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A Functional Medicine Protocol for Fatigue: Lab Testing, Nutrition, and Helpful Supplements

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A Functional Medicine Protocol for Fatigue: Lab Testing, Nutrition, and Helpful Supplements

Our society feels exhausted and worn out. Living at a constant on-the-go speed, battling chronic health conditions, piling on stress, and unhealthy lifestyles have left many Americans feeling fatigued. Fatigue is one of the top 10 reasons individuals seek care from their primary care providers. This state of being can be debilitating, making it hard for you to carry out activities of daily living. Getting to the root of your fatigue through functional medicine care can provide comprehensive insight and complementary treatment options. 


What is Fatigue?

Fatigue is a state of impactful tiredness that results in diminished energy and can have both physical and psychological implications. There are three critical classifications of fatigue: physiological, secondary, and chronic. Having too much on your plate and not getting enough rest is an example of physiological fatigue. If this or other demanding life circumstances are ongoing, with little rest, for more than six months, it can result in chronic fatigue. Secondary fatigue is due to medical conditions that impact your body in various ways. Two examples of medical conditions that can result in secondary fatigue are hypothyroidism and fibromyalgia

What Are The Possible Causes of Fatigue?

There are numerous implications to fatigue. Here are some of the most common causes of experiencing fatigue. 

Lifestyle Factors

Imbalanced and unhealthy ways of living can be a leading factor contributing to fatigue. Sleep, diet, mental stress, movement, and environmental exposures play a dynamic role in keeping one healthy. Sleep helps regulate your circadian rhythm and assists the body in recovering from both mental and physical strain. 

Specific sleep disorders like insomnia, sleep apnea, narcolepsy, and restless leg syndrome can all leave you in sleep deprivation and chronic fatigue. Your diet can significantly compromise your health. Not getting adequate nutritional intake, especially B vitamins, can result in low energy and fatigue.  Stress can impact every aspect of your life, including mental fatigue. Prolonged stress can put your body into a state of “fight-or-flight,” which, over time, leads to a downstream of effects such as exhaustion. Research on the topic states that there is a bidirectional relationship between stress and fatigue, meaning one impacts the other. Both components need to be addressed to heal.

Movement is critical to energy production and keeping fatigue in check. One study showed that maintaining daily activity with limited prolonged sedentary time frames could improve energy and decrease fatigue. What we are exposed to in our environment can also impact how we feel daily. Lead and mercury are two heavy metals we should be aware of that, when impacted by, can have adverse effects. 

Medical Conditions 

Various medical conditions can result in fatigue. You may already have a diagnosis of one of these conditions, but if not, assessment for the root cause of your fatigue can help you overcome the exhaustion you are feeling. Here are some categories of conditions that have components of fatigue.

Infectious Disease

Mental Health


Cardiac and Lung Conditions

  • Postural orthostatic tachycardia syndrome (POTS)
  • Heart Disease
  • Chronic obstructive pulmonary disease (COPD)


While your state of health may require you to take a prescription medication, the side effects may be the culprit to the fatigue you are experiencing. Some prescription medicines can deplete nutrients that are necessary for mitochondria function and energy production. Here are a few common medications that can cause physical or mental fatigue: antidepressants, anxiety medication, antihistamines, beta-blockers, muscle relaxors, pain medications, and seizure medication.

Functional Medicine Labs to Test for Root Cause of Fatigue

Depending on your clinical presentation, your practitioner may choose to run one or a variety of these labs. 

Complete Blood Count (CBC)

A CBC test will help assess for anemias and infections that can result in fatigue. By evaluating the biomarkers in a CBC, our practitioner can provide an appropriate treatment plan to address any dysfunction that may be present. 

Cortisol Testing

Obtaining multiple cortisol readings can provide context into your stress response and whether or not that is playing a role in your fatigue. Cortisol is best evaluated through Diurnal Salivary Cortisol testing, like the option ZRT Laboratory offers. This test requires four salivary collections throughout the day, which evaluates fluctuations in your cortisol levels throughout the day. 

Comprehensive Thyroid Panel

Completing a full Thyroid Panel from Genova Diagnostics will help determine if your symptoms are connected to thyroid hormones or Hashimoto’s disease. Ruling this out as a cause of persistent fatigue will aid in treating the root cause.

Micronutrient Evaluation

Vitamin and nutrient deficiencies due to infections, medical conditions, a poor diet, or medications can play a role in your energy status. Ruling out any deficiencies in B vitamins, iron, vitamin C, and folate is helpful in getting to the root cause of fatigue. SpectraCell's Micronutrient Test is a comprehensive test that will look at these markers, plus more. This is an effective method for implementing nutraceutical therapy while addressing the root cause of your fatigue.

Pathogen Panels

Some infectious agents produce antibodies and biomarkers that can be detected through blood work. Obtaining an Epstein-Barr Evaluation can provide context as to whether you have an active new infection or a reactivation of a chronic infection. A comprehensive Lyme disease panel can look at not only the bacteria, Borrelia burgdorferi, that is commonly known to cause Lyme but also co-infections that are often concomitant with this condition. 

Autoimmunity Screening

Being that various autoimmune conditions can cause fatigue, investigating this avenue may be necessary in ruling out an autoimmunity condition such as Lupus or Rheumatoid Arthritis. Access Medical Laboratories has an AutoImmune Analyzer test that measures the marker for autoimmunity, antinuclear antibody, plus numerous condition-specific antibody biomarkers. 

Cardiac Health Panel 

If you have suspected cardiac health issues or are symptomatic with a family history of cardiac disease, obtaining a full cardiac blood workup may be warranted. Access Med Labs offers a Cadiac Health Panel that evaluates the most common biomarkers associated with heart disease risk. 


Conventional Treatment for Fatigue

Depending on the cause of the fatigue, conventional medicine will provide some solutions. In terms of secondary fatigue due to infections and pathological causes, prescription medications may be recommended. If a root cause such as anemia is determined, normalizing iron and the cause of anemia will be addressed. 

When it comes to physiological fatigue, lifestyle recommendations are often given to improve sleep and manage stress. Conditions such as autoimmunity will typically be treated with medications and decrease inflammation and the particular organ system that is most affected. In many primary care practices, the goal is symptom relief and addressing pathological processes. 

Integrative Medicine Protocol for Fatigue

Receiving integrative medicine care for fatigue can help address the root cause while also providing symptomatic relief. Integrating a therapeutic diet and evidence-based supplements are helpful tools in this process.

Therapeutic Diet For Fatigue

Implementing an anti-inflammatory diet can help combat fatigue. Chronic low-grade inflammation is a contributing factor to many of the above-mentioned conditions that can lead to low energy, tiredness, and persistent fatigue. Rather than focusing on a single nutrient to counteract fatigue, creating a nutrition regimen of nutrient-dense whole foods has shown promising results. An anti-inflammatory diet consists of amino acids, omega-3 fatty acids, anti-oxidants, polyphenols, and probiotic-rich foods. 

In one review on the topic, it found that diets such as the “fatigue reduction diet”, the leaky gut diet, the Mediterranean diet, and the Nordic diet all had beneficial results in decreasing inflammation. Patients suffering from fatigue could benefit from these types of diets in addition to other lifestyle and therapeutic interventions. Rarely is it dietary changes alone that will improve fatigue, but it does play an important role in the whole picture. 

Best Supplements For Managing Fatigue

Along with diet and exercise, supplementation has the potential to alleviate symptoms of fatigue. 

Micronutrient Support

Providing the body with nutrients that you are deficient in can improve energy levels. Vitamin B12, Vitamin D, CoQ10, and Glutathione supplementation are all nutrients shown to reduce various forms of fatigue. Iron, magnesium, and zinc are micronutrients that, when depleted, can result in exhaustion, but restoration can revitalize you. It’s advised to test your levels through a comprehensive micronutrient panel, so you know what you are deficient in and what the appropriate nutrient and dosing should be. 

Herbal Supplements

Adaptogenic herbs typically benefit most when utilizing plant medicine for fatigue. Ashwagandha is one of the most widely used herbs for stress-related fatigue. This botanical is an excellent choice for those suffering from physical exhaustion, elevated cortisol, hypothyroidism, anxiety, and many other situations that result in fatigue. The recommended dosage is 500mg twice a day

Ginseng family herbal medicines have been used for centuries to enhance energy, stamina, and mental stress. Panax Ginseng was shown to be beneficial as an antifatigue intervention in patients experiencing idiopathic chronic fatigue. American Ginseng, also known as Panax quinquefolius, has shown similar results in reducing fatigue in people suffering from chronic illnesses. Dosing for Panax Ginseng starts at 200mg and goes up to 3 grams daily for three months. A general dosing for American Ginseng is 200-400mg twice daily for three to six months. As always, it’s best to consult with a holistic practitioner to determine your appropriate dosage. 

When To Retest Labs

The patient's clinical presentation and initial laboratory results play a key role when appropriate retesting is necessary. In acute fatigue caused by anemia, you’ll want to do follow-up blood work in a month to see if therapeutic interventions normalize the CBC and affected nutrients. In more chronic conditions such as Hashimoto’s or Lupus, monitoring the patient’s lab twice a year is the most clinically appropriate route. Many antibody markers will not shift quickly, and symptom presentation can provide more insight into the sometimes slowly shifting autoimmunity biomarkers. In cases of infections such as EBV and Lyme disease, you’ll want to do laboratory testing when flare-ups or worsening of symptoms are present. 



A functional medicine approach to fatigue can provide root cause answers and a comprehensive treatment approach. Through clinical expertise and specialized laboratory testing options, this integrative healthcare paradigm can be a valuable tool in your return to health. Taking the next steps to explore this holistic avenue could be key in your transformation from exhausted to vibrant. 

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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