Protein Biomarkers: Total Protein

Optimal Takeaways

Total protein reflects the amount of albumin and globulin in circulation. Albumin is essential as a transport protein and a key factor in maintaining fluid balance within blood vessels. Globulins represent the remaining proteins in circulation, including antibodies, lipoproteins, nutrient transporters, and hormone-binding globulins. The body can maintain consistent total protein by balancing albumin and globulins. However, low levels of total protein can be seen with malnutrition, liver disease, other chronic disorders, and certain medications. Chronic inflammation, pregnancy, dehydration, and certain medications may indicate elevated total protein.

Standard Range: 6.10 – 8.10 g/dL (61.00 – 81.00 g/L)

The ODX Range: 6.9 – 8.10 (69.00 – 81.00 g/L)

Low total protein is associated with malnutrition (Keller 2019, Zhang 2017), lung cancer (Samanta 2016), malabsorption, liver disease, nephrotic syndrome, glomerulonephritis, protein-losing enteropathy, burns, bleeding, and agammaglobulinemia (Medline Plus 2021). Certain medications, including estrogen, oral contraceptives, ammonium ions, and hepatotoxic drugs, can decrease total protein (Pagana 2021). Total protein can be significantly lower in cases of malnutrition (Keller 2019).

High total protein may be caused by chronic inflammation, multiple myeloma, Waldenstrom disease, and pregnancy (Medline Plus 2021). Certain medications can increase total protein, including androgens, anabolic steroids, progesterone, corticosteroids, growth hormone, insulin, dextran, and phenazopyridine (Pagana 2021).

Overview

Total protein measurement reflects the blood's most abundant proteins, i.e., albumin and globulin. Albumin is synthesized in the liver; is an important carrier of enzymes, hormones, drugs, and other compounds; and helps maintain the oncotic pressure that retains fluid within blood vessels.

Globulin measurement includes immunoglobulins (antibodies), complement proteins, prothrombin, fibrinogen, plasminogen, cholinesterase, and transport proteins, including lipoproteins, thyroid-binding globulin, cortisol-binding globulin, transferrin, and ceruloplasmin.

Some disorders may selectively alter albumin or globulin levels, in which case synthesis of the remaining protein will be adjusted to maintain a consistent total protein level. In such cases, the albumin-to-globulin ratio (generally above 1), or serum protein electrophoresis, can help evaluate the constituents of the total protein measurement (Pagana 2021).

A large retrospective cross-sectional study of 78,477 healthy individuals observed mean total protein levels from 6.98 to 7.44 g/dL with an overall range of 5.10 to 9.1 g/dL (Henok 2020). However, below-optimal levels of total protein may be indicative of malnutrition. A systematic review and meta-analysis of 111 studies comprising 52,911 older individuals found that a total protein of 6.54 g/dL and below was associated with a high risk of malnutrition as defined by a number of malnutrition classifications (Zhang 2017).

In a case-control study of individuals with pleural effusion, total protein was significantly lower in lung cancer (5.3 g/dL) than in tuberculosis (6.86 g/dL). Albumin was also significantly lower in lung cancer (3.25 g/dL) versus TB (3.93 g/dL), as was globulin (2.05 g/dL) versus 2.93 g/dL, respectively. Controls maintained a mean total protein of 7.0 g/dL, albumin of 4.14 g/dL, and globulin of 2.88 g/dL (Samanta 2016).

References

Henok, Josephine N et al. “Analysis of Reference Ranges of Total Serum Protein in Namibia: Clinical Implications.” Proteomes vol. 8,2 7. 15 Apr. 2020, doi:10.3390/proteomes8020007

Keller, Ulrich. “Nutritional Laboratory Markers in Malnutrition.” Journal of clinical medicine vol. 8,6 775. 31 May. 2019, doi:10.3390/jcm8060775

Medline Plus. Total Protein. https://medlineplus.gov/ency/article/003483.htm

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

Samanta, Sumeru et al. “Significance of Total Protein, Albumin, Globulin, Serum Effusion Albumin Gradient and LDH in the Differential Diagnosis of Pleural Effusion Secondary to Tuberculosis and Cancer.” Journal of clinical and diagnostic research : JCDR vol. 10,8 (2016): BC14-8. doi:10.7860/JCDR/2016/20652.8379

Zhang, Zhiying et al. “Evaluation of Blood Biomarkers Associated with Risk of Malnutrition in Older Adults: A Systematic Review and Meta-Analysis.” Nutrients vol. 9,8 829. 3 Aug. 2017, doi:10.3390/nu9080829