Uric Acid

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Uric Acid

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Uric Acid
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Chronic high levels of plasma uric acid is a precipitating factor nephrolithiasis and gout. It is also a strong risk factor for metabolic syndrome and cardiovascular disease (de Oliveira and Burini, 2012, Noone and Marks, 2013).

In COVID-19, both low and high uric acid levels have been used as biomarkers and predictors of severity (Kara et al.., 2021; Chen et al., 2021; Li et al., 2021).

In children suffering from COVID-19, the strongest predictor of moderate-severe COVID-19 infections was uric acid (Kara et al., 2021).


Jin Z, Zheng M, Shi J, Ye X, Cheng F, Chen QL, Huang J, Jiang XG - "Correlation Analysis Between Serum Uric Acid, Prealbumin Level, Lactate Dehydrogenase, and Severity of COVID-19" Front Mol Biosci 8:615837 (2021)

Kara AA, Böncüoğlu E, Kıymet E, Arıkan KÖ, Şahinkaya Ş, Düzgöl M, Cem E, Çelebi M, Ağın H, Bayram SN, Özkan B, Devrim İ - "Evaluation of predictors of severe-moderate COVID-19 infections at children: A review of 292 children" J Med Virol. 2021 Jul 27. doi: 10.1002/jmv.27237. Epub ahead of print. PMID: 34314067
"The strongest predictor of moderate-severe COVID-19 infections in the children was uric acid, with an odds ratio of 1.6 (95% CI 1.14-2.13, p = 0.005)..."

Chen B, Lu C, Gu HQ, Li Y, Zhang G, Lio J, Luo X, Zhang L, Hu Y, Lan X, Chen Z, Xie Q, Pan H - "Serum Uric Acid Concentrations and Risk of Adverse Outcomes in Patients With COVID-19" Front Endocrinol (Lausanne)" 12:633767 (2021)
This study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation.

Li G, Wu X, Zhou CL, Wang YM, Song B, Cheng XB, Dong QF, Wang LL, You SS, Ba YM - "Uric acid as a prognostic factor and critical marker of COVID-19" Sci Rep 11(1):17791 (2021)
"This retrospective study determined that the lowest concentration of UA during hospitalization can be used as a prognostic indicator and a marker of disease severity in severe patients with COVID-19."


At levels known to cause dental fluorosis, fluoride increases uric acid in rats and children (Wei et al., 2021; Malin et al., 2019), while uric acid levels appear reduced at higher fluoride intakes (Bouaziz et al., 2007; He at al., 2014; Shivarajashankara et al., 2001; Ruiz-Payan, 2006)). Lower uric acid levels were accompanied by lower T3 levels induced by fluoride in Mexican teenagers (Ruiz-Payan, 2006).

Elevated uric acid levels are also observed in organic fluoride poisoning (PFAS) (Zheng et al., 2019; Lin et al., 2020).

Wei Y, Zhu J, Wetzstein SA - "Plasma and water fluoride levels and hyperuricemia among adolescents: A cross-sectional study of a nationally representative sample of the United States for 2013-2016" Ecotoxicol Environ Saf 208:111670 (2021)
https://www.sciencedirect.com/science/a ... via%3Dihub

Malin AJ, Lesseur C, Busgang SA, Curtin P, Wright RO, Sanders AP - "Fluoride exposure and kidney and liver function among adolescents in the United States: NHANES, 2013-2016" Environ Int 132:105012 (2019) doi: 10.1016/j.envint.2019.105012. Epub 2019 Aug 8. PMID: 31402058; PMCID: PMC6754771

Shanthakumari D, Subramanian S - "Effect of Fluoride Intoxication on Bone Tissue of Experimental Rats" Research Journal of Environmental Sciences, 1:82-92 (2007)

Shivarajashankara YM, Shivashankara AR, Hanumanth Rao S, Gopalakrishna Bhat P - "Oxidative stress in children with endemic skeletal fluorosis" Fluoride 34(2)103-107 (2001)
https://www.scopus.com/record/display.u ... 214903f316

He H, Wang H, Han M, Jiao Y, Ma C, Zhang H, Zhou Z - "Study on changes of clinical indicators and key proteins from fluoride exposure" Biol Trace Elem Res 160(1):73-8 (2014)

Feng P, Wei JR, Zhang ZG - "Influence of selenium and fluoride on blood antioxidant capacity of rats" Exp Toxicol Pathol 64(6):565-8 (2012)

Lin TW, Chen MK, Lin CC, Chen MH, Tsai MS, Chan DC, Hung KY, Chen PC - "Association between exposure to perfluoroalkyl substances and metabolic syndrome and related outcomes among older residents living near a Science Park in Taiwan" Int J Hyg Environ Health 230:113607 (2020)

Zeng XW, Lodge CJ, Dharmage SC, Bloom MS, Yu Y, Yang M, Chu C, Li QQ, Hu LW, Liu KK, Yang BY, Dong GH - "Isomers of per- and polyfluoroalkyl substances and uric acid in adults: Isomers of C8 Health Project in China" Environ Int 133(Pt A):105160 (2019)

Bouaziz H, Crouteb F, Boudawarac T, Soleilhavoupb J, Zeghala N - "Oxidative stress induced by fluoride in adult mice and their suckling pups" Exp. Toxicol. Pathol 58:339-349 (2007)
https://www.sciencedirect.com/science/a ... 9306001138

Ruiz-Payan A - "Chronic effects of fluoride on growth, blood chemistry and thyroid hormones in adolescents residing in three communities in Northern Mexico" ETD Collection for University of Texas, El Paso. AAI3214004 (2006)

Cenesiz S, Ozcan A, Necati K, Baysu N, Karabulut AB - "Chronic effects of fluoride in TUJ sheep on serum levels of total protein, albumin, uric acid, and nitric acid and activities of lactate dehydrogenase and leucine aminopeptidase" Fluoride 38(1):52–56 2(2005)

Giri DK, Ghosh RC, Kashyap DK, Dewangan G, Maiti SK - "Haemato-Biochemical Alterations in Subacute Oral Toxicity of Sodium Fluoride in Wistar Rats" Journal of Animal Research, 5, 595-598 (2018)

Kinawy AA - "Potential toxicity of aluminum and fluoride on some biochemical aspects of male rat’s offspring" JoBAZ 80:18 (2019) https://doi.org/10.1186/s41936-019-0087-1

These results suggest that hyperglycemia/diabetes-induced enhanced expression of Gq/11α and PLCβ proteins and signaling may be attributable to the enhanced oxidative stress due to augmented levels of H(2)O(2) and not to peroxynitrite." (Descorbeth et al., 2010)
Descorbeth M, Anand-Srivastava MB - "Role of oxidative stress in high-glucose- and diabetes-induced increased expression of Gq/11α proteins and associated signaling in vascular smooth muscle cells" Free Radic Biol Med 49(9):1395-405 (2010)

Kırça M, Oğuz N, Çetin A, Uzuner F, Yeşilkaya - "Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ" J Recept Signal Transduct Res 37(2):167-173 (2017)

Zhuang Y, Feng Q, Ding G, Zhao M, Che R, Bai M, Bao H, Zhang A, Huang S - "Activation of ERK1/2 by NADPH oxidase-originated reactive oxygen species mediates uric acid-induced mesangial cell proliferation" Am J Physiol Renal Physiol 307(4):F396-406 (2014)


Kalra S, Aggarwal S, Khandelwal D - "Thyroid Dysfunction and Dysmetabolic Syndrome: The Need for Enhanced Thyrovigilance Strategies" Int J Endocrinol 2021:9641846 (2021)

Desideri G, Bocale R, D'Amore AM, Carnassale G, Necozione S, Barini A, Barini A, Lombardi CP - "Thyroid hormones modulate uric acid metabolism in patients with recent onset subclinical hypothyroidism by improving insulin sensitivity" Intern Emerg Med 15(1):67-71 (2020)


Chang YC, Hua SC, Chang CH, Kao WY, Lee HL, Chuang LM, Huang YT, Lai MS - "High TSH Level within Normal Range Is Associated with Obesity, Dyslipidemia, Hypertension, Inflammation, Hypercoagulability, and the Metabolic Syndrome: A Novel Cardiometabolic Marker" J Clin Med 8(6):817 (2019)
"Elevated hsTSH within the normal range is a cardiometabolic risk marker associated with central obesity, insulin resistance, elevated blood pressure, dyslipidemia, hyperuricemia, inflammation, and hypercoagulability."

Feng X, Huang J, Peng Y, Xu Y - "Association between decreased thyroid stimulating hormone and hyperuricemia in type 2 diabetic patients with early-stage diabetic kidney disease" BMC Endocr Disord 21(1):1 (2021)
"TSH is negatively correlated with SUA, and decreased TSH is an independent risk factor for hyperuricemia in type 2 diabetic patients with early-stage DKD. These results indicate that thyroid hormones, TSH in particular, might participate in regulating uric acid metabolism in patients with early-stage DKD."

Torkian P, Mansournia MA, Mansournia N - "Evaluation of biochemical markers of kidney function in patients with subclinical hypothyroidism in comparison with euthyroid people" J Family Med Prim Care 9(8):4234-4239 (2020)
NOTE: "Within the SCH group, there was a significant positive correlation between TSH and the level of creatinine (P = 0.001, r = 0.302)."
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