Protein, Total
Total protein measures all proteins in your blood — primarily albumin (made by the liver, ~60%) and globulins (including antibodies, ~40%). These proteins maintain fluid balance, transport substances, and fight infections. Low total protein may indicate liver disease, kidney protein loss, or malnutrition. High total protein may suggest dehydration, chronic infection, inflammation, or plasma cell disorders like multiple myeloma.
Total protein measures the combined amount of all proteins circulating in your blood. The two main components are albumin (made by the liver) and globulins (including antibodies made by the immune system). Together, these proteins perform vital functions — maintaining fluid balance, transporting substances, fighting infections, and supporting countless biological processes.
Why does this matter? Abnormal total protein levels can signal problems with the liver (which makes albumin), kidneys (which can lose protein), immune system (which makes antibodies), or nutritional status. Both high and low levels have significance — low protein may indicate liver disease, malnutrition, or protein loss, while high protein may suggest chronic inflammation, infection, or certain blood disorders.
Total protein is a screening test that provides an overall picture. When abnormal, further testing (albumin, globulins, protein electrophoresis) identifies which specific proteins are affected and guides diagnosis.
Key Benefits of Testing
Total protein provides a quick assessment of protein status reflecting liver function, kidney function, nutritional health, and immune activity. Abnormalities prompt more specific testing that can uncover liver disease, kidney disease, immune disorders, or nutritional problems.
This test is also useful for monitoring chronic conditions. In liver disease, falling total protein (especially albumin) indicates declining liver function. In kidney disease, protein loss can be tracked. In immune disorders, changes in globulins reflect disease activity.
What Does This Test Measure?
Total protein measures the sum of all proteins in blood serum. The two major categories are:
Albumin (About 60% of Total Protein)
Albumin is made exclusively by the liver. It performs critical functions:
Maintains fluid balance: Albumin keeps fluid in blood vessels. Low albumin allows fluid to leak into tissues, causing swelling (edema).
Transports substances: Carries hormones, medications, fatty acids, bilirubin, and other molecules through the bloodstream.
Reflects liver synthetic function: Since only the liver makes albumin, low levels can indicate liver disease or malnutrition.
Globulins (About 40% of Total Protein)
Globulins are a diverse group including:
Immunoglobulins (antibodies): Made by the immune system to fight infections. Include IgG, IgA, IgM, and others.
Transport proteins: Carry hormones, lipids, metals, and other substances (like transferrin for iron, ceruloplasmin for copper).
Clotting factors: Some globulins participate in blood clotting.
Inflammatory proteins: Increase during inflammation and infection.
The Albumin/Globulin Ratio
When total protein is measured, albumin is often measured separately, allowing calculation of globulins (total protein minus albumin) and the A/G ratio. This ratio helps interpret results:
Normal ratio: Slightly more albumin than globulins
Low ratio: May indicate increased globulins (inflammation, infection, immune disorders) or decreased albumin (liver disease, malnutrition)
High ratio: Less common, may indicate underproduction of globulins
Why This Test Matters
Assesses Liver Function
The liver produces albumin and many globulins. Low total protein, especially with low albumin, can indicate liver disease — the liver isn’t making enough protein. This is an important marker of liver synthetic capacity.
Detects Kidney Disease
Healthy kidneys retain protein in the blood. Damaged kidneys leak protein into urine, lowering blood levels. Low total protein can be an early sign of kidney disease, prompting urine testing to confirm protein loss.
Evaluates Nutritional Status
Protein malnutrition — from inadequate intake, malabsorption, or increased needs — lowers total protein levels. This is relevant in chronic illness, eating disorders, malabsorptive conditions, and situations with increased protein requirements.
Screens for Immune Disorders
High total protein, especially with elevated globulins, can indicate chronic infections, autoimmune diseases, or blood disorders like multiple myeloma (where abnormal antibodies are overproduced). These conditions warrant further investigation with protein electrophoresis.
Monitors Chronic Conditions
In liver disease, kidney disease, or immune disorders, tracking total protein over time helps assess disease progression and treatment response.
What Can Affect Your Total Protein?
Causes of Low Total Protein
Decreased production:
- Liver disease (cirrhosis, hepatitis) — reduced albumin production
- Malnutrition — inadequate protein intake
- Malabsorption (celiac disease, IBD, pancreatic insufficiency)
- Severe illness with increased protein breakdown
Increased loss:
- Kidney disease (nephrotic syndrome) — protein lost in urine
- Severe burns — protein lost through damaged skin
- Protein-losing enteropathy — protein lost through GI tract
- Hemorrhage — protein lost with blood
Dilution:
- Overhydration or excess IV fluids
- Pregnancy (plasma volume expansion)
Causes of High Total Protein
Increased globulin production:
- Chronic infections (HIV, hepatitis, tuberculosis)
- Chronic inflammation
- Autoimmune diseases (lupus, rheumatoid arthritis)
- Multiple myeloma and related plasma cell disorders
- Waldenström macroglobulinemia
Dehydration:
- Concentrates blood, making protein appear higher
- Most common cause of mildly elevated total protein
Testing Considerations
Dehydration can falsely elevate results; overhydration can falsely lower them. Prolonged tourniquet use during blood draw can concentrate proteins locally. Body position affects results slightly — standing increases levels compared to lying down. Certain medications may affect protein levels.
When Should You Get Tested?
Symptoms Suggesting Protein Abnormalities
Unexplained swelling (edema), especially in legs or around eyes, may indicate low albumin. Fatigue, weakness, unexplained weight loss, or recurrent infections warrant evaluation.
Suspected Liver Disease
Symptoms like jaundice, abdominal swelling, easy bruising, or known liver problems warrant comprehensive testing including total protein.
Suspected Kidney Disease
Foamy urine (suggesting protein loss), swelling, high blood pressure, or known kidney problems should prompt evaluation.
Nutritional Concerns
Unintended weight loss, restrictive diets, eating disorders, malabsorptive conditions, or prolonged illness warrant assessment of protein status.
Suspected Immune Disorders
Recurrent infections, unexplained bone pain, fatigue, or symptoms suggesting autoimmune disease may prompt testing.
Routine Health Screening
Total protein is commonly included in comprehensive metabolic panels during routine checkups, providing baseline information.
Monitoring Chronic Conditions
People with liver disease, kidney disease, or immune disorders benefit from regular monitoring.
Understanding Your Results
Your lab provides reference ranges. Total protein is interpreted alongside albumin and other tests:
Within reference range: Overall protein production and retention are normal. Liver, kidneys, and immune system are functioning appropriately from this perspective.
Below reference range: Indicates protein deficit — either decreased production (liver disease, malnutrition) or increased loss (kidney disease, GI loss). Check albumin to determine which component is low. Investigate for underlying cause.
Above reference range: Often due to dehydration (most common). If persistent, may indicate increased globulin production from chronic infection, inflammation, or plasma cell disorders. Protein electrophoresis can identify specific abnormalities.
Interpreting with Albumin
Low total protein + Low albumin: Suggests liver disease, malnutrition, or protein loss (kidney or GI)
Low total protein + Normal albumin: Suggests decreased globulins (rare)
High total protein + Normal albumin: Suggests increased globulins — investigate for infection, inflammation, or plasma cell disorder
High total protein + Low albumin: Suggests markedly increased globulins overcompensating for low albumin — concerning for plasma cell disorders
When to Investigate Further
Abnormal total protein typically warrants:
- Separate albumin and calculated globulin measurements
- Liver function tests if albumin is low
- Urinalysis and kidney function tests if protein loss is suspected
- Protein electrophoresis if globulins appear elevated
What to Do About Abnormal Results
For Low Total Protein
Determine the cause: Is production decreased (liver, nutrition) or is protein being lost (kidney, GI)?
Check albumin: If albumin is low, evaluate liver function and nutritional status.
Check for protein loss: Urine protein testing detects kidney loss. Stool testing may be needed for GI protein loss.
Address underlying cause:
- Liver disease — manage the underlying condition
- Malnutrition — improve dietary protein intake, address malabsorption
- Kidney disease — treat underlying kidney condition, may need nephrology referral
For High Total Protein
Rule out dehydration: Ensure adequate hydration and repeat test if dehydration was likely.
If persistent, investigate globulin elevation: Protein electrophoresis identifies which globulins are increased.
Evaluate for underlying conditions:
- Chronic infections — test for HIV, hepatitis, others as indicated
- Autoimmune diseases — appropriate workup based on symptoms
- Plasma cell disorders — if abnormal protein band found, hematology referral
Monitor Over Time
Repeat testing confirms persistent abnormalities and tracks response to treatment. Trending is often more informative than single values.
Related Health Conditions
Liver Disease
Reduced Albumin Production: As liver disease advances, albumin production falls, lowering total protein. This indicates declining liver synthetic function.
Nephrotic Syndrome
Protein Loss in Urine: Damaged kidneys leak large amounts of protein, especially albumin, into urine. Causes low total protein, edema, and other complications.
Multiple Myeloma
Abnormal Antibody Production: This blood cancer causes plasma cells to produce excessive abnormal antibodies, markedly elevating total protein and globulins. Detected on protein electrophoresis.
Chronic Infections
Elevated Globulins: Long-term infections stimulate antibody production, raising globulins and total protein. HIV, hepatitis, and other chronic infections can cause this pattern.
Malnutrition
Protein Deficiency: Inadequate dietary protein or malabsorption leads to low albumin and total protein, with consequences for fluid balance and overall health.
Why Regular Testing Matters
Total protein changes can signal developing liver disease, kidney problems, or immune disorders before other symptoms appear. Regular monitoring catches these changes early. For those with chronic conditions, tracking protein levels helps assess disease progression and treatment effectiveness.
As part of routine metabolic panels, total protein provides ongoing baseline information about your overall health.
Related Biomarkers Often Tested Together
Albumin — The main component of total protein. Measures liver synthetic function and nutritional status.
Globulin — Calculated from total protein minus albumin. Reflects immune activity.
ALT and AST — Liver enzymes. Help evaluate liver health when protein is abnormal.
Creatinine and BUN — Kidney function markers. Important when protein loss is suspected.
Urinalysis — Detects protein in urine, indicating kidney protein loss.
Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.
Frequently Asked Questions
Total protein measures all proteins in your blood, primarily albumin (made by the liver) and globulins (including antibodies). These proteins maintain fluid balance, transport substances, fight infections, and perform many other vital functions.
Common causes include liver disease (reduced production), kidney disease (protein loss in urine), malnutrition (inadequate intake), and malabsorption. Overhydration can also dilute blood proteins.
Dehydration is the most common cause (concentrates blood). Persistent elevation may indicate chronic infections, autoimmune diseases, or plasma cell disorders like multiple myeloma that cause excessive antibody production.
Albumin is made by the liver and maintains fluid balance. Globulins include antibodies and transport proteins made by the immune system and liver. Together they make up total protein. Their ratio (A/G ratio) provides diagnostic information.
Yes — severe protein malnutrition lowers total protein, especially albumin. However, eating a high-protein meal doesn’t significantly raise levels in the short term. The liver maintains protein levels within a range despite normal dietary variation.
Fasting is not typically required. Hydration status affects results more than recent food intake.
Mild abnormalities often reflect hydration status. Your provider may recommend repeat testing with attention to hydration, or proceed to measure albumin separately to better characterize the abnormality.
For routine screening: as part of annual comprehensive metabolic panel. For monitoring chronic conditions: as recommended by your provider. For investigating symptoms: as part of appropriate workup.
References
Key Sources:
- Busher JT. Serum Albumin and Globulin. In: Walker HK, et al., eds. Clinical Methods. 3rd ed. Butterworths; 1990.
- Kwo PY, et al. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol. 2017;112(1):18-35.
- O’Connell TX, et al. Understanding and interpreting serum protein electrophoresis. Am Fam Physician. 2005;71(1):105-112.
