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Globulin Test: High & Low Levels + Normal Range

Written by Puya Yazdi, MD | Last updated:
Medically reviewed by
SelfDecode Science Team | Written by Puya Yazdi, MD | Last updated:

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Globulins transport nutrients and fight infections; high and low levels can both spell trouble. A globulin test is also known as the “gamma gap”. Learn more about what results mean here.

What is a Globulin Test?

Globulins are a group of proteins that help transport nutrients and fight infections.

Globulin proteins include carrier proteins, enzymes, antibodies (immunoglobulins), and other proteins. Most globulins are made by the liver, and they help transport nutrients and fight infections [1].

There are four types of globulins: alpha 1, alpha 2, beta, and gamma. Two types of globulin tests can be used to measure globulins: a total protein test and a serum protein electrophoresis test.

The total protein test measures alpha 1, alpha 2, beta globulin, and another liver protein called albumin. Low protein levels may signal liver or kidney disease.

The serum protein electrophoresis measures gamma globulin and other proteins in the blood. Doctors can use this test to diagnose immune system disorders and other conditions.

Globulin levels may also help your doctor diagnose an inflammatory disorder, autoimmune disease, or infection. This is because gamma globulins contain antibodies, the increased production of which can signal these diseases. High globulins may also indicate certain types of cancer such as multiple myeloma [2].

However, abnormal results may also be a result of certain medications, dehydration, or other factors.

Additionally, the results of this test alone are not sufficient for diagnosis. Your doctor will evaluate your results taking into account your overall health status and other lab markers.

Normal Range of Globulins

Globulin levels are determined by subtracting albumin from total protein, also known as the “gamma gap.”

The normal range of globulin is around 2.0-3.9 g/dL or 20-39 g/L. Some lab-to-lab variability occurs due to differences in equipment, techniques, and chemicals used.

Globulin in the normal range usually implies a normal balance of carrier proteins, enzymes, and antibodies that are needed for many biological processes. It also likely means that there is no viral infection or an inflammatory or immune disorder [2].

However, it’s important to remember that a normal test doesn’t mean a particular medical condition is absent. Your doctor will interpret your results in conjunction with your medical history and other test results.

High Globulin Levels

Causes

The conditions we discuss here are commonly associated with high globulin, but this single symptom is not enough for a diagnosis. Work with your doctor to discover what underlying condition might be causing high globulin levels and to develop an appropriate plan to improve your health.

High globulin is commonly caused by:

  • Viral and bacterial infections [3, 4, 1]
  • Dehydration [2, 5]
  • Heavy chain disease [6]
  • Inflammatory or immune disorders [1]
  • Cancers, such as Hodgkin’s lymphoma or multiple myeloma [7, 8, 9, 1]
  • Certain drugs, such as amiodarone (Cordarone, Nexterone), used to treat and prevent irregular heartbeat [10, 1]

Symptoms depend on the underlying cause.

Health Effects

Studies are now revealing that high globulin (gamma gap) is linked with an increased risk of disease and death.

A review of more than 12k people found an increased risk of death from all causes in people with a gamma gap above 3.1 g/dL. Similarly, a gamma gap over 3.1 g/dL could predict death in a study of 870 people over the age of 90 [11, 12].

In an observational study of 27,000 healthy people, a low albumin-to-globulin ratio (similar to a high gamma gap), was linked with increased rates of cancer and death [13].

Why is high globulin/gamma gap linked with bad health? One possible answer is that increased production of immunoglobulins is linked with inflammation; inflammatory factors like c-reactive protein and IL-6, for example, increase immunoglobulins [12].

Inflammation also rises with aging, which could explain why older people with higher gamma gaps were more likely to die than those with lower gamma gaps. It also suggests that the globulin/gamma gap can be used as a marker of inflammation [12].

Factors that Reduce Globulin Levels

1) Treat Underlying Condition

The most important thing is to work with your doctor to treat any underlying conditions causing your high globulin levels.

The additional strategies below are other things that you may try if you and your doctor determine that they could be appropriate.

2) Exercise

Exercise more often. Both aerobic and strength exercise may help significantly decrease globulin levels in people [14].

In both men and women, more days per week of either aerobic or strength exercise were significantly associated with lower globulin [14].

You may also need to stop taking protein supplements, as these may be causing higher protein and globulin levels [15].

3) Hydration

Drink more water to prevent dehydration [2, 16].

Zinc may help prevent dehydration due to diarrhea, according to limited studies [17].

Electrolytes can also help with dehydration due to diarrhea [18].

Limit alcohol intake; alcohol can worsen dehydration [19].

4) Reduce stress

Try to reduce stress, since acute stress may increase certain types of globulins [20].

Suggested Tests if You Have High Globulin

Albumin, total serum protein, sodium (Na), chloride (Cl), cortisol, creatinine, blood urea nitrogen (BUN), alanine aminotransferase (AST), aspartate aminotransferase (ALT), total bilirubin, alkaline phosphatase (ALP), calcium, serum gastrin, IgA, IgM, IgG, HCT (hematocrit), HGB (hemoglobin)

Low Globulin

The conditions we discuss here are commonly associated with low globulin, but this single symptom is not enough for a diagnosis. Work with your doctor to discover what underlying condition might be causing low globulin levels and to develop an appropriate plan to improve your health.

Low globulin can be caused by:

  • Kidney disease (nephrotic syndrome), which can cause protein loss [2, 1]
  • Liver disease [21, 22, 1]
  • Inborn (Congenital) immune deficiency, which decreases globulin production [2]
  • Malnutrition or lack of nutrients from the diet, which decreases globulin production [2]
  • Acromegaly, a disorder which results from excess growth hormone [23]
  • Lung cancer [24]
  • Oxidative stress in women with pregnancy-induced hypertension (limited evidence) [25]

Symptoms

  • Swelling due to fluid buildup (edema) [26]
  • Susceptibility to infectious diseases [2]
  • Symptoms of liver disease, which include yellowing of the skin and whites of the eyes (jaundice), nausea, vomiting, fatigue, and fluid buildup [2, 27]

Symptoms depend on the underlying cause.

Factors that Increase Globulin Levels

The most important thing is to work with your doctor to treat any underlying conditions causing your low globulin levels. The additional strategies below are other things that you may try if you and your doctor determine that they could be appropriate.

Eating a diet with enough nutrients will prevent malnutrition and prevent your protein levels from becoming too low. Eating lean protein, such as fish and turkey, can help improve your total protein levels [2].

Also, it may be helpful to increase the consumption of foods that help with liver and kidney detoxification. These include asparagus, beets, cabbage, broccoli, garlic, and onions [28].

Probiotic supplements (Lactobacillus plantarum and Bacillus polyfermenticus) might also help increase globulins, specifically immunoglobulins, according to limited research [29, 30].

Suggested Tests If You Have Low Globulin

Albumin, total serum protein, sodium (Na), chloride (Cl), cortisol, creatinine, blood urea nitrogen (BUN), alanine aminotransferase (AST), aspartate aminotransferase (ALT), total bilirubin, alkaline phosphatase (ALP), calcium, serum gastrin, IgA, IgM, IgG, HCT (hematocrit), HGB (hemoglobin)

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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