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Cost-effectiveness of vitamin D3 supplementation in older adults with vitamin D deficiency in Ireland.
Lacey, LF, Armstrong, DJ, Royle, E, Magee, P, Pourshahidi, LK, Ray, S, Strain, JJ, McSorley, E
BMJ nutrition, prevention & health. 2022;5(1):98-105
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Clinical vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration below <30nmol/L) increases the risk of excess mortality and disease. Vitamin D deficiency, as measured by serum 25(OH)D, is particularly high among older Irish adults. The aim of this study was to investigate the cost-effectiveness of vitamin D3 supplementation in older adults in Ireland, with year-round vitamin D deficiency. This study investigated three age groups: (1) ≥50 years, (2) ≥60 years and (3) ≥70 years. Results show that cost-effectiveness of vitamin D3 supplementation is most robust in adults ≥70 years. Furthermore, the results of the cost-effectiveness analysis are most sensitive to the mortality risk reduction following vitamin D3 supplementation. Authors conclude by proposing the implementation of a GP-monitored, vitamin D3 supplementation programme for adults ≥70 years of age.
Abstract
Background: This study investigated the cost-effectiveness of vitamin D3 supplementation in older adults in Ireland, with year-round vitamin D deficiency (serum 25-hydroxyvitamin D concentration <30 nmol/L) (13% of Irish adults), from the perspective of the Health Service Executive. Methods: Three age groups were investigated: (1) ≥50 years, (2) ≥60 years and (3) ≥70 years. Based on the clinical literature, vitamin D3 supplementation may: (1) decrease all-cause mortality by 7% and (2) reduce hip fractures by 16% and non-hip fractures by 20%. A discount rate of 4% was applied to life years and quality-adjusted life years (QALYs) gained, and healthcare costs. The annual healthcare costs per patient used in the model are based on the average annual health resource use over the 5-year time horizon of the model. Results: The cost/QALY estimates in all three age groups are below the usually acceptable cost-effectiveness threshold of €20 000/QALY. The most cost-effective and least costly intervention was in adults ≥70 years. For this age group, the average annual costs and outcomes would be approximately €5.6 million, 1044 QALYs gained, with a cost/QALY of approximately €5400. The results are most sensitive to the mortality risk reduction following vitamin D3 supplementation. Conclusion: The cost-effectiveness of vitamin D3 supplementation is most robust in adults ≥70 years. Clinical uncertainty in the magnitude of the benefits of vitamin D3 supplementation could be further addressed by means of: (1) performing a clinical research study or (2) conducting a pilot/regional study, prior to reaching a decision to invest in a nationwide programme.
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Dietary Vitamin D Intake, Pain Incidence, and Pain Changes in Older Adults: The Seniors-ENRICA-1 Cohort.
Carballo-Casla, A, de Paz-Cantos, S, Ortolá, R, García-Esquinas, E, Sotos-Prieto, M, Banegas, JR, Rodríguez-Artalejo, F
Nutrients. 2022;14(18)
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A growing body of evidence supports foods and nutrients as a potential means to prevent and reduce pain. Among the most promising is vitamin D. Low serum vitamin D concentrations are frequent among older adults and have also been associated with conditions such as widespread pain, muscle pain, arthritis, and low-back pain. The aim of this study was to study the association of habitual dietary vitamin D intake with (1) pain incidence and (2) pain changes over a 5-year follow-up in a cohort of community-dwelling older adults. This study is based on data from the Seniors-ENRICA-1 study, a cohort of community-dwelling adults ≥60 years in Spain. Results show that higher dietary vitamin D intake was associated with lower pain incidence and favourable pain changes over 5 years. These associations were consistent in main and sensitivity analyses and highlight the potential role of dietary vitamin D intake as an adjunctive pain prevention and management strategy. Authors conclude that diet is often measured with some error, can change over time, and its effects on health could be cumulative, larger observational studies with repeated assessment of vitamin D intake should replicate these findings.
Abstract
BACKGROUND Vitamin D plays a role in bone health, pain signaling, and inflammation. We examined the largely unknown relation of dietary vitamin D intake with pain incidence and pain changes over time in older adults. METHODS Data were taken from the Seniors-ENRICA-1 cohort, which included 950 individuals aged ≥60 years. Habitual vitamin D intake was assessed in 2012 with a validated diet history, and pain both in 2012 and 2017 with a scale ranging from 0 (no pain) to 6 (highest pain), according to its severity, frequency, and number of locations. Analyses on pain incidence and pain changes were performed in the 524 participants free of pain at baseline and the overall sample, respectively. RESULTS Higher dietary vitamin D intake was associated with lower 5-year pain incidence; the multivariable-adjusted odds ratio (95% confidence interval) was 0.88 (0.79,0.99) for every 1-µg/day increase in vitamin D intake, and 0.49 (0.28,0.88) for the highest (>3.52 µg/day) vs. lowest (<1.85 µg/day) tertile. Dietary vitamin D intake (highest vs. lowest tertile) was also associated with 5-year favorable pain changes: the multivariable-adjusted odds ratio of pain worsening vs. no change/pain improvement was 0.55 (0.36,0.86), and the β coefficient for changes in the pain scale was -0.56 (-1.03,-0.09). Similar results were found for pain severity, frequency, and number of pain locations. CONCLUSIONS In an older adult population, where compliance with vitamin D intake recommendations was very low, a slightly increased dietary intake was associated with lower pain incidence and favorable pain changes over 5 years.
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Circulating levels of maternal vitamin D and risk of ADHD in offspring: results from the Vitamin D Antenatal Asthma Reduction Trial.
Chu, SH, Huang, M, Kelly, RS, Kachroo, P, Litonjua, AA, Weiss, ST, Lasky-Su, J
International journal of epidemiology. 2022;51(3):910-918
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Acting as both a nutrient and a hormone, vitamin D has been found to play a critical role in neurodevelopment across sensitive periods in utero, infancy and early childhood. Among neurodevelopmental and behavioural disorders in early life, attention-deficit/hyperactivity disorder (ADHD) is the most common among children worldwide. Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent ADHD. The aims of this study were to (i) determine the association between maternal vitamin D levels in the first and third trimesters of pregnancy and the risk of offspring ADHD by age 6 years or later; and (ii) to identify potential sensitive periods in utero during which vitamin D levels might be most important for reducing risk of ADHD. This is an ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The VDAART was a randomised, double-blinded, multicentre, clinical trial in which 876 participating mothers were recruited between 10–18 weeks of gestation and assigned to receive either 4400 or 400 IU/day of vitamin D throughout pregnancy. Results show protective associations between maternal 25(OH)D sufficiency in the third trimester and child ADHD, but not at baseline. Furthermore, both at baseline and in the third trimester, there were higher odds of ADHD in male offspring as compared with female offspring with 25(OH)D insufficient mothers (analyses limited by small sample sizes) Authors conclude that higher levels of maternal vitamin D during pregnancy may play a protective role against risk of ADHD in offspring, but further studies are needed to confirm this association and any therapeutic potential therein.
Expert Review
Conflicts of interest:
None
Take Home Message:
Ensure that women in pregnancy, and possibly also those seeking to conceive, have adequate vitamin D status in order to reduce the risk of ADHD in offspring.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
This paper describes a secondary data analysis from an RCT that looked at the effect of prenatal vitamin D supplementation on risk of childhood asthma in offspring. Enrolled women aged 18–39 years with a history of asthma, eczema or allergic rhinitis, or whose partner (biological father of child) had a history of the aforementioned condition, received either 400 IU or 4400 IU vitamin D daily for the duration of their pregnancy. Offspring follow-up is still ongoing.
Aims
The current study aims were twofold: (i) to determine the association between maternal vitamin D levels in trimesters 1 and 3 and the risk of attention deficit/hyperactivity disorder (ADHD) in offspring diagnosed by age 6 years or later; and (ii) to identify potentially sensitive periods during gestation in which vitamin D levels may be especially important for reducing risk of ADHD.
Methods
The analytical sample included 679 mother-child pairs, from the original sample of 876 participating mothers. No sample size calculation was reported, though the sample was considered representative of the overall RCT study population.
Maternal vitamin D (serum 25(OH)D) was classified as follows
- Highly deficient <12 ng/mL
- Deficient 12 ng/mL to 19.9 ng/mL
- Insufficient 20 ng/mL to 29.9 ng/mL
- Sufficient ≥30 ng/mL
ADHD status was assessed through parental reporting between ages 6 and 9 years.
Results
No baseline associations between a vitamin D sufficient status and offspring ADHD in maternal samples collected during trimester 1 were observed (OR 1.06, 95% CI 0.51–2.19; P.0.871), though this association became statistically significant at trimester 3 (OR 0.47, 95% CI 0.26–0.84; P.0.011). This translated to a 53% less chance of having a child with ADHD at age 6 or later among mothers with vitamin D sufficiency compared with children of mothers with vitamin D deficiency. There was also a linear trend in the protective association of vitamin D sufficiency (≥30 ng/mL) on reduced risk of offspring ADHD at age 6 years or later in data from trimester 3. Stratified analyses revealed a protective association for sufficient maternal vitamin D status and offspring ADHD among males (OR 0.47, 95% CI 0.23–0.94).
Conclusions
The authors concluded that vitamin D sufficiency (≥30 ng/mL) in the 3rd trimester of gestation may decrease the risk of ADHD development in offspring.
Notes: The authors reported no relevant conflicts of interest.
Clinical practice applications:
Ensuring a sufficient vitamin D status by the 3rd trimester of pregnancy may help to lessen the risk of ADHD in offspring. Nutritional therapists and other clinicians working with pregnant women or women looking to conceive should consider checking vitamin D status and providing corrective supplementation and lifestyle advice to augment vitamin D levels where indicated.
Considerations for future research:
The authors of this study postulated that the statistically significant protective association between vitamin D at trimester 3 and ADHD in offspring was not significant in trimester 1 due to a low observed variability in vitamin D status (>75% of women were vitamin D insufficient), and thus the statistical test being underpowered to see difference between groups with sufficient or insufficient status.
Further research could expand upon this hypothesis to test whether vitamin D status in trimester 1, or preconceptually, may offer a protective association for ADHD and other related neurological conditions that may manifest in early life.
Abstract
BACKGROUND Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the association between 25(OH)D during fetal development and risk of childhood ADHD. METHODS Maternal plasma 25(OH)D was measured at 10-18 and 32-38 weeks of gestation, with sufficiency defined as 25(OH)D ≥ 30 ng/ml. Offspring ADHD status between ages 6-9 years was measured by parent report of clinical ADHD diagnosis among 680 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial. Association between maternal 25(OH)D and child ADHD was assessed using logistic regression, adjusting for maternal age, race and ethnicity. Effect modification by offspring sex was also assessed. RESULTS No associations between maternal 25(OH)D at 10-18 weeks of gestation and offspring ADHD were observed. In the third trimester, we observed associations between maternal vitamin D sufficiency and offspring ADHD [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.26-0.84], in addition to maternal 25(OH)D sufficiency category, comparing the deficient (OR 0.34, 95% CI 0.12-0.94), insufficient (OR 0.41, 95% CI 0.15-1.10) and sufficient (OR 0.20, 95% CI 0.08-0.54) categories against highly deficient 25(OH)D, respectively. Stratified analyses revealed a protective association for sufficient maternal 25(OH)D and child ADHD among males (OR 0.47, 95% CI 0.23-0.94); the synergy index for additive effect modification of risk was 1.78 (95% CI 0.62-5.08). CONCLUSIONS Higher levels of maternal vitamin D in the third trimester are associated with lower risk of ADHD in offspring, with modest evidence for a stronger effect among male offspring. However, larger studies will be necessary to confirm these findings.
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Vitamin D and miscarriage: a systematic review and meta-analysis.
Tamblyn, JA, Pilarski, NSP, Markland, AD, Marson, EJ, Devall, A, Hewison, M, Morris, RK, Coomarasamy, A
Fertility and sterility. 2022;118(1):111-122
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Miscarriage causes significant physical and psychological harm. Vitamin D deficiency (low serum levels of 25- hydroxyvitamin D) is a major global health concern, with pregnant women and those planning pregnancy at increased risk. The aim of this study was to evaluate the association between vitamin D status and pregnancy loss, including spontaneous miscarriage and recurrent miscarriage. This study is a systematic review and meta-analysis of ten studies (6 where observational studies and 4 interventional studies). Results show that women who were vitamin D deficient were at significantly increased risk of miscarriage compared with those who were vitamin D replete. This association was maintained when women with insufficient levels were included, with a biologic gradient evident. Authors conclude that new evidence-based interventions are required for women at risk of miscarriage.
Abstract
OBJECTIVE To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists. DESIGN Systematic review and meta-analysis. SETTING Not applicable. PATIENT(S): Women with miscarriage and RM. INTERVENTION(S): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included. MAIN OUTCOME MEASURE(S): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed. RESULT(S): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I2 = 18%). Combined analysis, including women who were vitamin D insufficient (50-75 nmol/L) and deficient (<50 nmol/L) compared with women who were replete (>75 nmol/L), found an association with miscarriage (odds ratio, 1.60; 95% confidence interval, 1.11-2.30; 6 studies; n = 6,338; I2 = 35%). Although 4 randomized controlled trials assessed the effect of vitamin D treatment on miscarriage, study heterogeneity, data quality, and reporting bias precluded direct comparison and meta-analysis. The overall study quality was "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach. CONCLUSION(S): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown. REGISTRATION NUMBER CRD42021259899.
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Examining the Vitamin D Status of Children With Solid Tumors.
Juhász, O, Jakab, Z, Szabó, A, Garami, M
Journal of the American College of Nutrition. 2020;39(2):128-134
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Literature shows that 75% of the adult population worldwide experience vitamin D deficiency, of whom 13% fall under the category of extremely severe vitamin D deficiency (<10 ng/ml). The aim of this retrospective study was to compare the Vitamin D status of children with tumours or without. A secondary aim was to analyse the effects of vitamin D supplementation (as a complement to cancer treatment) on the vitamin D levels of children. The study included 173 children (males n=96; females n=77) aged between 0 and 18 who were treated for cancer. The control group consisted of 569 (males n=310; females n=259) children, aged 0 to 4 who received treatment at the clinic for reasons other than cancer. Results indicate that initial Vitamin D levels were significantly lower among children with cancer (19% lower than in the control group). A correlation between insufficient and deficient initial serum vitamin D levels and unfavourable prognosis was found. Authors suggest that vitamin D supplementation would be most efficient if medicine would follow the present trend of personalised therapy.
Abstract
Objective: Our aims were to compare the vitamin D status of children with and without cancer and to examine the possible correlation between vitamin D levels in children with cancer before initiating treatment and prognosis.Method: We compared the data of 173 children with cancer with those of 569 children without cancer.Results: We measured a significant difference (p = 1.34E-08) between the vitamin D levels of children with cancer before treatment and children without cancer. There was a significant correlation between the initial vitamin D levels of children with cancer and the prognosis (p = 0.016, odds ratio = 51.33) at 5% significance.Conclusions: The average vitamin D level was 19.76% lower in the population with cancer compared with the average of the control group, and we found a correlation between the lower vitamin D levels in children with cancer and the adverse prognosis. We suggest that supplying vitamin D is reasonable and a prospective study of vitamin D in pediatric patients with cancer is recommended.
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Association of serum vitamin D concentrations with dietary patterns in children and adolescents.
Ganji, V, Martineau, B, Van Fleit, WE
Nutrition journal. 2018;17(1):58
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In the absence of not enough exposure to sunlight , diet is an important contributor of vitamin D status. Henceforth, this study aimed to examine the correlation of blood plasma status of vitamin D to any dietary pattern. Data was collected through National centre of health statistics of USA in which, a 216-item food frequency questionnaire was included to gather information on dietary pattern of children and adolescents. The results from this study suggests that the greatest plasma concentrations of vitamin D status occurred in individuals who consumed a healthier diet, emphasising on vegetables, fruits, and some fish and lean meat. The authors though concluded that the difference seen in plasma vitamin D status could also be other than diet such as season, sun exposure and intake of vitamin D supplements as well as that, the bioavailibilty of vitamin D may be low in those who are overweight. Henceforth, from public health perspective children hould be encouraged to eat healthily.
Abstract
BACKGROUND Because children have been advised on the dangers of sun exposure, diet is an important contributor of serum 25 hydroxyvitamin D [25(OH)D] concentrations. Aim of this study was to determine whether serum 25(OH)D concentrations were associated with any specific dietary patterns in US children. METHODS Data from 2 cycles of National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2005-2006 for individuals aged 2 to ≤19 y, were used to study relation between dietary patterns and serum 25(OH)D. We derived 2 major dietary patterns based on the food frequency questionnaire data. These were labeled as High-Fat-Low-Vegetable Dietary (HFLVD) pattern and Prudent Dietary (PD) pattern. RESULTS In multivariate adjusted analysis, there was no significant relationship between serum 25(OH)D concentrations and tertiles of HFLVD and PD dietary pattern scores in all subjects, boys, and girls. When dietary patterns scores were used as a continuous variable in adjusted analysis, children (all) with higher PD contribution scores to overall diet showed a significant positive relation with serum 25(OH)D (β = 59.1, P = 0.017). When data were stratified by sex, a significant positive relation was observed in girls between serum 25(OH)D concentration and PD pattern scores (β = 82.1, P = 0.015). A significant negative relation was observed in girls between serum 25(OH)D and HFLVD pattern scores (β = - 88.5, P = 0.016). CONCLUSION Overall, serum 25(OH)D were associated with PD pattern but not with HFLVD pattern in US children. In public health perspective, it is important to encourage children, especially girls who are consuming HFLVD pattern to shift to healthier diet.