Albumin: Diagnostic Significance and Clinical Insights

Authors: Payal Bhandari, M.D.

Contributors: Tia Ketsan, Amer Džanković, Hailey Chin, Nigella Umali Ruguian, Vivi Chador 



Albumin


Albumin is a protein produced in the liver. Albumin helps maintain osmotic pressure to keep blood from leaking out of blood vessels and move minerals, vitamins, hormones, medicines, and other important substances throughout the body. Abnormally high albumin levels are typically caused by dehydration and the gut’s inability to digest a high protein diet. Abnormally low albumin levels are typically caused by liver, small intestines, or kidney problems, malnutrition, and/or chronic systemic inflammation. 



Typical Adult Range


Ranges and thresholds can vary due to: 

(1) Lab-specific equipment, techniques, and chemicals, and 

(2) Patient demographics, including age, sex, and ethnicity.



Key Insights 

The human body is mostly made of proteins, with albumin and globulin being the main ones. Albumin makes up about 60% of the total protein and is made in the liver. It plays a key role in nutrition, liver health, and overall wellness. High albumin levels in the blood can mean dehydration or issues with gut health, leading to inflammation. Low levels might point to malnutrition or problems with multiple organs. Trouble absorbing or using protein can lead to health issues like heart disease, autoimmune disorders, cancer, and infections. Tracking albumin levels in the blood can help spot diseases early. Diet, medications, stress, and health conditions can affect albumin levels. Managing these factors can improve health and lower the risk of long-term inflammation.



What is Albumin? 

Albumin, fibrinogen, and globulins are the main proteins in the blood, essential for the body’s normal functions. Most of these proteins are made in the liver, except gamma globulins, which are produced by immune cells.

  • Globulins (30–40% of total protein): Store and transport hormones, fats, and drugs; help fight infections and inflammation; maintain blood vessel fluid balance.

  • Fibrinogen (4% of total protein): Helps form blood clots and repair wounds by turning into fibrin.

  • Albumin (55–60% of total protein): Maintains fluid balance in blood vessels and carries hormones, vitamins, and drugs. Most albumin is in the blood, with smaller amounts in muscles, skin, and body fluids like sweat and bile.


Figure 1: The majority of proteins in the blood are albumin, fibrinogen, and globulins. They are all synthesized in the liver, except gamma globulins produced by B lymphocytes. Albumin accounts for 55-60 percent of total plasma proteins. Fibrinogen accounts for 4 percent of total plasma proteins. Globulin accounts for 30 to 40 percent of the total protein and are divided into three types with specific functions: alpha (α), beta (β), and gamma (γ). 



Albumin is a protein made of 585 amino acids. Proteins differ based on the order of these amino acids and how the chain folds and interacts with its surroundings. Amino acids are small molecules with three main parts: an amino group (-NH2), a carboxyl group (-COOH), and a unique side chain (R). While there are hundreds of amino acids in nature, only 20 are essential for building proteins in the human body. The body cannot make essential amino acids, so they must come from food.


Figure 2: Proteins are repeating amino acid units arranged in unique patterns and connected by a peptide bond . Amino acids are made up of an amino group (-NH2), a carboxyl group (-COOH), and a differing side chain (R) that are connected by peptide bonds.


Albumin is a large protein that stays in blood vessels and helps balance fluids and particles like sodium (Na+). Its negative charge attracts sodium and water, keeping the blood’s fluid levels stable. It also helps maintain normal blood pH by interacting with ions like chloride (Cl-).

Albumin carries important substances in the blood, including bilirubin (a waste product), hormones, vitamins, minerals, fatty acids, and some drugs like Methadone and Warfarin. By transporting fatty acids, albumin helps the body use fat for energy and prevents fat buildup in damaged blood vessels, reducing the risk of inflammation and heart disease.


                   

Figure 3: Albumin binds to sodium (Na+) and chloride (Cl-) in blood vessels, helping water flow properly into smooth muscle cells. This keeps osmotic pressure balanced in capillaries, stopping blood from leaking into areas like peritoneal fluid or urine. By doing this, albumin helps control inflammation and supports normal body functions.


Albumin Formation and Regulation 

The liver is the main organ that makes albumin, producing 10–18 grams daily in an average adult. About 30–40% of this albumin enters the bloodstream, while the rest goes into the spaces around cells and eventually returns to the blood through the lymphatic system. Albumin stays in the bloodstream for about three weeks.

The kidneys filter 180 liters of blood daily, process large amounts of albumin, and prevent its loss in urine. Albumin production happens when the body has enough nutrients and is influenced by:

  • Blood vessel pressure and cell fluid balance,

  • Kidney function to prevent albumin loss,

  • Levels of receptors that bind albumin on cells.

Clinical Significance of a High Albumin Blood Level

Elevated albumin blood level is called hyperalbuminemia. It is due to either increased albumin synthesis in the liver and storage in the skin or decreased loss in the urine or peritoneal fluid. The skin is the most important extra storage pool for albumin. 


Dehydration

Dehydration is a major reason the liver increases albumin production. When you don’t drink enough water, the amount of ions outside cells rises, causing cells to shrink and struggle with normal functions. This makes cells more prone to damage, releasing harmful byproducts into the blood and tissues.

Common causes of fluid loss or low blood volume include:

  • Severe burns

  • Diarrhea or vomiting

  • Overuse of diuretics or laxatives

  • Sweating from exercise, fever, or heatstroke

  • Not drinking enough water

  • Heavy menstrual cycles

  • Blood loss from surgery, trauma, or donations

  • Chronic blood loss from conditions like hemolysis, worsened by dehydration

Long-term dehydration can increase pressure in blood vessels, reduce organ blood flow, and harm gut health. The gut helps digest food, absorb nutrients, and remove waste. Poor blood flow due to dehydration can disrupt digestion, lead to nutrient deficiencies, and increase undigested food particles in the gut and bloodstream.



                               

Figure 4: Effects of water osmosis on the integrity and functioning of blood cells. Water osmosis is the transportation of water throughout a cell that is determined by the cell’s solute concentration. Hypotonic cells have a higher solute concentration inside the cell than outside, causing more water to be transported inside the cell. Isotonic cells have the same solute concentration inside and outside the cell, causing water to be transported into and out of the cell equally. Hypertonic cells have less solute concentration inside the cell, causing the cell to transport water out of the cell.     

Figure 5: Healthy gut microbiota plays a crucial role in maintaining overall digestive health and metabolic balance. In contrast, decreased concentration and abundance of healthy bacteria in the gastrointestinal tract (dysbiosis) can dysregulate metabolic pathways, reduce energy harvesting, and increase the concentration of proinflammatory proteins and reactive oxygen species in the circulation.



Undigested food particles in the bloodstream make it harder for red blood cells (RBCs) to deliver oxygen, leading to low oxygen levels (hypoxia) and increased RBC destruction. The liver produces more albumin to clear out toxins from damaged cells, triggering inflammation. This causes harmful chemicals to disrupt normal body functions and damage cells.

The liver slows fat metabolism and breaks down glucose and muscle for energy. Blood sugar rises, and hemoglobin from destroyed RBCs makes it harder for oxygen to reach tissues. Reactive oxygen species (ROS) also turn cholesterol into substances that build up in blood vessels, leading to atherosclerosis.

High albumin levels cause chronic inflammation, worsening atherosclerosis. This damages organs, raises blood pressure, and reduces blood flow, causing organs like the heart and pancreas to enlarge and lose function.



            

Figure 6: Rising albumin levels in the blood are closely linked to reduced arterial blood flow, excess fat and scar tissue deposition, and clot formation mounting inflammatory processes that damage blood circulation in various parts of the body and dysregulate energy expenditure.  


Stress

Stress, from physical or emotional triggers like trauma, surgery, or illness, causes the body to release hormones like cortisol and catecholamines (epinephrine and norepinephrine). These hormones lead to:

  1. Muscle breakdown: Proteins in muscles are turned into glucose for energy.

  2. Fat and protein issues: Less fat and protein are processed, causing inflammation.

  3. Fat storage: Fat builds up in organs, blood vessels, and tissues, reducing energy and organ function.

  4. Hormonal changes: More thyroid and growth hormones are made.

  5. Chronic inflammation: Atherosclerosis and anemia worsen, increasing albumin production.

Chronic sleep loss is a common cause of stress that raises albumin levels. High cortisol at night affects insulin and glucose, raising blood sugar. The liver increases thyroid hormones (T4 and T3), which help energy production, but prolonged stress can lead to hyperthyroidism and more albumin.

Too much T3 in the liver raises energy use and inflammation. Over time, this causes organs to struggle, and white blood cells can attack the body, leading to autoimmune diseases and organ failure.

A review of studies showed that 15-76% of people with thyroid issues had abnormal albumin levels. Treating thyroid problems improved liver function in 70% of cases. Regular thyroid and liver checks help understand albumin changes and prevent issues like atherosclerosis, autoimmune diseases, and organ damage.

Diet 

Animal Protein Versus Plant-Forward Diet

Diet affects protein metabolism and blood albumin levels. After eating protein, the liver makes more albumin. Animal proteins like meat, eggs, and milk provide all essential amino acids, including methionine. Too much methionine can increase glutathione (GSH), which boosts liver activity to make albumin and the enzyme GGT. GGT breaks down GSH, releasing hydrogen sulfide (H2S), which can damage cells and raise albumin levels if nutrients like B vitamins are low. Eating more plant-based foods rich in B vitamins and reducing methionine can lower H2S and GGT, helping balance GSH and albumin.


Figure 7: Eating too much protein from animal products and nuts can affect the body’s ability to recycle important amino acids like homocysteine, methionine, and cysteine. This leads to a decrease in the antioxidant glutathione (GSH) and an increase in the harmful substance hydrogen sulfide (H2S). Deficiencies in B vitamins, zinc, and iron—often found in green vegetables and other nutrient-rich plants—can reduce GSH levels, cause more cell damage from H2S, and trigger inflammation. This inflammation can raise albumin production and blood albumin levels . 


Heme-Iron Versus Non-Heme-Iron Rich Diet 

Food has two types of iron: heme and non-heme. Non-heme iron is in plant foods like grains, beans, and vegetables. Heme iron is in animal products like meat, fish, and eggs and is easier for the body to absorb. Red meat has more heme iron than chicken. Eating meat also helps the body absorb both types of iron.

Heme iron is important for making proteins in the liver that help carry oxygen. It makes up 95% of the body’s functional iron. In Western countries, most stored iron comes from heme, even though we eat less of it. High heme iron diets change liver functions and can help infections and cancer cells grow by supporting white blood cells and platelets.


Figure 8: The protein heme in meat fuels cancer cell progression and albumin synthesis. Compared to normal cells, cancer cells increase the expression of heme transporters, such as albumin, enabling free heme uptake from the bloodstream and regulating inflammatory processes. 



Liver Toxins

Smoking limits blood flow to organs and increases harmful molecules that damage the liver. The cadmium in nicotine disrupts liver functions, lowering important proteins and causing inflammation that raises albumin levels. Over time, smoking weakens the liver and immune system, reducing albumin production.

Alcohol changes liver genes that process ethanol, raising harmful acetaldehyde levels. This lowers antioxidants, allowing damage that increases albumin levels. Studies show that cutting back on alcohol helps the liver repair damage and balance albumin levels.


Pharmaceutical Medications

Long-term use of some drugs can damage the liver and affect albumin production. These drugs often need high levels of iron and oxygen, which can harm other organs. Common drugs that cause liver damage include:

  • Corticosteroids, hormones, and NSAIDs

  • Statins and cholesterol drugs

  • Acetaminophen (Tylenol)

  • Antibiotics, antifungals, and antivirals

  • Opioids

  • Chemotherapy drugs like busulfan

  • Vitamin A (Retinoids)

  • Cocaine

  • Methamphetamines

Drug-induced liver injury (DILI) is a leading cause of liver failure and can be fatal. It can be intrinsic (predictable) or idiosyncratic (unpredictable).

  • Intrinsic DILI: A known drug dose causes liver damage (e.g., high doses of acetaminophen).

  • Idiosyncratic DILI: Unpredictable and can take weeks or months to appear, affecting 10-15% of liver failure cases.

DILI often looks like a viral liver infection and is hard to diagnose without symptoms like jaundice or rashes.


Figure 9: Drug-Induced Liver Injury. The accumulation and metabolism of drugs in the liver can cause a variety of pathophysiologic complications that dysregulate albumin synthesis. 


Clinical Significance of a Low Albumin Blood Level


Hypoalbuminemia is when blood albumin levels are too low. This can happen if the liver doesn’t make enough albumin or if too much albumin is lost through urine, fluid, or skin. Conditions like nephrotic syndrome or severe burns can cause albumin loss. Albumin helps move substances like hormones, fats, and nutrients through the body. Low albumin can cause fluid to move out of blood vessels, leading to dehydration and swelling. It can also affect development in children and cause problems like weakness, fatigue, and swelling in older adults. Low albumin increases the risk of falls and fractures, especially in people over 70. Hypoalbuminemia is common in hospitalized, critically ill, and elderly patients, with over 70% of elderly hospitalized patients affected.


Multiorgan Failure

End-Stage Liver Disease

End-stage liver disease lowers protein production, affecting energy use and nutrient processing. The body prioritizes tissue repair, which reduces quality of life and increases sensitivity to drugs.

Chronic liver inflammation damages the liver and other organs, causing scar tissue, clots, and organ failure. The liver overprocesses proteins and fats, leading to extra fat and proteins in the blood. This imbalance harms the body, raising the risk of heart disease and fluid loss.

 

Chronic Kidney Disease

Dehydration or fluid loss can reduce blood flow to the kidneys, affecting the body’s fluid balance, vitamin D, and red blood cell production. This can cause the kidneys to release more water, minerals, and proteins like albumin in the urine, leading to low albumin levels (nephrotic syndrome). Chronic dehydration also makes it harder to absorb nutrients and produce proteins like albumin.

Nephrotic syndrome can occur at any age and is made worse by medications, toxins, or an overactive immune system. Diseases like lupus can damage kidney cells, leading to lower albumin levels and possible organ failure.

A urine dipstick test can detect albumin in the urine, a sign of kidney damage. If the albumin-creatinine ratio is over 30, the risk of heart and kidney failure increases.

Prevalence & Significance of Abnormal Blood Albumin Levels 

Abnormal albumin levels in the blood are linked to liver and kidney problems. Between 2001 and 2020, about 9-10% of U.S. adults had albumin issues, with higher rates in women, those over 70, Black non-Hispanics, and people with diabetes, high blood pressure, or severe kidney disease.

Liver and kidney diseases are rising globally. In the U.S., liver disease was the 8th leading cause of death in 2016, and chronic kidney disease (CKD) grew from 8.5% in 2000 to 11.2% in 2020. Aging, diabetes, high blood pressure, obesity, and artery disease make kidney function worse.

Public health programs, like KEEP, have increased CKD detection by 15% from 2014 to 2024. However, CKD progression continues due to rising risk factors.

CKD rates are higher in non-Hispanic Black Americans (18.9%) than Hispanics (12%). People with lower incomes and education are also more affected, likely due to limited healthcare access and more health issues.

Conclusion 

Albumin is an important protein in the blood that helps control fluid balance, blood flow, blood pressure, and nutrient transport. It also reflects a person’s nutritional status and overall health. Low or high levels of albumin can indicate inflammation, which may lead to health issues like heart disease, autoimmune disorders (like diabetes), infections, cancer, and organ damage. Improving hydration, eating a plant-based diet, practicing intermittent fasting, adjusting protein intake, taking the right medications, exercising regularly, and managing stress can help balance albumin levels. Monitoring albumin levels regularly can help doctors understand and treat different health conditions.


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