Excess Uric Acid associated with low vitamin D

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Gout and Vitamin D in VitaminDWiki

Gout and Vitamin D - many studies has the following summary and image

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Uric Acid and some Kidney stones

Overview Kidney Stones and vitamin D
Note: A fraction of Kidney stones are associated with Uric Acid (low vitamin D)

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Uric acid reduced by Vitamin D - meta-analysis June 2024

Effect of vitamin D administration on serum uric acid concentrations: A systematic review and meta-analysis of clinical trials
PharmaNutrition https://doi.org/10.1016/j.phanu.2024.100391
Luis E. Simental-Mendía a, Yéssika Weyman-Vela a, Mario Simental-Mendía b 1

Highlights

• Vitamin D administration is associated with a significant reduction in the levels of serum uric acid.
• Notably, results derived exclusively from randomized clinical trials as reference.
• Clinical relevance of the potential mechanisms remains to be elucidated in further studies.

Background
It has been suggested the potential uric acid-lowering effect of vitamin D; however, clinical trials evaluating the impact of vitamin D administration on serum uric acid levels are scarce. The aim of this meta-analysis of clinical trials was to examine the effect of vitamin D administration on serum uric acid concentrations.

Methods
A systematic search was performed in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Randomized clinical trials (parallel or cross-over design) with data at baseline and at the end of intervention. Trials without intervention, without control group, and incomplete data of uric acid concentrations were excluded. A random-effects model and sensitivity analysis generic inverse variance method were used for the meta-analysis.

Results
Meta-analysis was carried out using a random-effects model and sensitivity analysis. The meta-analysis of seven clinical trials, involving 959 participants, indicated a significant reduction of uric acid levels after vitamin D administration (WMD: −16.64 µmol/L, 95% CI: −25.25, −8.03, p <0.001, I2 = 74%). Additionally, the impact of this vitamin on uric acid concentrations was robust in the leave-one-out sensitivity analysis.

Discussion
Given that few clinical trials were included, the number of subjects analyzed was limited. However, our results suggest that vitamin D administration is associated with a significant reduction in the levels of serum uric acid in randomized clinical trials.

Introduction
Uric acid, a scavenger of oxygen radicals, is an essential antioxidant that maintains the regulation of blood pressure and oxidative stress. Multiple factors are involved in determining serum uric acid levels including age, sex, renal function, and dietetic factors such as fructose, purine, and alcohol intake. Excessive purine intake, endogenous defects in purine metabolism, and/or inadequate uric acid excretion lead to hyperuricemia [1]. Thus, an abnormal uric acid concentration may be associated with several disorders such as hyperuricemia, gout, metabolic syndrome, cardiovascular disease, and chronic kidney disease [2], [3], [4]. The usual treatment for hyperuricemia consists of the administration of uric acid-lowering drugs, however, it has been reported that therapeutic interventions to reduce uric acid concentrations are underused in patients recently diagnosed with hyperuricemia [5].

Recently, other therapeutic options have shown a beneficial effect in decreasing serum uric acid levels, including vitamin D supplementation [6]. Vitamin D is a steroid hormone that in addition to regulating calcium and phosphorus absorption and bone metabolism, exerts many pleiotropic actions in organs and tissues in the body. The recommendation for the pleiotropic effects of vitamin D is a target 25(OH)D concentration of 30 ng/mL (75 nmol/L), and age-, body weight-, disease-status, and ethnicity using vitamin D doses between 400 and 2000 IU/day [7]. A large population-based study indicated that the serum 25(OH) D, dietary vitamin D intake, vitamin D supplementation, and total vitamin D intake were inversely associated with hyperuricemia in men, while inverse associations between 25(OH) D, dietary vitamin D intake, and total vitamin D intake with hyperuricemia were observed in women [8]. However, evidence in this field is still scarce; therefore, the aim of this meta-analysis of clinical trials was to examine the effect of vitamin D administration on serum uric acid concentrations.

Section snippets
Search strategy
We performed the present study According to the Systematic Review of Controlled Trials - PRISMA - Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [9]. The systematic search was conducted from inception to October, 2023 in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. The following terms were searched in titles and abstracts: (“vitamin D supplementation” OR “vitamin D” OR “vitamin D2” OR “vitamin D3” OR “25(OH)D” OR …

Study selection process
In summary, 478 articles were found through the search in databases, and 428 were removed
Subsequently, 17 full-text articles were reviewed and six were not selected by lack of control group (n=3), incomplete data on uric acid levels (n=6), and duplicate data (n=1). Finally, 7 clinical trials were included for the meta-analysis. The complete study selection process is …

Discussion
The results of this systematic review and meta-analysis indicate that serum uric acid levels significantly decrease after vitamin D administration. To the best of our knowledge, this is the first meta-analysis in determining the impact of vitamin D on uric acid levels with clinical trials as reference….

The precise mechanism by which vitamin D administration may decrease serum uric acid levels is not fully understood. Some studies have demonstrated an inverse correlation between vitamin D levels…

Conclusions
Our results suggest that vitamin D administration is associated with a significant reduction in the levels of serum uric acid in randomized clinical trials. However, further clinical trials are warranted in order to clarify the role of vitamin D on uric acid metabolism….

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Uric acid does not build-up in people with a high level of vitamin D (China in this case) – May 2024

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis
Nutrients. 2024 May 15;16(10):1492. doi: 10.3390/nu16101492.
Zhuang Ma 1, Ting Xiong 1, Yan Li 2, Binxuan Kong 3, Wenlong Lu 2, Ziyang Zhang 2, Liangkai Chen 3, Yuhan Tang 3, Ping Yao 3, Jingfan Xiong 2, Yanyan Li 2, Yuanjue Wu 1

Background: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents.

Objective: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents.

Methods: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose-response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM.

Results: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07-2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36-0.84). Longitudinal analysis indicated that the annual change of SUA was from -4.80 (β, 95%CI: -10.74, 1.13) to -9.00 (β, 95%CI: -15.03, -2.99) and then to -6.77 (β, 95%CI: -12.83, -0.71, p for trend = 0.0212) μmol/L when increasing the quartile of vitamin D3.

Conclusions: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism.
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Potential causal associations between vitamin D and uric acid: Bidirectional mediation analysis - Sept 2015

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Association Between Vitamin D and Hyperuricemia Among Adults in the United States- Nov 2020

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Uric acid and Vitamin D linked to PTH - July 2021

Vitamin D and Uric Acid: Is Parathyroid Hormone the Missing Link?
Journal of Clinical & Translational Endocrinology. Available online 8 July 2021, https://doi.org/10.1016/j.jcte.2021.100263
Letters to the editor

With interest, we read the article of Nimitphong et al. [1], which revealed the potential uric-lowering effect of vitamin D supplementation in patients with prediabetes and hyperuricemia. The result of this study supports the causal association between vitamin D deficiency and insufficiency and elevated serum uric acid that has been shown in previous observational studies 2 independent of the fact that the association might also be confounded by presence of comorbid obesity and metabolic syndrome.
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Some amount of Vitamin D reduces uric acid concentations - meta-analysis of clinical trials May 2024

Effect of vitamin D administration on serum uric acid concentrations: a systematic review and meta-analysis of clinical trials
PharmaNutrition online 17 May 2024,https://doi.org/10.1016/j.phanu.2024.100391 PDF behind paywall
Luis E. Simental-Mendía a, Yéssika Weyman-Vela a, Mario Simental-Mendía b 1

Background
It has been suggested the potential uric acid-lowering effect of vitamin D; however, clinical trials evaluating the impact of vitamin D administration on serum uric acid levels are scarce. The aim of this meta-analysis of clinical trials was to examine the effect of vitamin D administration on serum uric acid concentrations.

Methods
A systematic search was performed in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Randomized clinical trials (parallel or cross-over design) with data at baseline and at the end of intervention. Trials without intervention, without control group, and incomplete data of uric acid concentrations were excluded. A random-effects model and sensitivity analysis generic inverse variance method were used for the meta-analysis.

Results
Meta-analysis was carried out using a random-effects model and sensitivity analysis. The meta-analysis of seven clinical trials, involving 959 participants, indicated a significant reduction of uric acid levels after vitamin D administration (WMD: -16.64 µmol/L, 95% CI: -25.25, -8.03, p <0.001, I2 = 74%). Additionally, the impact of this vitamin on uric acid concentrations was robust in the leave-one-out sensitivity analysis.

Discussion
Given that few clinical trials were included, the number of subjects analyzed was limited. However, our results suggest that vitamin D administration is associated with a significant reduction in the levels of serum uric acid in randomized clinical trials.

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Association Between Vitamin D and Uric Acid in Adults:A Systematic Review and Meta-Analysis - Sept 2020

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Low D, high Uric - meta-analysis March 2019

Vitamin D insufficiency and deficiency are associated with a higher level of serum uric acid: A systematic review and meta-analysis
Mod Rheumatol. 2019 Mar 4:1-6. doi: 10.1080/14397595.2019.1575000
Charoenngam N1, Ponvilawan B2, Ungprasert P3.
1 Department of Medicine, Faculty of Medicine Siriraj Hospital , Mahidol University , Bangkok , Thailand.
2 Department of Pharmacology, Faculty of Medicine Siriraj Hospital , Mahidol University , Bangkok , Thailand.
3 Department of Research and Development, Faculty of Medicine Siriraj Hospital, Clinical Epidemiology Unit , Mahidol University , Bangkok , Thailand.
INTRODUCTION/OBJECTIVES:
Several epidemiological studies have suggested that patients with vitamin D insufficiency and deficiency tend to have a higher level of serum uric acid compared with those with adequate vitamin D level although the results were inconsistent across the studies. The current systematic review and meta-analysis was conducted with the aim to summarize all the available data.

METHODS:
A systematic review was conducted using MEDLINE and EMBASE database from inception to May 2018 to identify all studies that compared the level of serum uric acid between individuals with normal vitamin D level and patients with vitamin D insufficiency/deficiency. Eligible studies must be cohort or cross-sectional studies that consisted of two groups of adult participants, one with normal level of vitamin D (vitamin D level >30 ng/ml) and one with vitamin D insufficiency (vitamin D level 20-30 ng/ml) or vitamin D deficiency (vitamin D level of <20 ng/ml). Mean serum uric acid level and standard deviation of participants were extracted from each study to calculate mean difference (MD). Pooled MD was then calculated by combining MDs of each study using random-effects model.

RESULTS:
A total of seven cross-sectional studies were eligible for the meta-analyses. Individuals with normal vitamin D level had a significantly lower serum uric acid level than patients with vitamin D insufficiency with the pooled MD of -0.33 mg/dl (95%CI, -0.61, -0.04), and also had a significantly lower serum uric acid level than patients with vitamin D deficiency with the pooled MD of -0.45 mg/dl (95%CI, -0.82, -0.08). The statistical heterogeneity of these meta-analyses was high with the I2 of 78% and 89%, respectively. Funnel plots of both meta-analyses were fairly symmetric and did not provide a suggestive evidence for the presence of publication bias.

CONCLUSION: Both patients with vitamin D insufficiency and patients with vitamin D deficiency had a significantly higher level of serum uric acid compared with individuals with normal vitamin D level.
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