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Effect of vitamin D supplementation on depression in older Australian adults.
Rahman, ST, Waterhouse, M, Romero, BD, Baxter, C, English, DR, Almeida, OP, Berk, M, Ebeling, PR, Armstrong, BK, McLeod, DSA, et al
International journal of geriatric psychiatry. 2023;38(1):e5847
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Depression can considerably impair daily function. However, although medications and psychological therapy can be effective in treating depression, non‐compliance with and/or side effects of antidepressants are common. Thus, identifying alternative or adjunctive therapies to prevent or treat depression may help to overcome some limitations of current management strategies. The aim of this study was to examine whether supplementing older Australians with monthly doses of 60,000 IU of vitamin D3 for 5 years would reduce depressive symptoms or incidence of antidepressant use, as a surrogate for a formal diagnosis of depression. This study used data from the D‐Health Trial, a large population‐based randomised controlled trial. Authors randomly selected potential participants aged between 60 and 79 years from the Australian Commonwealth Electoral Roll. The participants who accepted the invitation were randomly allocated to either 60,000 IU of cholecalciferol (vitamin D3) or placebo in a 1:1 ratio. Results show that there wasn’t an overall benefit of monthly supplementation with 60,000 IU of vitamin D for up to 5 years on measures of depression. However, pre‐specified subgroup analyses suggested a potential beneficial effect of vitamin D supplementation in people taking antidepressants at baseline or with lower predicted baseline vitamin D3 concentration. However there was an unfavourable effect in participants with a body mass index <25 kg/m2 or those with higher predicted baseline vitamin D3 concentration. Authors conclude that routine supplementation with vitamin D in populations with a low prevalence of vitamin D deficiency is unlikely to be of benefit for depression and may cause harm in people with low body mass index or normal vitamin D status.
Abstract
OBJECTIVES To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use. METHODS We used data from the D-Health Trial (N = 21,315), a randomized double-blind placebo-controlled trial of monthly vitamin D3 for the prevention of all-cause mortality. Participants were Australians aged 60-84 years. Participants completed the Patient Health Questionnaire (PHQ-9) at 1, 2 and 5 years after randomization to measure depressive symptoms; national prescribing records were used to capture antidepressant use. We used mixed models and survival models. RESULTS Analyses of PHQ-9 scores included 20,487 participants (mean age 69·3 years, 46% women); the mean difference (MD) in PHQ-9 score (vitamin D vs. placebo) was 0·02 (95% CI -0·06, 0·11). There was negligible difference in the prevalence of clinically relevant depression (PHQ-9 score ≥10) (odds ratio 0·99; 95% CI 0·90, 1·08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69·4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1·04; 95% CI 0·96, 1·12). In subgroup analyses, vitamin D improved PHQ-9 scores in those taking antidepressants at baseline (MD -0·25; 95% CI -0·49, -0·01; p-interaction = 0·02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration <50 nmol/L (HR 0·88; 95% CI 0·75, 1·02; p-interaction = 0·01) and increased risk in those with predicted 25(OH)D ≥ 50 nmol/L (HR 1·10; 95% CI 1·01, 1·20). CONCLUSION Monthly supplementation with high-dose vitamin D3 was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses. CLINICAL TRIAL REGISTRATION The trial is registered on the Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/.
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The effect of vitamin D supplementation on the gut microbiome in older Australians - Results from analyses of the D-Health Trial.
Pham, H, Waterhouse, M, Rahman, S, Baxter, C, Duarte Romero, B, McLeod, DSA, Ebeling, PR, English, DR, Hartel, G, O'Connell, RL, et al
Gut microbes. 2023;15(1):2221429
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Microbiota are communities of microorganisms that co-exist with the host ecosystem in a specific environment. The term microbiome refers to the microbial genome. The aim of this study was to investigate the effect of supplementing older adults with 60,000 IU of vitamin D per month on the gut microbiome for a period of five years, using a subsample (n = 835) of participants recruited from the large population-based D-Health Trial. This study is based on a subsample from the D-Health Trial, which was a randomised, double-blind trial with two parallel arms. Participants were randomly allocated (1:1 ratio) to monthly doses of either 60,000 IU of cholecalciferol (vitamin D3) or matching placebo. Results showed that monthly doses of 60,000 IU vitamin D over 5 years did not alter the composition of the gut microbiome in a population that is largely vitamin D replete. Authors conclude that further investigation is required to examine whether non-bolus doses of vitamin D would influence the gut microbiome or whether vitamin D supplementation would be beneficial in populations with a higher prevalence of vitamin D deficiency.
Abstract
Observational studies suggest a link between vitamin D and the composition of the gut microbiome, but there is little evidence from randomized controlled trials of vitamin D supplementation. We analyzed data from the D-Health Trial, a randomized, double-blind, placebo-controlled trial. We recruited 21,315 Australians aged 60-84 y and randomized them to 60,000 IU of vitamin D3 or placebo monthly for 5 y. Stool samples were collected from a sample of 835 participants (417 in the placebo and 418 in the vitamin D group) approximately 5 y after randomization. We characterized the gut microbiome using 16S rRNA gene sequencing. We used linear regression to compare alpha diversity indices (i.e. Shannon index (primary outcome), richness, inverse Simpson index), and the ratio of Firmicutes to Bacteroidetes between the two groups. We analyzed between-sample (beta) diversity (i.e. Bray Curtis distance and UniFrac index) using principal coordinate analysis and used PERMANOVA to test for significant clustering according to randomization group. We also assessed the difference in the abundance of the 20 most abundant genera between the two groups using negative binomial regression model with adjustment for multiple testing. Approximately half the participants included in this analysis were women (mean age 69.4 y). Vitamin D supplementation did not alter the Shannon diversity index (mean 3.51 versus 3.52 in the placebo and vitamin D groups, respectively, p = 0.50). Similarly, there was little difference between the groups for other alpha diversity indices, the abundance of different genera, and the Firmicutes-to-Bacteroidetes ratio. We did not observe clustering of bacterial communities according to randomization group. In conlusion, monthly doses of 60,000 IU of vitamin D supplementation for 5 y did not alter the composition of the gut microbiome in older Australians.
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Association of Vitamin D Level and Maternal Gut Microbiome during Pregnancy: Findings from a Randomized Controlled Trial of Antenatal Vitamin D Supplementation.
Aparicio, A, Gold, DR, Weiss, ST, Litonjua, AA, Lee-Sarwar, K, Liu, YY
Nutrients. 2023;15(9)
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Changes in the gut bacteria during pregnancy and a lack of vitamin D can have negative health consequences for both mother and child. Vitamin D has important functions in the human body and is key in regulating immune and inflammatory responses. Evidence suggests that vitamin D helps to maintain gut wall integrity and regulate inflammatory mechanisms in response to bacteria. Gut bacteria themselves have immune regulatory functions, and unfavourable disruptions in the composition of the bacteria are associated with chronic inflammatory diseases. Evidence shows gut bacteria composition is influenced by Vitamin D. During pregnancy, a substantial alteration in gut bacteria composition occurs and as pregnancy advances, there's typically an increase in bacteria linked to inflammation. This study analysed the data from the Vitamin D Antenatal Asthma Reduction Trial (VDAART, 2014), a randomised placebo controlled trial which gathered information on the impact of vitamin D on various markers as well as gut microbiome composition in pregnant women. For the study all participants took a daily multivitamin with 400 IU Vitamin D during the third trimester of pregnancy, and were given either an additional 4000IU of Vitamin D or a placebo. Results were drawn from 114 participants and their baseline vitamin D levels in early pregnancy, its changes over the trial period, as well as gut bacteria composition. The vitamin D levels at the start aligned with expected outcomes and was strongly linked to race, income, and education level. The baseline vitamin D level in early pregnancy also showed a connection to certain gut microbiome composition. However, these bacterial constellations remained robust and did not show any changes in response to Vitamin D supplementation throughout pregnancy. During the trial, most participant's vitamin D levels increased, especially those in the 4400 IU treatment group. Interestingly, women whose vitamin D levels did not increase much throughout the trial displayed a higher abundance of a bacteria called Desulfovibrio. Desulfovibrio is associated with an increased incidence of respiratory and inflammatory bowel diseases and the authors suggested that increasing vitamin D during pregnancy might help prevent the growth of more unfavourable bacteria like Desulfovibrio. Further long-term research is needed to confirm this idea.
Abstract
Shifts in the maternal gut microbiome and vitamin D deficiency during pregnancy have been associated, separately, with health problems for both the mother and the child. Yet, they have rarely been studied simultaneously. Here, we analyzed the gut microbiome (from stool samples obtained in late pregnancy) and vitamin D level (from blood samples obtained both in early and late pregnancy) data of pregnant women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized controlled trial of vitamin D supplementation during pregnancy, to investigate the association of vitamin D status on the pregnant women's microbiome. To find associations, we ran linear regressions on alpha diversity measures, PERMANOVA tests on beta diversity distances, and used the ANCOM-BC and Maaslin2 algorithms to find differentially abundant taxa. Analyses were deemed significant using a cut-off p-value of 0.05. We found that gut microbiome composition is associated with the vitamin D level in early pregnancy (baseline), the maternal gut microbiome does not show a shift in response to vitamin D supplementation during pregnancy, and that the genus Desulfovibrio is enriched in women without a substantial increase in vitamin D level between the first and the third trimesters of pregnancy. We conclude that increasing the vitamin D level during pregnancy could be protective against the growth of sulfate-reducing bacteria such as Desulfovibrio, which has been associated with chronic intestinal inflammatory disorders. More in-depth investigations are needed to confirm this hypothesis.
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The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults.
Draxler, A, Franzke, B, Kelecevic, S, Maier, A, Pantic, J, Srienc, S, Cellnigg, K, Solomon, SM, Zötsch, C, Aschauer, R, et al
Redox biology. 2023;61:102640
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Aging is associated with a decline in physiological and physical function resulting in reduced physical activity, all of which are driving factors to the onset of chronic diseases and physical impairment. Older adults are often deficient in micronutrients, specifically vitamin D, which has been shown to have detrimental effects on the immune system, inflammatory and healing processes of fractured bones and also cardiovascular health beyond other musculoskeletal effects. The aim of this study was to investigate the effect of different vitamin D regimens in older individuals during an ongoing strength training period of 10 weeks while receiving vitamin D supplementation at the recommended level of 800 IU per day vs. a single dose of 50.000 IU per month. The data presented in this paper are part of the NutriAging Vitamin D study. The study was a randomised placebo-controlled double-blind trial which recruited one hundred community-dwelling women and men (aged 65–85 years). Participants were randomly allocated into three intervention groups, either the control group, the vitamin D daily (VDD) or the vitamin D monthly group (VDM). Results showed that oxidative stress might have played a role in the detrimental progress on chromosomal stability parameters since the protective effect of GSH (reduced glutathione) was reduced in all study groups at the end of the intervention, but the least reduction occurred in the VDD group. Authors concluded that a supplementation with the recommended dose of 800 IU vitamin D per day might be more advantageous when it comes to chromosomal stability parameters in older, formerly untrained participants undergoing demanding resistance exercise for 10 weeks.
Abstract
Older adults lack of proper physical activity which is often accompanied by vitamin D deficiency. Those factors are known to contribute to health issues in the later years of life. The main goal of this intervention study was to investigate the effect of different vitamin D supplementation strategies for 4 weeks solely or combined with a 10-week strength training program on chromosomal stability in peripheral blood mononuclear cells in community-dwelling older people. One hundred women and men (65-85 years) received either vitamin D3 daily (800 IU), a monthly dose (50.000 IU) or placebo for 17 weeks. All groups received 400 mg calcium daily. The fitness status of the study participants was measured using the 30- second chair stand test, the handgrip strength test and the 6-min walk test. The cytokinesis block micronucleus cytome (CBMN) assay was applied to analyze chromosomal anomalies, including cytotoxic and genotoxic parameters. Changes in antioxidant markers were measured in plasma. Walking distance and chair stand performance improved significantly. Increased levels of the parameters of the CBMN assay were detected for all intervention groups at study end. At baseline micronuclei (MNi) frequency correlated significantly with BMI in both sexes (females: r = 0.369, p = 0.034; males: r = 0.265, p = 0.035), but not with vitamin D serum levels. In females, body fat (r = 0.372, p < 0.001) and functional parameter using the 30-s chair stand test (r = 0.311, p = 0.002) correlated significantly with MNi frequency. Interestingly, not vitamin D supplementation but 10 weeks of resistance training increased MNi frequency indicating elevated chromosomal instability and also adverse effects on antioxidant markers including glutathione and FRAP were detected in the group of community-dwelling older adults.
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Effects of multi-domain intervention on intrinsic capacity in older adults: A systematic review of randomized controlled trials (RCTs).
Liao, X, Shen, J, Li, M
Experimental gerontology. 2023;174:112112
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With the increase of age, the physiological reserve of the elderly decreases, which leads to the increase of physical vulnerability and the decrease of anti-stress ability, showing a series of frailty manifestations. Intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) is central to maintaining function in older adults, and maintaining optimal intrinsic capacity is important to promote healthy aging. The aim of this study was to assess randomised controlled trials of multidomain interventions to further validate their effectiveness in the maintenance and enhancement of function in older adults, and to formulate strategies for preventive care and clinical practice. This study was a systematic review and meta-analysis of twenty-five publications. Results showed that multi-domain interventions can improve indicators of vital domains in older adults and integrate to optimise intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) through potential interaction mechanisms. Authors concluded that because older adults may not be able to receive overly complex interventions due to limitations in their integrative abilities, the involvement of older adults and the sustainability of interventions should be considered before implementing them.
Abstract
Intrinsic capacity is central to the maintenance of function in older adults, and maintaining optimal intrinsic capacity is of great importance to promote healthy aging. The purpose of this systematic review and meta-analysis was to analyze the impact of multi-domain interventions on intrinsic capacity in older adults, intervention components, and potential interactions between components. A total of 6740 published articles were screened until August 2022, and the review included 25 randomized controlled trials that analyzed populations, interventions, control groups, and outcomes. The meta-analysis showed improvements in the primary outcome indicators in the intervention group compared to the control group. These included increased scores on the Mini-Mental State Examination as an indicator of cognitive function, decreased scores on the Geriatric Depression Scale (GDS-15) as an indicator of psychological ability and increased scores on the Short Physical Performance Battery (SPPB) as an indicator of physical performance, with only the SPPB indicator analyzed showing greater heterogeneity. Significant improvements were also seen in the secondary indicators Time-to-Walk Test (TUG), gait speed, Chair Stand Test (CST), grip strength values and BMI. There was insufficient data for the Mini Nutritional Assessment (MNA) as an indicator of vitality to conduct a meta-analysis. Studies were of moderate to high quality. The results of this review indicate that multi-domain interventions can maintain the level of intrinsic capacity in older adults and are equally effective in older adults with declining self-care abilities.
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Effect of vitamin D supplementation on cardiac-metabolic risk factors in elderly: a systematic review and meta-analysis of clinical trials.
Qorbani, M, Zarei, M, Moradi, Y, Appannah, G, Djalainia, S, Pourrostami, K, Ejtahed, HS, Mahdavi-Gorabi, A, Naderali, EK, Khazdouz, M
Diabetology & metabolic syndrome. 2022;14(1):88
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Modifiable risk factors such as dyslipidemia, hyperglycemia, obesity, and hypertension are characteristics of cardio-metabolic disorder which may lead to diabetes or cardiovascular disease. Previous research has shown an association between vitamin D deficiency and cardio-metabolic disorders. Studies have also shown that vitamin D deficiency is prevalent in older people. Therefore, this systematic review and meta-analysis evaluated the beneficial effects of Vitamin D supplementation (VDS) on the cardio-metabolic profile in elderly people. Twelve studies are included in this systematic review and meta-analysis. VDS dosage ranged from 400 IU/day to 4000 IU/day generally in most of the included studies, and the duration of intervention ranged from two months to one year. This systematic review and meta-analysis showed an improvement in total cholesterol and triglycerides followed by VDS in elderly participants. The subgroup analysis revealed improved glycaemic indices in elderly people with glycaemic irregularities. Longer-term VDS intervention improved glycaemic control. Further robust studies are required as there is high heterogeneity in the form of the vitamin D, dosage, duration, route of administration and study design of the included studies in this research. However, healthcare professionals can use the results of this study to understand the therapeutic value of VDS in improving the cardio-metabolic health of elderly people.
Abstract
BACKGROUND There has been a longstanding interest in the potential effect of vitamin D in preventing cardiac-metabolic diseases. However, there are divergent results regarding the impact of vitamin D supplementation (VDS) on managing cardiac-metabolic outcomes in the elderly population. MATERIAL AND METHOD We systematically searched electronic databases; Web of Science, PubMed, Scopus, EMBASE, Cochrane, and ProQuest. We included all trials that evaluated the effect of VDS on cardiac-metabolic risk factors in the elderly population, which were published until 30 September 2021. The effects of VDS on cardiac-metabolic outcomes were assessed using standardized mean difference (SMD). A random-effect model was used to pool the SMD and 95% confidence interval (CI). RESULT The literature search identified 4409 studies, of which 12 trials met inclusion criteria. Results of random effect meta-analysis indicated a significant reduction in total cholesterol (TC) (SMD: - 0.14 mg/dl; 95% CI: - 0.25, - 0.02) and triglyceride (TG) (SMD: - 0.45 mg/dl; 95% CI: - 0.86, - 0.04) with VDS compared to the placebo. The subgroup analyses revealed that the reduction of TG in patients with diabetes and vitamin D deficiency was significant. Furthermore, short-term intervention (≤ 6 months) induced a significantly lower level of TG and insulin in comparison to longer duration (> 6 months). CONCLUSION The study suggests that VDS could improve insulin concentration and dyslipidemia in the elderly population. The systematic review was registered in Alborz university of medical sciences with 2060-01-03-1397 number and the Ethics council IR.ABZUMS.REC.1397.207 number.
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The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto's Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial.
Robat-Jazi, B, Mobini, S, Chahardoli, R, Mansouri, F, Nodehi, M, Esfahanian, F, Saboor Yaraghi, AA
Iranian journal of allergy, asthma, and immunology. 2022;21(4):407-417
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Hashimoto’s thyroiditis is an autoimmune disease characterized by the presence of antibodies against thyroid proteins such as thyroperoxidase (TPO) and thyroglobulin (TG), the local accumulation of inflammatory cells and immune-mediated destruction of the thyroid gland. Disease manifestation is due to a genetic disposition but is also influenced by several environmental factors, including stress, smoking, infections, and levels of nutrients like iodine, selenium and vitamin D. Many cells of the immune system have receptors for Vitamin D and thus have the potential to be influenced by Vitamin D. Indeed, numerous findings demonstrated that vitamin D can exert anti-inflammatory effects on the immune system. This double-blind, randomized, placebo-controlled trial investigated 40 Hashimoto's thyroiditis subjects and the effect of Vitamin D supplementation on various markers of the immune system that mediate the inflammatory response as part of the interferon-gamma-induced protein 10 (IFNγ-IP10) axis. 20 of the enrolled candidates received 50000 IU of Vitamin D (cholecalciferol) once a week – an equivalent to about 7140 IU per day - over three months. The other half received a placebo. All candidates had a fixed dose of thyroid hormone replacement levothyroxine for the duration of the trial. Before and after the intervention several blood biomarkers were investigated relating to Vitamin D levels, D-receptors, immune activity and inflammation. Upon completion of the trial, the intervention group who supplemented Vitamin D had significantly higher Vitamin D levels, which had increased from an average of 25.29 ng/ml to 50.65ng/ml. In addition, several inflammatory factors were significantly decreased. These findings affirmed Vitamin D’s ability to favourably regulate the IFNγ-IP10 axis, which could slow disease progression. This effect may also be useful for the management of other autoimmune disorders involving IP10 overproduction, which attracts other inflammatory cells. More studies in larger groups would help to get more information on other variables not considered in this trial.
Abstract
Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group. During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.
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High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.
Annweiler, C, Beaudenon, M, Gautier, J, Gonsard, J, Boucher, S, Chapelet, G, Darsonval, A, Fougère, B, Guérin, O, Houvet, M, et al
PLoS medicine. 2022;19(5):e1003999
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The Coronavirus Disease 2019 (COVID-19) caused hundreds of thousands of deaths, mostly in older adults. The aim of this study was to test whether a single oral high-dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults who are positive to COVID-19. This study is an investigator-initiated, multicentre, open-label, parallel group, intent-to-treat, randomised controlled superiority clinical trial which involves the collaboration of 9 medical centres. Eligible participants (n=260) were randomly assigned to receive a single oral dose of either 400,000 IU (n=130) or 50,000 IU (n=130) cholecalciferol on the day of inclusion. Results show: - reduced overall mortality at day 14. - that high-dose cholecalciferol was safe and did not result in more frequent adverse effects compared to the standard dose. - that some benefits were also found on the 14-day mortality due to COVID-19 as well as on the overall mortality between day 6 and day 14. - that there was no evidence that the single high-dose vitamin D3 administered early in COVID-19 provided any benefit on overall mortality for up to 28 days. Authors conclude that high-dose oral cholecalciferol supplementation is a simple, safe, and inexpensive treatment which may be of interest as an adjuvant to provide a bridge to recovery for at-risk older adults facing the emergence of immune escape variants.
Abstract
BACKGROUND Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION ClinicalTrials.gov NCT04344041.
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Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.
Sabico, S, Enani, MA, Sheshah, E, Aljohani, NJ, Aldisi, DA, Alotaibi, NH, Alshingetti, N, Alomar, SY, Alnaami, AM, Amer, OE, et al
Nutrients. 2021;13(7)
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A highly contagious virus called SARS-CoV-2 is responsible for the Covid-19 pandemic. Vitamin D adjuvant therapy has been identified as a promising strategy for reducing the severity of Covid-19 outcomes in the elderly. Also, a low Vitamin D status significantly correlates with Covid-19 severity. This multi-centre randomised, open-label clinical trial evaluated the beneficial effects of 5000 IU versus 1000 IU Vitamin D3 daily supplementation for two weeks on recovery of symptoms in patients with mild-to-moderate Covid-19 and suboptimal Vitamin D status. Thirty-six Covid-19 patients received 5000 IU Vitamin D3 daily, and thirty-three Covid-19 patients received 1000 IU Vitamin D3 daily. The 5000 IU Vitamin D3 group was significantly younger and had a significantly lower BMI than the 1000 IU Vitamin D3 group. The 5000 IU Vitamin D3 group showed significant improvements in the severity of the Covid-19 symptoms compared to the 1000 IU Vitamin D3 group. Further robust studies are needed to evaluate the effects of Vitamin D3 supplementation in patients with high BMI, severe Covid-19 symptoms, and prevention of Covid-19. Healthcare professionals can use the results of this study to understand the effects of different doses of Vitamin D3 supplements in patients with mild-to-moderate Covid-19 symptoms and suboptimal Vitamin D status.
Abstract
OBJECTIVE Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.
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A Narrative Review of The Role of Foods as Dietary Sources of Vitamin D of Ethnic Minority Populations with Darker Skin: The Underestimated Challenge.
Guo, J, Lovegrove, JA, Givens, DI
Nutrients. 2019;11(1)
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Vitamin D is essential for healthy bones, and low vitamin D status is associated with an increased risk of chronic diseases such as cardiovascular disease and type 2 diabetes. Ethnic minority populations with darker skin are considered as a high-risk group for vitamin D deficiency, owing mainly to having less ability to synthesise vitamin D from sunlight due to the skin pigment melanin and/or reduced skin exposure due to clothing required by religious or cultural traditions. The aim of this literature review was to evaluate vitamin D intake and status of ethnic minority populations with darker skin. The authors examined previous observational studies and randomised controlled trials. Ethnic minority populations generally have a lower vitamin D status than white populations. Compared with Caucasians, there is evidence that Asians require approximately three times longer periods of sunlight exposure, and Africans six times the same exposure, to achieve the same blood levels of vitamin D. The main food sources for dietary vitamin D intake were different for ethnic minority populations and white populations. There is limited evidence on the impact of vitamin D supplementation on different ethnic groups. The authors concluded that food fortification could be explored to increase dietary vitamin D intake in ethnic minority populations who generally have lower levels of vitamin D.
Abstract
In recent years, vitamin D deficiency has attracted attention worldwide. Especially many ethnic minority populations are considered at high-risk of vitamin D deficiency, owing to a lesser ability to synthesis vitamin D from sunlight (ultraviolet B), due to the skin pigment melanin and/or reduced skin exposure due to coverage required by religious and cultural restrictions. Therefore, vitamin D intake from dietary sources has become increasingly important for many ethnic minority populations to achieve adequate vitamin D status compared with the majority of the population. The aim of the study was critically evaluate the vitamin D intake and vitamin D status of the ethnic minority populations with darker skin, and also vitamin D absorption from supplements and ultraviolet B. Pubmed, Embaase and Scopus were searched for articles published up to October 2018. The available evidence showed ethnic minority populations generally have a lower vitamin D status than the majority populations. The main contributory food sources for dietary vitamin D intake were different for ethnic minority populations and majority populations, due to vary dietary patterns. Future strategies to increase dietary vitamin D intake by food fortification or biofortification needs to be explored, not only for the majority population but more specifically for ethnic minority populations who are generally of lower vitamin D status.