Empirical dietary index for lower urate concentrations and risk of gout: evidence from cohort studies

doi:10.1016/j.ajcnut.2025.06.021

. 2025 Jun 30:S0002-9165(25)00378-8.

doi: 10.1016/j.ajcnut.2025.06.021. Online ahead of print.

Empirical dietary index for lower urate concentrations and risk of gout: evidence from cohort studies

Xiaowen Wang¹, Sharan K Rai², Wangjian Zhang³, Molin Wang⁴, Binkai Liu¹, Yang Hu¹, Siyue Wang¹, Han Han¹, Yuantao Hao⁵, Hyon K Choi⁶, Qi Sun⁷

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
² Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
³ Department of Medical Statistics, School of Public Health & Sun Yat-sen Global Health Institute & Center for Health Information Research, Sun Yat-sen University, Guangzhou, China.
⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
⁶ Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: qisun@hsph.harvard.edu.

PMID: 40602608
PMCID: PMC12329690 (available on 2026-06-30)
DOI: 10.1016/j.ajcnut.2025.06.021

Empirical dietary index for lower urate concentrations and risk of gout: evidence from cohort studies

Xiaowen Wang et al. Am J Clin Nutr. 2025.

. 2025 Jun 30:S0002-9165(25)00378-8.

doi: 10.1016/j.ajcnut.2025.06.021. Online ahead of print.

Authors

Xiaowen Wang¹, Sharan K Rai², Wangjian Zhang³, Molin Wang⁴, Binkai Liu¹, Yang Hu¹, Siyue Wang¹, Han Han¹, Yuantao Hao⁵, Hyon K Choi⁶, Qi Sun⁷

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
² Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
³ Department of Medical Statistics, School of Public Health & Sun Yat-sen Global Health Institute & Center for Health Information Research, Sun Yat-sen University, Guangzhou, China.
⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
⁶ Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: qisun@hsph.harvard.edu.

PMID: 40602608
PMCID: PMC12329690 (available on 2026-06-30)
DOI: 10.1016/j.ajcnut.2025.06.021

Abstract

Background: High blood urate concentrations are a causal risk factor for the development of gout. There is no dietary pattern that specifically targets on lowering plasma urate concentrations or gout risk.

Objectives: This study aimed to derive a dietary pattern that predicts lower plasma urate concentrations and to examine this diet in relation to the risk of gout and related cardiometabolic conditions, including hypertension, coronary artery disease (CAD), stroke, and type 2 diabetes (T2D).

Methods: An Empirical Dietary Index for Normo-Uricemia (EDINU) was developed using 7-d diet records and plasma urate concentrations in the Lifestyle Validation Study (LVS) and prospective associations between the EDINU and disease risks were assessed using multivariable Cox regression in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS), using prospective cohort data. Replications were conducted in National Health and Nutrition Examination Survey (NHANES) and UK Biobank.

Results: The EDINU positively ranks low-fat milk, blueberries, grapes, and cheese as negative predictors of urate and negatively ranks mixed vegetables, liquor, red meat, liver, artificially sweetened beverages, tomato products, wine, and salad dressing as positive predictors. The EDINU showed significant correlations with plasma urate concentrations in both discovery and replication studies (Spearman correlation of -0.23 in LVS or -0.33 in NHANES). Higher EDINU scores were associated with lower gout risk in 3 independent cohort studies with a hazard ratio, comparing extreme quintiles, of 0.48 (95% confidence interval: 0.42, 0.55) in the NHS/HPFS or 0.65 (0.48, 0.88) in UK Biobank. The EDINU was inversely associated with a lower risk of hypertension, stroke, and T2D, but not CAD, in the NHS/HPFS.

Conclusions: A replicated empirical index predicting lower plasma urate is associated with significantly lower risks of gout and related cardiometabolic conditions. Consuming such a diet with lower uricemic potentials could be a novel, promising approach to preventing gout.

Keywords: diet; dietary index; dietary patterns; gout; hypertension; plasma urate; stroke; type 2 diabetes; uric acid.

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Conflict of interest statement

Conflict of interest The authors declare no conflict of interest.

References

1. Collaborators GBDG. Global, regional, and national burden of gout, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2024;6(8):e507–e17. doi: 10.1016/S2665-9913(24)00117-6. - DOI - PMC - PubMed
1. McCormick N, Yokose C, Challener GJ, Joshi AD, Tanikella S, Choi HK. Serum Urate and Recurrent Gout. JAMA. 2024;331(5):417–24. doi: 10.1001/jama.2023.26640. - DOI - PMC - PubMed
1. Choi HK, Mount DB, Reginato AM, American College of P, American Physiological S. Pathogenesis of gout. Ann Intern Med. 2005;143(7):499–516. doi: 10.7326/0003-4819-143-7-200510040-00009. - DOI - PubMed
1. Choi HK, McCormick N, Lu N, Rai SK, Yokose C, Zhang Y. Population Impact Attributable to Modifiable Risk Factors for Hyperuricemia. Arthritis Rheumatol. 2020;72(1):157–65. doi: 10.1002/art.41067. - DOI - PMC - PubMed
1. Yokose C, McCormick N, Lu N, Joshi AD, Curhan G, Choi HK. Adherence to 2020 to 2025 Dietary Guidelines for Americans and the Risk of New-Onset Female Gout. JAMA Intern Med. 2022;182(3):254–64. doi: 10.1001/jamainternmed.2021.7419. - DOI - PMC - PubMed

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[1] Collaborators GBDG. Global, regional, and national burden of gout, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2024;6(8):e507–e17. doi: 10.1016/S2665-9913(24)00117-6. - DOI - PMC - PubMed

[2] Collaborators GBDG. Global, regional, and national burden of gout, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2024;6(8):e507–e17. doi: 10.1016/S2665-9913(24)00117-6. - DOI - PMC - PubMed

[3] McCormick N, Yokose C, Challener GJ, Joshi AD, Tanikella S, Choi HK. Serum Urate and Recurrent Gout. JAMA. 2024;331(5):417–24. doi: 10.1001/jama.2023.26640. - DOI - PMC - PubMed

[4] McCormick N, Yokose C, Challener GJ, Joshi AD, Tanikella S, Choi HK. Serum Urate and Recurrent Gout. JAMA. 2024;331(5):417–24. doi: 10.1001/jama.2023.26640. - DOI - PMC - PubMed

[5] Choi HK, Mount DB, Reginato AM, American College of P, American Physiological S. Pathogenesis of gout. Ann Intern Med. 2005;143(7):499–516. doi: 10.7326/0003-4819-143-7-200510040-00009. - DOI - PubMed

[6] Choi HK, Mount DB, Reginato AM, American College of P, American Physiological S. Pathogenesis of gout. Ann Intern Med. 2005;143(7):499–516. doi: 10.7326/0003-4819-143-7-200510040-00009. - DOI - PubMed

[7] Choi HK, McCormick N, Lu N, Rai SK, Yokose C, Zhang Y. Population Impact Attributable to Modifiable Risk Factors for Hyperuricemia. Arthritis Rheumatol. 2020;72(1):157–65. doi: 10.1002/art.41067. - DOI - PMC - PubMed

[8] Choi HK, McCormick N, Lu N, Rai SK, Yokose C, Zhang Y. Population Impact Attributable to Modifiable Risk Factors for Hyperuricemia. Arthritis Rheumatol. 2020;72(1):157–65. doi: 10.1002/art.41067. - DOI - PMC - PubMed

[9] Yokose C, McCormick N, Lu N, Joshi AD, Curhan G, Choi HK. Adherence to 2020 to 2025 Dietary Guidelines for Americans and the Risk of New-Onset Female Gout. JAMA Intern Med. 2022;182(3):254–64. doi: 10.1001/jamainternmed.2021.7419. - DOI - PMC - PubMed

[10] Yokose C, McCormick N, Lu N, Joshi AD, Curhan G, Choi HK. Adherence to 2020 to 2025 Dietary Guidelines for Americans and the Risk of New-Onset Female Gout. JAMA Intern Med. 2022;182(3):254–64. doi: 10.1001/jamainternmed.2021.7419. - DOI - PMC - PubMed

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Empirical dietary index for lower urate concentrations and risk of gout: evidence from cohort studies

Affiliations

Empirical dietary index for lower urate concentrations and risk of gout: evidence from cohort studies

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