Kresser Institute

Tools, Training & Community for Functional Health Professionals

Functional Blood Chemistry Manual


Marker Name: Globulin


Laboratory reference range: 1.5–4.5 g/dL

Functional reference range: 2.4–2.8 g/dL


In the context of laboratory assessment and biomarkers, globulins are any plasma proteins other than albumin. Globulins make up 40 percent of plasma proteins and include carrier proteins, enzymes, complement, clotting factors, and immunoglobulins.1-3 Globulins play many different physiological roles in the body according to type. Immunoglobulins and complement play important roles in the adaptive and innate immune systems, for example. With the exception of immunoglobulins, virtually all globulins are synthesized in the liver.4

Circulating immunoglobulins (i.e., antibodies), as opposed to membrane-bound immunoglobulins, are primarily produced by activated plasma cells.5,6 Their production is stimulated by exposure to antigens. After antigen exposure, antibodies are housed in memory B cells, which are long-lived cells that can respond rapidly to future provocations by antigens.6 Barring a disease of the immune system, additional antigen exposures result in a short-lived and relatively intense increase in circulating immunoglobulins. Other circulating globulins are held at rather constant levels in the blood under normal conditions, balanced between synthesis and degradation, utilization and excretion.

Serum globulins are usually estimated from other directly measured substances on a liver panel, namely total protein and albumin. Since circulating plasma proteins are either albumin or globulins, serum globulin level is estimated by subtracting albumin from total protein.3 While elevated globulin levels may be apparent from this calculation from measured values, decreased globulin levels may be less apparent, especially when deficiencies in relatively minor globulins exist.

Serum proteins can be further separated by electrophoresis, which separates albumin from globulins. Globulin fractions migrate into four bands on electrophoresis gel: α1, α2, β, and γ.1,3 Immunoglobulins tend to migrate to and cluster in the γ band on electrophoresis and, as such, are sometimes referred to as gamma globulins.1 Elevated immunoglobulin levels can be further characterized by immunoelectrophoresis, establishing if the increase is composed of one immunoglobulin type (i.e., monoclonal) or several types (i.e., polyclonal).3

Elevated globulin levels in the serum generally reflect overproduction. For example, multiple myeloma is a neoplastic proliferation of plasma cells that results in substantial elevations in monoclonal immunoglobulin.7 Autoimmune diseases can also increase the level of circulating globulins.2 Likewise, acute inflammation can cause a transient increase in serum globulin levels. Hemoconcentration, or a relative lack of intravascular water, can result in relative hyperglobulinemia.

Decreased globulin levels are usually the result of the underproduction of immunoglobulins.2 This may be due to genetic abnormality (e.g., X-linked agammaglobulinemia) or hematologic malignancy (chronic lymphocytic leukemia). There is a normal period of hypogammaglobulinemia in neonates within the first six months of life; however severe deficits in gamma globulin levels or prolonged hypogammaglobulinemia is abnormal.8


High in:4,9,10

  • Hemoconcentration
    • Inadequate water intake
    • Excessive diuresis
  • Acute infection
  • Acute inflammation
  • Chronic inflammatory disease
  • Hematological neoplasm
    • Multiple myeloma
    • Monoclonal gammopathy of undetermined significance
    • Lymphoma
    • Leukemia
    • Macroglobulinemia (e.g., Waldenstrom macroglobulinemia)

Low in:4,8,11-16

  • Hemodilution
    • Intravenous fluids
    • Advanced congestive heart failure
    • Polydipsia
  • Inflammation
  • Protein malnutrition
  • Protein malabsorption
  • Liver failure
  • Advanced liver disease
  • Renal failure
  • Nephrotic syndrome
  • Protein-losing enteropathy
    • Primary gastrointestinal mucosal diseases (e.g., ulcerative colitis)
    • Increased interstitial pressure or lymphatic obstruction (e.g., sarcoidosis)
    • Non-erosive upper gastrointestinal diseases (e.g., celiac sprue)
  • Primary humoral immunodeficiency (e.g., agammaglobulinemia)
  • Transient hypogammaglobulinemia of infancy (normal and pathological)


High in:

  • Hypochlorhydria (protein malabsorption)
  • Inflammation and oxidative stress

Low in:

  • Hypochlorhydria
  • Inflammation
  • Anemias
  • Blood loss (hemorrhage, dysmenorrhea, etc.)


Kresser Institute Icon ADAPT Health Coach Training Program Icon ADAPT Practitioner Training Program Icon ADAPT Courses Icon