Monoclonal Gammopathies of Undetermined Significance (MGUS)

February 2, 2017

Monoclonal gammopathy of undetermined significance or MGUS is a disorder where plasma cells (specialized bone marrow cells that secrete antibodies/immunoglobulins) begin to function abnormally, producing increased quantities of an immunoglobulin that does not work normally. When this immunoglobulin is produced from genetically identical (clonal) plasma cells, it is able to be identified on a blood test (serum protein electrophoresis). This abnormal protein is called a paraprotein (monoclonal gamma globulin, hence “monoclonal gammopathy”).

MGUS is linked to the immune system, which helps the body fight infection and disease. The immune system is made up of organs such as the bone marrow, the spleen, lymph nodes (or lymph glands) and a type of white blood cell called lymphocytes.

Lymphocytes are made in the bone marrow (inside the bones). The two main types of lymphocytes are Bcells and T-cells. Some B-cell lymphocytes develop into plasma cells and make antibodies to help fight infections. Antibodies are made from a protein called immunoglobulin.

MGUS occurs when particular plasma cells produce abnormally large amounts of one type of antibody. This abnormal antibody or immunoglobulin is called a paraprotein (or M-protein). The paraprotein doesn’t do anything useful, and it isn’t harmful.

MGUS is not a cancer. Some cancers, such as myeloma (a cancer of the plasma cell) and lymphoma (cancer of the lymphatic system), also produce large amounts of paraproteins. Although the levels of paraprotein are raised in MGUS, they’re not as high as the amount produced in people with cancer. Most people with MGUS remain well and never have any problems related to it. A small number of people may go on to develop more serious problems, so everyone with MGUS has regular checks.

MGUS is much more common in older people over 70. The cause of MGUS is unknown. It’s more common in people with conditions that affect the immune system, such as rheumatoid arthritis and certain infections.


The cause of MGUS is not fully understood at this time. It is thought that genetic damage to a single plasma cell gives this cell a survival advantage, leading to proliferation of this plasma cell. It is known that there is an increased risk of MGUS in first-degree relatives of patients with MGUS and myeloma. This does not mean all first-degree relatives will get MGUS, only that the risk is increased compared to the general population. It is not known at this time if this is due to shared genetic factors, or shared environment (same upbringing).

Risk Factors

Factors that increase the risk of monoclonal gammopathy of undetermined significance include –

  • Age – The risk of monoclonal gammopathy of undetermined significance increases as people get older. The highest incidence is among adults age 85 and older.
  • Race – Blacks are more likely to experience this condition than are whites.
  • Sex – Monoclonal gammopathy of undetermined significance is more common in men than it is in women.
  • A family history – If other people in the family have monoclonal gammopathy of undetermined significance, the risk of developing the disorder may be higher.


MGUS does not typically cause any symptoms. There is no evidence of bone damage, kidney damage, anemia (low levels of red blood cells), or elevated calcium levels. The average risk of progression to multiple myeloma is one percent per year. The risk of progression to malignancy is about 20 to 25 percent of people during their lifetime.

It has always been recognized that some cases of MGUS progressed to symptomatic multiple myeloma but recent studies have shown that multiple myeloma is consistently preceded by MGUS.


Some people with monoclonal gammopathy of undetermined significance develop a more serious condition, such as multiple myeloma or other cancers or blood disorders.

Doctors can’t definitively predict who will go on to develop a more serious condition, but they can determine who has the greatest risk. The doctor takes into account several factors when determining the risk, including –

  • The amount of M protein in the blood
  • The type of M protein
  • The amount of another small protein (free light chain) in the blood

The risk of developing a more serious condition increases the longer people had monoclonal gammopathy of undetermined significance. Also, the more risk factors people have, the higher the risk of developing a more serious condition.

Other complications associated with monoclonal gammopathy of undetermined significance include fractures and blood clots.


MGUS does not require any active treatment, however monitoring is recommended. Monitoring of MGUS includes regular clinical assessment and follow up measurements of serum protein. The serum protein should be checked after 3 months and then again at 6 months to establish a firm diagnosis of MGUS.

A risk-assessment model can predict the risk of progression to multiple myeloma. This model uses the size and type of the abnormal protein and a special blood test called the serum free light chain assay.

If some have monoclonal gammopathy of undetermined significance and bone loss, the doctor may recommend treatment with medications called bisphosphonates that help increase the bone density. Examples of bisphosphonates include alendronate (Binosto, Fosamax), risedronate (Actonel, Atelvia), ibandronate (Boniva) and zoledronic acid (Reclast, Zometa).

Alternative Treatment

Alpha lipoic acid is an antioxidant that is commonly used in supportive therapy for peripheral neuropathy in people treated for multiple myeloma. It is an antioxidant that is normally made in the body, but people can also take extra alpha lipoic acid through supplements.

Calcium – People with MGUS may take calcium along with vitamin D to help support their bones. However, bone breakdown during multiple myeloma also releases unhealthy amounts of calcium in the blood, so patients should consult their doctors before considering calcium supplements.

Curcumin, a compound found in the spice turmeric, may work to kill myeloma cells and prevent them from multiplying. For those who have the pre-cancer conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma, curcumin may slow progression to active multiple myeloma, but this has not yet been supported by clinical research.

Fish oils commonly contain plenty of omega-3 fatty acids, which may boost peripheral nerve health. For this reason doctors sometimes recommend them for MGUS.

Green Tea – A compound found in green tea, called epigallocatechin-3-gallate (EGCG), may aid in killing myeloma cells and prevent MGUS. However, it may also block the anti-cancer activity of Velcade, leading researchers to advise people with multiple myeloma undergoing Velcade therapy to avoid green tea products and EGCG supplements.

Magnesium may help with peripheral neuropathy. It also helps regulate calcium levels and can help strengthen bone. Green leafy vegetables, almonds, cashews, and halibut are all good sources of this essential mineral.

Iron – Anemia (low red blood cell counts) is a symptom of multiple myeloma and is also a common side effect of many myeloma treatments. Iron supplements may help certain people with their anemia.

Potassium – Doctors may recommend potassium for people getting treated for MGUS.

B vitamins, including vitamin B-1 (thiamine), vitamin B-2 (riboflavin), vitamin B-6, vitamin B-12, and folic acid, are important for the formation of red blood cells, enhance the immune and nervous systems, and more.

Vitamin C – As an antioxidant, vitamin C helps protect cells from environmental damage that may lead to cancer. It also functions in protecting the immune system.

Vitamin D works with calcium to build bone, and recent research suggests it might be important in reducing some signs and symptoms of MGUS.

Vitamin E – For those suffering from MGUS, vitamin E supplements may help. This antioxidant vitamin may protect nerves during therapy, especially with Velcade or thalidomide.


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