A Functional Medicine Approach to Fatigue

Fatigue is an extreme lack of energy that drives many to seek medical care. In the United States, at least 24% of adults report having fatigue, and two-thirds of these people cannot identify the cause. While fatigue can be a normal response to many physical activities and events, unrelenting fatigue warrants a medical workup. Unfortunately, results from conventional lab studies only affect medical management in 5% of patients, leaving many still needing solutions. (1)

Functional medicine doctors are expert detectives at diving deep into lifestyle factors that can negatively affect energy levels. By considering the complex interworkings of the body's systems, a holistic approach to fatigue can be more effective in improving symptoms.

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What is Fatigue?

Fatigue is a sense of severe tiredness, exhaustion, or lack of energy. Fatigue can be classified as secondary, physiologic, or chronic. Secondary fatigue is caused by an underlying medical condition, generally lasting less than six months. An imbalance in daily lifestyle routines causes physiologic fatigue; it usually resolves with rest and has minimal impact on the ability to perform activities of daily living. Chronic fatigue lasts longer than six months and does not improve with rest. (1, 2)

Fatigue Symptoms

Because many use the word "fatigue" to describe different sensations, it is worth having your patient clearly characterize what the word means to them. Many report fatigue in the context of being sleepy, lacking motivation or concentration, or decreased endurance.

Fatigue often occurs along with other symptoms, such as (3):

• Changes in mood: depression, anxiety, nervousness, and irritability
• Trouble concentrating
• Low motivation
• Muscle weakness
• Muscle and joint pain

Red flag signs and symptoms indicating a more serious cause of fatigue include (4):

• Unexplained weight loss
• Chronic fever
• Night sweats
• Enlarged, tender lymph nodes
• Difficulty breathing
• Confusion
• Coughing or throwing up blood

What Causes Fatigue?

There are many processes that can cause fatigue. Below are some of the most common ones:

Physiologic Fatigue

Physiologic fatigue results from situations that would cause most people fatigue. These may include (3):

• Prolonged periods of concentration, attention, and alertness
• Mental stress
• Over- or under-stimulation
• Lack of sleep due to shift work, jet lag, etc.
• Poor diet
• Sedentary lifestyle
• Excessive exercise without sufficient caloric intake for repletion
• Excessive alcohol intake

Medical Conditions

The differential diagnosis for fatigue is broad, as almost every disease can present with fatigue as a symptom. More often than not, prominent symptoms accompanying fatigue will provide clues to narrow the diagnosis.

The most common disorders that manifest primarily as recent fatigue lasting less than a month include adverse reactions from medications, anemia, mental stress, and depression (4).

The most common disorders that manifest primarily as fatigue lasting one to six months include diabetes mellitus, hypothyroidism, sleep apnea, and cancer (4).

The most common disorders manifesting primarily as fatigue lasting longer than six months include postviral fatigue, depression, chronic fatigue syndrome (CFS), and drug/substance abuse (4).

Sleep Disorders

Undiagnosed or unmanaged sleep disorders disrupt healthy sleep and contribute to pathologic fatigue. Examples include insomnia (having trouble falling and/or staying asleep), sleep apnea (reduced or stopped breathing during sleep due to the blockage of the airways), and narcolepsy (extreme daytime sleepiness and sudden, brief episodes of deep sleep).

Medications

Many commonly prescribed medications cause sleepiness as a common side effect. While this side effect may resolve as the body adapts to the medication, this is only the case for some. The most common culprits for medication-induced fatigue include:

• Antihistamines used for allergies, hives, and rashes
• Muscle relaxants
• Antidepressants
• Topiramate to treat seizures and prevent migraines
• Beta-blockers, commonly prescribed for cardiovascular conditions
• Opioids to treat pain
• Benzodiazepines used to treat anxiety, insomnia, and seizure disorders
• Antibiotics
• Chemotherapy

Environmental Exposures

Much environmental lead exposure is due to the past use of leaded gasoline, lead-based paint, and industrial facilities. Lead can also be found in various home products, including ceramics, water piping, and plastics.

A majority of mercury exposure results from eating fish and shellfish. Other common sources of mercury include occupational exposures and amalgam dental fillings.

Carbon monoxide is a colorless, odorless gas that competes with oxygen to bind to the oxygen-carrying protein in the blood, reducing the blood's ability to carry oxygen to vital organs. Vehicle exhaust, fuel-burning furnaces, fireplaces, and gas water heaters are all potential sources of carbon monoxide emission in the home.

Functional Medicine Labs to Test for Root Cause of Fatigue

The beginning of a fatigue evaluation should include a thorough review of the patient's complete list of medications and supplements, sleep routine and quality, exercise, and drug and alcohol use.

Fatigue often accompanies depression, so having a patient complete a screening PHQ-9 questionnaire can be helpful.

A complete physical exam can also provide many clues suggestive of secondary causes of fatigue. Be mindful of signs like lymphadenopathy (enlarged lymph nodes), cardiac murmur, goiter (enlarged thyroid) edema, poor muscle tone, and abnormal neurologic findings.

Preliminary lab work screens for the most common causes of fatigue if the patient's history and physical exam are not conclusive for obvious causative factors. Standard labs typically ordered in the initial workup of unexplained fatigue can indicate signs of infection, hormonal imbalance, blood sugar dysregulation, and other chronic diseases. Abnormal results can then be followed up with additional diagnostic blood work and imaging as indicated. Labs included in this general panel often include the following:

Complete Blood Count (CBC)

A CBC measures the blood's red blood cells, white blood cells, hemoglobin, hematocrit, and platelets. These markers screen overall health and can help identify anemia, infection, and nutritional deficiencies.

Comprehensive Metabolic Panel (CMP)

A CMP measures 14 markers related to the body's metabolic processes, including blood glucose, electrolytes, proteins, and liver and kidney function markers. Abnormal results can indicate liver/kidney diseases, electrolyte and nutrient deficiencies, and blood sugar imbalances contributing to fatigue.

Hemoglobin A1c (HbA1c)

HbA1c measures the average blood sugar over the last three months. It can be used to diagnose and monitor diabetes.

Thyroid Panel

Hypothyroidism is a prevalent cause of fatigue. Adrenal fatigue, nutrient depletion, and environmental exposures can contribute to low thyroid hormone levels. Even if your labs do not show overt hypothyroidism, precursory subclinical hypothyroidism can cause low energy. TSH is usually the only marker used to screen for thyroid dysfunction in the conventional world but can miss up to 7% of thyroid dysfunction. A complete thyroid panel includes multiple thyroid-related hormones and antibodies to screen for imbalances in the thyroid cascade that can contribute to fatigue.

Iron Panel

Iron deficiency contributes to low energy, mood disturbance, and iron-deficiency anemia (IDA). An iron panel measures six biomarkers associated with iron status in the body to diagnose suboptimal iron status.

Erythrocyte Sedimentation Rate (ESR)

ESR is an inflammatory marker that elevates in the presence of inflammation due to infection, autoimmunity, and cancer.

Urinalysis

A urinalysis is a urine test that can screen for urinary tract infections, kidney disease, and diabetes.

Pregnancy Test

A pregnancy test should be ordered for women of reproductive age to screen for pregnancy. Hormonal changes and common nutrient deficiencies associated with pregnancy can often cause fatigue in women.

Specialty testing not routinely ordered in a conventional setting but that can be helpful in the evaluation and management of unidentified fatigue include:

Comprehensive Hormone Assessment

Cortisol Awakening Response (CAR) measures the change in cortisol levels upon waking to help assess for adrenal dysfunction and stress.

Salivary cortisol and melatonin levels can be measured throughout the day to identify hormonal imbalances in the circadian rhythm contributing to excessive tiredness.

A comprehensive hormone panel, like the DUTCH Complete, assesses melatonin and cortisol, along with sex hormones and their metabolites, to give a broad overview of hormonal imbalances that can contribute to fatigue.

Food Sensitivities

Unidentified food sensitivities can contribute to low-grade systemic inflammation and often manifest as fatigue. A food sensitivity panel can identify adverse food reactions contributing to fatigue symptoms.

Nutritional Testing

A micronutrient test is a more comprehensive evaluation of common vitamins, minerals, and antioxidants that can contribute to fatigue and stress when depleted.

An organic acid test is another type of nutritional and metabolic screening that can identify mitochondrial dysfunction, nutrient deficiencies, dysbiosis, and hormonal imbalances leading to fatigue.

Conventional Treatment for Fatigue

Secondary fatigue is treated by addressing the cause. When possible, medications causing fatigue are replaced or discontinued. Maintenance of normal red blood cell markers and ferritin levels is a common goal in patients with cancer, renal disease, and anemia. Antidepressants have been shown to improve energy levels in patients with depression. (1)

Physiologic fatigue is addressed through lifestyle modifications and the formation of healthy sleep habits. Limiting naps to less than one hour in the early afternoon; minimizing light, screen, and noise exposure before bedtime; and avoiding caffeine, nicotine, alcohol, and excessive food/fluid intake in the evenings can enhance sleep quality and quantity. Using the bedroom for only sleep and sex and maintaining the same wake-up and bedtimes every day of the week are also helpful habits in supporting sleep health. (1)

Symptom management is the primary treatment focus for patients with CFS. Anti-depressants, pain medications, and counseling are common treatment recommendations. (1, 5)

Conventional treatment plans for any type of fatigue typically emphasize a structured exercise routine consisting of stretching and aerobic exercise. Stimulants like caffeine and modafinil may be prescribed for short-term use when alertness is required. (1)

Integrative Medicine Treatment for Fatigue

The conventional guidelines supporting healthy sleep hygiene and regular exercise routines are all fundamental aspects of an integrative treatment approach to fatigue. Your functional doctor may also recommend prescription medications to provide quick palliative relief as other imbalances are being corrected. A more holistic approach that integrates nutritional therapy, botanical medicine, and dietary supplements can effectively improve energy levels, so the long-term use of prescriptions is unnecessary.

Nutrition

Anti-inflammatory diets characterized by a high intake of polyunsaturated omega-3 fatty acids, antioxidant vitamins and minerals, polyphenols, and protein positively affect energy levels in patients with fatigue.

Peaks and dips in blood sugar causing hyper- and hypoglycemic events can negatively impact mood and energy levels. Eating balanced meals can ensure that blood sugar is stabilized throughout the day. Balancing complex carbohydrates with foods high in fiber, healthy fats, and protein will encourage blood sugar stability after and between meals.

Support the Adrenal Glands

Chronic stress and fatigue are signs that your adrenals are overworked. Supporting the adrenal glands and resetting the body's stress pathways can be important in treating fatigue, especially if results show abnormalities in CAR and cortisol. Along with eating a nutrient-dense diet focusing on foods rich in B vitamins, vitamins C and E, and magnesium, adaptogenic herbs like Ashwagandha, Schisandra, and Rhodiola effectively reduce feelings of stress and support adrenal function.

Lifestyle habits like avoiding caffeine late in the day and exposure to early morning light are also shown to reset the circadian rhythm and support healthy cortisol secretion patterns.  

Support the Thyroid

Ensuring optimal status of thyroid-supportive nutrients is crucial to supporting the thyroid; vitamins A, Bs, and D, selenium, magnesium, iron, and zinc can be maximized through diet and supplements. Correcting intestinal dysbiosis and maximizing detoxification pathways can also improve thyroid function.

Balance Sex Hormones

Imbalances in estrogen, progesterone, and testosterone can cause fatigue and contribute to feelings of depression and anxiety. Ensuring that each hormone is within optimal range and in a healthy ratio compared to one another can support mood and energy. Eating microbiome- and liver-friendly foods like garlic, artichokes, beans, dark leafy greens, and cruciferous vegetables support the elimination of excess estrogen. Reducing alcohol and caffeine intake can also help estrogen metabolism by decreasing stress on the liver. Chaste tree berry can help a healthy estrogen-to-progesterone ratio through its modulatory effects on the pituitary gland. Stress management and exercise, especially strength training, can optimize testosterone levels.

Treat the Gut

Chronic stress, dysbiosis, and inflammatory foods can increase the permeability of the gut lining and cause leaky gut syndrome. Leaky gut syndrome is correlated with low-grade systemic inflammation and many vague symptoms, including fatigue and brain fog. Additionally, intestinal inflammation often leads to nutrient malabsorption, contributing to dysfunctional cortisol secretion, hormonal imbalances, and anemia. Avoiding food sensitivities, probiotics, L-glutamine, and anti-inflammatory herbs like ginger and curcumin can aid in the restoration of the gut lining and intestinal microbiome.

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Summary

Treating fatigue can feel daunting, as many potential underlying causes must be ruled out. A comprehensive patient history and physical exam can provide many clues as to why fatigue may be occurring. Standard and specialty labs both have a role in ruling out serious underlying medical conditions and holistically evaluating for hormonal, immune, and nutritional imbalances that may be at play. Combining dietary and lifestyle modifications with botanical medicine and nutritional supplements to target identified imbalances can result in profound and lasting improvement in energy levels.