Chronic Fatigue

Chronic fatigue is not the normal feeling of tiredness after a full day of work or physical activity that is typically alleviated by rest. Rather, it is a sensation of exhaustion during or after usual daily activities, or a lack of energy to even begin these activities. Fatigue is associated with many medical conditions and is frequently the reason that people seek out medical help. In fact, it has long been recognized that an average of 20% of patients consulting primary care physicians will have fatigue as a complaint.1–5 However, more recent studies indicate that the prevalence may be even higher. One study of primary care physicians concluded that fatigue affects around one-third of the general population, with short-term fatigue (<6 months) at 5%, chronic fatigue (>6 months) at 31%, and Chronic Fatigue Syndrome-like fatigue at 1%.6,7 [It should be noted that Chronic Fatigue Syndrome or CFS (recently renamed by the Institute of Medicine as Systemic Exertion Intolerance Disease8 ) is distinct from general chronic fatigue. The diagnosis of CFS is based not only on duration and nature of fatigue but also upon specific accompanying symptoms.]

Chronic fatigue appears to be multidimensional; a single cause has not yet been identified. For the evaluation of fatigue, physicians will perform a detailed history and physical examination. In addition, the clinician will order conventional laboratory and other testing to rule out common causes such as viral infections, anemia, nutritional deficiencies, thyroid dysfunction, cardiovascular issues, or (more rarely) cancer. If such causes are found, treatments are oriented to that condition; for instance, iron supplements for anemia, medications for thyroid and/or blood sugar regulation, antibiotics for infections, recommendations for dietary and activity changes, etc.9

Studies have shown that conventional directed testing for fatigue is found abnormal in only around 5%-8% of cases.10,11 One recent observational cohort study of 571 patients with a 1-year follow-up12 found that clear somatic pathology was diagnosed in only 8.2% of fatigue patients. This leaves a large percentage of people continuing to struggle with the condition, leading to frustration for both patients and physicians. As these studies indicate, its non–specific nature and high prevalence make chronic fatigue a complex problem that deserves attention, not only as a symptom of underlying specific disease, but as a distinct clinical condition. 12

Specialty testing available through Genova Diagnostics can evaluate potential areas of dysfunction that have been associated with both chronic fatigue and CFS but which are not generally assessed in conventional diagnostics. These areas include in-depth nutritional status, environmental-toxin exposure, endocrine function, and gastrointestinal/immune function.

Nutritional: Studies have evaluated the association between specific nutrients and fatigue. Key nutrients include B-complex vitamins, amino acids, essential fatty acids, vitamin D, CoQ10, carnitine, magnesium, and zinc13 Specialty profiles to consider:

  1. NutrEval
  2. Organix Profile or Metabolic Analysis Profile
  3. Amino Acids Analysis or Amino Acids Profile
  4. Fatty Acids Profile or Essential and Metabolic Fatty Acids Analysis
  5. Elemental Analysis or Nutrient and Toxic Elements
  6. Vitamin D
  7. CoQ10+ Vitamin Profile

Environmental: Exposure to toxic elements (such as mercury) or to man-made toxic chemicals found in the environment has been associated with fatigue.14,15 Specialty testing can evaluate the body burden of such toxins. Profiles to consider:

  1. Toxic Element Clearance
  2. Toxic Effects Core


– There is a body of research relating fatigue to the hypothalamic-pituitary-adrenal axis; evaluation of circadian adrenal-hormone release can provide insight into increased risk for fatigue.1,16

– In–depth thyroid assessment (including those markers not routinely assessed in the conventional setting, such as reverse T3, anti-TG antibodies, and anti-TPO antibodies) provide understanding of both central and peripheral thyroid function, as well as thyroid auto-immunity.

– A decline or imbalance in reproductive-hormone production may be a factor in the symptom of fatigue.

Profiles to consider:

  1. Adrenocortex Stress Profile
  2. Comprehensive Thyroid Assessment
  3. Complete Hormones
  4. Complete Male Hormones

Gastrointestinal/Immune: Recent research indicates that chronic-fatigue patients exhibit marked alterations in microbial flora, compromised barrier function, and altered mucosal immunity.17 Specialty profiles to consider:

  1. GI Effects® or Comprehensive Digestive Stool Analysis (CDSA)™

Specialty testing provides additional valuable insight into the potential areas of dysfunction in chronic fatigue, including the central energy-production pathways, adrenal and thyroid hormone biomarkers, neurotransmitter metabolism and status of amino-acid precursors, functional micronutrient deficits, and potential toxin exposures.

1) King MS. Adrenal insufficiency: an uncommon cause of fatigue. The Journal of the American Board of Family Practice / American Board of Family Practice. Sep-Oct 1999;12(5):386-390.

2) Saulz J. Taylor's Cardiovascular Diseases: A Handbook. In: Taylor R, David AK, Fields SA, Phillips DM, Scherger JE, eds2005.

3) Buchwald D, Umali P, Umali J, Kith P, Pearlman T,Komaroff AL. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Annals of internal medicine. Jul 15 1995;123(2):81-88.

4) Kroenke K, Wood DR, Mangelsdorff AD, Meier NJ, Powell JB.Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA : the journal of the American Medical Association. Aug 19 1988;260(7):929-934.

5) Pawlikowska T, Chalder T, Hirsch SR, Wallace P, WrightDJ, Wessely SC. Population based study of fatigue and psychological distress. BMJ (Clinical research ed.). Mar 191994;308(6931):763-766.

6) Gendelman O, Amital H. Is it tiring to deal with fatigue? The Israel Medical Association journal : IMAJ. Sep 2012;14(9):566-567.

7) van't Leven M, Zielhuis GA, van der Meer JW, Verbeek AL,Bleijenberg G. Fatigue and chronic fatigue syndrome-like complaints in the general population. European journal of public health. Jun 2010;20(3):251-257.

8) IOM. Beyond my algicencephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington,DC: Institute of Medicine; 2015.

9) Fatigue. 2015;

10) Moses S. Fatigue. [Electronic]. 2012; Accessed September 25, 2014.

11) Lane TJ, Matthews DA, Manu P. The low yield of physicalexaminations and laboratory investigations of patients with chronic fatigue. The American journal of the medicalsciences. May 1990;299(5):313-318.

12) Nijrolder I, van der Windt D, de Vries H, van der Horst H.Diagnoses during follow-up of patients presenting with fatigue in primary care. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. Nov 102009;181(10):683-687.

13) Brown BI. Chronic fatigue syndrome: a personalizedintegrative medicine approach. Alternativetherapies in health and medicine. Jan-Feb 2014;20(1):29-40.

14) Wojcik DP, Godfrey ME, Christie D, Haley BE. Mercurytoxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand generalpractice setting (1994-2006). Neuroendocrinology letters. Aug 2006;27(4):415-423.

15) Bell IR, Baldwin CM, Schwartz GE. Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia. The American journal of medicine. Sep 28 1998;105(3A):74S-82S.

16) Nater UM, Maloney E, Boneva RS, et al. Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. The Journal of clinical endocrinology and metabolism. 3/20082008;93(3):703-709.

17) Lakhan SE, Kirchgessner A. Gut inflammation in chronic fatigue syndrome. Nutrition &metabolism. 2010;7:79.

Order Test Kits