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Are you constantly waking up feeling tired, yet facing another busy day at work? Do you survive on coffee, energy drinks or sugar laden foods to give you the energy to get through the day? Adrenal fatigue and chronic fatigue syndrome have both been linked to ongoing levels of chronic stress. Chronic stress, often from the pressures of work, finances, and family commitments can lead to high levels of burnout resulting in depression, anxiety and fatigue. The World Health Organisation (WHO) has classified stress as the “health epidemic of the 21st century.”

Fatigue is an extremely common condition and is most prevalent in females aged in their late 30’s to early 40s. It is the most common unexplained complaint presenting to GPs with just 4% of cases receiving a medical diagnosis after conventional lab testing. Worse still, 43% of cases are given a final diagnosis of ‘tiredness’1. Together with fatigue many people will experience depression and weight gain.

Fatigue is defined as “that state… characterised by a lessened capacity or motivation for work… usually accompanied by a feeling of weariness, sleepiness, irritability or loss of attention”1. Acute, or short-lasting fatigue results from short term sleep loss, or resulting from brief periods of physical or mental exertion. The affects of acute fatigue are short-lived and can usually be reversed with sleep and relaxation. Chronic fatigue is an often-debilitating condition which lasts six months or longer.

If you’ve been struggling with chronic fatigue you may be suffering from increased job or emotional stress resulting in burnout which can be measured via our DUTCH testing procedure. The most characteristic component of burnout is emotional exhaustion, feeling as if you’re over extended, depleted of emotional and physical strength. Burnout is often due to adrenal fatigue and can show up as low cortisol, a blunted Cortisol Awakening Response (CAR) and depression2.

Fatigue is often a symptom of other underlying conditions. Common causes of fatigue are;

- Nutrient deficiencies
- Fibromyalgia
- Adrenal Fatigue
- Thyroid problems
- Metabolic syndrome
- Mitochondrial dysfunction & Oxidative stress
- Hormonal imbalances like PMS

How we can help your underlying causes of fatigue;

1. Macro or micronutrient deficiencies 
It has long been established that nutrient deficiencies can cause fatigue. Identifying these deficiencies and more importantly the cause of such deficiencies is key in designing a program to help you recover from chronic fatigue and regain normal energy levels. I often see people in clinic who rely on caffeine or sugar to get through the day. This can often make fatigue levels worse in the long term.

Whilst standard blood tests are a good place to start for measuring imbalances in micronutrients such as Iron, functional lab testing can dive deeper in identifying other causes of your fatigue.

2. Mitochondrial Dysfunction: Mitochondria and the energy they produce play an essential role in health and disease.

Organic acid testing (OAT) can identify disturbances in the functioning of the mitochondria via the excretion via urine of TCA cycle intermediates and other organic acids related to mitochondrial function3. From your OAT, Dr Clegg can help you replace the necessary micronutrients to help restore mitochondrial function and regain normal energy levels 4-14. In addition to specific amino acids, vitamins and minerals, Dr. Clegg utilizes a novel Lipid Replacement Therapy (LRT) which due to its action on the mitochondrial membrane, has been shown to improve fatigue and aid in weight loss12,15.

Mitochondrial dysfunction is caused by a number of factors including; Heavy metals and environmental toxins18,19, gut health20, viruses21 and household pollutants such as mycotoxins (mould)18.

Fibromyalgia is an often debilitating, painful disorder which affects around 5% of the population, predominately women. It’s been suggested in the literature that mitochondrial dysfunction and oxidative stress has a role to play in the aetiology of fibromyalgia.
If you suspect that your fatigue is related to mitochondrial dysfunction speak with Dr. Clegg to organise functional lab testing.

3. Adrenal Fatigue (HPA axis dysfunction)

The chronic stress response and subsequent imbalances in cortisol can be extremely damaging to your health, resulting in fatigue and other conditions such as;

- Anxiety22
- Decreased immunity which can result in infections and intestinal inflammation23
- Development of food sensitivities and allergies24
- Depression25
- Type II Diabetes26
- Weight gain27
- Fibromyalgia and Chronic Fatigue Syndrome28

The Kalish Method of Functional Medicine and Clinical Nutrition as practiced by Dr Clegg can help you correct a dysfunctional HPA axis, improve your metabolic resilience and balance stress hormones such as cortisol29-32.

It is important to determine which “stage” of Adrenal Fatigue you are in before any treatment protocols are established2. To measure your Adrenal hormones Dr. Clegg prefers the DUTCH test as it provides a greater level of information than blood or saliva testing 33-36.

4. Thyroid problems

An underactive thyroid can often cause fatigue and has been associated with conditions such as fibromyalgia 8. Hypothyroidism has been linked to cortisol and adrenal dysfunction37. Hashimoto’s thyroiditis, the most common cause of an underactive thyroid is a type of autoimmune disorder. The root cause of which has been linked to increased intestinal permeability.


1. Wilson, J., Morgan, S., Magin, P., Van Driel, M. (2014) Fatigue – a rational approach to investigation. Australian Family Physician 43 (7) 457-461

2. Guilliams, T.G. (2015) The Role of Stress and the HPA Axis in Chronic Disease Management. Point Institute

3. Lord, R.S., Bralley, J.A. (2012) Laboratory Evaluations for Integrative and Functional Medicine. 2nd Ed. Metametrix Institute

4. Sugino, T., Aoyagi, S., Shirai, T., Kajimoto, Y., Kajimoto, O. (2007) Effects of Citric Acid and L-Carnitine on Physical Fatigue. J. Clin. Biochem Nutr., (41). 224-230

5. Harris, C.H., Chowanadisai, W., Mishchuk, D.O., Satre, M.A., Slupsky, C.M., Rucker, R.B. (2013) Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J. Nutr Biochem. (24) 2076 - 2084

6. Bralley, J.A., Lord, R.S. (1994) Treatment of chronic fatigue syndrome with specific amino acid supplementation. J. Applied Nutrition. 46 (3) 74 - 78

7. Haskell, C.F., Robertson, B., Jones, E., Forster, J., Jones, R., Wilde, A., Maggini, S., Kennedy, D.O. (2010) Effects of a multi-vitamin/mineral supplement on cognitive function and fatigue during extended multi-tasking. Hum. Psychopharmacol Clin Exp (25) 448 - 461

8. Gould, R.L., Pazdro, R. (2019) Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis. Nutrients 11 (1056) 1 - 21

9. Yamamano et al (2016) Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles. Nature Scientific Reports. 6:34990 | DOI: 10.1038/srep34990

10. Abraham, G.E et al (1992) Management of fibromyalgia: Rationale for the use of magnesium and malic acid. J. Nutr Medicine 3 (1) 49-61

11. Fluge, O et al (2016) Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. doi:10.1172/jci.insight.89376 

12. Nicolson, G.L. (2014) Mitochondrial Dysfunction and Chronic Disease - Treatment with Natural Supplements. Integrative Medicine. 13(4) 35-43

13. Kennedy, D.O et al (2016) Multivitamins and minerals modulate whole-body energy metabolism and cerebral blood-flow during cognitive task performance- a double-blind, randomised, placebo-controlled trial. Nutrition & Metabolism. 13 (11) 1-16

14. Heap, L.C et al (1999) Vitamin B status in patients with chronic fatigue syndrome. J. of the Royal Academy Medicine. 92. 183-185

15. Lipid Replacement Therapy Functional Food Formulation with NT Factor for Reducing Weight, Girth, Body Mass, Appetite and Fatigue While Improving Blood Lipid Profiles.pdf

16. Lipid Replacement Therapy with a Glycophospholipid-Antioxidant-Vitamin Formulation Significantly Reduces Fatigue Within One Week

17. Nicolson, G.L., Ash, M.E. (2014) Lipid Replacement Therapy/ A natural medicine approach to replacing damaged lipids in cellular membranes and organelles and restoring function. Biochimica et Biophysica Acta. 1838. 1657-1679

18. Jia, G et al. (2015) Mitochondrial Functional Impairment in Response to Environmental Toxins in the Cardiorenal Metabolic Syndrome. Arch Toxicol 89(2) 147-153

19. Meyer, J.N et al. (2013) Mitochondria as a Target of Environmental Toxicants. Toxicological Sciences. 134(1) 1-17

20. Jackson, D.N., Theiss, A.L. (2019) Gut bacteria signalling to mitochondria in intestinal inflammation and cancer. Gut Microbes
21. Ohta, A., Nishiyama, Y (2011) Mitochondria and viruses. Mitochondrion (11) 1-12

22. Brewer, J.H et al (2013) Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome. Toxins (5) 605-617

23. Faravelli, C et al (2012) Childhood stressful events, HPA axis and anxiety disorders. World Journal of Psychiatry. 2(1) 13-25

24. Campos-Rodriguez, R. et al (2013) Stress modulates intestinal secretory immunoglobulin A. Frontiers in Integrative Neuroscience 7(86) 1-10

25. Lin, T-K et al (2017) Association between Stress and the HPA Axis in the Atopic Dermatitis. Int. J. Mol. Sci. (18) 2131 1-15

26. Keller, J et al (2017) HPA Axis in Major Depression- Cortisol, Clinical Symptomatology, and Genetic Variation Predict Cognition. Mol Psychiatry 22(4) 1-26

27. Rosmond, R. (2003) Stress induced disturbances of the HPA axis/a pathway to Type 2 diabetes? Med Sci Monit 9(2) RA35-39

28. Bose, M et al (2009) Stress and obesity- the role of the hypothalamic–pituitary– adrenal axis in metabolic disease. Curr Opin Endocrinol Diabetes Obes. 16(5) 340-346

29. F. Tanriverdi et al (2007) The hypothalamo–pituitary–adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome, Stress, 10:1, 13-25, DOI:

30. Liao, L-Y et al (2018) A preliminary review of studies on adaptogens- comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide. Chin Med 13(57) 1-12

31. Panossian, A., Wikman, G. (2010) Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity. Pharmaceuticals (3) 188-224

32. Starks, M.A et al (2008) The effects of phosphatidylserine on endocrine response to moderate intensity exercise. Journal of the International Society of Sports Nutrition. 5(11) 1-6

33. Lee, D.Y. (2015) Technical and clinical aspects of cortisol as a biochemical marker of chronic stress. BMB Rep. 48(4): 209-216 

34. Vining, R.F. et al (1983) Salivary cortisol - a better measure of adrenal cortical function than serum cortisol. Ann Clin Biochem. 20: 329-335 

35. Hellhammer, D.H. et al (2009) Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology. 34, 163—171 

36. Clinical validity of DUTCH retrieved from: 

37. Walter, K.N. et al (2012) Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women. Thyroid Research 5(13) 1-6

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Dr. Adrian Clegg

When I began practicing eighteen years ago, people suffering from multiple debilitating conditions had few places to turn to receive the care they needed to get better. As the years have gone by, I began to realise that more and more people were suffering with chronic health problems—feeling tired, depressed, gaining weight, experiencing digestive problems, allergies and a host of hormone issues.

Over the years I have worked with 1000’s of people to help them overcome chronic health conditions using Functional Medicine and AO.

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