Vitamin D-fortified foods are a proven effective method of improving vitamin D status (1) ; however, the magnitude of the effect varies across populations and interventions (2) . This conservative meta-analysis and meta-regression aimed to assess the overall effect of vitamin D-fortified foods on serum 25-hydroxyvitamin D (25(OH)D) concentrations and to explore potential moderators influencing this response. A literature search of PubMed was conducted on 23 January 2024. A conservative approach was taken, with RCTs only eligible for inclusion if the control and intervention foods were identical, apart from vitamin D fortification of the treatment arm, allowing the effect of fortification to be isolated with minimal risk of confounding. Of 701 publications identified by the initial search, 25 studies were deemed eligible for inclusion. A random-effects meta-analysis was conducted to estimate the overall effect of fortification on serum 25(OH)D concentrations. Due to the limited number of studies, univariate meta-regression analyses were used to test potential moderators. Baseline serum 25(OH)D, vitamin D dose, intervention duration, sample size, and food type (animal or plant based) were included in this analysis. Significant moderators were then incorporated into a final multivariate model. Sensitivity analyses were performed to evaluate the robustness of findings. Random effects meta-analysis found that vitamin D-fortified foods significantly increase serum 25(OH)D concentrations (weighted mean difference: 24.4 nmol/L, 95% CI: 17.4 to 31.5, p < 0.001) but substantial heterogeneity (I 2 = 98%) was present. Meta-regression revealed that baseline serum 25(OH)D (p = 0.002) and dose (p < 0.001) were significant independent predictors of response, explaining 53.9% of the between-study variance (R 2 = 53.9%). Leave-one-out analysis identified two studies of note: exclusion of an outlier study, with an exceptionally high dose, reduced model fit and rendered dose non-significant (R 2 = 36.5%, dose p = 0.058), whereas removal of a second influential study increased model fit (R 2 = 72.5%). A model excluding both studies explained 61.8% of the heterogeneity, with dose (p = 0.004) and baseline 25(OH)D (p < 0.001) remaining significant predictors. This confirms the effectiveness of vitamin D-fortified foods in raising serum 25(OH)D concentrations, however, the degree of response is influenced by baseline 25(OH)D and dose, with poorer baseline status and higher doses generally producing greater increases. Surprisingly, duration was not found to moderate response, perhaps due to lower compliance at longer durations, or a reduced effect as concentrations increased. Substantial heterogeneity remains, suggesting the contribution of additional unmeasured factors.
Vitamin D and iron deficiencies are highly prevalent globally, with evidence of a complex interaction (1) . However, the extent to which these micronutrients interact, and whether this changes according to age and sex, remains uncertain. Understanding the association between vitamin D and iron could help address these nutrient insufficiencies concurrently, rather than as two independent public health concerns. The aim of this study was to determine the association between vitamin D (serum 25-hydroxyvitamin D (25(OH)D)) and iron (haemoglobin and ferritin) status in men and women of reproductive age. Secondary analysis of Years 9-11 (2016/17-2018/19) of the UK National Diet and Nutrition Survey (NDNS) Rolling Programme was conducted. Concentrations of blood biomarkers in adults aged 19-49 years were compared to UK Scientific Advisory Committee on Nutrition (SACN) guidance. Spearman’s bivariate correlations were performed to investigate associations between vitamin D and iron status using IBM SPSS Statistics (2024). Descriptive analyses found the percentage of men and women with serum 25(OH)D concentrations below the SACN threshold for increased risk of deficiency (<25nmol/L) (2) , were 18.4% and 17.9%, respectively. Moreover, 62.0% of men and 49.8% of women had insufficient 25(OH)D concentrations (<50nmol/L). For ferritin, 17.0% of women had concentrations below the 15µg/L deficiency threshold, compared to 0.0% of men (3) . Similarly, for haemoglobin, 8.7% of women were below the 120g/L diagnostic deficiency threshold compared to 2.3% of men (<130g/L) (3) . Haemoglobin (g/L) and 25(OH)D (nmol/L) concentrations were not associated in men (rs(172)=-0.019, p=0.802) or women (rs(244)=0.034, p=0.595). However, despite no association found between ferritin (µg/L) and 25(OH)D (nmol/L) in men (rs(175)=-0.022, p=0.766), a significant correlation was observed in women (rs(259)=0.184, p=0.003), albeit with a small effect size. Furthermore, a Kruskal-Wallis test showed a significant difference when comparing median ferritin concentrations by vitamin D status (deficient <25.00nmol/L; insufficient 25-49.99nmol/L; replete ≥50nmol/L) in women (H(2)=8.888, p=0.012). Post-hoc testing revealed no significant difference between ferritin concentrations in women classified as deficient or insufficient (p=0.687 – Bonferroni correction p=1.000), whereas, there was a significant difference between the ferritin concentrations of women who were vitamin D deficient and replete (p=0.015 – Bonferroni correction p=0.046), or insufficient and replete (p=0.015 – Bonferroni correction p=0.046). A significant correlation was found between 25(OH)D and ferritin concentrations in women; moreover, a significant difference was identified when comparing ferritin concentrations by vitamin D status. No associations were found between haemoglobin and 25(OH)D concentrations. In conclusion, these results suggest a potential association between vitamin D and iron status; and that vitamin D adequacy or deficiency/insufficiency may influence concentrations of ferritin, as a marker of iron, and/or vice versa. To further explore these associations between vitamin D and iron status, further analysis will adjust ferritin concentrations by C-reactive protein concentrations and investigate whether seasonality influences observed associations.
BACKGROUND:Vitamin D status has been found to be inversely associated with risk of respiratory tract infections (RTIs). Although vitamin D status varies by ethnicity, the relationship between serum 25-hydroxyvitamin D (25[OH]D) and RTIs in United Kingdom ethnic groups remains unclear. OBJECTIVES:This study aimed to investigate the association between serum 25(OH)D status and hospitalization for RTI in United Kingdom adults. METHODS:An unmatched case-control study was conducted using data from United Kingdom Biobank, which includes 500k adults with serum 25(OH)D status and hospital episodes from linked records. Survival analyses and binary logistic regression models were used to explore the association between serum 25(OH)D and RTIs. RESULTS:Of the 36,258 participants included in the analysis, 34% were White, 28% Asian, 19% Black, 11% other, and 7% of mixed ethnicity. The RTI rate was 8.5% (median time to RTI, 14.8 y). Higher serum 25(OH)D (each +10 nmol/L increase) was significantly associated with a 4% lower hazard ratio (HR) for RTI hospitalization [HR: 0.96, 95% confidence interval (CI), 0.94, 0.99]. When stratifying for serum 25(OH)D, compared to those with ≥75 nmol/L (reference), those with <15 nmol/L had a higher HR for RTI hospitalization (HR: 1.33, 95% CI: 1.05, 1.67). Categories 15 to 24 nmol/L, 24 to 49 nmol/L, and 50 to 74 nmol/L were not statistically significant. Logistic regression models supported the above findings. Inclusion of an interaction term for 25(OH)D × ethnicity was trialed in the survival analysis, but the interaction term was not statistically significant. CONCLUSIONS:Serum 25(OH)D status <15 nmol/L is associated with 33% higher HR for RTI hospitalization among United Kingdom adults, compared with ≥75 nmol/L. Furthermore, studies are warranted to validate these findings and explore the mechanisms underlying the association between vitamin D status and RTIs in different ethnic groups.
Objective: Studies show a high prevalence of vitamin D deficiency in Greece and Cyprus despite an abundance of sunlight. We investigate the vitamin D status of Greeks and Cypriots living in the UK, where sunlight availability is more limited. Design: Cross-sectional study of serum 25-hydroxyvitamin D (25(OH)D) using the UK Biobank cohort. Setting: The UK Biobank is a study of over 500K UK dwelling participants, with baseline measurements from 2006-2010. Participants: A sample of 325 Greek/Cypriot and 4158 British/Irish participants (aged 40-69 years). Results: The Greeks/Cypriots had statistically significantly lower median serum 25-hydroxyvitamin D (25(OH)D) (40.3 nmol/L) compared to the British/Irish (47.6 nmol/L). Eleven percent of British/Irish and 22.8% of Greeks/Cypriots had serum 25(OH)D < 25 nmol/L. Being exposed to summer sunlight for >30 min/d, as well as having a blood draw in summer or autumn, was statistically significantly associated with lower odds of 25 (OH))D < 50 nmol/L. Living in Scotland, having a winter blood draw, and not using a vitamin D-containing supplement were associated with increased odds of 25(OH)D < 50 nmol/L. Ethnicity was not a predictor of 25(OH)D < 50 nmol/L after confounder adjustment (Greek/Cypriot OR = 1.18 (95% CI 0.85, 1.63; British/Irish OR = 1.0). Conclusions: UK dwelling Greeks/Cypriots have a higher prevalence of vitamin D deficiency (<25 nmol/L) compared to the British/Irish population, but evidence from the literature is mixed as to whether they have a higher prevalence than when living in their country of origin. Public health interventions are required to improve 25(OH)D status in UK ethnic minority groups.
Vitamin D deficiency is highly prevalent in the UK (1-2). Low exposure to the sun in winter months, as well as higher risk of deficiency amongst some ethnic minority populations (1), means that fortification of food and beverages remains an important potential route to ensure optimal vitamin D status. However, it is unclear as to whether type of fortified food affects ability to raise vitamin D status. Animal foods (e.g. dairy foods) would be expected to lead to higher vitamin D absorption than would non-animal-based foods (e.g. bread, juice), due to their higher fat content. The primary aim of this systematic review and meta-analysis was to investigate the effectiveness of animal and non-animal-based vitamin D fortified foods on raising serum 25-hydroxyvitamin D (25(OH)D). The literature search was conducted using PubMed on 23 January 2024. Inclusion criteria were as follows: data on non-pregnant/non-lactating adults or data on children, randomised controlled trial; data for 25(OH)D measurement. Initial search results retrieved 701 publications, and 593 ineligible records were removed. Next, 108 records were screened by title and abstract, with 63 records excluded, for the following reasons: off topic (n=54); pregnant or breastfeeding (n=6); non-human (n=1); preterm infants (n=1) and duration <4 weeks (n=1). After full text eligibility screening, 28 publications remained for systematic review and meta-analysis. Ethical approval was not required as this was a literature review. The end point data meta-analysis showed (for all studies combined) a significant increase in 25(OH)D (+23.4 (95% CI 17.0, 29.7) nmol/L (24 studies)). For specific food types, results were as follows: ‘animal’ +21.7 (95% CI 14.1, 29.3) nmol/L (17 studies); mixture of ‘animal’ and ‘non-animal’ +26.1 (95% CI 10.8, 41.4) nmol/L (1 study); ‘non-animal’ +28.1 (95% 12.0, 44.2) nmol/L (6 studies). Contrary to what would be expected, non-animal mode of fortification (e.g. bread, juice) had a similar effect size to animal modes (e.g. dairy), so can be considered equivalent in effectiveness in raising 25(OH)D concentration. Differences in dose, duration and population groups between the non-animal and animal modes (in terms of health and baseline vitamin D status) mean the results should be taken with caution, and future studies where these factors are standardised could be useful to provide further evidence of effectiveness.
CONTEXT:Researchers have identified differences in metabolic activity between vitamins D2 and D3. Moreover, it is suspected from randomized controlled trial data that vitamin D2 supplementation increases the metabolic clearance of 25-hydroxyvitamin D3 [25(OH)D3], but this effect has yet to be quantified. OBJECTIVE:This study sought to undertake a systematic review and meta-analysis of the effect of vitamin D2 supplementation on serum 25(OH)D3 concentrations. DATA SOURCES:PUBMED was searched for articles published from January 1, 1975, to February 1, 2023. Of the 202 articles retrieved, 20 were included in this review, and of those, 11 were suitable for meta-analysis. DATA EXTRACTION:Randomized controlled trials reporting either baseline and postintervention serum 25(OH)D3 concentrations (nmol/L) or absolute changes in concentrations were included. Random-effects meta-analyses were calculated using Review Manager (version 5.3; The Cochrane Collaboration). Mean differences were reported with 95% CIs. DATA ANALYSIS:In meta-analyses there was a reduction in serum 25(OH)D3 after vitamin D2 supplementation compared with control for end-of-trial between-groups data (random weighted mean difference [WMD] = -17.99 nmol/L; 95% CI, -25.86 to -10.12; P < .00001) and absolute change over the trial (random WMD = -9.25 nmol/L; 95% CI, -14.40 to -4.10; P = .0004). CONCLUSIONS:Study participants who received vitamin D2 supplementation showed statistically significant reductions in serum 25(OH)D3 concentrations, compared to controls without supplementation. An inverse relationship between vitamin D2 and D3 concentrations has been proposed in the literature. A regulatory mechanism that increases the disposal rate of 25(OH)D after an increase in vitamin D concentrations could explain these results. However, further research is needed to establish whether vitamins D2 and D3 elicit different changes in overall vitamin D metabolism that might influence clinical advice to recommend vitamin D3 supplements over vitamin D2 supplements, where appropriate.
Daily 24 h rhythms in bone turnover have been demonstrated but whether these rhythms are intrinsically generated circadian rhythms is not known. We thus aimed to investigate this using the commonly used constant routine protocol where external factors such as meals, activity, sleep/wake and light/dark are kept constant. Serum procollagen type I N-terminal propeptide (sPINP) (marker of bone formation) and C-terminal telopeptide of type 1 collagen (sCTX) (marker of bone resorption), were measured in 2 hourly blood samples taken sequentially across 26 h in healthy individuals (n = 22, aged 19–33 years, 50% female). Concentration of sCTX showed a cosine rhythm in all males (acrophase (peak) time (mean ± SEM) 02:48 ± 14 h:min, amplitude 0.15 ± 0.02 ng/mL). All of the females had a statistically significant cosine + linear fit (acrophase 03:24 ± 20 h:min, amplitude 0.05 ± 0.01 ng/mL). There was no sex difference in acrophase, but females had a significantly smaller amplitude (P < 0.001). For sP1NP, only 4 males (36%) and 1 female showed statistically significant rhythms for either cosine, or cosine + linear models. Overall, sCTX, but not sPINP, exhibited a robust circadian rhythm in both males and females. This finding suggests that the circadian clock regulation of bone resorption by osteoclasts is robust, whereas circadian clock regulation of bone formation by osteoblasts is minimal.
The number of people following a plant-based (PB) diet has increased in recent years. This has led to concerns regarding vitamin D intake, as natural dietary sources of vitamin D are primarily animal based(1) and cross-sectional studies have reported lower intakes amongst vegetarians and vegans(2). Some PB foods, primarily dairy alternatives, are now fortified with vitamin D. Whilst vitamin D is synthesised in the skin following exposure to UV light, this does not happen in the autumn and winter months in areas of northern latitude (such as the UK). Hence, dietary supply of vitamin D becomes particularly important. This study aimed to investigate whether it is possible to maintain dietary vitamin D intake when transitioning to a PB diet, through careful choice of PB alternatives.A subset of 4-day diet diaries, from 81 women (72 Caucasian and 9 South Asian, mean age 52 ± 12y) living in South East England, was randomly selected from those collected for the D-FINES study (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England, 2006–2007; FSA funded Project N05064, NHS REC 06/Q1909/1)(3)and analysed for vitamin D intake. No subjects followed an entirely PB diet at baseline. Data modelling was carried out to substitute animal-based foods with equivalent amounts of PB alternatives. For dairy products, the equivalent fortified PB alternatives were chosen. Meat, fish and eggs were replaced with equivalent amounts of protein from PB sources, such as lentils and tofu, as no fortified direct alternatives were found. The diaries were then re-analysed. Pre- and post-substitution intakes were compared by paired t test, and ethnic groups by independent t test.There were no differences in Vitamin D intake between ethnicities either at baseline (p = 0.087) or post-substitution (p = 0.361). Vitamin D intake increased in the South Asian group post-substitution (from 2.4 ± 1.3 to 4.3 ± 1.8 µg/day, p = 0.002), with no change observed in the Caucasian group (3.6 ± 2.0 to 3.7 ± 1.8 µg/day, p = 0.660). There was no difference between vitamin D intake pre- and post-substitution overall (3.5 ± 2.0 and 3.8 ± 1.8 µg/day respectively, p = 0.222). Twenty cases decreased by ≥1 µg/day, all in the Caucasian group, with the largest decrease being from 9.6 to 2.2 µg/day.This study demonstrates that it is possible to move to a PB diet, whilst maintaining existing dietary patterns, without a reduction in vitamin D intake, but it is largely dependent on dairy intake in the original diet, as no meat/fish substitutes in the UK are currently fortified. It also requires care when choosing PB dairy substitutions as many, including organic options, are not fortified. Mean daily intakes, both pre- and post-substitution, were substantially below the recommended intake of 10 µg/day(4), suggesting that supplementation may be necessary, particularly during winter months.
Abstract Objective: This systematic review and meta-analysis examined the evidence for a potential relationship between vitamin D status and vitamin D supplementation on immune function biomarkers and prevention of acute respiratory tract infections (ARTI) in dark-skinned individuals. Design: Six databases were searched (inception to December 2021) for randomised controlled trials (RCT) and observational studies. A narrative synthesis and random-effects meta-analysis were used to synthesise the findings. Setting: Not applicable. Participants: Ethnic groups other than white, with or without a white comparator. Results: After duplicates were removed, 2077 articles were identified for screening. A total of eighteen studies (n 36 707), including seven RCT and 11 observational studies, met the inclusion criteria, and three RCT (n 5778) provided sufficient data of high enough quality to be included in a meta-analysis. An inverse association between vitamin D status and at least one inflammatory biomarker in black adults was found in three studies, and vitamin D status was inversely associated with ARTI incidence in black and Indigenous groups in two studies. There was no significant effect of vitamin D supplementation on differences in ARTI incidence in ethnic minority groups (OR, 1·40; 95 % CI: 0·70, 2·79; P = 0·34), nor African American (OR, 1·77; 95 % CI: 0·51, 6·19; P = 0·37) or Asian/Pacific (OR, 1·08; 95 % CI: 0·77, 2·68; P = 0·66) subgroups. Conclusions: There is a lack of conclusive evidence supporting an association between vitamin D status and immune function or ARTI incidence in dark-skinned individuals. Further RCT in diverse ethnic populations are urgently needed.
Vitamin D status has been found to be inversely associated with risk of respiratory tract infections (RTIs)(1). It varies by ethnicity, with several ethnic minority groups in the United Kingdom (UK) reported to be at a higher risk of vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentrations <25 nmol/L) compared to their white counterparts(2, 3). However, the relationship between serum 25(OH)D concentrations and incidence of RTIs by ethnicity in the UK remains unclear. This study aimed to investigate the association between serum 25(OH)D concentrations and likelihood of hospitalisation for RTI in UK ethnic groups. A nested, case-control study was conducted using data from UK Biobank, which has data for 500k adults for serum 25(OH)D and hospital episodes from linked records. Binary logistic regression models were used to explore the association between serum 25(OH)D concentrations and likelihood of RTIs overall, and by ethnicity. Of the 36,772 participants included in the analysis, 12,638 (34%) were white Caucasian, 10,311 (28%) Asian, 7,138 (19%) black, 4,034 (11%) other, and 2,651 (7%) of mixed ethnicity. In fully adjusted models, compared to participants with a serum 25(OH)D concentration <15 nmol/L (severe deficiency), those with 25-49 nmol/L, 50-74 nmol/L, and ≥75 nmol/L were found to have statistically significantly lower odds of RTI hospitalisation, with odds ratios (ORs) of 0.53 (95% CI: 0.37, 0.75), 0.61 (95% CI: 0.40, 0.92) and 0.54 (95% CI: 0.30, 0.97), respectively. In the subgroup analysis, ethnic minorities and white individuals with vitamin D deficiency (<25 nmol/L) were more likely to be hospitalised with RTI compared to those that were not deficient, with ORs of 1.36 (95% CI: 1.02, 1.81) and 2.03 (95% CI: 1.30, 3.17), respectively. This association was not statistically significant within ethnic minority subgroups when analysed separately. Serum 25(OH)D concentrations above 25 nmol/L are associated with lower likelihood of RTI hospitalisation among UK adults. This finding was noted across white and ethnic minority groups, although ethnic minorities with vitamin D deficiency had a lower likelihood of RTIs compared to white individuals. Further studies are warranted to validate these findings and explore the mechanisms underlying the association between vitamin D status and RTIs in different ethnic groups. Acknowledgements This project was conducted using the UK Biobank resource under project 15168.
There are known differences in biological functionality between vitamin D2 and D3. It is suspected from randomised control trial (RCT) data that vitamin D2 supplementation causes a reduction in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations (1), but the size of the effect has yet to be fully assessed across multiple studies. The aim of this study was to undertake a systematic review and meta-analysis of the effect of vitamin D2 supplementation on serum 25(OH)D3 concentrations.PUBMED was searched for publications from 1st January 1975 to 1st February 2023. Of the 182 papers retrieved, 29 were included in the systematic review, and of those, 18 were suitable for meta-analysis.The meta-analysis found significant reductions in serum D3 after vitamin D2 supplementation compared with control, for both end of trial between groups data (weighted mean difference (WMD) (random) = −13.51 nmol/L; 95% CI: −20.14, −6.89; P < 0.0001) and absolute change over the trial (WMD (random) = −9.25 nmol/L; 95% CI: −14.40, −4.10; P = 0.0004). Similar results were found when D2 supplementation was compared to D3 supplementation, although as expected, the magnitude of the difference was larger, with WMD (random) = −46.20 nmol/L (95% CI: −60.80, −31.60; P < 0.00001) for end of trial data, and WMD (random) = −56.23 nmol/L (95% CI: -69.17, −43.28; P < 0.00001) for absolute change.Overall, we found that vitamin D2 supplementation produces significant reductions in serum 25(OH)D3 concentrations, when compared to either control or vitamin D3 supplementation. An inverse relationship between vitamin D2 and D3 concentrations has been proposed in the literature (2). A regulatory mechanism that disposes of 25(OH)D after an increase in vitamin D concentrations could explain our results (3). Moreover, supplementation with vitamins D2 and D3 has differential effects on gene expression (4). However, longer-term research is needed to establish whether clinical advice should recommend vitamin D3 supplements over vitamin D2 supplements, where appropriate.
For decades, there has been a large amount of debate concerning the 25-hydroxyvitamin D thresholds used to define vitamin D deficiency and sufficiency, as well as optimal status. In this chapter, we discuss the arguments for the use of the 25 and 50 nmol/L cutoff points, as recommended by UK SACN (25 nmol/L), and the US/Canada IOM, EFSA, and Nordic countries (50 nmol/L). We critique the use of these thresholds and the approach used to define them. In addition, we discuss the issues with reaching 25(OH)D thresholds that apply to specific subpopulations and suggest that extra support for ensuring vitamin D health may be required for these groups. We end with a discussion of other issues surrounding definitions of thresholds for assessing vitamin D status.
The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim of this study was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women living at latitude 51°14′ N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant’s home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13–2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44–2.92). Our results provide an insight into the connection between residential greenness, lifestyle, and vitamin D status comparing two ethnicities in a country with a temperate climate and with a high degree of urbanization.
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Numerous studies show a high prevalence of vitamin D de fi ciency in the UK (1) but similar data have been found in Greece and Cyprus, despite an abundance of UV light and skin vitamin D production being possible for almost the whole the year. (2) Moreover, there is no data on vitamin D status in Greek and Cypriot populations living in higher latitude countries, such as the UK. The aim of this study was to assess differences in vitamin D status and vitamin D intake between Greek/Cypriot UK residents (born in Greece or Cyprus) and a British/Irish comparison group. A cross sectional study of n = 140 Greeks, n = 185 Cypriots and a randomly sampled group of n = 4158 British/Irish participants (self-reported ethnicity, 40 – 69 years old), all of whom were part of the UK Biobank cohort (baseline). Serum 25-hydroxyvitaminD (25 (OH)D) levels were measured using DiaSorin Liaison XL assay and vitamin D intake was estimated using the Oxford WebQ (24 h food frequency questionnaire). The Greek/Cypriot group had a median 25(OH)D of 40.3 nmol/L, which was statistically signi fi cantly lower than the British/Irish group (47.6nmol/L) (P < 0.001). A total of 11% of British/Irish and 22.8% of Greek/Cypriot participants did not meet the 25nmol/L cut-off (so were deemed de fi cient). The 50 nmol/l cut-off point (adequate) was not met by 53.1% of British/Irish and 62.3% of Greek/ Cypriot participants. Vitamin D intake was similar in the Greek/Cypriot (1.41 μ g/d) and British/Irish group (1.77 μ g/d)
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 serumpotassium 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.