associated with risk of contracting SARS-CoV-2 and/or developing COVID-19. We aimed to assess whether there is an association between serum 25(OH)D status and odds of testing positive for SARS-CoV-2, when controlling for confounders such as body mass index (BMI) and ethnicity.

The spread of novel SARS-CoV-2 virus, and the disease COVID-19 that is caused by SARS-CoV-2, continues apace. Saving lives and slowing the worldwide pandemic remain of utmost importance to everyone: the public, healthcare professionals, scientists, industry and governments. It is absolutely essential that advice given to the public is evidence-based, accurate and timely; anything less would mislead and has the potential to cause harm. Popular information channels, such as social media platforms, have been rife with misinformation that has been perpetuated by fear and uncertainty. This has been the case particularly for diet and lifestyle advice. There are recommendations for the prevention of the spread of COVID-19 from the WHO,1 the UK,2 Irish3 and USA4 governments and the European Commission,5 as well as public health and healthcare agencies, including key direction on self-isolation.6 This short original report aims to provide a balanced scientific view on vitamin D and SARS-CoV-2 virus/COVID-19 disease. It provides a succinct summary of the current scientific evidence of associations between vitamin D, influenza, upper respiratory tract infections (URTIs) and immune health. Importantly, the paper concludes with lifestyle strategies for avoiding vitamin D deficiency and ensuring a healthy balanced diet at any time, including during the current pandemic. The overarching messages are as follows: (1) Vitamin D is essential for good health. (2) Many people, particularly those living in northern latitudes (such as the UK, Ireland, Northern Europe, Canada and the northern parts of the USA, northern India and China), have poor vitamin D status, especially in winter or if confined indoors. (3) Low vitamin D status may be exacerbated during this COVID-19 crisis (eg, due to indoor living and hence reduced sun exposure), and anyone who is self-isolating with limited access to sunlight is advised to take a vitamin D supplement according to their government’s recommendations for the general population (ie, 400 IU/day for the UK7 and 600 IU/day for the USA (800 IU for >70 years))8 and the European Union (EU).9 (4) There is no strong scientific evidence to show that very high intakes (ie, mega supplements) of vitamin D will be beneficial in preventing or treating COVID-19. (5) There are evidenced health risks with excessive vitamin D intakes especially for those with other health issues such as a reduced kidney function.

Vitamin D deficiency may have an important role in the development of Type-2 diabetes(Reference Pittas, Dawson-Hughes, Sheehan, Ware, Knowler and Aroda1,Reference Kayaniyil, Vieth, Retnakaran, Knight, Qi and Gerstein2) . Low vitamin D concentration has broad-ranging effects that are both directly (by activation of the vitamin D receptor) and indirectly (by modulation of intracellular calcium concentration) related to impaired pancreatic β-cell function and insulin resistance(Reference Norman, Frankel, Heldt and Grodsky3). The purpose of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on insulin resistance and glycaemic control in participants with prediabetes.

Adequate intakes of the B vitamins are essential for health; however there is a lack of data concerning B vitamin intakes in UK dwelling South Asian (SA) groups. We aimed to investigate whether UK SA women meet the LRNI for B vitamins, and whether their intake differs from same-age White Caucasian (WC) women. We used summer 2006 dietary intake data from the Food Standards Agency (FSA) funded D-FINES study (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England, project N05064). After removal of over- and under-reporters (energy: BMR ratio < 1 or > 1.6) there were n = 29 SA and n = 146 WC subjects. The two groups did not differ significantly in age and BMI. Overall mean (SD) for age was 50.6 (13.6) years and for BMI was 26.8 (4.8). In SA, 41% were Bangladeshi or Pakistani, 28% were Indian and 31% were of other ethnicity. Independent T-tests, using log transformed data, showed no statistically significant differences for any B vitamin (Bonferroni revised p value: < 0.008). Results were as follows, giving median (IQR): Thiamine (mg) 1.5 (0.5) SA vs 1.4 (0.5) WC; (P = 0.8); Riboflavin (mg) 1.3 (0.5) SA vs. 1.5 (0.6) WC (P = 0.08); Niacin (mg) 30.7 (13.7) SA vs 33.3 (9.8) WC (P = 0.4); B6 (mg) 1.7 (0.5) SA vs 1.9 (0.7) WC (P = 0.2); B12 (micrograms) 2.8 (0.05) SA vs 3.6 (2.5) WC (P = 0.02); Folate (micrograms) 213 (93) SA vs 231 (82) WC (P = 0.8). In terms of percentages below the LRNI: Thiamine 0% SA and 0.7% (n = 1) WC; Riboflavin 0% SA and 1.4% (n = 2) WC; B12 10% (n = 3) SA and 0% WC. For Niacin, B6 and Folate no women in either group were below the LRNI. Overall, there were no ethnic differences in B vitamin intake by ethnicity. There was a trend for a slightly lower B12 intake in SA but this did not reach statistical significance after adjustment for multiple testing. It is of concern that 10% of SA did not meet the LRNI for B12. Of this 10%, the majority were not vegetarian or vegan. The sample size for SA was very small and further research is now required in a larger sample to confirm this finding. The D-FINES study was funded by the UK FSA (N05064). The views expressed are those of the authors alone.

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.

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.

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.

Published studies have suggested a high prevalence of 25-hydroxyvitamin D (25OHD) deficiency in western dwelling South Asians, particularly in women. However, sample sizes have been relatively small with few men. Moreover, South Asians are vastly under-represented in national dietary surveys and further research into 25(OH)D status is needed. The UK Biobank is a cohort of 500,000 individuals; n 6433 are of South Asian ethnicity and have baseline serum 25(OH)D data (2006–2010, aged 40–69 years). Blood draws were spread across the year. Of note, the 25(OH)D measurements were produced using the DiaSorin Liaison XL assay which underestimates 25(OH)D by 4% at 25nmol/L, but overestimates 25(OH)D by 5–10% at ≥ 40nmol/\L(1). We used the commonly used cut-points of < 25nmol/L (deficiency), < 50nmol/L (insufficiency). In women (n 2927), median (IQR) was 24.3 (20.5) nmol/L with 50.4% < 25nmol/L, and 88.6% < 50nmol/L. In men (n 3506), median (IQR) was 21.7 (16.2) with 58.4% < 25 nmol/L and 93.8% < 50 nmol/L. Of concern, 17.8% of women and 21.1% of men had 25(OH)D < 15nmol/L. A Mann Whitney test showed that gender differences were statistically significant (P < 0.0001). In terms of ethnic sub-groups, in the Bangladeshi group (n 207), median (IQR) was 26.1 (14.3) nmol/L with 43.5% < 25nmol/L and 91.3% < 50nmol/L. In the Indian group (n 4792), median (IQR) was 23.8 (19.3) with 52.0% < 25nmol/L and 90.4% < 50nmol/L. Finally, in the Pakistani group (n 1434) median (IQR) was 19.3(14.5) with 65.7% < 25nmol/L and 94.9% < 50nmol/L. A Kruskal Wallis test showed that ethnic subgroup differences were statistically significant (P < 0.0001). To the authors’ knowledge, this is the largest analysis to date of 25(OH)D status in European dwelling South Asians. Deficiency of 25(OH)D was almost universal, with 50% or more not even reaching 25nmol/L. Of great concern, 20% of participants had levels < 15nmol/L which, although not a widely used cut-off point, still represents severe deficiency and likely osteomalacia. Moreover, these results are most probably an underestimation of this societal challenge as the UK Biobank is likely to contain participants that are healthier and more educated than the general population. In conclusion, our analyses suggest the need for urgent public health interventions to prevent and treat vitamin D deficiency in UK South Asians. This research was conducted using the UK Biobank Resource under application number 15168.

Osteosarcopenia is a condition of combined osteoporosis and sarcopenia, both of which are associated with aging. Osteoporosis, sarcopenia, and osteosarcopenia are all highly prevalent globally in aging populations. Vitamin D has been associated with a variety of health conditions, including musculoskeletal health, heart disease, cancer, autoimmune disease, and infectious disease. It is therefore a potential contributing factor to the risk of osteosarcopenia. Like osteosarcopenia, vitamin D deficiency is highly prevalent globally in older people. If vitamin D deficiency contributes to the development of osteoporosis, sarcopenia, and osteosarcopenia then it will be important to address vitamin D deficiency and concurrent high parathyroid concentrations. This chapter will discuss how vitamin D and parathyroid hormone affect bone and muscle health. It will also discuss research assessing the impact of vitamin D deficiency on osteoporosis and sarcopenia as separate entities, as well as newer research assessing the impact of vitamin D deficiency on osteosarcopenia specifically.

Vitamin D deficiency is a global health issue(Reference Wilson, Tripkovic and Hart1). However, little is known about the vitamin D status of the United Kingdom (UK) African-Caribbean (AC) population, even though this population group is likely at increased risk of vitamin D deficiency, due to latitude and skin type(Reference Wilson, Tripkovic and Hart1,Reference Clemens, Adams and Henderson2) . This cross-sectional study explored the 25(OH)D concentration and vitamin D intake of AC individuals from the UK Biobank Cohort, who were aged 40 years and over at baseline (2006–2010). For context, the AC population was also compared to the African (AF), South Asian (SA) and White European (WE) subsets of the UK Biobank. For AC, n = 4046 had a valid 25(OH)D measurement. Of these, n = 1499 (37.0%) were deficient (50nmol/L). Median (IQR) for 25(OH)D was 30.0 (20.9) nmol/L and median vitamin D intake was 1.6 (2.6) μg/day, with only n = 64 (4.8%) of AC meeting the UK recommended nutrient vitamin D intake of 10μg/day. For the other ethnic groups, the median (IQR) for 25(OH)D concentration was 30.2 (20.0) nmol/L in AF, 20.7 (18.5) nmol/L in SA and 49.2 (29.5) nmol/L in WE. Logistic regression showed that brown/black skin type (OR 1.77, 95% CI 1.19,2.63), winter blood draw (OR 1.22, 95% CI 0.98, 1.51), not consuming oily fish (OR 1.74, 95% CI 1.19, 2.54) and not using vitamin D supplements (OR 2.97, 95% CI 2.50, 3.53) were predictors of increased odds of vitamin D deficiency (

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.

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.

Aims: There has been uncertainty whether SGLT2 inhibition predisposes to hyperkalaemia or is protective from it. We therefore performed a meta-analysis to assess effects of SGLT2 inhibition on serum-potassium and hyperkalaemia-events in T2DM.Methods: MEDLINE and PubMed databases were searched for 'hyperkalaemia' or 'potassium', with SGLT2 inhibitors in T2DM, to 31st December 2020. Randomised controlled trials, with potassium or hyperkalaemia as primary or secondary outcomes, were included. Cochran's Q test and I2 statistic assessed statistical heterogeneity. Meta-analyses were performed using Cochrane-RevMan with two outcomes: i) Odds ratio (OR) of hyperkalaemia-events between SGLT2 inhibitor and placebo (fixed-effects), ii) Mean difference (MD) in change from baseline potassium between SGLT2 inhibitor and placebo (random-effects).Results: Of 1724 identified publications, nine were included in the meta-analysis (n=3 hyperkalaemia event; n=5 serum-potassium; n=1 reported both outcomes). Pooled OR for hyperkalaemia-events for SGLT2 inhibitor vs placebo was 0.72 [95% confidence interval (CI) 0.61 to 0.85, P<0.001], I2 of 9%. The pooled MD in serum-potassium concentration with SGLT2 inhibitor vs placebo was -0.04 mmol/L [95% CI -0.08 to 0.00 mmol/L; P=0.04], I2 of 89%.Conclusions: Use of SGLT2 inhibitors in T2DM reduced odds of inducing hyperkalaemia but had a minimal effect of lowering serum potassium.Keywords: SGLT2; diabetes mellitus; hyperkalaemia; nephrology; potassium.

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

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.

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.

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

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.

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

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.

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.

The Ehlers-Danlos Syndromes (EDS) are disorders of the connective tissue. EDS presents clinical manifestations potentially related to hypovitaminosis D, such as skeletal and bone health issues (musculoskeletal pain, osteopenia, osteoporosis, osteoarthritis) (Reference Tinkle, Castori and Berglund1), whilst other characteristics of this syndrome can hinder vitamin D intake, such as gastrointestinal issues, dysphagia and disordered eating (Reference Baeza-Velasco, Lorente and Tasa-Vinyals2). Concomitantly, pain and dysautonomia may promote indoor living (Reference Kalisch, Hamonet and Bourdon3) and reduce exposure to UVB irradiation, which could affect vitamin D status. This study aimed to identify whether females with EDS are more likely to have lower serum 25- hydroxyvitamin D (25(OH)D). This was a cross-sectional study, analysing data from 224 EDS cases and 224 controls, using UK Biobank baseline data. The UK Biobank cohort includes over 500 K individuals, aged 40–69 years at baseline (data collection 2006–2010). The UK Biobank study was conducted according to the Declaration of Helsinki and all procedures were approved by the UK North West Multi-Centre Research Ethics Committee (MREC); application 11/NW/0382. Written informed consent was obtained from all subjects.

The aim of the present study was to assess the seasonal relationship between serum 25(OH)D concentration, lean mass and muscle strength. This was a secondary data analysis of a subgroup of 102 postmenopausal women participating in the 2006–2007 D-FINES (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) study. The cohort was assessed as two age subgroups:

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.

Vitamin D is unlike any other nutrient, with the majority of the vitamin derived from sunlight rather than food(Reference Chen, Chimeh and Lu1,Reference Jones2) . There is a lack of research looking into the vitamin D status of the African-Caribbean population worldwide. This population may be at high risk of vitamin D deficiency because of their darkly pigmented skin that hinders ability to synthesise vitamin D cutaneously, especially in those living at higher latitudes(Reference Chen, Chimeh and Lu1). The aim of this study was to investigate the vitamin D status (as measured by 25(OH)D and dietary intake) of the African-Caribbean population globally.

Little published data has assessed the association between socio-economic deprivation and 25- hydroxyvitamin D (25(OH)D) concentration. One study found low socio-economic status predicted vitamin D deficiency(Reference Leger-Guist'hau, Domingues-Faria and Miolanne1), but another did not(Reference Ersoy, Kizilay and Yilmaz2). Our objective was to assess the relationship between 25(OH)D and Townsend Deprivation Index (TDI) in a large sample, using data from the UK Biobank Cohort, which has data on 502,000 individuals (baseline 2006–2010, aged 40 years or over). Blood draws, for measurement of serum 25(OH)D by the DiaSorin Liaison XL assay, were spread across the year with each participant sampled once. The UK Biobank holds ethical approval from UK North West Multi-Centre Research Ethics Committee (11/NW/0382).

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.

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.

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.

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

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

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.

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

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 (

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.

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.

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.

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.

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 

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.

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.

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.