What Causes ME/CFS? What Researchers Are Studying

Scientists don't yet know what causes myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). It may have more than one cause, or be set off by environmental triggers. Research is looking at infections, how the body uses energy, how people respond to infection, inflammation, toxins or injury, and genetics.

Infections

ME/CFS often begins with an illness like the flu, which has led researchers to suspect an infection can trigger it.

• About 1 in 10 people infected with Epstein-Barr virus, Ross River virus or Coxiella burnetii later develop an ME/CFS-like illness — especially if their infection was severe. But not everyone with ME/CFS has had these infections.
• People have also reported ME/CFS-like illness after COVID-19, known as Long COVID.
• Some people develop chronic symptoms after other acute infections that resemble ME/CFS, so ME/CFS may be a long-term illness following an unknown infection.

Immune system changes

ME/CFS may stem from changes in the immune system, or in how it responds to infection or stress. It shares some features with autoimmune diseases — in which the immune system attacks healthy tissue, as in rheumatoid arthritis:

• both are more common in women;
• both involve increased inflammation.

But other signs of autoimmune disease, such as tissue damage, haven't been found in people with ME/CFS.

Stress and body chemistry

People with ME/CFS often report an infection or physical or emotional stress before becoming ill. Some have lower levels of cortisol — the "stress hormone," which helps calm the immune system — and low cortisol may lead to more inflammation and chronic immune activation. But their levels are low within the normal range, so cortisol can't be used to diagnose or treat ME/CFS. Other hormones may be altered too.

Energy production

Scientists have found differences in how the cells of people with ME/CFS turn food into energy, leaving less fuel for the brain and muscles. More research is needed to know whether this is always true, and why.

Genes

ME/CFS sometimes runs in families. Twin and family studies suggest genes and environment may both play a role, but the specific genes or environmental factors haven't been found.

Sources

Based on "What Causes ME/CFS," Centers for Disease Control and Prevention; a work of the United States government in the public domain.