Many illnesses can throw off the balance between albumin and globulin in your blood. Read on to learn what results are considered normal, the causes of high and low ratios, and what you can do to fix them.
What is an Albumin/Globulin Ratio Test?
The albumin/globulin ratio (A/G ratio for short) is a test that compares the concentrations of albumin and globulin in the blood [1, 2, 3]
Albumin and globulin are proteins that are naturally found in the serum, the liquid part of your blood that doesn’t include blood cells or clotting components [1].
An imbalance in the ratio of albumin to globulin may signify ongoing inflammation, liver problems, or in rare cases immunodeficiency. There is emerging evidence that a low ratio (less albumin and more globulin) may be associated with the risk of cancer and may also predict worse outcomes in cancer and heart disease patients [4, 5, 6, 7].
Overview of Serum Proteins
Albumin is the most common protein found in the bloodstream. Its main function is to maintain osmotic pressure, the mechanism that prevents fluids from leaking out of the blood vessels and into surrounding tissues [1].
Many substances (including some hormones, nutrients, and medications) can attach to albumin, making it an important transporter in the blood. Albumin also binds fats and helps with fat metabolism [1].
Globulins are a class of proteins found in the blood which come in several forms. Alpha and beta globulins act as transporters and can inhibit some enzymes. Gamma globulins, the immunoglobulins, act as antibodies. They bind to pathogens like viruses and play a vital role in the immune system [1].
Both albumin and globulin are primarily made in the liver, although some types of globulin are created by white blood cells [1].
Check out our articles on albumin and globulin for more information on each protein.
Albumin/Globulin Ratio
Your albumin/globulin ratio is usually checked during routine health examinations. The A/G ratio is derived from a total protein test, which uses a blood sample to measure the total combined amount of albumin and globulin in the blood [1].
In turn, the total protein test is part of a comprehensive metabolic panel (CMP), which is a series of 14 tests that check how well your metabolism is functioning. CMPs are commonly performed at annual checkups or during hospital stays [8].
As the name implies, results are reported as a ratio of albumin to globulin. For example, a result of 2:1 means you have twice as much albumin than globulin in your blood.
Because globulin is always set to a value of 1 in the ratio, results will sometimes omit the globulin number. For example, a ratio of 1.5:1 can be shortened to 1.5 instead. We’ll use this shortened version in the rest of the article for clarity.
Normal Albumin/Globulin Ratio
In general, an albumin/globulin ratio between 1.1 and 2.5 is considered normal, although this can vary depending on the laboratory performing the test [4].
Your blood usually contains a little more albumin than globulin, which is why a normal ratio is slightly higher than 1 [1].
For reference, the total amount of albumin in the blood is normally around 3.4 to 5.4 g/dL, and the total amount of globulin should be about 2.0 to 3.9 g/dL [1, 9].
Low Albumin/Globulin Ratio
Causes
There are several ways your albumin/globulin ratio may become low.
- Your albumin is normal, but your globulin is very high
- Your globulin is normal, but your albumin is very low
- Your albumin is low and your globulin is high
Causes listed below have been commonly associated with a low A/G ratio. Your doctor will interpret your value, taking into account your medical history, symptoms, and other test results.
Here we’ll explore the common reasons for low albumin or high globulin levels in the blood.
Low Albumin
A wide range of health problems can cause low albumin in the blood, a condition called hypoalbuminemia.
One of the most common causes of low albumin is inflammation. During an illness or injury, your body focuses on producing proteins involved with the immune system, such as C-reactive protein (CRP). Under this kind of stress, the liver creates more immune-related proteins and less albumin [10, 11].
Liver disease is also a big factor. Albumin is made in the liver, so any disorder that affects the liver (like cirrhosis) may reduce albumin production [12].
Some other health conditions that can reduce albumin include:
- Chronic illness and infection [13, 14, 15]
- Malnutrition or gut disorders that cause malabsorption of protein, such as celiac or Crohn’s disease (also decrease globulin) [16, 13, 14, 1]
- Kidney disease (also decrease globulin) [17]
- Heart failure [18]
- Extensive burns [19]
- Obesity [20]
High Globulin
High levels of globulin in the blood may be caused by:
- Viral and bacterial infections [1, 21]
- Inflammatory disorders [1]
- Autoimmune disease [22, 23]
- Liver disease [1]
- Some types of cancer [24, 25, 26, 27]
- Some drugs, such as amiodarone (Cordarone, Nexterone), used to treat and prevent irregular heartbeat [28]
The immunoglobulins, a common type of globulin also known as antibodies, bind to pathogens and foreign material, tagging them for your immune system to attack. Your body naturally produces more antibodies during an infection, resulting in higher globulin levels [29, 21].
High globulin levels are also commonly seen in people with chronic liver diseases like cirrhosis. The liver breaks down excess globulin and eventually eliminates it from the body. Liver disease can reduce this ability to remove globulins, and these proteins can build up in the blood [30].
Certain drugs may cause globulin to rise as well. A small study of 15 people found that some patients who experience toxicity from amiodarone also have high globulin levels; the reason for the rise in globulins is unknown [28].
Health Effects
Low albumin/globulin ratios are associated with a poor prognosis in many different diseases, which is unsurprising, given that these proteins are linked to inflammation and immune system dysfunction [1, 31].
In this section, we’ll explore the potential long-term effects of low A/G ratios, according to research. Keep in mind that it’s not clear if albumin or globulin themselves cause disease; rather, a low A/G ratio probably represents a deeper, underlying issue [1, 31].
1) Is Associated With The Risk of Cancer
A low albumin/globulin ratio may be putting you at risk for developing cancer. In an observational study of almost 27,000 people, participants with A/G ratios below 1.1 had an increased risk of developing cancer on average, even if they were otherwise healthy [4].
Liver and blood cancers were the most common in this study, but low ratios were associated with over 10 types of cancer altogether, including breast and lung cancers [4].
Researchers believe the common denominator and root cause is chronic inflammation, which leads to both lower A/G ratios and higher incidences of cancer [4, 32].
2) May Help Predict Cancer Mortality
Apart from being associated with the risk of developing cancer, an A/G ratio may also indicate how well a cancer patient will respond to treatment [31].
In several studies, a lower A/G ratio has been associated with worse overall survival in:
- Lung cancer [33]
- Esophageal cancer [34]
- Liver cancer [35, 36]
- Colon cancer [37]
- Kidney cancer [38]
- Lymphoma [39]
- Pancreatic cancer [40]
- Intestinal cancer [40]
A study in 276 lung cancer patients has found that people with A/G ratios less than 1.29 were 1.35 times more likely to die on average than people with ratios greater than 1.29 [33].
How does this information help? If a doctor finds that a cancer patient has a low A/G ratio, they may decide to use a more intensive treatment to improve the chances of survival [31, 37, 34].
3) Is Associated With The Risk of Dying From Heart Diseases
One study investigated A/G ratios in 570 patients who had experienced a heart attack. They found that a ratio below 1.12 was associated with a 47% risk of death within 4 years of the heart attack. On the other hand, a ratio greater than 1.34 was associated with only a 10% risk of death [41].
Multiple studies have also found a link between low A/G ratios and the risk of death in heart failure patients. In an observational study of over 13,000 patients with heart failure, an A/G ratio below 1.1 was associated with a higher risk of dying within 1 year [5, 6, 7].
Another study of 999 people found very similar results: a ratio of less than 1.2 was a strong predictor of dying within a year in heart failure patients [6].
4) May Predict Poor Outcomes After Stroke
A study of 319 people found that stroke patients with ratios under 1.45 may be more likely to develop additional blood clots (and, thus, suffer another stroke) in the future [42].
According to a different study, a low A/G ratio increased both the risk of another stroke and death in 125 stroke patients [43].
These studies are relatively small. More independent studies are needed to support these findings.
5) May Predict Severity of Myasthenia Gravis
Myasthenia gravis is an autoimmune disorder wherein a person’s antibodies attack their own nerves. This type of nerve damage leads to muscle weakness, drooping eyelids, and trouble speaking [44].
A study of 135 patients with myasthenia gravis found that people with albumin/globulin ratios below 1.34 had more severe symptoms and generally did worse than people with higher ratios [45].
Again, additional independent studies are needed to confirm this.
6) Linked to Cognitive Decline
According to one study of 151 people, those with mild cognitive impairment tended to also have lower A/G ratios. These are both likely symptoms of a deeper problem, such as a chronic inflammation [46].
High Albumin/Globulin Ratio
A high albumin/globulin ratio could mean that your albumin levels are high, your globulin levels are low, or both. There are only a few reasons why the A/G ratio may be high and a high ratio is much less common compared to a low ratio.
In this section, we’ll explore how your albumin can become high or how your globulin levels can become low.
Causes
Causes listed below have been commonly associated with a high A/G ratio. Your doctor will interpret your value, taking into account your medical history, symptoms, and other test results.
High Albumin
By far, the most common reason for high albumin is dehydration. There is some evidence that a high-protein diet may also increase albumin levels [1, 47].
On the other hand, dehydration and high-protein intake can also increase levels of globulin, leaving the ratio of albumin to globulin largely unchanged [1, 48].
There are several studies that have found a link between insulin resistance and higher blood albumin levels [49, 50, 51]. Therefore, a high insulin may contribute to a high A/G ratio.
However, a drug interaction is the most likely culprit behind high albumin in a high A/G ratio. A couple of studies have shown that certain medications can increase the production of albumin, including:
- Prednisolone (a corticosteroid used to treat inflammatory disease) [52]
- Human growth hormone (somatropin, used to treat some growth disorders in children) [53, 54]
Low Globulin
Many factors that lower globulin levels can also lower albumin, such as malnutrition and kidney disease. These conditions are less likely to alter the albumin/globulin ratio because they lower both types of protein at similar rates [55, 1].
However, a few factors lower only globulin. For example, genetic defects can cause a disorder called immunodeficiency, which disrupts the body’s ability to create antibodies (immunoglobulins). This condition, thus, lowers total globulin levels [1, 56].
There is also acromegaly, a disorder characterized by excess production of growth hormone, usually caused by a tumor. Symptoms typically include abnormal growth, headaches, and joint pain [57].
In one study of 35 people with acromegaly, almost half of the participants had low levels of globulin [58].
Finally, some immunosuppressive drugs, such as corticosteroids, can decrease globulin levels [1].
Health Effects
Few studies have looked at the effects of a high albumin/globulin ratio. Research does show that higher ratios may improve survival in cancer, but it’s unknown if this benefit extends to ratios above the normal range [31].
A high A/G ratio result may be more useful as an indicator of an underlying genetic disorder. A rare disease called immunodeficiency occurs when genetic defects prevent the body from properly creating antibodies. This leads to low globulin levels and a high A/G ratio, though other tests would be needed to confirm the diagnosis [1, 59].
How To Normalize Your Albumin/Globulin Ratio
Remember that a low or high A/G ratio usually stems from an underlying condition, such as inflammation, liver disease, or drug interactions. You need to consult with your doctor to treat any potential underlying cause to manage your A/G ratio. Only a qualified physician can ascertain the cause of the abnormal ratio and make recommendations to fix it.
Takeaway
An albumin/globulin ratio compares the concentrations of albumin and globulin (two types of protein) in the blood. A low albumin/globulin ratio may put you at risk for developing cancer. Low ratios may also increase the risk of death for those with cancer or heart disease. A low ratio usually indicates some kind of underlying disorder, such as liver or kidney disease. Treating the underlying condition is the best way to correct the balance of albumin and globulin.
