Total Protein

Why Total Protein Testing Matters

1. Optimize Protein Nutrition (if Low Total Protein)

Adequate protein intake:1.0-1.5 g/kg body weight daily. Higher needs if elderly, ill, or recovering from illness. Example:70-105g for 70kg person

High-quality protein sources:Eggs (6-7g per egg), chicken breast (30g per 4oz), fish, Greek yogurt (15-20g per cup), cottage cheese, legumes, whey protein

Distribute throughout day:20-30g protein per meal for optimal synthesis. Don't consume all protein in one meal

Leucine-rich foods:Whey protein, eggs, chicken, dairy. Leucine triggers muscle protein synthesis

Consider supplementation:Whey protein (20-40g daily), essential amino acids (10-15g daily) if inadequate dietary intake

Address malabsorption:If celiac, Crohn's, pancreatic insufficiency present, treat underlying condition and ensure digestive enzyme adequacy

2. Address Underlying Liver Disease

Identify cause:Viral hepatitis (B/C), alcoholic liver disease, NAFLD, autoimmune hepatitis, cirrhosis

Specific treatments:Antiviral therapy for hepatitis, alcohol cessation, weight loss for NAFLD, immunosuppression for autoimmune hepatitis

Support liver function:Milk thistle (140-280 mg 2-3x daily), N-acetylcysteine (600-1200 mg daily), adequate protein intake

Avoid hepatotoxins:Eliminate alcohol, minimize acetaminophen (<2000 mg/day), review all medications

Monitor progression:Low total protein with low albumin in cirrhosis indicates advanced disease. Consider transplant evaluation if albumin <3.0 g/dL

3. Prevent and Treat Protein Loss

Nephrotic syndrome (kidney):ACE inhibitors or ARBs reduce proteinuria. Treat underlying glomerular disease with immunosuppression if indicated. Target <1g protein loss per day

Protein-losing enteropathy (GI):Treat inflammatory bowel disease, celiac disease, intestinal lymphangiectasia. High-protein diet (1.5-2.0 g/kg) to compensate

Increase protein intake:Compensate for losses with higher dietary protein while treating underlying cause

Monitor urine protein:24-hour urine collection or spot protein-to-creatinine ratio. Goal <150 mg/day (normal)

Albumin infusion:If severe hypoalbuminemia (<2.5 g/dL) with symptomatic edema, consider IV albumin while addressing cause

4. Address Immune and Inflammatory Causes (if High Globulins)

Investigate chronic infections:Test for hepatitis B/C, HIV, tuberculosis. Treat with appropriate antivirals or antibiotics

Manage autoimmune disease:Optimize treatment for lupus, rheumatoid arthritis, Sjögren's, inflammatory bowel disease

Anti-inflammatory interventions:Mediterranean diet, omega-3 fatty acids (2-4g EPA+DHA daily), minimize processed foods

Rule out malignancy:If globulin >4.5 g/dL, order SPEP to screen for multiple myeloma, lymphoma, chronic lymphocytic leukemia

Monitor treatment response:Total protein and globulins should decrease with successful treatment of infection or inflammation

5. Correct Hydration Status

If elevated total protein (>8.5 g/dL):Likely dehydration. Increase fluid intake to 2-3 liters daily. Retest after proper hydration—should normalize if dehydration was cause

If low total protein with edema:May reflect overhydration or dilution. Check albumin and globulin—low albumin causes fluid shifts and apparent dilution

Optimize hydration:30-35 ml/kg body weight daily for most adults. More if exercising, hot climate, or illness

Electrolyte balance:Ensure adequate sodium, potassium. Severe hyponatremia can dilute protein concentrations

Diuretics:If edema from low albumin, judicious use of diuretics (furosemide, spironolactone) can help but address underlying cause

Low Total Protein

• Edema:Swelling of legs, ankles, feet, or generalized edema (if albumin component is low)
• Ascites:Abdominal swelling and fluid accumulation (severe cases)
• Fatigue and weakness:Due to underlying disease and malnutrition
• Recurrent infections:If low globulins causing immunodeficiency
• Poor wound healing:Protein essential for tissue repair
• Muscle wasting:Prolonged protein deficiency causes loss of muscle mass
• Weight loss or failure to thrive:Despite adequate calorie intake if malabsorption present

Note: Symptoms depend on which protein fraction is low and underlying cause. Low albumin causes edema;low globulins cause recurrent infections. Severity correlates with degree of reduction—total protein <5.5 g/dL typically causes noticeable symptoms.

High Total Protein

• High total protein is often asymptomatic
• Dehydration symptoms:Thirst, dry mouth, decreased urination, dizziness, dark urine (if dehydration is cause)
• Symptoms of underlying condition:If high globulins are cause, may have symptoms of chronic infection (fever, night sweats), autoimmune disease (joint pain, rash), or multiple myeloma (bone pain, fatigue, recurrent infections)
• Hyperviscosity syndrome:If extreme elevation (>10 g/dL from high globulins), blood becomes thick causing headaches, vision changes, bleeding, confusion—rare but medical emergency

Note: Mild elevations (8.0-8.5 g/dL) from dehydration typically resolve with rehydration. Persistent elevation requires investigation of globulin fraction and underlying causes.

Low Total Protein:

• Malnutrition:Inadequate protein intake, eating disorders, extreme dieting, malabsorption (celiac, Crohn's, pancreatic insufficiency)
• Liver disease:Chronic hepatitis, cirrhosis from any cause—reduces albumin synthesis. Advanced cirrhosis also elevates globulins (A/G ratio inverted)
• Nephrotic syndrome:Massive urinary protein loss (>3g/day) from kidney disease. Check urinalysis and 24-hour urine protein
• Protein-losing enteropathy:GI protein loss from inflammatory bowel disease, celiac disease, intestinal lymphangiectasia
• Chronic inflammation:Cancer, chronic infections suppress albumin as negative acute-phase reactant
• Burns and major trauma:Large wounds cause protein loss and increased catabolism
• Overhydration:Dilutional effect from excess IV fluids or SIADH (syndrome of inappropriate ADH)
• Combined causes:Often multiple factors contribute (e.g., cirrhosis causes low albumin + high globulins, partially offsetting total protein)

High Total Protein:

• Dehydration:Most common cause. Volume depletion concentrates proteins. Resolves with hydration
• Chronic infections:Hepatitis B/C, HIV, tuberculosis, chronic osteomyelitis—elevate globulins
• Autoimmune diseases:Lupus, rheumatoid arthritis, Sjögren's—polyclonal hyperglobulinemia
• Multiple myeloma:Malignant plasma cells produce monoclonal immunoglobulin. Globulin often >5 g/dL. Requires SPEP for diagnosis
• Lymphoma and chronic lymphocytic leukemia:Can elevate globulins
• Monoclonal gammopathy (MGUS):Benign monoclonal protein production (requires monitoring)
• Waldenström macroglobulinemia:Rare B-cell cancer producing IgM
• Chronic liver disease:Cirrhosis elevates globulins despite low albumin;total protein may be normal or high

Total Protein as Health Status Indicator

Total protein serves as a broad indicator of health status, reflecting nutritional state, liver function, immune activity, and protein balance. While less specific than albumin or globulin individually, abnormal total protein prompts investigation of these fractions. Studies show low total protein independently predicts mortality and poor surgical outcomes, though this effect is driven primarily by the albumin component.

Source:Levitt DG, et al. Human serum albumin homeostasis:a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements. Int J Gen Med. 2016;9:229-255.

Protein Malnutrition in Elderly

Low total protein (<6.5 g/dL) is common in elderly populations and strongly associated with frailty, functional decline, and mortality. Often reflects inadequate protein intake (<0.8 g/kg daily) combined with age-related anabolic resistance. Increasing protein to 1.2-1.5 g/kg daily improves protein status, muscle mass, and physical function in older adults.

Source:Deutz NE, et al. Protein intake and exercise for optimal muscle function with aging:recommendations from the ESPEN Expert Group. Clin Nutr. 2014;33(6):929-936.

A/G Ratio in Disease Diagnosis

The albumin/globulin ratio (calculated from total protein and albumin) is diagnostically valuable. Normal ratio is 1.2-2.2. Ratio <1.0 indicates either low albumin (liver disease, malnutrition) or high globulins (chronic infection, autoimmune disease, malignancy). Inverted A/G ratio (<1.0) in cirrhosis correlates with advanced disease and poor prognosis.

Source:Duffy MJ, et al. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers:European group on tumor markers 2014 guidelines update. Int J Cancer. 2014;134(11):2513-2522.

Nephrotic Syndrome and Protein Loss

Nephrotic syndrome causes massive urinary protein loss (>3g/day), predominantly albumin, leading to low total protein and characteristic edema. Total protein often <6.0 g/dL with albumin <3.0 g/dL. Treatment with ACE inhibitors/ARBs reduces proteinuria by 30-50%, while immunosuppression may be needed for underlying glomerular disease. Persistent heavy proteinuria requires nephrology management.

Source:Kodner C. Diagnosis and management of nephrotic syndrome in adults. Am Fam Physician. 2016;93(6):479-485.

Multiple Myeloma Screening

Multiple myeloma typically elevates total protein (often >8.5 g/dL) due to monoclonal immunoglobulin production. However, some myelomas produce light chains only without increasing total protein. Any unexplained elevation in total protein, especially with elevated globulins (>4.5 g/dL) or A/G ratio <1.0, warrants SPEP and immunofixation to screen for myeloma. Early diagnosis improves treatment outcomes.

Source:Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548.

Frequently Asked Questions About Total Protein