IngredientsAlbumin (from the Latin albumen, meaning "white of egg") is a family of globular, water-soluble proteins found widely throughout the animal and plant kingdoms. In biomedical and clinical contexts, the term most commonly refers to human serum albumin (HSA), the predominant protein of human blood plasma. In the dietary supplement and food-protein context, the term equally describes egg white albumin (principally ovalbumin), the protein fraction obtained from avian egg white.
Albumin is a simple protein present both in animal and plant physiological fluids and tissues. In adult humans, albumin is the most abundant plasma protein with a concentration ranging from 35 to 50 g/L. It is a single chain protein with a low molecular weight of approximately 66.5 kDa, containing 585 amino acids. It is a simple, non-glycosylated polypeptide with hydrophobic patches and cavities, and it lacks prosthetic groups. The human albumin gene is located on chromosome 4q (11â22), and mutations of this gene will end in anomalous protein. This gene has 1,691 nucleotides and contains 14 introns and 15 exons; albumin's structure, composed of three domains homologous in structural features, has been elucidated by X-ray crystallography.
Ovalbumin is the first protein isolated in pure form and constitutes about half of the total egg albumen protein. Egg white mainly consists of water (88%) and protein (11%), with the remainder consisting of carbohydrates, ash, and trace amounts of lipids. The primary proteins are ovalbumin (54%), ovotransferrin (12%), ovomucoid (11%), lysozyme (3.5%), and ovomucin (3.5%), with several minor proteins also present. Ovalbumin is defined as a protein with a molecular mass of 45 kDa, composed of 385 amino acids, and belonging to the serpin family; it features a significant hydrophobic and acidic residue composition, exhibits a secondary structure of 30% α-helix and 32% ÎČ-sheet, and can undergo thermal denaturation to form a more stable variant known as S-ovalbumin. Ovalbumin displays sequence and three-dimensional homology to the serpin superfamily, but unlike most serpins it is not a serine protease inhibitor.
Albumin is a major protein in mammalian blood plasma or serum, where its concentration in healthy organisms is about 600 ÎŒM. The albumin molecule consists of three domains (I, II, and III), each of which includes two subdomains (A and B). The albumin molecule contains 17 disulfide bonds and a free thiol group of Cys34.
The main endogenous ligands of albumin are fatty acids (FAs), which can bind to seven fatty acid binding sites (FA1â7). Two additional FA binding sites (FA8 and FA9) are located in the cleft between domains I and III and can only be occupied in the presence of short-chain FAs or saturating amounts of FAs, respectively. The binding of exogenous ligands occurs at two main drug sites: site 1 (Sudlow site I, overlapping with FA7 in subdomain IIA) and site 2 (Sudlow site II, overlapping with FA3 and FA4 in subdomain IIIA). Site 3, located in subdomain IB and overlapping with FA1, which binds compounds such as hemin and bilirubin, was later also identified.
Human serum albumin undergoes conformational changes upon ligand binding. Drugs, fatty acids, heme, and anesthetics can allosterically modulate binding at other sites. Fatty acid binding, particularly by long-chain molecules such as myristate, induces domain rearrangements that alter drug-site affinities. Ambient pH also affects protein structure, with acidic, neutral, and basic forms showing differing solubility, α-helical content, and ligand-binding properties.
Albumin is a water-soluble, nonimmunogenic protein characterized by a long half-life, low toxicity, and high stability. The molecular weight of albumin is approximately 66 kDa, and it has a half-life of 21 days. This relatively long half-life is attributed to its molecular size and its interaction with the neonatal Fc receptor (FcRn), which helps recycle albumin and prevents its rapid degradation.
Human albumin is synthesized in hepatocytes as preproalbumin and modified to proalbumin within the endoplasmic reticulum. The N-terminal 6-amino acid peptide is cleaved by the furin enzyme in Golgi vesicles, producing mature serum albumin, a single-chain protein of 585 residues. Fully processed albumin is secreted constitutively from hepatocytes without significant intracellular storage, entering the bloodstream continuously. Nascent albumin becomes detectable in circulation within 30 to 60 minutes of Golgi processing.
Hepatocytes in the liver synthesize albumin and rapidly release it into the bloodstream at a rate of 10 g to 15 g per day. Minimal albumin is stored in the liver, with the majority entering the circulation rapidly. Albumin is located in every tissue and bodily secretion, with extracellular protein comprising 60% of total albumin. About 30% to 40% of circulating albumin remains in the bloodstream, with the rest distributing into extravascular spaces before returning to circulation via the lymphatic system.
In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (approximately 6%), gastrointestinal (approximately 10%), and catabolic (approximately 84%) clearances. Its sites of degradation are widespread throughout the body and include the kidneys, capillaries, and liver sinuses. The catabolic rate of albumin slowly decreases when serum albumin levels are low, as seen in protein deficiency, cirrhosis, nephrotic syndrome, and gastrointestinal diseases.
Maintenance of plasma albumin concentrations can be achieved with only 10% of normal hepatocyte mass. During inflammatory states, the body decreases albumin production and increases its breakdown (catabolism). Increased capillary permeability allows albumin to leak from blood vessels into interstitial spaces, further reducing its circulating half-life. This can happen rapidly, even in adequately nourished individuals following trauma or acute illness.
The use of egg white as a therapeutic and practical material has ancient roots. In the 1750s, egg whites were believed to prevent swelling, and were used for that purpose. For about 400 years, egg white was used to coat and protect paintings without detailed understanding of its molecular properties. The albumen from egg white was used as a binding agent in early photography during an 1855â90 period; such prints were called albumen prints. Egg white's role as a foodstuff and culinary ingredient â for foaming, gelling, and structure â is attested across centuries of European and global cuisine.
The modern clinical use of purified human serum albumin dates specifically to the Second World War. Edwin Cohn, appointed to the Harvard Medical School in 1920, was commissioned by the United States military in 1940 to develop a stable albumin solution to treat blood/plasma loss from battlefield injury. Albumin was first produced at the Harvard pilot plant using Cohn's five-variable, ethanol precipitation process, which was rapidly transferred to private industry for industrial manufacture.
The first commercial human albumin solution (25% concentration) was authorized for production in January 1942 and became available for clinical use by 1944, following successful trials starting in April 1941. When war broke out in December 1941, Cohn's laboratory shipped human serum albumin (processed Fraction V) using plasma from the Red Cross to treat casualties of the Pearl Harbor attack. A small number of severely burned patients were given albumin and all showed prompt clinical improvement. Albumin continued to be the highest-priority product, notably in 1944 during the Allied invasion of Normandy.
Albumin preparations obtained by separation of human plasma have been used clinically for more than 50 years to reverse hypoalbuminemia and to allow for reversal of abnormalities in substance transport. All fractionation today is done via the Cohn Cold Fractionation Process, named after Dr. Edwin J. Cohn who developed it in the 1940s. The Cohn Process involves modifying the pH, ethanol concentration, and temperature to separate proteins through precipitation into five fractions. The separated proteins then undergo an extensive purification process that includes cryoprecipitation, nanofiltration, solvent detergent treatments, and incubation to produce a sterile, virally inactivated protein product.
The separation methods for egg white proteins have been developed since the early 1900s, but preparation methods of these proteins for commercial applications are still under development. As one of the first proteins purified in crystalline form, ovalbumin was among the earliest proteins to be readily available in abundance. This contributed to ovalbumin becoming one of the most extensively characterized and best-understood antigens, contributing to our understanding of the structureâfunction relationship of antigenâantibody interactions.
As the most abundant protein in the circulatory system, with typical blood concentrations of 5 g/100 ml, serum albumin contributes 80% to colloid osmotic blood pressure. It is the main regulator of plasma oncotic pressure; any alteration in the oncotic pressure can lead to the stimulation of HSA synthesis. This oncotic function directly governs the distribution of fluid between the vascular compartment and the interstitial tissues, forming the physiological basis for using albumin infusions as a plasma expander.
Human serum albumin is the primary modulator of plasma oncotic pressure and serves as a transporter for various substances termed "ligands." Examples of endogenous ligands include bilirubin, ions, and fatty acids, while exogenous ligands include drugs. Although albumin has a broad affinity for small, negatively charged aromatic compounds, it has high affinities for fatty acids, hematin, and bilirubin. Additionally, it forms covalent adducts with pyridoxal phosphate cysteine, glutathione, and various metals, such as Cu(II), Ni(II), Hg(II), Ag(II), and Au(I). It is widely accepted in the pharmaceutical industry that the overall distribution, metabolism, and efficacy of many drugs can be altered based on their affinity to serum albumin.
Serum albumin plays a key role in antioxidant defence under both normal and oxidative stress conditions. As a carrier of many biologically active compounds, blood is exposed to oxidants to a greater extent than the intracellular environment. This function involves both enzymatic and non-enzymatic activities of albumin that determine its participation in redox modulation of plasma and intercellular fluid.
Whereas small thiols cysteine and glutathione (GSH) are the major antioxidants contributing to intracellular redox homeostasis, the most abundant thiol in plasma is the Cys34 residue in albumin, which exerts anti-oxidative activity and circumvents systemic oxidative stress. The Cys34 residue scavenges multiple reactive oxygen and nitrogen species such as hydrogen peroxide (HâOâ), peroxynitrite (ONOOâ»), superoxide (Oââ»), and hypochlorous acid (HOCl).
In human vascular smooth muscle cells, albumin reduces superoxide levels by inhibiting membrane recruitment of the NADPH oxidase cytosolic subunit p47phox, a critical enzyme involved in oxygen-derived free radical production in cardiovascular diseases. Albumin is usually one of the first proteins to be influenced by oxidative stress; therefore, its redox status is widely used as a biomarker of various pathological conditions.
Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogenous and exogenous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. In 1959, Casida and Augustinsson suggested that, in addition to its binding capacity, albumin possesses hydrolytic activity.
It has been determined that albumin is chiefly responsible for the maintenance of blood pH. Other functions include a pivotal role in acidâbase homeostasis, transport of a number of key molecules including drugs, and scavenging of reactive oxygen species.
Albumin's biological functions include maintenance of oncotic pressure, solubilization and transport of hydrophobic substances, antioxidant function via its free sulfhydryl group at cysteine-34, metal binding at its N-terminus, immunomodulation and/or endothelial stabilization via binding and inactivation of endotoxin. The interaction of albumin with blood cells, blood vessels, and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin.
Ovalbumin is best known for its various biological activities, including anticancer, antihypertensive, antimicrobial, antioxidant, and immune-modulating activities. As a 43 kDa glycoprotein composed of 385 amino acids, ovalbumin is one of only two proteins that adequately meet the entire dietary requirement for amino acids; it is suggested that its normal physiological function in the egg is to serve as nutritional storage for the developing chick. Another potential role is metal ion storage and transport.
Restoration of blood volume, emergency treatment of shock, acute management of burns, and other situations associated with hypovolemia are some of the clinical applications of albumin. Albumin serves as a colloid solution for fluid resuscitation, particularly in the setting of trauma (i.e., hypovolemic shock) or large-volume paracentesis. The effects on blood volume and hypoproteinemia are firmly established in patients with an intact capillary system.
The evidence base for these indications is strong, deriving from decades of clinical use, guideline endorsements, and pharmacological data. However, the therapeutic implications of a capillary "permeability lesion" are a subject of current debate, as such lesions occur following extensive injuries and in patients with septic pulmonary failure.
Cardiovascular abnormalities form the essential background for the development of ascites and other clinical complications of cirrhosis, all characterized by extreme effective hypovolaemia, such as hepatorenal syndrome (HRS), post-paracentesis circulatory dysfunction (PPCD), and renal failure induced by spontaneous bacterial peritonitis (SBP). As a result, the maintenance of the central blood volume represents a major objective in the management of patients with advanced cirrhosis. Based on its capacity to act as a plasma-expander, the use of human albumin is currently proposed by international guidelines to treat HRS, in association with vasoconstrictor drugs, and to prevent PPCD and renal failure induced by SBP.
In the setting of spontaneous bacterial peritonitis (SBP), a seminal prospective randomised trial reported that administration of high-dose human albumin (1.5 g/kg at diagnosis of SBP and 1 g/kg on day 3), together with antibiotic treatment, significantly decreased the incidence of type 1 HRS and improved in-hospital and 3-month survival. However, whether all patients with SBP should receive human albumin in addition to antibiotics is still uncertain, as the most striking effects are obtained in patients with more advanced disease defined by a serum bilirubin greater than 4 mg/dL and serum creatinine greater than 1 mg/dL at the time of diagnosis.
Until more information becomes available, the Clinical Practice Guidelines of the European Association for the Study of the Liver (EASL) recommend that all patients who develop SBP should be treated with broad-spectrum antibiotics and human albumin (1.5 g/kg on day 1 and 1 g/kg on day 3). The evidence in this specific indication is strong (Level I evidence from a landmark RCT, replicated in subsequent trials), though it is worth noting that the benefit is largest in the highest-risk subgroup.
Albumin, a key plasma protein, is effective in the management of fluid imbalance, circulatory dysfunction, and inflammation-related complications. However, its role in sepsis is more intricate and characterized by ongoing debate and varied results from clinical studies. In sepsis, the potential benefits of albumin include maintaining vascular integrity and modulating inflammation, yet its consistent clinical efficacy is not as definitive as that in cirrhosis.
The landmark SAFE trial â which randomised ICU patients to 4% albumin or normal saline for intravascular fluid resuscitation for 28 days â found no difference in 28-day mortality, and although a pre-specified subgroup analysis of patients with severe sepsis signalled a benefit for albumin, this too did not reach statistical significance.
Albumin supplementation is widely used for hypoalbuminemia treatment in patients with critical illness, especially those with cirrhosis. However, studies have demonstrated that routine albumin administration is not always advantageous. A large retrospective observational study using the TriNetX global research platform identified 1,147,433 patients who developed sepsis and hypoalbuminemia with albumin levels <3.5 g/dL. The study found that patients with sepsis with hypoalbuminemia who received albumin supplementation exhibited high 30-day mortality rates and increased risks of shock, heart failure, and pulmonary edema compared with those who did not. These findings indicate that routine albumin administration may be linked with unfavorable outcomes in these patients. This retrospective study carries significant limitations, including potential confounding by indication.
Expert consensus groups recommend that albumin should be administered to septic shock patients who remain hemodynamically unstable after resuscitation with 30 mL/kg crystalloids, and define hemodynamic instability specifically in terms of failure to maintain a mean arterial pressure (MAP) of 65 mmHg or higher despite intravenous norepinephrine.
Serum albumin has been advocated as a marker of nutritional status. However, expert opinion has increasingly recognized that serum albumin primarily reflects the presence of systemic inflammation rather than nutritional state alone. Serum albumin level has been used classically as a biomarker of protein nutritional status, with the level <35 g/L defined as hypoalbuminemia, but low serum albumin level is currently viewed more as a risk factor and a predictor of morbidity/mortality regardless of the implicated diseases.
A 2017 meta-analysis of low serum albumin levels in orthopedic populations found a 2.5-fold increase in the risk of surgical site infection across a range of interventions. Procedures evaluated included femur fracture management in trauma settings, total knee arthroplasty, total hip arthroplasty, and spinal operations. Serum albumin concentrations less than 3.5 g/dL were associated with the increased risk described.
Hypoalbuminaemia in sepsis is a poor prognostic factor for mortality, probably reflecting the severity of disease through endothelial dysfunction and decreased serum albumin half-life. It is widely believed clinically that patients with low serum albumin require human serum albumin as nutritional supplementation to increase levels; however, there is currently no reliable evidence that exogenous albumin infusion functions as meaningful nutritional support. The use of albumin as an intravenous nutrient is clearly inappropriate according to established clinical pharmacology reviews.
Acute management of burns is among the established clinical applications of albumin. This use was the original context for clinical albumin development in the 1940s. The fluid loss from battlefield burns can lead to severe shock, and historical evidence from World War II military medicine demonstrates the life-saving potential of albumin in this setting. Current clinical guidelines include albumin as part of burn resuscitation protocols, though evidence comparing albumin to other colloids and crystalloids in modern burn care continues to evolve.
Substantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients. For many years, hypoalbuminemia has been recognized as a predictor of cardiovascular morbidity and mortality in HD patients.
Observational and mechanistic research has examined the relationship between albumin levels, oxidative stress, and endothelial function in pregnancy. One study examined whether levels of oxidative stress, human serum albumin, and endothelial function correlate in pregnant women and whether human serum albumin reduces levels of superoxide produced by NADPH oxidase activation in human vascular smooth muscle cells. Pregnant women with preeclampsia (n=33) and without preeclampsia (n=37) were recruited to determine levels of reactive oxygen species and flow-mediated dilation (FMD). Women in the preeclampsia group demonstrated lower FMD and higher serum d-ROM values than those in the normal group. This is observational research and does not establish albumin supplementation as a treatment for preeclampsia; evidence in this area remains preliminary.
Ovalbumin is one of only two proteins that adequately meet the entire dietary requirement for amino acids, making egg white a complete protein source. Ovalbumin is the first protein isolated in pure form and has long served as a high-quality dietary protein. Ovalbumin is widely used as a nutrient supplement. A raw U.S. large egg contains around 33 grams of egg white with 3.6 grams of protein, 0.24 grams of carbohydrate, and 55 milligrams of sodium. It contains no cholesterol. While egg white is recognized as a high-biological-value protein, specific randomized clinical trials powered to assess egg white albumin supplementation on muscle protein synthesis as a primary outcome are limited; most data derive from studies on dietary protein quality generally.
Serum albumin is recognized as a biomarker for liver function synthesis, and also for several diseases, such as inflammatory disorders, brain tumors, rheumatoid arthritis, myocardial ischemia, cancer, bloodâbrain barrier (BBB) damage, kidney disease, cerebrovascular disease, cardiovascular risk disease, and disorders which require blood sugar control.
Albumin is administered in clinical settings exclusively in intravenous form when used as a pharmaceutical product. Egg white albumin is consumed orally as a food or dietary supplement. The following dosages are drawn from sourced clinical references only.
No standardized clinical dosing regimen has been established for egg white albumin as a discrete dietary supplement. The protein content of egg white is approximately 3.6 g per large egg white, and commercially available egg white powders vary in protein content by product. Clinical trials examining supplementation with egg white protein are limited compared to other protein sources (such as whey), and no specific gram-per-day dosages from clinical trials are available from the authoritative sources reviewed here.
Since albumin solution is a human-derived blood product, adverse effects are rare. While the colloid is safe, it may rarely induce an anaphylactoid reaction. With larger doses, albumin infusions can cause fluid overload and electrolyte disturbances.
Known Y-site incompatibilities include vancomycin, midazolam, and fat emulsions. Hypersensitivity to any component in albumin preparations or excipients is a contraindication.
Caution is warranted in conditions where hypervolemia and its consequences or hemodilution could represent a special risk (e.g., heart failure, arterial hypertension, esophageal varices, pulmonary edema, hemorrhagic diathesis, severe anemia, renal and post-renal anuria).
Albumin is a blood product and therefore carries a small risk of transmission of viral diseases. Modern viral inactivation steps built into the Cohn fractionation process have substantially reduced â but not entirely eliminated â this theoretical risk.
Regarding neonates, the 25% concentration should be used with extreme caution in neonates, owing to risk of intraventricular hemorrhage from rapid expansion of intravascular volume.
The combination of albumin's binding capacity, esterase activity, and abundance in human blood is responsible for its influence on the clinical efficacy and safety of several drugs. For example, drugs such as warfarin and phenytoin compete for the same albumin binding sites, meaning they will displace each other, rendering their subsequent pharmacodynamic effects unpredictable and potentially harmful. If such drugs are used in critical illness, they should be titrated carefully according to established therapeutic drug monitoring procedures.
The use of common drugs (such as non-steroidal anti-inflammatories and oral hypoglycaemic agents) alongside fluoroquinolone antibiotics results in an increased free fraction of antibiotics, which may result in increased risk of important clinical adverse effects such as peripheral neuropathy.
When multiple drugs that bind to albumin are taken at the same time, they compete for the available binding sites. A drug with a stronger affinity for albumin will displace a drug with a weaker affinity, increasing the free concentration of the displaced drug. Although often brief and not clinically significant, this competition can be risky when the displaced drug is highly protein-bound and has a narrow therapeutic range.
Drug binding to HSA can be affected by the presence of other drugs or endogenous compounds, or by the change of HSA structure in certain types of diseased states. A change in the free fraction may result in altered pharmacokinetics and pharmacodynamics.
Decreased binding of model ligands for the benzodiazepine binding site II was found in patients with end-stage liver disease. Extracorporeal albumin dialysis using the molecular adsorbents recirculating system (MARS) has been found to improve this binding. Impaired albumin function in cirrhosis also includes alterations in fatty acid binding and impaired metal binding. Impaired albumin function may be caused by oxidative albumin damage, which has been found in several disease conditions including chronic liver failure.
Infusion of albumin may slowly increase its catabolic rate. This must be taken into consideration by clinicians when managing serum albumin levels in chronic diseases.
Egg white albumin as a food protein and dietary supplement ingredient is generally recognized as safe (GRAS) when consumed as part of normal dietary intake. However, egg white is one of the major food allergens worldwide; sensitized individuals may experience reactions ranging from mild urticaria to anaphylaxis upon exposure. Additionally, raw egg white contains avidin, a glycoprotein that binds dietary biotin with high affinity; avidin is another protein prominent in egg white, concentrated in 1941 by Eakin, Snell, and Williams. A unit was defined as the amount of concentrate capable of inactivating 1 gram of biotin. Cooking or pasteurization denatures avidin, abolishing this biotin-binding effect. The liquid egg white mixture is pasteurized to eliminate pathogenic microorganisms, including Salmonella bacteria.
Health conditions that Albumin may help support.
Body systems that Albumin may help support.
Go back