Complement C3

Introduction

As a functional medicine nurse practitioner in Florida, I leverage biomarkers like Complement C3 to gain deep insights into immune function, inflammation, and disease risk. Below, we explore C3’s role, optimal ranges, clinical implications, and factors that influence its levels.

What Is Complement C3?

Complement C3 is the most abundant protein in the complement cascade—a vital arm of innate immunity that opsonizes pathogens, recruits inflammatory cells, and forms membrane attack complexes. It integrates signals from the classical, lectin, and alternative pathways to mount an effective defense.

Normal and Optimal Ranges

• Standard Range: 82.00–185.00 mg/dL (0.82–1.85 g/L)
  
• Optimal Range: 82.00–112.00 mg/dL (0.82–1.12 g/L)

   

Testing C3 alongside Complement C4 enhances diagnostic accuracy, particularly when evaluating inflammation or immune function.

Clinical Implications of C3 Levels

Low C3 Levels

• Systemic Lupus Erythematosus (SLE): Chronic complement consumption in SLE drives C3 below optimal, correlating with disease flares and organ involvement.
  
• Immune Deficiencies: Genetic or acquired complement deficiencies can manifest as recurrent infections.

   

High C3 Levels

• Metabolic Syndrome: Elevated C3 associates with metabolic syndrome and insulin resistance.
  
• Cardiovascular Disease: Chronic low-grade inflammation reflected by high C3 increases the risk of cardiovascular dysfunction.
  
• Obesity & Diabetes: Adiposity-driven inflammation raises C3, linking to type 2 diabetes development.

   

Interfering Factors & Drug Associations

• Raised by: Acute infections, corticosteroids, hormone replacement
  
• Lowered by: Immunosuppressants, chemotherapy agents

   

Always consider these when interpreting C3 to avoid misdiagnosis.

When to Measure Complement C3

C3 testing is indicated for:

• Monitoring autoimmune activity (e.g., SLE)
  
• Assessing chronic inflammatory and metabolic disorders
  
• Stratifying cardiovascular risk in patients with comorbid inflammation

   

Conclusion

Incorporating Complement C3 into functional medicine allows for a holistic, root-cause approach, guiding targeted nutrition, lifestyle, and therapeutic interventions rather than merely treating symptoms. As a functional medicine practitioner, I combine C3 profiling with personalized care plans to optimize immune health and prevent chronic disease.

Interested in advancing your care? Explore our Medical Weight Loss program—designed to support metabolic health and inflammation control.

Further Reading

• Mastellos, D. C., Ricklin, D., & Lambris, J. D. (2017). Complement C3-targeted therapy: Replacing long-held dogmas in complement medicine. Frontiers in Immunology, 8, 1618. https://pmc.ncbi.nlm.nih.gov/articles/PMC5447467/

• Hajishengallis, G., Hasturk, H., & Lambris, J. D. (2021). Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. The Journal of Clinical Investigation, 131(23), e152973. https://www.jci.org/articles/view/152973

• Ricklin, D., Mastellos, D. C., Reis, E. S., & Lambris, J. D. (2022). Compstatins: The dawn of clinical C3-targeted complement inhibition. Immunological Reviews, 307(1), 194-224. https://pmc.ncbi.nlm.nih.gov/articles/PMC9553322/

• Suttorp, M. J., & Ricklin, D. (2025). AMY-101 as complement C3 inhibitor for periodontitis therapy. Frontiers in Immunology, 16, 1587126. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1587126/full