Common – and Often Overlooked – Causes of Fatigue in Lyme disease

Fatigue is one of the most common and debilitating symptoms associated with Lyme disease and other tickborne infections. This fatigue can either be persistent and low-grade or can be cyclical with other symptoms associated with the infection(s). For some people suffering from fatigue from Lyme disease, they have to manage how much energy they can expend in a day, while others can hardly get out of bed. Reduced levels of energy greatly interfere with normal day-to-day activities such as work and household chores, and can also affect relationships.

Fatigue impacted Allie’s Relationships – and Life

When I first met Allie she was on disability leave from her work. Her work was not physically difficult, but due to her debilitating symptoms, she could not keep up with the demands. Her husband had taken over most of the household duties, including caring for their two small children. Allie had been suffering from severe fatigue, generalized joint and muscle pain, migraines, digestive issues and brain fog for the past three years, but she remembers some of these symptoms about ten years prior. 

In the three years before I met Allie had seen multiple doctors, from functional doctors to an infectious disease doctor at a university medical clinic. She was "diagnosed" with fibromyalgia, chronic fatigue syndrome, and even told she was just depressed. Allie tested positive for Lyme disease with the infectious disease doctor but was told it was a false-positive so it should be repeated. The repeat test was also positive however Allie was not offered treatment.

It is not uncommon for people to get labeled with chronic fatigue syndrome before a diagnosis of tick-borne infections is made. With any "syndrome," the symptoms are described but the underlying cause is not. Other infections such as Epstein-Barr virus and mycoplasma can also contribute to chronic fatigue.

What are the causes of Lyme-related fatigue

Lyme disease and other tickborne infections can affect different systems on the body, some that play a role in energy production. Chronic infections will cause a release of inflammatory cytokines which affect the different energy-producing systems in the body.


The endocrine system is one of those systems affected – in particular, the thyroid and the adrenal glands. Thyroid hormones influence energy production and metabolism. People with low thyroid often suffer from fatigue, weight gain, brain fog, cold hands/feet, and constipation. Lyme disease can cause decreased thyroid hormone production by direct damage to the thyroid such as in autoimmune thyroiditis, indirectly to the hypothalamus or pituitary, or by a functional hypothyroidism such as poor conversion of the T4 hormone to the active T3 hormone.

It is important to test all thyroid markers including TSH, T4 free, T3 free, Reverse T3, and anti-TPO and anti-thyroglobulin antibodies. A high-normal TSH or Reverse T3, or low-normal T3 free and T4 free could be contributing to a functional hypothyroidism. I estimate 60%-70% of my patients with tickborne infections suffer from hypothyroidism and feel much better when it is corrected.

Treatment for hypothyroidism is often accomplished by taking thyroid medication. Synthetic thyroid medication is usually only prescribed as T4 (levothyroxine, Synthroid), however, T3 is the active form of thyroid hormone and should be taken concurrently. A more natural form of thyroid medication is Armour or Nature-thyroid, which is thyroid glandular and includes T3 and T4. Some dietary supplements are also used to support thyroid function. People who are properly treated for hypothyroidism and do not feel better should consider being properly tested for tickborne infections or other causes of fatigue listed here.

Adrenal Fatigue

The adrenal glands produce the hormone cortisol, which is the stress response hormone. In normal stressful circumstances, our bodies produce cortisol for a short period of time to protect us. However, during periods of prolonged stress - such as with a chronic infection - our adrenal function becomes compromised. This adrenal dysfunction can cause fatigue and reduce our ability to withstand stress. Since cortisol is an anti-inflammatory steroid hormone, low levels can also contribute to increased inflammation. Adequate adrenal function improves energy, but also increases resilience to stress, improves immune function and reduces systemic inflammation. 

Restoring adrenal function starts by reducing – or better managing – stress. In addition, adaptogenic herbs such as ashwaganda, ginseng, and rhodiola. Adaptogenic herbs are like food for the adrenal glands – they nourish the adrenal glands so the function can be restored. Occasionally, someone with severe adrenal fatigue will need to take prescription hydrocortisone to return cortisol to physiological levels.

Mitochondrial Dysfunction

Likely the most common – and often overlooked – cause of fatigue in chronic tick-borne infections is mitochondrial dysfunction. The mitochondria are the energy-producing "engines" in most cells in our body. Oxidative damage from exposures such as infections and toxicants lead to mitochondrial dysfunction, which causes a reduction in ATP production – the fuel that the mitochondria produce. Damage can occur in the mitochondrial structure and function, and repair to both is required to restore the mitochondria's ability to produce sufficient amounts of ATP.

Research has shown the gut microbiome influences mitochondrial function, so digestive health plays an important role in our energy levels. This one of the concerns using long-term antibiotics to treat chronic Lyme disease. Organs with higher energy demands like the heart and the brain have higher concentrations of mitochondria per cell.

The good news is mitochondrial function and structure can be repaired. It starts by removing the sources of the damage (infections, toxicants), then providing adequate nutrients. Phosphatidyl choline helps to restore the structure of mitochondria, and nutrients such as CoQ10, carnitine, and the B-vitamin nicotinamide riboside (NAD) improve function.

Cell Danger Response

A recent discovery as a potential cause of chronic fatigue syndrome is a reduced metabolic state referred to as cell danger response. In this scenario, cells sense a "danger" then respond by going into a conservative metabolic mode to protect cells and the human from harm. This is like a cell phone switching to a low power mode to conserve energy. Dangers to cells come in the form of chemical, physical and/or infectious causes that threaten or kill cells. Chemical forms of danger include heavy metals, pesticides, and plasticizers. Viral, bacterial, fungal and parasitic infections can all trigger cell danger response and create reduced metabolic function. Physical damage can come in the form of heat, radiation or pH imbalance.

Once the trigger, or triggers, of cell danger response, are removed, the metabolic pathways are restored and the body begins to heal. If the cell danger response persists for a long period of time, entire body metabolic is compromised including multiple organ systems and the gut microbiome.

Researches determined certain biochemicals were increased while others were decreased in cell danger response, creating a chemical signature. One of the primary compounds decreased in cell danger response was phosphatidyl choline. Ozone therapy has also been shown to address the metabolomic changes that occur in cell danger response.

Treating the Cause of Fatigue

I ordered a number of tests on Allie, including a tickborne infections panel, thyroid panel, adrenal hormones, and markers to assess mitochondrial function. She was positive for Lyme disease (borreliosis), bartonellosis, and her adrenal and mitochondrial function was compromised. I started Allie on nutrients for mitochondrial support, herbs for adrenal repair, and ozone therapy to improve the metabolic changes that had occurred from her chronic illness. Within a couple months her symptoms improved, and after 4 months of treatment was able to return to work. She was also able to be more involved in her children's lives again

As you can see, there are multiple causes of fatigue that are associated with Lyme disease and other tickborne infections. The key is to identify what system or systems have been affected by the infections and address the causes. When this happens, your energy can improve and you can start to enjoy a higher quality of life again!