Glycine, Glutamine May Reduce Risk of Hospitalized Gout

Natalie McCormick, PhD

Credit: Harvard University

New research has found associations between a number of metabolites and the risk of incident hospitalized gout.¹

“Our objective was to prospectively investigate pre-diagnostic population-based metabolome for risk of hospitalized gout (i.e., most accurate, severe, and costly cases), accounting for serum urate,” lead investigator Natalie McCormick, PhD, instructor in medicine, Massachusetts General Hospital, Harvard Medical School, and Arthritis Research Canada, Vancouver, Canada, and colleagues wrote.¹

McCormick and colleagues analyzed pre-diagnostic metabolomes of 249,677 United Kingdom Biobank participants from baseline blood samples collected from 2006 to 2010 without a history of gout. They conducted NMR metabolomic profiling, looking at 168 metabolites, including 8 amino acids. After multivariable adjustment, they calculated hazard ratios (HRs) for incident hospitalized gout, before and after adjusting for serum urate levels, and also analyzed non-hospitalized incident gout cases in a sensitivity analysis. They used 2-sample Mendelian randomization to evaluate potential causal effects.¹

The investigators found that after correcting for multiple testing, 107 metabolites were associated with the incidence of hospitalized gout (N=2735) before urate adjustment. These included glycine (HR, 0.64 [95% CI, 0.54-0.75]; P = 8.3x10-8) and glutamine (HR, 0.69 [95% CI, 0.61-0.78]; P = 3.3x10-9) inversely,between extreme quintiles, and glycoprotein acetyls (GlycA; HR, 2.48 [95% CI, 2.15-2.87]; P = 1.96x10-34). After adjusting for urates, the associations remained significant and directionally consistent, with respective HRs of 0.83 (95% CI, 0.70-0.98), 0.86 (95% CI, 0.76-0.98), and 1.41 (95% CI, 1.21-1.63) between extreme quintiles, with corresponding HRs per standard deviations of 0.91 (95% CI, 0.86-0.97), 0.94 (95% CI, 0.91-0.98), and 1.10 (95% CI, 1.06-1.14).¹

Sensitivity analyses including non-hospitalized incident gout cases corroborated the potential causal role of these metabolites on hyperuricemia or gout risk, with Mendelian randomization showing a change in urate levels of -0.05 mg/dL (-0.08, -0.01) per SD of glycine and a change of -0.12 mg/dL (-0.22, -0.03)per SD of glutamine. Accordingly, odds ratios per SD were 0.94 (95% CI, 0.88-1.00) for glycine and 0.81 (95% CI, 0.67-0.97) for gout.¹

“These prospective findings with causal implications could lead to biomarker-based risk prediction and potential supplementation-based interventions with glycine or glutamine,” McCormick and colleagues concluded.¹

Other recent research on urates found that circulating uric acid have a potential role in accelerating biological aging among older adults. Investigators found that uric acid levels increased as frailty severity increased from non-frail to frail (P = .002). Frail adults presented with greater serum uric acid levels than non-frail adults (P = .002).

After adjusting for age, sex, and other comorbidities, investigators found serum uric acid levels were significantly greater in frail participants than in non-frail participants (P < .001). The study showed serum uric acid concentrations were positively correlated to the frail index (P < .001). Moreover, per 1 mg/dL increase in serum uric acid, the odds for frailty were 1.22 (95% confidence interval [CI], 1.12 – 1.33; P < .001), and the risks were 25% and 22% as shown in the age- and sex-adjusted and multivariable-adjusted models, respectively (P < .001).

“These results clinically underscore the potential of circulating [uric acid] as a pro-aging factor rather than an anti-aging one in this demographic,” wrote investigators, led by Min-gu Kang, from Chonnam National University Bitgoeul Hospital in South Korea.² “Moreover, this research adds to the growing body of evidence that suggests serum UA could serve as a potential blood-based biomarker for detecting frailty in older adults.”

REFERENCES

1. McCormick N, Joshi AD, Yokose C, et al. Pre-Diagnostic Amino Acid Metabolites and Risk of Gout, Accounting for Serum Urate: Prospective Cohort Study and Mendelian Randomization. Published online August 21, 2024. Arthritis Care Res. Doi:10.1002/acr.25420
2. Kang MG, Baek JY, Jo Y, et al. Higher serum uric acid as a risk factor for frailty in older adults: A nationwide population-based study. J Cachexia Sarcopenia Muscle. Published online August 18, 2024. doi:10.1002/jcsm.13561