Since so much about ME/CFS is unknown, the causes of the condition are even more a mystery. Currently there are a few competing ideas, with interactions among these factors under evaluation:
- Infection: ME/CFS bears some remarkable similarities to other infections, especially mononucleosis. Testing people for Epstein-Barr (EBV), herpesvirus, enterovirus, mycobacterium, rubella, retrovirus, Candida (yeast) have all proved inconclusive. Many sufferers of ME/CFS can relate a story of having an infection or flu-like illness before becoming ill with ME/CFS, but this is not necessarily true with all sufferers.
- Immune System: Some researchers believe that ME/CFS is an autoimmune disease similar to lupus, but this has also proven inconclusive. The immune system is affected in many people with ME/CFS as a decrease in immune function; and a propensity to allergic symptoms is also very common among sufferers.
- Hormonal Imbalance: The most common hormonal problem in ME/CFS sufferers is disruption of the hypothalamic-pituitary-adrenal axis. This hormonal system is responsible for the fight or flight response, typically experienced as anxiety and nervousness. Physical or emotional stressors can cause a dysregulation of this hormonal system, which can lead to further stress and anxiety, a sort of vicious cycle. Constant stress and anxiety can also reduce the immune system function.
- Hypotension: Many people with ME/CFS have hypotension (low blood pressure). Scientists are puzzled by this low blood pressure and suggest that it may be the result of problems with the nervous system. Hypotension leads to fatigue and tiredness.
- Nutritional Deficiency: Many people with ME/CFS have nutritional deficiencies, but it is difficult to determine if this is the cause or a result of the disease. Typically, ME/CFS sufferers are low in B-vitamins, magnesium, vitamin D, and many other nutrients.
- Mitochondrial Dysfunction: Recent research suggests some factor interfering with the highly complex mechanism of energy production at the cellular level.
- Central Sensitivity: It is suggested that symptoms of ME/CFS and often-overlapping conditions such as fibromyalgia are manifestations of central nervous system sensitization - "an exaggerated response of the central nervous system [spinal cord and brain] to stimuli."
- Predisposing Genetic Factors: As suggested by the ongoing gene-expression research, differences in symptoms experienced and severity may correspond with a number of genomic ME/CFS subtypes.
More than likely, the cause of ME/CFS is the result of a combination of factors, where one factor can affect the other. For example, stress can reduce the effectiveness of the immune system. With a lowered immune system, infection is more likely, and having a chronic infection can lead to more stress. There are many systems in the body that interrelate in similar ways.
