Hypovitaminosis of vitamin D in patients with gout (data from a pilot study)

   The relationship between serum levels of vitamin D and uric acid (UA) in the blood may be bidirectional, yet remains unexplored in patients with gout.

   The aim of this study was to identify the association between serum levels of UA and vitamin D deficiency in patients with gout.

   Materials and Methods. This single-center observational study included 79 patients with a confirmed diagnosis of gout (72 [91.1 %] men and 7 [8.9 %] women) who were not receiving urate-lowering therapy (ULT). All patients underwent evaluation of uric acid (UA), vitamin D, parathyroid hormone, C-reactive protein (СRP), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum calcium levels, alongside calculating the estimated glomerular filtration rate (eGFR). The levels of vitamin D and the frequency of vitamin D deficiency were compared across groups with different levels of UA in blood (quartiles): <426 µmol/L, 427 to 479 µmol/L, 480 to 540 µmol/L, and ≥ 540 µmol/L.

   Results. The mean level of vitamin D was below the normal reference values, at 22 (17–27) ng/mL (Median). Among the patients, 63 (80 %) exhibited vitamin D levels indicative of deficiency (< 30 ng/mL). A moderate correlation was found between vitamin D levels and serum calcium (ρ = 0.343, p = 0.002), while weak correlations were also noted between vitamin D levels and CRP (ρ = –0.204, p = 0.071) as well as parathyroid hormone (ρ = –0.216, p = 0.056). The levels of uric acid were categorized into quartiles: < 426 µmol/L, 427 to 479 µmol/L, 480 to 540 µmol/L, and ≥ 540 µmol/L. The analysis of vitamin D levels among different quartiles of UA revealed no significant relationship (p = 0.672).

   Conclusions. Vitamin D deficiency is prevalent in the majority of patients with gout (80 %); however, the severity of hyperuricemia is not associated with serum vitamin D levels. Further investigations are required to identify the causes of the high frequency of vitamin D deficiency in patients with gout.

1. Charoenngam N., Shirvani A., Holick M. F. Vitamin D for skeletal and non-skeletal health: What we should know. J. Clin. Orthop. Trauma. 2019; 10 (6): 1082–1093. doi: 10.1016/j.jcot.2019.07.004

2. Prietl B., Treiber G., Pieber T. R., Amrein K. Vitamin D and immune function. Nutrients. 2013; 5 (7): 2502–2521. Published 2013 Jul 5. doi: 10.3390/nu5072502

3. Palacios C., Gonzalez L. Is vitamin D deficiency a major global public health problem?. J. Steroid. Biochem. Mol. Biol. 2014; 144 Pt A: 138–145. doi: 10.1016/j.jsbmb.2013.11.003

4. Charoenngam N. Vitamin D and Rheumatic Diseases: A Review of Clinical Evidence. Int J. Mol. Sci. 2021; 22 (19): 10659. Published 2021 Oct 1. doi: 10.3390/ijms221910659

5. Isnuwardana R., Bijukchhe S., Thadanipon K. et al. Association Between Vitamin D and Uric Acid in Adults : A Systematic Review and Meta-Analysis. Horm Metab Res. 2020; 52 (10): 732–741. doi: 10.1055/a-1240-5850

6. Zhang Y. Y., Qiu H. B., Tian J. W. Association Between Vitamin D and Hyperuricemia Among Adults in the United States. Front. Nutr. 2020; 7: 592777. Published 2020 Nov 20. doi: 10.3389/fnut.2020.592777

7. Han Y, Han K, Zhang Y, Zeng X. Serum 25-hydroxyvitamin D might be negatively associated with hyperuricemia in U.S. adults: an analysis of the National Health and Nutrition Examination Survey 2007–2014 [published correction appears in J. Endocrinol Invest. 2022 Apr; 45 (4): 907. DOI: 10.1007/s40618-021-01734-x ]. J. Endocrinol Invest. 2022; 45 (4): 719–729. DOI: 10.1007/s40618-021-01637-x

8. Charoenngam N., Ponvilawan B., Ungprasert P. Vitamin D insufficiency and deficiency are associated with a higher level of serum uric acid : A systematic review and meta-analysis. Mod. Rheumatol. 2020; 30 (2): 385–390. doi: 10.1080/14397595.2019.1575000

9. Han Y., Zhang Y., Zeng X. Assessment of causal associations between uric acid and 25-hydroxyvitamin D levels. Front. Endocrinol. (Lausanne). 2022; 13: 1024675. Published 2022 Dec 13. doi: 10.3389/fendo.2022.1024675

10. Al-Naqeeb J., Saeed M., Dye B., Jeranko M. Association of Gout with Vitamin D: A Population-Based Study [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10).

11. Neogi T., Jansen T. L., Dalbeth N. et al. 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative [published correction appears in Arthritis Rheumatol. 2016 Feb; 68 (2): 515. doi: 10.1002/art.39536. Vaquez-Mellado, Janitzia [corrected to Vazquez-Mellado, Janitzia]]. Arthritis Rheumatol. 2015; 67 (10): 2557–2568. doi: 10.1002/art.39254

12. Dedov I. I., Mel’nichenko G.A., Mokrysheva N. G. et al. Draft federal clinical practice guidelines for the diagnosis, treatment, and prevention of vitamin D deficiency. Osteoporosis and Bone Diseases. 2021; 24 (4): 4–26. (In Russ.). doi: 10.14341/osteo12937

13. Holick MF. Vitamin D deficiency. N Engl. J. Med. 2007; 357 (3): 266–281. doi: 10.1056/NEJMra070553

14. Heaney RP. Vitamin D in Health and Disease. Clin. J. Am. Soc. Nephrol. 2008; 3 (5): 1535–1541. doi: 10.2215/CJN.01160308

15. Pigarova E. A., Rozhinskaya L. Ya., Katamadze N. N. et al. Prevalence of vitamin D deficiency in various regions of the Russian Federation: results of the first stage of the multicenter cross-sectional randomized study. Osteoporosis and Bone Diseases. 2020; 23 (4): 4–12. (In Russ.). doi: 10.14341/osteo12701

16. Chen W, Roncal-Jimenez C, Lanaspa M et al. Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo. Metabolism. 2014; 63 (1): 150–160. doi: 10.1016/j.metabol.2013.09.0181

17. Del Pinto R, Viazzi F, Pontremoli R. et al. The URRAH study. Panminerva Med. 2021 Dec; 63 (4): 416–423. doi: 10.23736/S0031-0808.21.04357–3

18. Eliseev M. S., Barskova V. G. Vestn. Ross. Akad. Med. Nauk. 2008; (6): 29–32. (In Russ.)

19. Dobrovolskaya O. V., Demin N. V., Kozyreva M. V. et al. Bone mineral density in women with rheumatoid arthritis: A link between immune and biochemical markers. Terapevticheskii arkhiv. 2024; 96 (5): 494–499. (In Russ.). doi: 10.26442/00403660.2024.05.202705

20. Mohammed E, Browne LD, Kumar A UA. et al. Prevalence and treatment of gout among patients with chronic kidney disease in the Irish health system: A national study. PLoS One. 2019 Jan 25; 14 (1): e0210487. doi: 10.1371/journal.pone.0210487

21. Lin KM, Lu CL, Hung KC et al. The Paradoxical Role of Uric Acid in Osteoporosis. Nutrients. 2019 Sep 5; 11 (9): 2111. doi: 10.3390/nu11092111

22. Eliseev M. S. ACR management guidelines for the treatment of gout: What’s new and what’s controversial. Rheumatology Science and Practice. 2021; 59 (2): 129–133. (In Russ.). doi: 10.47360/1995-4484-2021-129-133