Protein Biomarkers: Albumin

Optimal Takeaways

Albumin is a vital protein that carries nutrients, hormones, enzymes, and medications. It has anti-inflammatory, anti-coagulant, and antioxidant effects and maintains the oncotic pressure that helps prevent blood vessel fluid from leaking into tissues.

Decreased albumin levels may associated with liver disease, inflammation, infection, surgery, oxidative stress, ischemia, heart disease, stroke, fluid overload, advanced malnutrition, diabetes, advanced kidney disease, cognitive decline, and Alzheimer’s. Optimal levels are associated with reduced surgical complications, short-term and long-term survival in hospitalized patients, and reduced mortality in healthy adults. High levels may be related to dehydration.

Standard Range: 3.60 - 5.10 g/dL (36.00 g/L)

The ODX Range: 4.50 – 5.00 g/dL (45.00 – 50.00 g/L)  

Low albumin is associated with metabolic acidosis (Sajgure 2017), liver disease, kidney disease, diabetes, cardiovascular disease, infection, inflammation, oxidative stress, ischemia, advanced malnutrition, fluid overload (Arques 2018), tissue necrosis, burns, surgery, stress, and myocardial infarction (Pagana 2021). Hypoalbuminemia is a prognostic factor for MI, stroke, and heart failure (Alsancak 2018) and a predictive factor for mortality in hospitalized patients (Eckart 2020).

High albumin levels may indicate dehydration, so hydration status must be assessed if levels are above optimal.

Overview

Albumin is produced in the liver and is the most abundant protein in the blood. It accounts for ~60% of the protein in circulation and is part of the total protein measurement along with globulin. Albumin is a primary carrier of hormones, enzymes, nutrients, and drugs. It is instrumental in maintaining the colloidal osmotic or “oncotic” pressure that prevents fluid from leaking out of blood vessels and into interstitial spaces (Pagana 2021). Very low albumin levels can lead to edema or even anasarca, which is severe generalized edema.

Albumin acts as “protein storage, “ which can be catabolized to release amino acids for protein synthesis and energy generation. This catabolism also releases nutrients such as zinc that are transported by albumin (Malavolta 2015).

Assessment of albumin can be complex as synthesis decreases with impaired liver function but also decreases acutely with inflammation, infection, burns, and surgery. Levels can also decrease with oxidative stress, ischemia, heart disease, stroke, fluid overload, advanced malnutrition, diabetes, and advanced kidney disease. A reduction in albumin will ultimately compromise its valuable antioxidant, anti-inflammatory, and anticoagulant effects (Arques 2018).

Inflammation, especially systemic inflammation, can reduce albumin synthesis and increase its degradation and leakage into intercellular spaces. Albumin can also be lost into the urine with kidney disorders and into the gastrointestinal tract with protein-losing enteropathies. Declining albumin coupled with unexplained weight loss may reflect advancing cancer and should be further investigated (Keller 2019).

Albumin is considered a potent antioxidant and accounts for 70% of the free-radical trapping ability of serum. It can bind oxidative metal ions, including copper, iron, nickel, vanadium, and cobalt. Excessive oxidative stress or ischemia can damage albumin and interfere with its vital functions. Ischemia-modified albumin can be measured and is approved as an early diagnostic biomarker in myocardial infarction (Sitar 2013). Albumin inhibits the activation and aggregation of platelets and endothelial cell apoptosis (Alsancak 2018).

Albumin at the low end of the conventional lab range is associated with an increased risk of surgical complications and increased mortality (Bendersky 2017). An earlier meta-analysis of 8 studies found a significant increase in coronary heart disease risk with albumin of 3.8 versus 4.2 g/dL (Danesh 1998). Low albumin in elderly subjects is associated with increased sepsis and mortality following surgery for hip fracture (Keller 2019).

A prospective study of 2,465 medical inpatients found that hypoalbuminemia was independently associated with inflammation and increased nutrition risk and that all three comorbidities were independently predictive of mortality (Eckart 2020).

Albumin above 4.5 g/dL has been associated with the most significant short-term and long-term survival in hospitalized patients (Akirov 2017). Maintaining albumin above 4.5 g/dL was associated with reducing all-cause mortality in healthy adults and can be considered an optimal goal (Fulks 2010). Albumin may appear falsely elevated in dehydration, so hydration must be considered during clinical assessment.

A review of data of 1,752 participants at least 65 years of age from a nationally representative population-based study found that a decreasing serum albumin level was significantly associated with cognitive impairment on a dose-response basis. Those with the lowest albumin (2.2-3.8 g/dL) were up to six times more likely to be cognitively impaired than those with an albumin of 4.4-5.3 g/dL (Llewellyn 2010). It is possible the association between albumin and impaired cognitive function is enhanced in carriers of the Apolipoprotein E (APOE) gene. APOE is a significant genetic risk factor for Alzheimer’s (Min 2022).

Alzheimer's disease is characterized by cerebral intraneuronal neurofibrillary tangles and extracellular deposits of beta-amyloid protein, a process that can begin 10-15 years before the onset of related cognitive symptomatology. Albumin sequesters beta-amyloid plaque and binds 90-95% of beta-amyloid in the blood. A reduction in albumin can impair the brain’s ability to excrete beta-amyloid into circulation. Serum albumin was inversely associated with cerebral beta-amyloid deposition and beta-amyloid positivity in a study of 396 adults without dementia. An albumin below 4.4 g/dL was significantly associated with beta-amyloid positivity and retention in the brain compared to albumin above 4.5 g/dL (Kim 2020).

References

Akirov, Amit et al. “Low Albumin Levels Are Associated with Mortality Risk in Hospitalized Patients.” The American journal of medicine vol. 130,12 (2017): 1465.e11-1465.e19. doi:10.1016/j.amjmed.2017.07.020

Alsancak, Yakup, et al. "Role of calcium–albumin ratio in severity of coronary artery disease assessed by angiographic SYNTAX score." Archives of Clinical and Experimental Medicine 3.3 (2018): 174-178.

Arques, Stephane. “Human serum albumin in cardiovascular diseases.” European journal of internal medicine vol. 52 (2018): 8-12. doi:10.1016/j.ejim.2018.04.014

Bendersky, Victoria et al. “Determining the Optimal Quantitative Threshold for Preoperative Albumin Level Before Elective Colorectal Surgery.” Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract vol. 21,4 (2017): 692-699. doi:10.1007/s11605-017-3370-9

Eckart, Andreas et al. “Relationship of Nutritional Status, Inflammation, and Serum Albumin Levels During Acute Illness: A Prospective Study.” The American journal of medicine vol. 133,6 (2020): 713-722.e7. doi:10.1016/j.amjmed.2019.10.031

Danesh, J et al. “Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.” JAMA vol. 279,18 (1998): 1477-82. doi:10.1001/jama.279.18.1477

Fulks M, Stout RL, Dolan VF. Albumin and all‐cause mortality risk in insurance applicants. J Insur Med. 2010;42: 11–17.

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

Kim, Jee Wook et al. “Serum albumin and beta-amyloid deposition in the human brain.” Neurology vol. 95,7 (2020): e815-e826. doi:10.1212/WNL.0000000000010005

Llewellyn, D J et al. “Serum albumin concentration and cognitive impairment.” Current Alzheimer research vol. 7,1 (2010): 91-6. doi:10.2174/156720510790274392

Malavolta, Marco et al. “Serum copper to zinc ratio: Relationship with aging and health status.” Mechanisms of ageing and development vol. 151 (2015): 93-100. doi:10.1016/j.mad.2015.01.004

Min, Jin-Young et al. “Chronic Status of Serum Albumin and Cognitive Function: A Retrospective Cohort Study.” Journal of clinical medicine vol. 11,3 822. 3 Feb. 2022, doi:10.3390/jcm11030822

Noh, Eul et al. “The clinical role of serum albumin in Organophospate poisoning.” Basic & clinical pharmacology & toxicology vol. 128,4 (2021): 605-614. doi:10.1111/bcpt.13546

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

Sajgure, A D et al. “The Relationship between Metabolic Acidosis and Nutritional Parameters in Patients on Hemodialysis.” Indian journal of nephrology vol. 27,3 (2017): 190-194. doi:10.4103/0971-4065.202404

Sitar, Mustafa Erinç et al. “Human serum albumin and its relation with oxidative stress.” Clinical laboratory vol. 59,9-10 (2013): 945-52