COVID-19 pandemic and vitamin D: rising trends in status and in daily amounts of vitamin D provided by supplements.

OBJECTIVES: Since the onset of the COVID-19 pandemic in 2020, there have been plausible suggestions about the need to augment vitamin D intake by supplementation in order to prevent SARS-CoV2 infection and reduce mortality. Some groups have advocated supplementation for all adults, but governmental agencies have advocated targeted supplementation. We sought to explore the effect of the COVID-19 pandemic on both vitamin D status and on the dose of new-to-market vitamin D supplements. SETTING: University hospital, Dublin, Ireland. PARTICIPANTS: Laboratory-based samples of circulating 25-hydroxyvitamin D (25OHD) (n=100 505). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: comparing yearly average 25OHD prior to the pandemic (April 2019 to March 2020) with during the pandemic (April 2020 to March 2021) and comparing the dose of new-to-market vitamin D supplements between 2017 and 2021 (n=2689). SECONDARY OUTCOME: comparing prevalence of vitamin D deficiency and vitamin D excess during the two time periods. RESULTS: The average yearly serum 25OHD measurement increased by 2.8 nmol/L (61.4, 95% CI 61.5 to 61.7 vs 58.6, 95% CI 58.4 to 58.9, p<0.001), which was almost threefold higher than two similar trend analyses that we conducted between 1993 and 2016. There was a lower prevalence of low 25OHD and a higher prevalence of high 25OHD. The dose of new-to-market vitamin D supplements was higher in the years 2020-2021 compared with the years 2017-2019 (p<0.001). CONCLUSIONS: We showed significant increases in serum 25OHD and in the dose of new-to-market vitamin D supplements. The frequency of low vitamin D status reduced indicating benefit, but the frequency of vitamin D excess increased indicating risk of harm. Rather than a blanket recommendation about vitamin D supplementation for all adults, we recommend a targeted approach of supplementation within current governmental guidelines to at-risk groups and cautioning consumers about adverse effects of high dose supplements on the market.

Nutrition policy: developing scientific recommendations for food-based dietary guidelines for older adults living independently in Ireland.

Older adults (≥65 years) are the fastest growing population group. Thus, ensuring nutritional well-being of the 'over-65s' to optimise health is critically important. Older adults represent a diverse population - some are fit and healthy, others are frail and many live with chronic conditions. Up to 78% of older Irish adults living independently are overweight or obese. The present paper describes how these issues were accommodated into the development of food-based dietary guidelines for older adults living independently in Ireland. Food-based dietary guidelines previously established for the general adult population served as the basis for developing more specific recommendations appropriate for older adults. Published international reports were used to update nutrient intake goals for older adults, and available Irish data on dietary intakes and nutritional status biomarkers were explored from a population-based study (the National Adult Nutrition Survey; NANS) and two longitudinal cohorts: the Trinity-Ulster and Department of Agriculture (TUDA) and the Irish Longitudinal Study on Ageing (TILDA) studies. Nutrients of public health concern were identified for further examination. While most nutrient intake goals were similar to those for the general adult population, other aspects were identified where nutritional concerns of ageing require more specific food-based dietary guidelines. These include, a more protein-dense diet using high-quality protein foods to preserve muscle mass; weight maintenance in overweight or obese older adults with no health issues and, where weight-loss is required, that lean tissue is preserved; the promotion of fortified foods, particularly as a bioavailable source of B vitamins and the need for vitamin D supplementation.

Association between vitamin D status in early pregnancy and atopy in offspring in a vitamin D deplete cohort.

BACKGROUND: Vitamin D status may play a role in the development of atopic diseases due to its action on lung development and immune system development and function. AIMS: Our objective was to assess whether 25-hydroxyvitamin D (25OHD) levels in maternal blood in pregnancy were associated with atopy in children. METHODS: We analysed 279 mother-child pairs from the ROLO study conducted in Dublin, Ireland. Serum 25OHD was measured at 13 and 28 weeks of pregnancy. Development of childhood atopy was self-reported by mothers at follow-up appointments at 6 months, 2 years or 5 years. Logistic regression analysis was used to evaluate associations between maternal 25OHD status and development of atopy. RESULTS: The mean (SD) 25OHD levels in early and late pregnancy were 41.9 (19.2) nmol/L and 40.2 (21.6) nmol/L, respectively. Maternal 25OHD status in early pregnancy, but not in late pregnancy, was associated with a reduced risk of atopy at 2 years (OR 0.972, CI 0.946-0.999). In early pregnancy, those with serum 25OHD levels < 30 nmol/L compared with those with 25OHD > 50 nmol/L had significantly greater risk of developing atopy at 2 years (OR 4.76, CI 1.38-16.47). CONCLUSIONS: The development of childhood atopy may be associated with maternal vitamin D deficiency in early pregnancy among a cohort of women at risk of vitamin D deficiency. Further research is required to explore the relationship between vitamin D and atopy, particularly among women with poor vitamin D status, and whether supplementation should be prioritised in early pregnancy to reduce childhood atopy.

Congenital hypophosphataemia in adults: determinants of bone turnover markers and amelioration of renal phosphate wasting following total parathyroidectomy.

Congenital hypophosphataemia (CH) is a collection of disorders that cause defective bone mineralisation manifesting with rickets in childhood and osteomalacia in adulthood. Bone turnover markers (BTMs) are surrogate measures of metabolic bone disease severity. We explored the utility of BTMs in 27 adults with CH: 23 had X-linked hypophosphataemia (XLH), of whom 2 were hypoparathyroid post-total parathyroidectomy (PTx); 2 had autosomal dominant hypophosphataemic rickets (ADHR), and 2 had none of the known mutations. We measured the renal tubular maximum reabsorption rate of phosphate (TmP/GFR), C-terminal fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), ionised calcium, 1,25-dihydroxyvitamin D [1,25(OH)2D], and a panel of BTMs: serum bone-specific alkaline phosphatase (bone ALP), osteocalcin (Oc), total procollagen type I amino-terminal propeptide (PINP), and carboxy-terminal telopeptide of type I collagen (CTX); and urine amino-terminal telopeptides of type I collagen (uNTX). After excluding 2 patients with XLH and PTx, the frequency of abnormal elevation in BTMs was: bone ALP (96%); CTX (72%); PINP (52%); uNTX (48%); Oc (28%). The strongest association with bone ALP was TmP/GFR. Those patients receiving phosphate supplements and alfacalcidol had significant elevation in CTX. The 2 patients with XLH and PTx had normalisation of TmP/GFR and near normalisation of BTMs post-operatively, despite marked elevation in both C-terminal and intact FGF23. In conclusion, BTMs in our CH patients indicated that most have abnormalities consistent with osteomalacia and many have mild secondary hyperparathyroidism; and the normalisation of TmP/GFR after total PTx in 2 cases of XLH remains unexplained, but possible causes are speculated.

Calcium intake in winter pregnancy attenuates impact of vitamin D inadequacy on urine NTX, a marker of bone resorption.

PURPOSE: Pregnancy is characterised by increased bone turnover, but high bone turnover with resorption exceeding formation may lead to negative maternal bone remodelling. Recent studies are conflicting regarding the effect of calcium on skeletal health in pregnancy. The aim of this study was to examine the seasonal effect of serum 25-hydroxyvitamin D (25OHD) and dietary calcium on a marker of bone resorption. METHODS: This was prospective study of 205 pregnant women [two cohorts; early pregnancy at 13 weeks (n = 96), and late pregnancy at 28 weeks (n = 109)]. Serum 25OHD and urine cross-linked N-telopeptides of type I collagen (uNTX) were measured at both time points. Intakes of vitamin D and calcium were recorded using 3-day food diaries at each trimester. RESULTS: Compared to summer pregnancies, winter pregnancies had significantly lower 25OHD and significantly higher uNTX. Higher calcium intakes were negatively correlated with uNTX in winter, but not summer. In late pregnancy, compared to those reporting calcium intakes ≥1000 mg/day, intakes of <1000 mg/day were associated with a greater increase in uNTX in winter pregnancies than in summer (41.8 vs. 0.9%). Increasing calcium intake in winter by 200 mg/day predicted a 13.3% reduction in late pregnancy uNTX. CONCLUSIONS: In late pregnancy, during winter months when 25OHD is inadequate, intakes of dietary calcium <1000 mg/day were associated with significantly increased bone resorption (uNTX). Additional dietary calcium is associated with reduced bone resorption in late pregnancy, with greater effect observed in winter. Further research regarding optimal dietary calcium and 25OHD in pregnancy is required, particularly for women gestating through winter.

Should Dual-Energy X-ray Absorptiometry Technologists Estimate Dietary Calcium Intake at the Time of DXA?

Adequate calcium intake is essential for bone health. Calcium is obtained from dietary sources and supplementation. Knowing the daily dietary calcium intake is helpful in deciding on the need for supplementation. Dietary calcium intake can be estimated quickly and accurately using an approach recommended by the National Osteoporosis Foundation. We sought to evaluate the usefulness of estimating dietary calcium intake by a technologist at the time of attendance for dual-energy X-ray absorptiometry (DXA) scanning. We conducted a retrospective survey of results on estimated dietary calcium intake in adults attending our DXA unit over 2 years (n=5569). We assessed intake with reference to the specifications of the Institute of Medicine according to sex and age. The average intake was 736 mg daily: Young adults had higher intakes than older adults (p<0.001), and men had higher intakes than women (p=0.017). According to Institute of Medicine's specification, we estimate that nearly 45% of Irish women need supplemental intake of 500 mg daily but <4% need supplemental intake of 1000 mg daily. Younger adults are apt to have intakes within, or higher than, the requirement. Having DXA technologists estimate dietary calcium intake at the time of DXA scanning may provide helpful information to the referring clinicians about the need for supplementation.

Vitamin D status in Irish children and adolescents: value of fortification and supplementation.

BACKGROUND: Vitamin D has important skeletal and extraskeletal roles but those living at northerly latitudes are at risk of suboptimal levels because of reduced sunlight exposure. AIM: To describe the vitamin D status of Irish children and identify factors predictive of vitamin D status. METHODS: A prospective cross sectional study was undertaken over a 12 month period. Two hundred and fifty two healthy children attending for minor medical or surgical procedures were recruited. All had 25-hydroxyvitamin D (25OHD), parathyroid hormone and bone profiles measured. RESULTS: The mean (standard deviation) for 25OHD was 51(25) nmol/L (20.4 (10) ng/mL). Forty-five percent had levels >50 nmol/L (20 ng/mL). The following variables were significantly associated with 25OHD levels >50 nmol/L (20 ng/mL): sample drawn in April-September, use of vitamin D supplements, consumption of formula milk, and non-African ethnicity. CONCLUSION: More than half of the children in this study had 25OHD levels less than 50 nmol/L (20 ng/mL). Vitamin D status was significantly improved by augmented oral vitamin D intake.

Hungry bone syndrome and normalisation of renal phosphorus threshold after total parathyroidectomy for tertiary hyperparathyroidism in X-linked hypophosphataemia: a case report.

INTRODUCTION: This is the first report of which the authors are aware to describe this c.2166delinsGG mutation in X-linked hypophosphataemia and to describe normalisation of renal threshold for phosphate excretion after parathyroidectomy for tertiary hyperparathyroidism in X-linked hypophosphataemia. CASE PRESENTATION: We present the case of a 34-year-old Caucasian woman with X-linked hypophosphataemia. She developed tertiary hyperparathyroidism with markedly high bone turnover requiring total parathyroidectomy and had prolonged requirement for intravenous calcium infusion after surgery. She had a novel mutation in her phosphate-regulating gene with homologies to endopeptidases on the X-chromosome and had an unusual degree of dependence on phosphate supplementation. Prior to operative intervention she had a trial of cinacalcet that improved bone turnover markers when used in isolation but which led to a paradoxical rise in parathyroid hormone levels when given with phosphate supplementation. After correction of hungry bone syndrome, the renal phosphorus threshold normalised as a manifestation of hypoparathyroid state despite marked elevation in level of fibroblast growth factor 23. CONCLUSIONS: This case illustrates the risk of tertiary hyperparathyroidism as a complication of treatment for hypophosphataemia; it highlights the morbidity associated with hungry bone syndrome and provides novel insight into renal handling of phosphorus.

Vitamin D dose response is underestimated by Endocrine Society's Clinical Practice Guideline.

OBJECTIVE: The recommended daily intakes of vitamin D according to the recent Clinical Practice Guideline (CPG) of the Endocrine Society are three- to fivefold higher than the Institute of Medicine (IOM) report. We speculated that these differences could be explained by different mathematical approaches to the vitamin D dose response. METHODS: Studies were selected if the daily dose was ≤2000 IU/day, the duration exceeded 3 months, and 25-hydroxyvitamin D (25OHD) concentrations were measured at baseline and post-therapy. The rate constant was estimated according to the CPG approach. The achieved 25OHD result was estimated according to the following: i) the regression equation approach of the IOM; ii) the regression approach of the Vitamin D Supplementation in Older Subjects (ViDOS) study; and iii) the CPG approach using a rate constant of 2.5 (CPG2.5) and a rate constant of 5.0 (CPG5.0). The difference between the expected and the observed 25OHD result was expressed as a percentage of observed and analyzed for significance against a value of 0% for the four groups. RESULTS: Forty-one studies were analyzed. The mean (95% CI) rate constant was 5.3 (4.4-6.2) nmol/l per 100 IU per day, on average twofold higher than the CPG rate constant. The mean (95% CI) for the difference between the expected and observed expressed as a percentage of observed was as follows: i) IOM, -7 (-16,+2)% (t=1.64, P=0.110); ii) ViDOS, +2 (-8,+12)% (t=0.40, P=0.69); iii) CPG2.5, -21 (-27,-15)% (t=7.2, P<0.0001); and iv) CPG5.0+3 (-4,+10)% (t=0.91, P=0.366). CONCLUSION: The CPG 'rule of thumb' should be doubled to 5.0 nmol/l (2.0 ng/ml) per 100 IU per day, adopting a more risk-averse position.

Vitamin D nutritional status in preterm infants and response to supplementation.

Little is known about vitamin D status in preterm infants and their response to supplementation. To investigate this, we assessed serum 25-hydroxyvitamin D (25OHD) levels using RIA in a consecutive sample of stable preterm very low birth weight (VLBW) infants (born ≤ 32 weeks gestation or birth weight ≤ 1·5 kg), and we explored associated factors. Serum 25OHD level was first assessed once infants were tolerating feeds (n 274). If this first 25OHD level was below 50 nmol/l (20 ng/ml), which is the level associated with covering requirements in terms of skeletal health in the majority, then we recommended prolonged augmented vitamin D intake ( ≥ 10 µg (400 IU) daily) from a combination of fortified feeds and vitamin supplements and follow-up re-assessment at approximately 6 weeks corrected age (n 148). The first assessment, conducted at a median for chronological age of 18 (interquartile range (IQR) 11-28) d, found that 78 % had serum 25OHD levels below 50 nmol/l. Multivariable analysis demonstrated that the determinants of serum 25OHD levels were duration of vitamin D supplementation and gestational age at birth (r 2 0·215; P< 0·001). At follow-up, after a median of 104 (IQR 78-127) d, 87 % achieved levels ≥ 50 nmol/l and 8 % had levels >125 nmol/l, a level associated with potential risk of harm. We conclude that low 25OHD levels are an issue for preterm VLBW infants, warranting early nutritional intervention. In infants with serum 25OHD levels < 50 nmol/l, a vitamin D intake of ≥ 10 µg (400 IU) daily achieves target levels in the majority; however, further work is needed to determine the exact dose to safely meet target levels without overcorrection.

The relationship between maternal and fetal vitamin D, insulin resistance, and fetal growth.

Evidence for a role of vitamin D in maintaining normal glucose homeostasis is inconclusive. We sought to clarify the relationship between maternal and fetal insulin resistance and vitamin D status. This is a prospective cohort study of 60 caucasian pregnant women. Concentrations of 25-hydroxyvitamin D (25-OHD), glucose, insulin, and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width, a marker of fetal adiposity. At delivery birth weight was recorded and fetal 25-OHD, glucose, C-peptide, and leptin measured in cord blood. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) equation. We found that those with lower 25-OHD in early pregnancy had higher HOMA indices at 28 weeks, (r = -.32, P = .02). No significant relationship existed between maternal or fetal leptin and 25-OHD, or between maternal or fetal 25-OHD and fetal anthropometry or birth weight. The incidence of vitamin D deficiency was high at each time point (15%-45%). These findings lend support to routine antenatal supplementation with vitamin D in at risk populations.

The effect of narrowband UV-B treatment for psoriasis on vitamin D status during wintertime in Ireland.

OBJECTIVES: To determine whether narrowband UV-B (NB-UV-B) may mediate its beneficial effect on psoriasis by increasing vitamin D levels, and to assess the effect of NB-UV-B on vitamin D status in patients with psoriasis in wintertime. DESIGN: A prospective controlled study from October 2008 to February 2009. SETTING: A dermatology outpatient department at a university teaching hospital. PATIENTS: Thirty consecutive patients with psoriasis treated with NB-UV-B and 30 control patients with psoriasis were recruited. Control patients were recruited within 1 week of treated patients to control for seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] levels. One patient with photo aggravated psoriasis was withdrawn from the study. INTERVENTION: Narrowband UV-B was administered 3 times per week. MAIN OUTCOME MEASURE: Serum 25(OH)D was measured at baseline, after 4 weeks and at completion of treatment. RESULTS: Levels of serum 25(OH)D increased significantly(P< .001) from a median (range) of 23 (9-46)ng/mL at baseline to 51 [rather than 59, as given in the originally published article] (32-112) ng/mL at the end of NB­UV-B treatment compared with no change in the control group [corrected]. The change in serum 25(OH)D level correlated with the number of exposures of NB-UV-B (r = 0.61; P < .001) and cumulative UV-B dose (r = 0.47; P = .01) but not with treatment response. At the end of the study, all patients in the treatment group were vitamin D sufficient, but 75% of the control group had vitamin D insufficiency [serum 25(OH)D level <20 ng/mL]. In a multiple regression model, prior phototherapy was the sole predictor of baseline serum 25(OH)D level (r(2) = 0.13; P = .006), whereas the number of exposures of NB-UV-B predicted change in serum 25(OH)D level (r(2) = 0.38; P = .001). CONCLUSIONS: Narrowband UV-B effectively increases serum 25(OH)D level while clearing psoriasis. Up to 75% of Irish patients with psoriasis were shown to be vitamin D insufficient during wintertime.