Hostname: page-component-6bb9c88b65-vpjdr Total loading time: 0 Render date: 2025-07-24T04:51:51.821Z Has data issue: false hasContentIssue false
  • English
  • Français

Association between caffeine metabolites in urine and serum uric acid levels: a cross-sectional study from NHANES 2011 to 2012

Published online by Cambridge University Press:  09 June 2025

Larissa S. Limirio  and
Erick P. de Oliveira Open the ORCID record for Erick P. de Oliveira [Opens in a new window]
Larissa S. Limirio
Affiliation:
Laboratory of Nutrition, Exercise and Health (LaNES), School of Medicine, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil
Erick P. de Oliveira*
Affiliation:
Laboratory of Nutrition, Exercise and Health (LaNES), School of Medicine, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil
*
Corresponding author: Erick P. de Oliveira; Emails: erick_po@yahoo.com.br; erickdeoliveira@ufu.br
Get access Rights & Permissions [Opens in a new window]

Abstract

Several studies have indicated a potential inverse association between caffeine intake from dietary sources – assessed through dietary questionnaires – and uric acid (UA) levels. However, to date, no study has examined the relationship between urinary caffeine metabolites, which serve as a reliable biomarker of caffeine intake and UA levels. Our aim was to evaluate the association between caffeine metabolites in urine and serum UA levels. A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2012, involving 1252 individuals aged 20–80 years. The study assessed caffeine and fourteen metabolites in spot urine samples, as well as serum UA levels. Hyperuricaemia was defined as UA levels exceeding 7·0 mg/dl for men and 6·0 mg/dl for women. In logistic regression analyses, theobromine (OR: 0·99, 95 % CI: 0·980, 0·999), 3-methyluric acid (OR: 0·91, 95 % CI: 0·837, 0·996), 7-methyluric acid (OR: 0·99, 95 % CI: 0·989, 0·998) and 3-methylxanthine (OR: 0·99, 95 % CI: 0·992, 0·999) were associated with decreased odds of hyperuricaemia. In linear regression analyses, paraxanthine (β = −0·004, P = 0·006), theobromine (β = −0·004, P =< 0·001), 7-methyluric acid (β = −0·003, P = 0·003), 3,7-dimethyluric acid (β = −0·029, P = 0·024), 3-methylxanthine (β = −0·001, P = 0·038) and 7-methylxanthine (β = −0·001, P = 0·001) were inversely associated with serum UA levels. In conclusion, our results indicate that several urinary caffeine metabolites are inversely associated with UA levels. These findings should be interpreted with caution due to the small magnitude of the observed associations.

Keywords

Caffeine metabolitesHyperuricaemiaBiomarkersEpidemiology

Information

Type
Research Article
Information
British Journal of Nutrition , First View , pp. 1 - 10
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Frary, CD, Johnson, RK & Wang, MQ (2005) Food sources and intakes of caffeine in the diets of persons in the United States. J Am Diet Assoc 105, 110–113.Google Scholar
Arnaud, MJ (2011) Pharmacokinetics and metabolism of natural methylxanthines in animal and man. In Methylxanthines, pp. 33–91 [Fredholm, BB, editor]. Berlin, Heidelberg: Springer.Google Scholar
Martínez-López, S, Sarriá, B, Baeza, G, et al. (2014) Pharmacokinetics of caffeine and its metabolites in plasma and urine after consuming a soluble green/roasted coffee blend by healthy subjects. Food Res Int 64, 125–133.Google Scholar
Batista-da-Silva, B, Limirio, LS & de Oliveira, EP (2024) Association between caffeine metabolites in urine and muscle strength in young and older adults: a cross-sectional study from NHANES 2011–2012. Clin Nutr 43, 1584–1592.Google Scholar
de Oliveira, EP, Limirio, LS & Batista-da-Silva, B (2025) Reply-Letter to the editor: exploring the roles of caffeine in the development of Sarcopenia for older adults. Clin Nutr 44, 1–3.Google Scholar
Fiani, B, Zhu, L, Musch, BL, et al. (2021) The neurophysiology of caffeine as a central nervous system stimulant and the resultant effects on cognitive function. Cureus 13, e15032.Google Scholar
Noguchi, K, Matsuzaki, T, Sakanashi, M, et al. (2015) Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects. J Pharmacol Sci 127, 217–222.Google Scholar
Park, KY, Kim, HJ, Ahn, HS, et al. (2016) Effects of coffee consumption on serum uric acid: systematic review and meta-analysis. Semin Arthritis Rheum 45, 580–586.Google Scholar
de Oliveira, EP & Burini, RC (2012) High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr 4, 12.Google Scholar
Kaneko, K, Aoyagi, Y, Fukuuchi, T, et al. (2014) Total purine and purine base content of common foodstuffs for facilitating nutritional therapy for gout and hyperuricemia. Biol Pharm Bull 37, 709–721.Google Scholar
Bobulescu, IA & Moe, OW (2012) Renal transport of uric acid: evolving concepts and uncertainties. Adv Chronic Kidney Dis 19, 358–371.Google Scholar
Johnson, RJ, Bakris, GL, Borghi, C, et al. (2018) Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the national kidney foundation. Am J Kidney Dis 71, 851–865.Google Scholar
de Oliveira, EP & Burini, RC (2012) High plasma uric acid concentration: causes and consequences. J Diabetol Metab Syndrome 4, 12.Google Scholar
Johnson, RJ, Lanaspa, MA & Gaucher, EA (2011) Uric acid: a danger signal from the RNA world that may have a role in the epidemic of obesity, metabolic syndrome, and cardiorenal disease: evolutionary considerations. Semin Nephrol 31, 394–399.Google Scholar
Ekpenyong, CE & Daniel, N (2015) Roles of diets and dietary factors in the pathogenesis, management and prevention of abnormal serum uric acid levels. PharmaNutrition 3, 29–45.Google Scholar
Fathallah-Shaykh, SA & Cramer, MT (2014) Uric acid and the kidney. Pediatr Nephrol 29, 999–1008.Google Scholar
Hayden, MR & Tyagi, SC (2004) Uric acid: a new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: the urate redox shuttle. Nutr Metab 1, 10–10.Google Scholar
Richette, P & Bardin, T (2010) Gout. Lancet 375, 318–328.Google Scholar
de Oliveira, EP, Moreto, F, Silveira, LV, et al. (2013) Dietary, anthropometric, and biochemical determinants of uric acid in free-living adults. Nutr J 12, 11.Google Scholar
Zuo, T, Liu, X, Jiang, L, et al. (2016) Hyperuricemia and coronary heart disease mortality: a meta-analysis of prospective cohort studies. BMC Cardiovasc Disord 16, 207.Google Scholar
Wei, X, Zhang, M, Huang, S, et al. (2023) Hyperuricemia: a key contributor to endothelial dysfunction in cardiovascular diseases. FASEB J 37, e23012.Google Scholar
Huang, Y, Li, YL, Huang, H, et al. (2012) Effects of hyperuricemia on renal function of renal transplant recipients: a systematic review and meta-analysis of cohort studies. PloS one 7, e39457.Google Scholar
Gonçalves, DLN, Moreira, TR & da Silva, LS (2022) A systematic review and meta-analysis of the association between uric acid levels and chronic kidney disease. Sci Rep 12, 6251.Google Scholar
Doria, A, Galecki, AT, Spino, C, et al. (2020) Serum urate lowering with allopurinol and kidney function in type 1 diabetes. N Engl J Med 382, 2493–2503.Google Scholar
Badve, SV, Pascoe, EM, Tiku, A, et al. (2020) Effects of allopurinol on the progression of chronic kidney disease. N Engl J Med 382, 2504–2513.Google Scholar
Rybak, ME, Sternberg, MR, Pao, C-I, et al. (2015) Urine excretion of caffeine and select caffeine metabolites is common in the US population and associated with caffeine intake. J Nutr 145, 766–774.Google Scholar
Pham, NM, Yoshida, D, Morita, M, et al. (2010) The relation of coffee consumption to serum uric acid in japanese men and women aged 49–76 years. J Nutr Metab 2010, 930757.Google Scholar
Choi, HK & Curhan, G (2007) Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey. Arthritis Care Res 57, 816–821.Google Scholar
Kiyohara, C, Kono, S, Honjo, S, et al. (1999) Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males. Br J Nutr 82, 125–130.Google Scholar
Limirio, LS, Santos, HO, dos Reis, AS, et al. (2021) Association between dietary intake and serum uric acid levels in kidney transplant patients. J Renal Nutr 31, 637–647.Google Scholar
Grandjean, AC (2012) Dietary intake data collection: challenges and limitations. Nutr Rev 70, S101–S104.Google Scholar
Park, Y, Dodd, KW, Kipnis, V, et al. (2018) Comparison of self-reported dietary intakes from the automated self-administered 24-h recall, 4-d food records, and food-frequency questionnaires against recovery biomarkers. Am J Clin Nutr 107, 80–93.Google Scholar
Centers for Disease Control and Prevention (CDC) & National Center for Health Statistics (NCHS) (2020) National Health and Nutrition Examination Survey Data, 2011–2012. Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.Google Scholar
Beard, JR, Officer, A, de Carvalho, IA, et al. (2016) The World report on ageing and health: a policy framework for healthy ageing. Lancet 387, 2145–2154.Google Scholar
Lohman, TG, Roche, AF & Martorell, R (1988) Anthropometric Standardization Reference Manual. Champaign, IL: Human Kinetics Books. Ergonomics 31, 1493–1494.Google Scholar
NHANES (2011) Centers for Disease Control and Prevention. Anthropometry Procedures Manual. –https://wwwn.cdc.gov/Nchs/Nhanes/2011–2012/BPX_G.htm (accessed January 2023).Google Scholar
Centers for Disease Control and Prevention (CDC) (2011) National Health and Nutrition Examination Survey: Bioprofile (BIOPRO_G), 2011–2012. –https://wwwn.cdc.gov/Nchs/Nhanes/2011–2012/BIOPRO_G.htm (accessed January 2023).Google Scholar
Johnson, RJ, Kang, D-H, Feig, D, et al. (2003) Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41, 1183–1190.Google Scholar
Levey, AS, Stevens, LA, Schmid, CH, et al. (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150, 604–612.Google Scholar
Friedewald, WT, Levy, RI & Fredrickson, DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18, 499–502.Google Scholar
Rybak, ME, Pao, C-I & Pfeiffer, CM (2014) Determination of urine caffeine and its metabolites by use of high-performance liquid chromatography-tandem mass spectrometry: estimating dietary caffeine exposure and metabolic phenotyping in population studies. Anal BioanalChem 406, 771–784.Google Scholar
Caudill, SP, Schleicher, RL & Pirkle, JL (2008) Multi-rule quality control for the age-related eye disease study. Stat Med 27, 4094–4106.Google Scholar
Centers for Disease Control and Prevention NCfHS (2012) NHANES 2011–2012: Urinary Caffeine and Caffeine Metabolites Data Documentation, Codebook, and Frequencies (Internet). Atlanta, GA: US Centers for Disease Control and Prevention.Google Scholar
Prentice, RL, Mossavar-Rahmani, Y, Huang, Y, et al. (2011) Evaluation and comparison of food records, recalls, and frequencies for energy and protein assessment by using recovery biomarkers. Am J Epidemiol 174, 591–603.Google Scholar
Blanton, CA, Moshfegh, AJ, Baer, DJ, et al. (2006) The USDA Automated Multiple-Pass Method accurately estimates group total energy and nutrient intake. J Nutr 136, 2594–2599.Google Scholar
Kiyohara, C, Kono, S, Honjo, S, et al. (1999) Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males. Br J Nutr 82, 125–130.Google Scholar
Li, X, Song, P, Li, J, et al. (2015) Relationship between hyperuricemia and dietary risk factors in Chinese adults: a cross-sectional study. Rheumatol Int 35, 2079–2089.Google Scholar
Park, KY, Kim, HJ, Ahn, HS, et al. (2016) Effects of coffee consumption on serum uric acid: systematic review and meta-analysis. Semin Arthritis Rheum 45, 580–586.Google Scholar
Cornish, HH & Christman, AA (1957) A study of the metabolism of theobromine, theophylline, and caffeine in man. J Biol Chem 228, 315–323.Google Scholar
Roddy, E & Doherty, MJ (2010) Epidemiology of gout. Arthritis Res Ther 12, 1–11.Google Scholar
Wu, SE & Chen, WL (2020) Exploring the association between urine caffeine metabolites and urine flow rate: a cross-sectional study. Nutrients 12, 2803.Google Scholar
Alsabri, SG, Mari, WO, Younes, S, et al. (2018) Kinetic and dynamic description of caffeine. J Caffeine Adenosine Res 8, 3–9.Google Scholar
Kalow, W, Tang, B-K (1991) Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 50, 508–519.Google Scholar
de Oliveira, EP, Batista-da-Silva, B & Limirio, LS (2024) Reply-Letter to the editor: association between caffeine metabolites in urine and muscle strength in young and older adults: a cross-sectional study from NHANES 2011–2012. Clin Nutr 43, 2069–2070.Google Scholar