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“I’m so tired” – Causes of fatigue and how integrative medicine can address them

Fatigue, tiredness, weakness.

These terms strike fear into the hearts of most medical practitioners. Many chronic diseases, biochemical abnormalities as well as hormone imbalances may lead to symptoms of fatigue.

When I was practicing in the emergency department, picking up a chart and seeing a chief complaint of weakness meant that, more than often than not, myself and the patient would be less than satisfied at the end the encounter. Often, we could not find a source for said “weakness.”

According to the British Medical Journal, up to 20% of primary care visits involve a description of fatigue or weakness—obviously, a very common problem.

Since opening my integrative medicine practice, fatigue has also been a common complaint. Only this time, in the integrated health setting, I actually enjoy being a medical detective to try and find out the root cause of the issue, and then structuring a treatment plan to support the patients and correct any imbalances we uncover.

Intrinsic or extrinsic fatigue?

A good way to think about fatigue is through a simple mental construct. Is your fatigue caused by something that has come into your body and created havoc or does it stem from a malfunctioning of an internal body system? Simply put: is the fatigue something originating extrinsic or intrinsic to your body?

Of course, if you are only sleeping four hours a night then we know where to focus our attention.

Extrinsic Causes vs Intrinsic Causes of Fatigue:

Extrinsic Causes of Fatigue

Dietary Triggers

Hippocrates, the Father of Western Medicine, said that all diseases begin in the gut.

Fatigue can be the manifestation of that disease. The pathway from food sensitivities to fatigue is well documented. Food sensitivities can increase the response of your enteric (gastrointestinal) immune system, leading to production of antibodies which disrupts the delicate lining of your G.I. tract. This leads to increased permeability and leaky gut. This triggers more of a response by your immune system.

In addition, over time the imbalance of healthy to disruptive bacteria becomes altered leading to a condition called dysbiosis. A common symptom along with the typical G.I. findings of bloating, cramping, constipation and diarrhea is fatigue. Being able to address these food sensitivities through a structured elimination diet, gut repair process and rebalancing of the microbiome is critical.


In this day and age, fatigue has been characterized as a clear result of Covid. More on Long Covid towards the end of this post.

Really, any infection can lead to symptoms of fatigue which are typically limited in duration, from days to a few weeks. In the ER, it was not uncommon to find a simple urinary tract infection as a cause of weakness and fatigue, especially in older patients.

Of course, more serious infections can lead to long-term fatigue especially if a hospitalization was required. The post-ICU syndrome (PICS) is a well-documented disorder that can result in long-term fatigue as one of the symptoms. The older we are, the more likely fatigue will be persistent after both viral and bacterial infections.


Toxins do not get a lot of notoriety in the traditional medical community. Considering there are 80,000 chemicals in our environment, with a thousand new ones added every year, and that most have not been tested for their impact on human beings, it is not hard to imagine how some of these can lead to negative impacts in our bodies.

The most common are heavy metals like mercury, solvents used in many commercial applications (including dry cleaning and hair styling), pesticides used in many agricultural applications and often used frequently at home. Certain types of mold, if exposed over a long period of time, can also result in profound fatigue.

All of these are reasons that I do environmental toxin screening for every new patient in my practice.


One of the more common causes of fatigue are medications; both prescribed and non prescription medications. Allergy medications, beta blockers, antidepressants, statin lowering drugs and muscle relaxants are some of the more common. The list includes some of the most commonly prescribed medications. Check out the list here.

Intrinsic Causes of Fatigue

Intrinsic causes are those that start within a particular body system. These may be a result of something outside your body but think about these as a primary internal imbalance.

Micronutrient Deficiency

These micronutrient deficiencies can rise over a long or short period of time. An acute infection can cause an imbalance in your sodium or potassium levels causing profound fatigue. The more common micronutrient deficiencies causing fatigue include:

  • Low iron levels due to a number of causes resulting in a drop in ferritin and eventually anemia. It is one of the common causes in menstruating women. It could also signify a more worrisome cause such as a slow bleeding in your G.I. tract due to a serious abnormality or cancer.

  • Low vitamin B-12 is known to result in profound fatigue and is much more common as we age due to difficulty in absorbing B-12 from our G.I. tract. This can also be seen in people who practice a vegetarian diet.

  • Low magnesium is found in 40% of US adults. Low magnesium impacts the metabolism of Vitamin D.

  • Folic acid/vitamin B-9 is critical for numerous chemical reactions in the body. Up to 40% of people have trouble efficiently utilizing folate due to a genetic variation called MTHFR.

  • Vitamin D deficiency is present in 42% of all Americans, 82% of African Americans and 69% of Hispanics and can also be a cause of fatigue. Supplementation corrects this abnormality.

Hormone Imbalances

Entire books can be (and have been) written on the impact of hormone imbalances and resulting fatigue. The most common ones include:

  • Hypothyroidism – low thyroid hormone levels are a very well known cause of fatigue. The incidence is much higher in women. While the typical thyroid hormone that is checked, thyroid stimulating hormone (TSH), is helpful, you need a more expansive panel to fully diagnose and effectively treat thyroid issues.

  • Adrenal Imbalance – chronic stress will result in long-term imbalance in the hypopituitary – adrenal axis (HPA). There is a delicate balance between the signaling hormone produced by the brain directed at the adrenal glands which produce cortisol and epinephrine (adrenaline). Imbalances due to chronic stress results in fatigue. The incidence of adrenal fatigue, a controversial topic as viewed by traditional doctors, can be as high as 15%.

  • Estrogen and Progesterone – these are the two major female hormones. A Very consistent finding in perimenopausal and menopausal women is fatigue. It is due to the reductions in circulating estrogen and increasing dominance of progesterone as women age. While all women do not experience the symptoms a thoughtful approach and evaluation for hormone replacement therapy can be life-changing in the appropriate patient.

Cardiovascular Disease

The final intrinsic cause of fatigue can be underlying cardiovascular disease.

I have evaluated numerous patients whose symptoms of isolated fatigue, especially on exertion, led to a diagnosis of a critical coronary artery lesion. It is a (less than) well-known fact that up to 70% of women present with fatigue as an early symptom of cardiovascular disease. It is one of the diagnoses that needs to be ruled out as part of a workup for fatigue.

Mitochondrial dysfunction is emerging as a possible final common pathway for fatigue. While this is an emerging field of research the mitochondria, which are responsible for the production of ATP which is the primary energy chemical in our bodies, may lose function as we age or as a result of insult from infection or toxins. Evidence of decreased levels of antioxidants, which help protect our bodies from metabolic insults, in patients with fatigue may also negatively impact our mitochondrial function.

What else could it be?

Two Particular types of fatigue deserve special mention:

  1. Chronic Fatigue Syndrome

  2. Post COVID (or long Covid) Fatigue

Chronic Fatigue Syndrome (also named myalgic encephalitis or ME/CFS) is a complex disease resulting in profound fatigue that impacts activities of daily living. Up to 2.5 million Americans have it and 90% have not been appropriately diagnosed. The classic symptom is profound fatigue after any type of exertion with symptoms lasting at least 6 months. An excellent resource is here.

Long Covid can impact up to 20% of all patients with COVID. Even mild cases are known to result in long COVID. Post COVID Fatigue is seen in up to 70% of patients with long COVID. It is, like ME/CFS, a complex disease not fully understood. Current treatments recommend a multidisciplinary approach depending on symptoms.

So that is a lot! By taking a structured approach to the evaluation of fatigue we can get to the root cause of the problem and significantly improve symptoms.

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