Confused about total protein, albumin, globulin, or the A/G ratio? Unsure if your results are normal and what the values mean? Read on to understand the total protein test, why your levels are low or high, and what you can do about them.

What is Total Protein?

Proteins are the primary building blocks of every cell. They are essential for growth and development, nutrient and hormone transport, and immune function [1].

Serum is a liquid fraction of the blood, not including red blood cells or clotting proteins. Normally, albumin makes up for slightly more than half of the proteins in the serum, and the remainder of the protein count is the total globulins [2].

The three common causes of low total protein are liver disease or poor nutrition (which may lower protein production) and kidney disease (which may accelerate protein loss) [2, 3].

Albumin

Albumin is produced in the liver and binds fats in the blood. For this reason, blood fats can rise when albumin is low. Additionally, albumin helps transport hormones, bilirubin, metals, vitamins, and drugs. It also attracts fluids, preventing them from leaking out of blood vessels, and it regulates the activity of some hormones [2].

During fasting or low protein intake, albumin production falls. Meanwhile, thyroid hormone, corticosteroids, growth hormone, and insulin increase the production of albumin [2].

Globulins

The globulin proteins are a mixture of enzymes, antibodies, carrier, and other proteins. Most of them are made in the liver, although antibodies are produced by some types of white blood cells. Globulins are often raised due to increased antibody (immunoglobulin) production [2].

Total protein is the sum of albumin and globulin in the serum. Albumin transports hormones and medicine, and globulin carries nutrients and antibodies.

The A/G Ratio

The A/G ratio measures the relative ratio of albumin to globulin. This ratio can provide important clues about what may be wrong with your health when total protein levels are abnormal. Normally, albumin levels are only slightly higher than globulin, which gives an A/G ratio slightly over 1 [2].

A low A/G ratio may indicate viral infections, myeloma, liver and kidney disease, or autoimmune disorders. These diseases increase globulin, thus lowering the A/G ratio [4].

A high A/G ratio may indicate diseases that make the body produce less globulin, such as genetic disorders or leukemia [2, 4].

Total Protein Test

This test measures albumin and total globulin levels in your blood. A healthcare professional will collect a blood sample from your vein and send it to a lab for analysis. The test is normally ordered as part of a comprehensive metabolic panel (CMP).

Why is the Test Performed?

The total protein test is often used to check for poor nutrition status and liver or kidney disease. Your doctor may order the total protein test if you have symptoms of malnutrition or of liver or kidney dysfunction, such as [2, 5, 6]:

  • Jaundice
  • Nausea and vomiting
  • Itching
  • Fatigue
  • Fluid buildup in the abdomen, feet, and legs
  • Loss of appetite
  • Weight loss
  • Spider-like blood vessels on the skin

How to Prepare for the Test

Dehydration may affect the test, so make sure you drink enough water before heading to the doctor’s office. Also, talk with your doctor to make sure you are not taking any medications that may interfere with the test. Potentially troublesome drugs include [7]:

  • Hormones (androgens, estrogens, progesterone, growth hormone)
  • Corticosteroids
  • Anabolic steroids
  • Dextran
  • Insulin
  • Phenazopyridine
  • Birth control pills

Normal Range

Adults

The normal ranges for adults can vary slightly between labs, but they are generally considered to be about [8, 9]:

  • Total protein: 6.0 to 8.3 g/dL (60 to 83 g/L)
  • Albumin: 3.4 to 5.4 g/dL (34 to 54 g/L)
  • Globulin: (total protein minus albumin)

Newborns and Children

In newborns, total protein is lower: 4.6 to 7.0 g/dL is normal. Total protein increases slowly during the first three years of life, after which values are similar to adults [10].

Low Total Protein Levels

Causes

Some possible causes of low total protein levels are [2, 11, 8, 12]:

  • Poor nutrition (lack of nutrients in the diet)
  • Malabsorption (e.g. from inflammatory bowel disease)
  • Liver disease
  • Kidney disease (e.g. nephrotic syndrome, glomerulonephritis)
  • Congestive heart failure
  • Agammaglobulinemia (inborn immune deficiency)
  • Bleeding (hemorrhage)
  • Severe burns
  • Protein-losing enteropathy
  • Donating blood too frequently
Low total protein is most often caused by poor nutrition. It can also sometimes be due to inflammatory bowel disease, kidney, and liver disease or other rare diseases.

How to Increase

The following are all good ways to increase Total Protein levels:

  • Eat a nutrient-rich diet and up your intake of proteins. Eat lean protein, such as fish and turkey, to improve your total protein levels
  • If you are taking any medications that may be causing low protein levels, consult with your doctor to see if there are any safe alternatives
  • If you are regularly donating blood, stop donating for a while
  • Branched Chain Amino Acids (BCAA) [13, 14, 15]
  • Probiotics (Bacillus subtilis, Lactococcus lactis, and Saccharomyces cerevisiae) [16]
Make sure you are eating a nutritious diet and get enough protein. Supplements such as BCAAs and certain probiotics may also help.

High Total Protein Levels

Causes

Some possible causes of high total protein levels are [2, 8, 17, 18] :

  • Dehydration
  • Viral hepatitis (type B & C)
  • HIV/AIDS
  • Chronic kidney disease
  • Liver disease
  • Amyloidosis
  • Waldenstrom disease
  • Certain cancers (e.g. multiple myeloma)
  • Monoclonal gammopathy of undetermined significance (MGUS)
The most common cause of high protein levels is dehydration. It can also sometimes be due to viral infections, cancer, liver/kidney disease or other rare diseases.

How to Decrease

The best natural strategies for lowering your levels include:

  • Drink more water to prevent dehydration
  • Limit your alcohol consumption: alcohol is a diuretic that causes your body to lose water, which can result in dehydration
  • If you are on any medications that might be causing high protein levels, consult with your doctor about possible alternatives
  • Check out our posts on globulin and albumin for more health recommendations
Make sure you drink enough fluids and be careful with medications that may cause dehydration.

High Gamma Gap

In the total protein test, globulin levels are determined by subtracting albumin from total protein, also known as the “gamma gap.” A high gamma gap usually coincides with a low A/G (albumin-to-globulin) ratio.

Causes

Studies are now revealing that a high 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 [4, 19].

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 [20].

Why are high gamma gaps 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 [19].

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 gamma gap can be used as a marker of inflammation [19].

Other blood tests can also point to chronic inflammation, which drives many chronic diseases.

High levels of globulin compared to albumin (high gamma gap) is linked with inflammation and a higher risk of disease and death. If you have a high gamma gap you may benefit from lowering your inflammation levels.

How to Lower

Inflammation is the most common underlying cause of a high gamma gap and low albumin levels. In the absence of obvious illness, an anti-inflammatory diet may be the best way to improve albumin levels.

These supplements can help lower a high gamma gap by increasing albumin:

You can also indirectly lower your gamma gap and increase albumin by reducing chronic inflammation and the key inflammatory markers c-reactive protein and interleukin-6.

Irregular Total Serum Protein Levels?

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Takeaway

The total protein test measures your albumin and total globulin levels in your blood. It is often used to check for poor nutrition status and liver or kidney disease.

The albumin portion makes up for slightly more than half of serum proteins, and the rest of the protein count is the total globulins.

If the ratio of albumin to globulin is unusually low, it may indicate viral infections, myeloma, liver and kidney disease, or autoimmune disorders. If the ratio is unusually high, it may indicate diseases that underproduce globulin, such as genetic disorders or leukemia.

To normalize your blood proteins, eat a nutritious, anti-inflammatory diet and avoid diuretic substances like alcohol.

About the Author

Jimmy Julajak, MSc

MS (Psychology)

Jimmy got his MSc from the University of Copenhagen.

Jimmy is a psychologist and researcher. He is particularly interested in the workings of the brain and strategies for improving brain health. He believes that people shouldn't hand over the responsibility for their health only to their doctors. His aim is to empower each person with easy-to-understand, science-based health knowledge.

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