Protein Biomarkers: Albumin Globulin Ratio

Optimal Takeaways

The albumin:globulin ratio helps assess relative changes in serum protein levels. The ratio will decrease as albumin decreases or globulins increase, a change that may not be reflected in total protein levels. A lower A/G ratio is associated with liver disease, infection, inflammation, rheumatoid arthritis, osteoporosis, and cognitive decline. A higher ratio is uncommon but may be related to dehydration.

Standard Range: 1.00 – 2.50 Ratio

The ODX Range: 1.40 – 2.10 Ratio

Low A/G ratio is associated with liver disease (Pagana 2021), HIV (Ranjit 2009), chronic inflammation, cognitive decline (Koyama 2016), infection (Zhang 2021), decreased bone mineral density (Furukawa 2016), rheumatoid arthritis (Chen 2021), and poorer outcomes in critical illness and infection (Bozkaya 2019, Zhang 2021, Liu 2021, Ye 2020).

High A/G ratio is uncommon but may be associated with dehydration.

Overview

The ratio of albumin to globulin (A/G ratio) helps assess liver function, infection, inflammation, and prognosis in acute illness. The A/G ratio is usually greater than 1 but may drop below 1, especially with reduced hepatic albumin synthesis (Pagana 2021). Alteration of the A/G ratio may indicate a disruption in homeostasis, with lower levels being associated with increases in hemoglobin A1C, dyslipidemia, hs-CRP, and risk of cognitive decline (Koyama 2016).

Compared to a ratio of 1.5 or greater, an A/G ratio of 1.0–1.1 has been associated with a 2.95-fold greater risk of mortality, a risk that increased to 4.38-fold with a ratio below 1. A lower A/G ratio may be related to cognitive decline, while a higher/optimal ratio has been found to correlate with better cognitive function. A ratio of 1.43 or above was independently associated with better cognitive performance in a group of 1,827 randomly selected elderly subjects 70-80 years old. Researchers suggest chronic inflammation and lower albumin may contribute to the lower A/G ratio in cognitive decline. This seems plausible, considering albumin functions as an antioxidant, helps eliminate toxins, and inhibits amyloid plaque development (Maeda 2019).

A lower A/G ratio, along with higher globulin and total protein, was strongly associated with the incidence of joint infection in a retrospective review of total joint arthroplasty patients. Those with periprosthetic joint infection had a mean A/G ratio of 1.16 compared to 1.41 in the aseptic group (Ye 2020). A lower mean A/G ratio of 1.02 or below was also associated with more complications, inflammation, and infection in patients with a pyogenic liver abscess (Zhang 2021).

Rheumatoid arthritis is characterized by decreased albumin, increased globulins, and a lower A/G ratio. Patients with an A/G ratio below 1.2 had significantly higher pro-inflammatory cytokine levels, dyslipidemia, and age-related illness than those with an A/G above 1.2 (Chen 2021).

Evaluating the A/G ratio may be an effective screening tool for osteoporosis, especially when albumin is low. A decreased A/G ratio of 0.96 and albumin of 3.3 g/dL was associated with decreased cortical bone density assessed via DXA scan (Furukawa 2016).

An A/G ratio above 1.2 was associated with better overall survival as well as progression-free survival in a study of 251 individuals with metastatic gastric cancer (Bozkaya 2019). A higher ratio of 1.1 and above were associated with better survival in critically ill patients (Liu 2021), while a higher ratio of 1.41 on day 7 was significantly associated with improved outcomes in acute ischemic stroke patients receiving IV thrombolytic treatment (Yang 2022).

References

Chen, Yong et al. “Albumin/Globulin Ratio as Yin-Yang in Rheumatoid Arthritis and Its Correlation to Inflamm-Aging Cytokines.” Journal of inflammation research vol. 14 5501-5511. 27 Oct. 2021, doi:10.2147/JIR.S335671

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Furukawa, Kayoko, et al. "Correlation of albumin/globulin ratio with forearm bone mineral density in women above 50 years of age." HAND 11.1_suppl (2016): 49S-49S.

Koyama, Teruhide et al. “Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case-control study.” BMC neurology vol. 16,1 253. 8 Dec. 2016, doi:10.1186/s12883-016-0776-z

Liu, Bin et al. “Albumin-Globulin Ratio Is an Independent Determinant of 28-Day Mortality in Patients with Critical Illness.” Disease markers vol. 2021 9965124. 25 Aug. 2021, doi:10.1155/2021/9965124

Maeda, Satomi et al. “Serum albumin/globulin ratio is associated with cognitive function in community-dwelling older people: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study.” Geriatrics & gerontology international vol. 19,10 (2019): 967-971. doi:10.1111/ggi.13751

Ranjit, Patil, and Raghuwanshi Uplabdhi. "Serum protein, albumin, globulin levels, and A/G ratio in HIV positive patients." Biomedical & Pharmacology Journal 2.2 (2009): 321-325.

Yang, Dehao et al. “Elevated Albumin to Globulin Ratio on Day 7 is Associated with Improved Function Outcomes in Acute Ischemic Stroke Patients with Intravenous Thrombolysis.” Journal of inflammation research vol. 15 2695-2705. 26 Apr. 2022, doi:10.2147/JIR.S347026

Ye, Yongyu et al. “Serum globulin and albumin to globulin ratio as potential diagnostic biomarkers for periprosthetic joint infection: a retrospective review.” Journal of orthopaedic surgery and research vol. 15,1 459. 7 Oct. 2020, doi:10.1186/s13018-020-01959-1

Zhang, Jia et al. “Clinical Significance of Serum Albumin/Globulin Ratio in Patients With Pyogenic Liver Abscess.” Frontiers in surgery vol. 8 677799. 30 Nov. 2021, doi:10.3389/fsurg.2021.677799