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Several nutritional deficiencies have been identified in patients with fatigue and widespread tenderness, including coenzyme Q10 (CoQ10) and carnitine, both absolutely critical in the cellular production of energy, proper cognitive function, and muscle function and metabolism.16,17 Studies also suggest that the use of supplements to include B vitamins, magnesium, and malic acid (malate) have shown positive results in FM patients.18-20 However, there is speculation that these interventions mainly aid in the biochemistry of energy production within the mitochondria of cells, including in muscles, which may alleviate the fatigue and muscle soreness often reported by patients diagnosed with FM, but they may not really be addressing issues specific to classic FM. In the author's experiences, in mild to moderate cases of fatigue and widespread achiness, supplementation with the above nutrients may have a significantly positive clinical effect. However, patients with severe fatigue usually do not respond adequately to these supplements alone, and require a more comprehensive functional approach. All of these functional disorders, and many more not mentioned, have the common denominator of potentially causing symptoms of low energy, fatigue, and widespread achiness, which are difficult to diagnose and often lead to an inappropriate diagnosis of FM.
The Importance of Optimal Thyroid Function
The thyroid gland is responsible for synthesizing several hormones that have vast effects on overall body metabolism. It is unique among endocrine glands in that large amounts of hormones are created and stored in the thyroid and then released very slowly. Iodine ingested from food and water is concentrated by the thyroid gland and combined with the amino acid tyrosine in various chemical configurations to create the active thyroid hormones triiodothyronine (T3) and thyroxine (T4). The numbers 3 and 4 are used to identify the number of iodine units incorporated into the hormone's structure. All reactions necessary for the formation of T3 and T4 are influenced and controlled by thyroid stimulating hormone (TSH), produced in the pituitary gland in the brain (see Figure 2).
As stated previously, thyroid function laboratory tests should be routinely performed in patients who present with complaints of widespread pain and fatigue in order to rule out overt hypothyroidism as the cause of these symptoms, including thyroperoxidase and thyroglobulin antibody tests to screen for cases of autoimmune thyroid conditions such as Graves' disease and Hashimoto's thyroiditis. However, more subtle presentations of thyroid dysfunction should also be considered, even when standard lab values are within normal range. Many cases of hypothyroidism will respond well to the use of common hormone replacement medications, such as Synthroid, Levothroid, or Levoxyl. However, these medications only contain synthetic L-thyroxine (T4). Many patients suffer from and inability to efficiently convert the relatively inactive T4 hormone to the much more active T3 hormone, often instead producing more of the relatively inactive reverse T3 (rT3) (see Figure 3).
This condition is sometimes referred to as euthyroid sick syndrome, low T3 syndrome, or thyroid peripheral conversion disorder. One possible reason for this can be elevations in the adrenal hormone cortisol due to acute or long-term stress. In these situations, patients often do not feel relief of their symptoms when placed on T4 thyroid hormone replacement therapy alone. The use of a combination of thyroxine (T4) and triiodothyronine (T3) therapy together (e.g., Armour Thyroid, Nature-Throid, or combination therapy of Synthroid and Cytomel) is very often required to adequately manage patients who do not adequately respond to T4 therapy alone. These patients may not have overt abnormalities on standard thyroid laboratory studies and may have been told that their thyroid is fine. Doctors need to pay close attention to patients' clinical symptoms and temperature, and also utilize closer inspection of laboratory testing and consider a trial of thyroid treatment for patients with clinical symptoms of hypothyroidism who have laboratory results in the lower part of the normal range for both total and free T3 and T4 and/or a TSH result in the upper part of the normal range. Since only the free (unbound) hormones can enter cells and bind to the thyroid hormone receptors on the cell nuclei, the free T3 and T4 hormones should be ordered and evaluated for comprehensive thyroid evaluation, something which is often not done by many conventional doctors, including endocrinologists. When these free hormones, particularly free T3, bind to the nuclear hormone receptor in a cell, they regulate DNA (genetic) control of various biochemical processes, thereby altering metabolism throughout the entire body. Lowered function of the thyroid gland, regardless of the cause, can result in profound physiologic effects throughout virtually all systems of the body. General signs and symptoms include fatigue, weakness, cold intolerance, low temperatures, weight changes (usually weight gain), and depression. Generally speaking, lower levels of thyroid hormone entering cells will slow overall metabolism and energy, while higher levels will increase overall metabolism and energy.14
Here's a checklist of symptoms that may be found in patients with a hypothyroid condition:
- Extreme fatigue/low energy
- Weight gain
- Muscle cramps/aches
- Difficulty with concentration
- Joint pain
- Inability to tolerate exercise
- Cold all the time
- Hard time remembering things
- Carpal tunnel syndrome
- Chronic infections
- High blood sugar
- Frequent postnasal drip
- High blood fats (cholesterol)
- Swollen look to face
It is the author's experience that undiagnosed subtle thyroid issues are one of the most prevalent reasons for complaints of fatigue, achiness, and cognitive dysfunction and the eventual misdiagnosis of FM, particularly in women. To learn more about functional hypothyroid disorders, please see the "Media/Articles" tab at DrDavidBrady.com.
Stress and the Adrenal Glands
It is also important for doctors to evaluate how the body responds to stress in all patients complaining of fatigue. This is often done by evaluating the status and functioning of the adrenal glands. This is necessary due to the fact that increases in adrenal catecholamines, the "fight-or-flight" stress hormones produced by the adrenal glands, and increases in the activity of the sympathetic nervous system have been implicated in FM. Evaluation of cortisol, another stress hormone produced by the adrenal glands, should also be assessed when screening for adrenal dysfunction. The pattern of low cortisol and elevated catecholamines is common in those diagnosed with FM and has also been associated with (PTSD, which may explain the common emergence of FM diagnoses in people who have undergone significant stress, life-altering events, and trauma.21 In patients with this classic pattern, psychological counseling and stress-reducing lifestyle modifications and cognitive behavioral therapy techniques are imperative.
In summary, there appears to be a certain subset of patients who may receive an inappropriate diagnosis of FM and do not display the entire spectrum of clinical elements indicative of classic FM, do not show any positive laboratory findings indicative of overt organic medical pathology or disease, yet have significant functional deficits in their metabolism and certain organ systems. The functional medicine approach to the treatment of these patients is not based on any one infectious agent or treatment modality as the curative, or even palliative, solution. It is based on the principle that restoration of proper cellular biochemistry and metabolism, in a manner unique to the individual's needs, through balancing the endocrine system, correction of nutritional deficiencies, and the reduction of cumulative toxic load and oxidative stress will allow normalization of mitochondrial function and cellular energy production, and ultimately lead to a reduction in the signs and symptoms of low energy, fatigue, and widespread achiness.23 Many of these factors can be addressed with simple lifestyle changes by the patient, including eating a varied and balanced fresh-food diet, consuming reasonable but targeted vitamin, mineral, and herbal supplements, and engaging in stress management techniques such as regular light exercise, proper sleep, adequate recreation and relaxation, deep-breathing exercises, guided imagery, yoga, meditation, prayer, biofeedback, and other forms of cognitive behavioral therapy.3
The old adage "diagnosis is half the cure" is certainly true. Very targeted and individualized treatment intervention is also key.
Basic General Supplementation Plan for Those Diagnosed with FM
This protocol can be helpful whether you actually have classic FM or not.
- Magnesium: 500–1000 mg per day in divided dosages (glycinate or malate form preferred)
- B-complex: 50–100 mg twice daily
- CoQ10 (oil-based soft gel): 100 mg twice daily
- L-carnitine: 500 mg 2–3 times daily
- 5-hydroxytryptophan (5-HTP): 50–100 mg 2–3 times daily (only under supervision)
- Melatonin (sustained release preferred): 3–6 mg 30 minutes prior to bedtime if patient is experiencing insomnia or unrefreshed sleep.
1. Avoid food allergens and caffeine.
2. The consumption of nonprocessed whole foods is critical in order to avoid chemical food additives as much as possible. Simple sugars should be limited as much as possible in the diet. A low allergy-sensitivity diet (avoid gluten, dairy, corn, etc.) should be followed for several weeks followed by reintroduction of foods one at a time in order to determine if any of these specific foods contribute to a worsening of symptoms. Variation in food consumption patterns should be strived for. Artificial sugar substitutes and caffeine should be entirely eliminated.
1. Keep predictable sleep patterns (in bed by 10 p.m., don't oversleep in morning)
2. Get moderate exercise, but do not overexercise
Current Drug Therapies
Treating all symptoms of central sensitization is the key focus of the three FDA-approved medications for FMS pain, including pregabalin, duloxetine, and milnacipran. In 2007 pregabalin (Lyrica), an alpha-2-delta (α2δ) ligand, became the first medication to gain FDA approval for treatment of FMS pain. Although, as with each of the three approved FMS medications, the exact mechanism of pregabalin's pain-relieving action is not yet clear, it is currently believed to function via reducing nervous system hyperexcitability. Pain reduction may also result from decreased release of pro-pain neurotransmitters in the spinal cord and through modulating pain transmission in the spinal cord.3
New Emerging Therapies
A recent Stanford University study using very low doses (3–4.5 mg at bedtime) of the medication naltrexone, an opiate blocker, demonstrated a 30% reduction in pain for all 10 of the patients in this small trial.23 Further research is called for, especially given the low cost and side-effect profile of this medication. Its mechanism of action is suspected to not be through its known opiate modulation capabilities, but instead may be through its pleomorphic anti-inflammatory and immune modulation capabilities and the possibility of its reducing the microglial inflammation deep in the brain now being reported in classic FM, though this still is yet to be clarified.24
Remember, Proper Diagnosis is Half the Cure
It is very important to know whether the patient is really are suffering from classic fibromyalgia (FM). You should never issue a diagnosis of FM unless you have fully explored all other possible causes for your patient's widespread pain and fatigue. This includes careful consideration of all other medical conditions, musculoskeletal problems, and functional metabolic issues. These other causes of widespread pain and fatigue are actually more common than classic FM and must be excluded or eliminated.
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David M. Brady, ND, DC, CCN, DACBN
Author of The Fibro-Fix, with Michael J. Schneider, DC, PhD