Study Links Pre-Diagnostic Amino Acid Metabolites to Gout Risk, Suggests Glycine and Glutamine for Future Interventions

The study, published in Arthritis Care & Research, identified several metabolites associated with an increased risk of developing hospitalized gout.

Gout, a painful form of arthritis characterized by high uric acid levels in the blood, is often influenced by various metabolic factors. Traditionally, serum urate levels have been a key marker for assessing gout risk. Natalie McCormick, Massachusetts General Hospital, Boston, MA, USA, and colleagues prospectively investigated pre-diagnostic population-based metabolome for risk of hospitalized gout (i.e., most accurate, severe, and costly cases), accounting for serum urate.

For this purpose, the researchers conducted pre-diagnostic metabolome-wide analyses on 249,677 UK Biobank participants who underwent NMR metabolomic profiling, measuring 168 metabolites, including eight amino acids, from baseline blood samples collected between 2006 and 2010. Participants had no prior history of gout.

The team calculated multivariable hazard ratios (HRs) for incident hospitalized gout, adjusting for serum urate levels and including non-hospitalized incident gout cases in a sensitivity analysis. Additionally, potential causal effects were assessed using two-sample Mendelian randomization.

The study led to the following findings:

• Correcting for multiple testing, 107 metabolites were associated with incidence of hospitalized gout (N=2735) before urate adjustment, including glycine and glutamine (inversely; HR=0.64 and HR=0.69 between extreme quintiles, respectively), and glycoprotein acetyls (GlycA; HR=2.48).
• Associations remained significant and directionally consistent following urate adjustment (HR=0.83, 0.86, 1.41 between extreme quintiles), respectively; the corresponding HR per SD were 0.91, 0.94, and 1.10.
• Findings persisted when including non-hospitalised incident gout cases.
• Mendelian randomization corroborated their potential causal role on hyperuricemia or gout risk; with changes in urate levels of -0.05 mg/dL, and -0.12 mg/dL, per SD of glycine and glutamine, respectively, and ORs 0.94, and 0.81, for gout.

"These findings highlight the potential of circulating uric acid to act as a pro-aging factor rather than an anti-aging one in this population," the researchers wrote. "Additionally, this research contributes to the expanding evidence suggesting that serum uric acid may be a valuable blood-based biomarker for identifying frailty in older adults."

"These prospective findings, with their causal implications, may pave the way for risk prediction using biomarkers and open up possibilities for supplementation-based interventions involving glycine or glutamine," they concluded.

Reference:

McCormick, N., Joshi, A. D., Yokose, C., Yu, B., Tin, A., Terkeltaub, R., Merriman, T. R., Zeleznik, O., Eliassen, A. H., Curhan, G. C., Ea, K., Nayor, M., Raffield, L. M., & Choi, H. K. Pre-Diagnostic Amino Acid Metabolites and Risk of Gout, Accounting for Serum Urate: Prospective Cohort Study and Mendelian Randomization. Arthritis Care & Research. https://doi.org/10.1002/acr.25420