Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: −0·038, n 22) and OC (MD: −0·610, n 24) with high heterogeneity and uNTX (MD: −8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 μg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21 315 participants (aged 60–84 years) were randomly assigned to a monthly dose of 60 000 IU vitamin D3 or matching placebo. Pain was measured using the six-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrolment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorisations of the score, namely ‘some or more pain impact’ and ‘presence of any bodily pain’) to estimate the effect of vitamin D on pain. We included 20 423 participants who completed ≥1 PIQ-6. In blood samples collected from 3943 randomly selected participants (∼800 per year), the mean (sd) 25(OH)D concentrations were 77 (sd 25) and 115 (sd 30) nmol/l in the placebo and vitamin D groups, respectively. Most (76 %) participants were predicted to have 25(OH)D concentration >50 nmol/l at baseline. The mean PIQ-6 was similar in all surveys (∼50·4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0·02 (95 % CI (−0·20, 0·25)). The proportion of participants with some or more pain impact and with the presence of bodily pain was also similar between groups (both prevalence ratios 1·01, 95 % CI (0·99, 1·03)). In conclusion, supplementation with 60 000 IU of vitamin D3/month had negligible effect on bodily pain.

Since the discovery of vitamin D, it has been accepted that its physiological supply is either from food or by endogenous synthesis in skin exposed to solar UV light. Yet vitamin D is a component of very few foods and its supply as a natural nutrient is unable to maintain good vitamin D status for human populations. One aspect of vitamin D physiology that has been ignored is that the mechanisms for its transport and processing from these two sources are quite different. Excess intake of vitamin D causes hypercalcaemic toxicity. However, experiments with different animal species have shown that long-term supply of oral vitamin D in apparently non-toxic amounts causes atherosclerosis in large arteries. A mechanism for this toxicity is proposed. Alternative strategies for addressing widespread vitamin D deficiency by food fortification should be considered in light of the angiotoxicity caused by oral vitamin D in animal experiments.

The co-existence of overweight or obesity with concurrent deficiency of one or more nutrients is referred to as double burden of malnutrition (DBM), and numerous mental health impairments have been associated with a variety of nutrient deficiencies. Although DBM is relevant for several health outcomes, the ubiquitous involvement of vitamin D across multiple systems and tissues suggests D insufficiency as a viable target for nutritional modification. The present study aimed to evaluate the contribution of DBM and mental health among adult women. Study participants included 300 women, aged 18–59 years, who presented to one of the 25 health centres in Tehran. Participants with a body mass index (BMI) of greater than 25 kg/m2 and a plasma concentration of 25-hydroxy vitamin D [25(OH)D] of >20 ng/ml were considered to have DBM. The 147-item food frequency questionnaire was used to estimate their dietary intake. Mental health status was assessed using the depression, anxiety and stress scales-21 (DASS-21). The mean ± standard deviation age, weight and BMI of the participants were 36⋅49 ± 8⋅38, 80⋅89 ± 12⋅45 kg and 31⋅04 ± 4⋅31 kg/m2, respectively. DBM was significantly associated with stress, after adjusting for potential confounders, including age, energy and marital status in model 1 (OR = 1⋅28, 95 % confidence interval (CI) 1⋅00, 1⋅65, P < 0⋅04) v. the crude model (OR = 1⋅22; 95 % CI 0⋅96, 1⋅55, P = 0⋅09). No significant association was seen among DBM and DASS-21 outcomes. In this cross-sectional study, stress and DBM were significantly associated. While vitamin D insufficiency was associated with mental health and obesity in opposing directions. Elucidation of whether vitamin D supplementation can improve mental health impairments requires further evaluation.

The coronavirus disease 2019 (COVID-19) pandemic has generated high interest in factors modulating risk of infection, disease severity and recovery. Vitamin D has garnered interest since it is known to modulate immune function and vitamin D deficiency is associated with increased risk of respiratory infections and adverse health outcomes in severely ill patients. There are no population representative data on the direct relationship between vitamin D status and severe acute respiratory syndrome coronavirus 2 infection risk and severity of COVID-19. Data from intervention studies are limited to four studies. Here we summarise findings regarding vitamin D status and metabolism and their alterations during severe illness, relevant to COVID-19 patients. Further, we summarise vitamin D intervention studies with respiratory disease outcomes and in critically ill patients and provide an overview of relevant patient and population guidelines. Vitamin D deficiency is highly prevalent in hospitalised patients, particularly when critically ill, including those with COVID-19. Acute and critical illness leads to pronounced changes in vitamin D metabolism and status, suggestive of increased requirements. This needs to be considered in the interpretation of potential links between vitamin D status and disease risk and severity and for patient management. There is some evidence that vitamin D supplementation decreases the risk of respiratory tract infections, while supplementation of intensive care unit patients has shown little effect on disease severity or length of treatment. Considering the high prevalence of deficiency and low risks associated with supplementation, pro-actively applying current population and patient management guidelines to prevent, monitor and correct vitamin D deficiency is appropriate.

Pancreatic-insufficient children with cystic fibrosis (CF) receive age-group-specific vitamin D supplementation according to international CF nutritional guidelines. The potential advantageous immunomodulatory effect of serum 25-hydroxy vitamin D (25(OH)D) on pulmonary function (PF) is yet to be established and is complicated by CF-related vitamin D malabsorption. We aimed to assess whether current recommendations are optimal for preventing deficiencies and whether higher serum 25(OH)D levels have long-term beneficial effects on PF. We examined the longitudinal relationship between vitamin D intake, serum 25(OH)D and PF in 190 CF children during a 4-year follow-up period. We found a significant relationship between total vitamin D intake and serum 25(OH)D (β = 0·02; 95 % CI 0·01, 0·03; P = 0·000). However, serum 25(OH)D decreased with increasing body weight (β = –0·79; 95 % CI –1·28, –0·29; P = 0·002). Furthermore, we observed a significant relationship between serum 25(OH)D and forced expiratory volume in 1 s (β = 0·056; 95 % CI 0·01, 0·102; P = 0·018) and forced vital capacity (β = 0·045; 95 % CI 0·008, 0·082; P = 0·017). In the present large study sample, vitamin D intake is associated with serum 25(OH)D levels, and adequate serum 25(OH)D levels may contribute to the preservation of PF in children with CF. Furthermore, to maintain adequate levels of serum 25(OH)D, vitamin D supplementation should increase with increasing body weight. Adjustments of the international CF nutritional guidelines, in which vitamin D supplementation increases with increasing weight, should be considered.

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks’ gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks’ gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

Recently, countries at high latitudes have updated their vitamin D recommendations to ensure adequate intake for the musculoskeletal health of their respective populations. In 2010, the dietary guidelines for vitamin D for Canadians and Americans aged 1–70 years increased from 5 μg/d to 15 μg/d, whereas in 2016 for citizens of the UK aged ≥4 years 10 μg/d is recommended. The vitamin D status of Canadian children following the revised dietary guidelines is unknown. Therefore, this study aimed to assess the prevalence and determinants of vitamin D deficiency and sufficiency among Canadian children. For this study, we assumed serum 25-hydroxy vitamin D (25(OH)D) concentrations <30 nmol/l as ‘deficient’ and ≥50nmol/l as ‘sufficient’. Data from children aged 3–18 years (n 2270) who participated in the 2012/2013 Canadian Health Measures Survey were analysed. Of all children, 5·6 % were vitamin D deficient and 71 % were vitamin D sufficient. Children who consumed vitamin D-fortified milk daily (77 %) were more likely to be sufficient than those who consumed it less frequently (OR 2·7; 95 % CI 1·4, 5·0). The 9 % of children who reported taking vitamin D-containing supplements in the previous month had higher 25(OH)D concentrations (OR 6·9 nmol/l; 95 % CI 1·1, 12·7 nmol/l) relative to those who did not. Children who were older, obese, of non-white ethnicity and from low-income households were less likely to be vitamin D sufficient. To improve vitamin D status, consumption of vitamin D-rich foods should be promoted, and fortification of more food items or formal recommendations for vitamin D supplementation should be considered.

The lower threshold plasma 25-hydroxy vitamin D (25(OH)D) level for optimal cardiovascular health is unclear, whereas the toxicity threshold is less clear. The aim of this study was to examine the cardiovascular–vitamin D dose–response curve in a normal rat model. Doses of cholecalciferol ranged from deficiency to toxic levels (equivalent to human doses of 0, 0·015, 0·25 and 3·75mg/d) for 4 weeks, and then cardiovascular health was examined using blood pressure telemetry and high-resolution ultrasound in normal male rats (n 16/group, 64 rats total). After 1 month, only the 0·25mg/d group had plasma 25(OH)D that was within current recommended range (100–125 nmol/l), and all groups failed to change plasma Ca or phosphate. Systolic blood pressure increased significantly (10–15 mmHg) in the rat groups with plasma 25(OH)D levels at both 30 and 561 nmol/l (groups fed 0 and 3·75mg/d) compared with the group fed the equivalent to 0·015mg/d (43 nmol/l 25(OH)D). Although not significant, the group fed the equivalent to 0·25mg/d (108 nmol/l 25(OH)D) also showed a 10 mmHg increase in systolic blood pressure. Carotid artery diameter was significantly smaller and wall thickness was larger, leading to higher peak carotid systolic blood velocity in these two groups. Despite these vascular changes, cardiac function did not differ among treatment groups. The key finding in this study is that arterial stiffness and systolic blood pressure both showed a U-shaped dose–response for vitamin D, with lowest values (best cardiovascular health) observed when plasma 25(OH)D levels were 43 nmol/l in normal male rats.

Whether supplemental Ca has similar effects to dietary Ca on vascular and bone markers is unknown. The present trial investigated the feasibility of applying dietary and supplemental interventions in a randomised-controlled trial (RCT) aiming to estimate the effect of supplemental Ca as compared with dietary Ca on vascular and bone markers in postmenopausal women. In total, thirteen participants were randomised to a Ca supplement group (CaSuppl) (750 mg Ca from CaCO3+450 mg Ca from food+20 µg vitamin D supplement) or a Ca diet group (CaDiet) (1200 mg Ca from food+10 µg vitamin D supplement). Participants were instructed on Ca consumption targets at baseline. Monthly telephone follow-ups were conducted to assess adherence to interventions (±20 % of target total Ca) using the multiple-pass 24-h recall method and reported pill count. Measurements of arterial stiffness, peripheral blood pressure and body composition were performed at baseline and after 6 and 12 months in all participants who completed the trial (n 9). Blood and serum biomarkers were measured at baseline and at 12 months. Both groups were compliant to trial interventions (±20 % of target total Ca intake; pill count ≥80 %). CaSuppl participants maintained a significantly lower average dietary Ca intake compared with CaDiet participants throughout the trial (453 (sd 187) mg/d v. 1241 (sd 319) mg/d; P<0·001). There were no significant differences in selected vascular outcomes between intervention groups over time. Our pilot trial demonstrated the feasibility of conducting a large-scale RCT to estimate the differential effects of supplemental and dietary Ca on vascular and bone health markers in healthy postmenopausal women.

The UK Food Standards Agency (FSA) convened an international group of scientific experts to review three Agency-funded projects commissioned to provide evidence for the relative contributions of two sources, dietary vitamin D intake and skin exposure to UVB rays from sunlight, to vitamin D status. This review and other emerging evidence are intended to inform any future risk assessment undertaken by the Scientific Advisory Committee on Nutrition. Evidence was presented from randomised controlled trials to quantify the amount of vitamin D required to maintain a serum 25-hydroxy vitamin D (25OHD) concentration >25 nmol/l, a threshold that is regarded internationally as defining the risk of rickets and osteomalacia. Longitudinal evidence was also provided on summer sunlight exposure required to maintain 25OHD levels above this threshold in people living in the British Isles (latitude 51°–57°N). Data obtained from multi-level modelling of these longitudinal datasets showed that UVB exposure (i.e. season) was the major contributor to changes in 25OHD levels; this was a consistent finding in two Caucasian groups in the north and south of the UK, but was less apparent in the one group of British women of South Asian origin living in the south of the UK. The FSA-funded research suggested that the typical daily intake of vitamin D from food contributed less than UVB exposure to average year-round 25OHD levels in both Caucasian and Asian women. The low vitamin D status of Asian women has been acknowledged for some time, but the limited seasonal variation in Asian women is a novel finding. The Workshop also considered the dilemma of balancing the risks of vitamin D deficiency (from lack of skin exposure to sunlight in summer) and skin cancer (from excessive exposure to sunlight with concomitant sunburn and erythema). Cancer Research UK advises that individuals should stay below their personal sunburn threshold to minimise their skin cancer risk. The evidence suggests that vitamin D can be produced in summer at the latitude of the UK, with minimal risk of erythema and cell damage, by exposing the skin to sunlight for a short period at midday, when the intensity of UVB is at its daily peak. The implications of the new data were discussed in the context of dietary reference values for vitamin D for the general population aged 4–64 years. Future research suggestions included further analysis of the three FSA-funded studies as well as new research.

25-Hydroxy vitamin D (25(OH)D) deficiency is linked with predisposition to autoimmune type 1 diabetes and multiple sclerosis. Our objective was to assess the relationship between serum 25(OH)D levels and thyroid autoimmunity. Subjects included students, teachers and staff aged 16–60 years (total 642, 244 males, 398 females). Serum free thyroxine, thyroid-stimulating hormone (TSH), and thyroid peroxidase autoantibodies (TPOAb), intact parathyroid hormone and 25(OH)D were measured by electrochemiluminescence and RIA, respectively. Thyroid dysfunction was defined if (1) serum TSH ≥ 5 μU/ml and TPOAb>34 IU/ml or (2) TSH ≥ 10 μU/ml but normal TPOAb. The mean serum 25(OH)D of the study subjects was 17·5 (sd 10·2) nmol/l with 87 % having values ≤ 25 nmol/l. TPOAb positivity was observed in 21 % of subjects. The relationship between 25(OH)D and TPOAb was assessed with and without controlling for age and showed significant inverse correlation (r − 0·08, P = 0·04) when adjusted for age. The prevalence of TPOAb and thyroid dysfunction were comparable between subjects stratified according to serum 25(OH)D into two groups either at cut-off of ≤ 25 or >25 nmol/l or first and second tertiles. Serum 25(OH)D values show only weak inverse correlation with TPOAb titres. The presence of such weak association and narrow range of serum 25(OH)D did not allow us to interpret the present results in terms of quantitative cut-off values of serum 25(OH)D. Further studies in vitamin D-sufficient populations with wider range of serum 25(OH)D levels are required to substantiate the findings of the current study.