Complete Testing & Optimization Guide
Optimal ranges, provider comparison, and strategies to improve your Globulin levels
Included in 6 of 10 major testing providers
Liver Function
liver disease
Abnormal Globulin levels can indicate underlying health issues that may go undetected without proper testing. Regular monitoring helps catch problems early when they're most treatable.
Understanding your Globulin levels enables targeted interventions, tracks treatment effectiveness, and helps optimize your overall health and performance.
Globulins are a diverse group of proteins in your blood that serve multiple vital functions, primarily related to immune system function and substance transport. They account for about 40-45% of total plasma protein. Globulins are typically calculated as Total Protein minus Albumin, though they can also be measured by serum protein electrophoresis (SPEP) which separates them into subfractions.
Globulins consist of several types:alpha-1 and alpha-2 globulins (transport proteins and acute phase reactants), beta globulins (including transferrin for iron transport and complement proteins for immunity), and gamma globulins (immunoglobulins or antibodies produced by plasma cells). The albumin/globulin (A/G) ratio is clinically useful—a low ratio suggests immune activation, chronic infection, or liver disease.
Elevated globulins typically indicate immune system activation from chronic infections, autoimmune diseases, or production of abnormal proteins (like in multiple myeloma). Low globulins suggest immune deficiency or protein loss. Unlike albumin which reflects liver synthesis and nutrition, globulins primarily reflect immune system activity and inflammatory status.
Bottom line: TSH and Free T4 alone miss people with conversion problems. Free T3 is the only way to know if you have enough active thyroid hormone at the tissue level.
| Range Type | Level | Clinical Significance |
|---|---|---|
| Optimal | 2.0-3.5 g/dL | Normal immune function with balanced inflammatory status. A/G ratio of 1.2-2.2 is optimal, indicating appropriate balance between liver protein synthesis (albumin) and immune proteins (globulins). Reflects absence of chronic infection, autoimmune disease, or significant inflammation. |
| Borderline High | 3.5-4.5 g/dL | Suggests mild immune activation or chronic inflammation. Common in chronic infections, mild autoimmune conditions, or chronic inflammatory states. Check A/G ratio—if <1.0, investigate further. Consider CRP, ESR, and SPEP. If isolated finding without symptoms, may reflect individual variation. Retest in 3-6 months. |
| Low (Hypoglobulinemia) | <2.0 g/dL | Indicates immunodeficiency, protein loss, or liver synthesis dysfunction. Check immunoglobulin levels (IgG, IgA, IgM) to assess immune function. Evaluate for primary immunodeficiency (genetic), secondary immunodeficiency (HIV, medications), protein-losing enteropathy, or nephrotic syndrome. If low albumin also present, suggests severe protein loss or malnutrition. |
| High (Hyperglobulinemia) | >4.5 g/dL | Indicates significant immune activation or pathological protein production. A/G ratio typically <1.0. Requires investigation with SPEP to differentiate polyclonal (multiple types) from monoclonal (single type) elevation. Polyclonal:Chronic infections (hepatitis, TB, HIV), autoimmune diseases (lupus, RA, Sjögren's), chronic liver disease. Monoclonal (>5 g/dL):Multiple myeloma, lymphoma, chronic lymphocytic leukemia. Urgent hematology referral if monoclonal spike present. |
Standard lab range:liver disease
Screen for chronic infections:Hepatitis B/C serology, HIV testing, tuberculosis (QuantiFERON or PPD), fungal infections if immunocompromised
Treat active infections:Antiviral therapy for hepatitis or HIV, antibiotics for chronic bacterial infections, antifungals if indicated
Support immune clearance:Adequate vitamin D (40-60 ng/mL), zinc (15-30 mg daily), vitamin C (500-1000 mg daily)
Probiotics:10-50 billion CFU daily may support immune function and reduce pathogenic bacteria
Monitor treatment response:Retest globulins after treating underlying infection;should normalize within 3-6 months
Autoimmune disease treatment:Follow specialist guidance for lupus, rheumatoid arthritis, Sjögren's syndrome, inflammatory bowel disease
Anti-inflammatory diet:Mediterranean diet, omega-3 fatty acids (2-4g EPA+DHA daily), minimize processed foods
Immunomodulatory supplements:Vitamin D (2000-5000 IU daily), omega-3s, curcumin (500-1000 mg daily), resveratrol
Stress management:Chronic stress worsens autoimmune conditions. Practice meditation, adequate sleep (7-9 hours)
Regular monitoring:Check globulins and A/G ratio every 3-6 months to assess disease activity
SPEP and immunofixation:Required if globulin >4.5 g/dL or A/G ratio <0.8 to detect monoclonal protein
MGUS vs Myeloma:Monoclonal protein <3 g/dL with normal calcium/kidney function suggests MGUS (benign but requires monitoring). Higher levels or organ damage suggest myeloma
Hematology referral:Urgent if monoclonal spike present. May require bone marrow biopsy, skeletal survey, free light chains
Monitor MGUS:If benign monoclonal gammopathy, monitor every 6-12 months (1% annual risk of progression to myeloma)
Treatment for myeloma:Chemotherapy, immunotherapy, or stem cell transplant if diagnosed with multiple myeloma
Immunoglobulin replacement:If severe immunodeficiency (<400 mg/dL IgG), may require IVIG (intravenous immunoglobulin) or SCIG (subcutaneous) therapy
Optimize nutrition:Adequate protein (1.0-1.2 g/kg), zinc (15-30 mg daily), vitamin A (5000-10000 IU daily), vitamin E (400 IU daily)
Avoid immunosuppressive medications:Review medications with doctor;corticosteroids and chemotherapy suppress globulin production
Vaccination:Ensure up-to-date on vaccines, though response may be impaired. Consider pneumococcal, flu, COVID-19 vaccines
Infection prevention:If immunodeficient, practice strict hand hygiene, avoid sick contacts, consider prophylactic antibiotics
Investigate protein loss:Check 24-hour urine protein (nephrotic syndrome causes >3g/day loss). Stool alpha-1 antitrypsin if GI protein loss suspected
Treat nephrotic syndrome:ACE inhibitors/ARBs reduce proteinuria. Immunosuppression if underlying glomerular disease
Manage protein-losing enteropathy:Treat inflammatory bowel disease, celiac disease, or intestinal lymphangiectasia
Increase protein intake:1.2-1.8 g/kg body weight daily to compensate for losses
Monitor response:Retest total protein, albumin, globulin every 4-8 weeks during treatment
Note: Low globulins primarily cause symptoms if immune function is impaired (IgG <400 mg/dL). Mild reductions (1.5-2.0 g/dL) may be asymptomatic. If recurrent infections present, check immunoglobulin subfractions (IgG, IgA, IgM).
Note: Symptoms correlate more with underlying cause than globulin level itself. Very high globulins (>5 g/dL) with bone pain, fatigue, or kidney dysfunction warrant urgent evaluation for multiple myeloma.
In chronic liver disease, the A/G ratio progressively decreases as cirrhosis advances. Albumin synthesis declines while globulins increase due to chronic immune activation. A/G ratio <1.0 is commonly seen in cirrhosis and correlates with disease severity. The ratio helps distinguish cirrhosis from other causes of low albumin.
Source:Busher JT. Serum Albumin and Globulin. In:Walker HK, et al., editors. Clinical Methods:The History, Physical, and Laboratory Examinations. 3rd edition. 1990.
Multiple myeloma typically presents with markedly elevated globulins (>5 g/dL) and A/G ratio <1.0 due to monoclonal immunoglobulin production by malignant plasma cells. SPEP reveals a characteristic monoclonal spike. Early detection through recognition of elevated globulins and appropriate workup improves outcomes, as treatment is most effective when started before significant organ damage.
Source:Kyle RA, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007;356(25):2582-2590.
Monoclonal gammopathy of undetermined significance (MGUS) affects 3-5% of people over age 50 and ~8% over age 70. Most cases are benign, but MGUS progresses to multiple myeloma at a rate of ~1% per year. Monitoring includes serial SPEP, free light chains, and clinical assessment. Higher risk features include elevated free light chain ratio and monoclonal protein >1.5 g/dL.
Source:Kyle RA, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362-1369.
Patients with IgG <400 mg/dL have significantly increased risk of recurrent bacterial infections, particularly encapsulated organisms (pneumococcus, H. influenzae). Immunoglobulin replacement therapy (IVIG or SCIG) reduces infection rates by 60-80% in patients with primary or secondary immunodeficiency causing hypoglobulinemia.
Source:Bonilla FA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186-1205.
Polyclonal hyperglobulinemia is common in autoimmune diseases, reflecting widespread B-cell activation and antibody production. In SLE, elevated globulins (3.5-5.5 g/dL) with low A/G ratio (<1.0) are typical. Globulin levels correlate with disease activity—decreasing with successful treatment and increasing during flares. Serial monitoring aids in disease management.
Source:Arbuckle MR, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.
| Provider | Includes Test | Annual Cost | Total Biomarkers |
|---|---|---|---|
 Superpower | ✓ | $199 | 100+ |
 WHOOP Advanced Labs | — | $349 | 65 |
 Labcorp OnDemand | — | $398 | 30+ |
| ✓ | $486 | 40+ | |
| — | $468 | 83 | |
| ✓ | $798 | 100+ | |
 InsideTracker | — | $680 | 48 |
 Function Health | ✓ | $499 | 100+ |
| ✓ | $900 | 70+ | |
| ✓ | $1150 | 110 | |
| — | $Varies | 75+ |
Choose from 6 providers that include this biomarker in their panels
Globulin is a liver function biomarker that Group of proteins including antibodies The normal reference range is liver disease. Regular testing helps track changes and identify potential health issues early.
6 out of 10 major blood testing providers include Globulin in their standard panels. These include Superpower, Blueprint, Mito Health and others.
For most people, testing Globulin 2-4 times per year is recommended to establish baseline levels and track trends. If you have abnormal results or are actively working to optimize this biomarker, more frequent testing (quarterly) may be beneficial. Always consult with your healthcare provider for personalized testing frequency recommendations.
The standard laboratory reference range for Globulin is liver disease. However, many functional medicine practitioners recommend tighter "optimal" ranges for peak health and performance. Your ideal range may vary based on your age, sex, health goals, and other individual factors. Work with a healthcare provider familiar with optimal ranges to determine your target levels.
Most direct-to-consumer blood testing services that include Globulin provide the physician order as part of their service. However, some states have restrictions on direct-to-consumer testing. Check with your chosen provider about availability in your state and whether they provide the necessary physician authorization.
Includes immune system antibodies. Elevated in chronic infections
This information is for educational purposes only and is not medical advice. Always consult with a qualified healthcare provider about your specific health needs and before making decisions about blood testing.
