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10 Nutrient Deficiencies Reported in Chronic Fatigue Syndrome

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Because the FDA has not yet approved a drug to treat ME/CFS, current chronic fatigue syndrome treatments focus primarily on managing symptoms. Protocols used may include pharmaceuticals (prescribed off-label), nutritional supplements, a variety of complementary therapies and various coping techniques.

A review in the January 2019 issue of the Biomedicine & Pharmacotherapy journal looked into the role nutrition and nutritional deficits play in the pathogenesis of chronic fatigue syndrome. A team of international researchers analyzed 27 studies related to nutritional interventions for ME/CFS. The authors noted 10 specific nutritional deficiencies that “appear to be important in the severity and exacerbation of CFS symptoms.”(1)

10 Nutrients Found Deficient in Chronic Fatigue Syndrome Patients


1. Vitamin C

Several studies have shown that vitamin C supplementation can bolster immune response, reduce inflammation, prevent oxidative stress and improve blood vessel health.(2,3,4) In one study, 25 disabled CFS patients with blood cell abnormalities were given 15 g of intravenous vitamin C. Within minutes, the abnormalities were corrected in 100% of the CFS patients.(5)

2. Vitamin B complex

The B-complex vitamins are known to play an important role in energy production, the proper function of the central nervous system and the repair of damaged cells as well as the creation of new ones. A 2014 clinical trial compared a multivitamin/mineral supplement containing a vitamin B complex and a placebo in 38 women with ME/CFS. After two months, the women taking the supplement reported decreases in fatigue, sleep disorders and autonomic nervous system symptoms. In addition they also experienced a reduction in the frequency and intensity of headaches.(6)

3. Sodium

Orthostatic intolerance (OI)––the inability to maintain a steady blood pressure and/or heart rate while upright––is common in ME/CFS. One of the underlying causes of OI is an endocrine dysfunction that results in the body being unable to hold onto sodium and fluids, which in turn creates lower than normal blood volume.(7) A common recommendation for treating OI is to increase salt and water intake.(8)

4. Magnesium

A magnesium deficiency has been connected to a number of illnesses, including ME/CFS. For example, a 1991 study found that 20 patients with ME/CFS had lower red cell magnesium concentrations than did 20 healthy matched controls. In the associated clinical trial, 32 ME/CFS patients received either intramuscular magnesium sulfate or a placebo every week for six weeks.

The patients treated with magnesium reported having improved energy levels, a better emotional state, and less pain. Red cell magnesium returned to normal in all of the patients on supplemental magnesium, but in only one patient on placebo. The authors concluded that magnesium may have a role in ME/CFS.(9) Several ME/CFS specialists, including Daniel Peterson, MD, Jay Goldstein, MD, Jacob Teitelbaum, MD, Charles Lapp, MD, and Paul Cheney, MD, recommend magnesium for muscle health and improved energy.

5. Zinc

A 2006 study found that serum zinc concentrations were significantly lower in chronic fatigue syndrome patients than in normal controls. The researchers also discovered a trend toward a significant negative correlation between serum zinc and the severity of CFS. Their findings “show that CFS is accompanied by a low serum zinc status and that the latter is related to signs of inflammation and defects in early T cell activation pathways.” The authors concluded, “The results of these reports suggest that some patients with CFS should be treated with specific antioxidants, including zinc supplements.”(10)

6. Folic acid

There is quite a bit of controversy surrounding the use of folic acid, which is the synthetic form of folate. ME/CFS specialist Charles Lapp, MD explains how this relates to people with ME/CFS:

MTHFR (or methylenetetrahydofolate reductase) is an enzyme required to convert folate to methionine, which is then used in the production of necessary amino acids and other compounds. When MTHFR genes are mutated, then MTHFR is not produced well, homocysteine (thought to be involved in atherosclerosis and other health issues) builds up and essential proteins are not made. There are at least 40 different MTHFR mutations known, but the two that occur at positions C677T or A1298C are most problematic. These occur in over 30% of individuals, but seem to be more common in [people with ME/CFS], in my experience.

The “treatment” is to take methyl-folate and methyl-cobalamin (B12), which is recommended for most [people with ME/CFS] anyway, so it is not necessary to take the blood test for these mutations. I generally recommend 400 to 1000 mcg of methyl-folate daily, and 1000 to 5000 mcg of methyl-B12, both of which are available over-the-counter.

7. L-carnitine

L-carnitine is an amino acid derivative that is essential for mitochondrial energy production and has been found to be low in people with ME/CFS.(11,12) A study of 30 CFS patients compared the anti-viral drug amantadine (Symmetrel) with 1 g of L-carnitine taken three times/day for two months. The authors noted that the L-carnitine was tolerated much better and resulted in greater clinical improvement than the amantadine.(13)

8. L-tryptophan

According to an article in the International Journal of Tryptophan Research, “There are several possible explanations for the observed decrease in tryptophan levels in CFS/FM patients. This decrease may be due to any primary genetic disorder, or may be due to malabsorptions created by an idiopathic irritable bowel syndrome, food intolerances, bacterial overgrowth and other bowel disorders. Silent or chronic infections can increase metabolic demands for tryptophan and vitamin B12. Nicotinamide absorption can be reduced through severe diarrhea. These listed observations imply that tryptophan, nicotinamide and B12 deficiencies can become a complication of CFS/FM.”(14)

9. Essential fatty acids

A 2005 study examined poly-unsaturated fatty acid (PUFA) levels in CFS. The research showed “that a decreased availability of omega-3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with––amongst other things––omega-3 PUFAs, such as EPA and DHA.”(15) The Omega-3 fatty acids DHA and EPA support the body’s cell membranes and effectively modulate the body’s inflammatory pathways. They are abundant in fish oil and krill oil.

10. Coenzyme Q10

Coenzyme Q10 (CoQ10) is present in virtually every cell in the body and is an essential component of each cell’s ability to produce energy. It is the job of the mitochondria to produce energy in the form of adenosine triphosphate (ATP). CoQ10 is the catalyst that makes it possible for the mitochondria to do their job. In two studies, both published in the International Journal of Clinical and Experimental Medicine, Dr. Sarah Myhill and colleagues demonstrated that the mitochondria are clearly dysfunctional in ME/CFS patients.(16,17) A 2009 study showed a close correlation between CoQ10 levels and severity of ME/CFS, especially related to fatigue, cognitive problems and autonomic symptoms. That same study identified low CoQ10 levels as a risk factor for cardiovascular disorders and early mortality in ME/CFS patients.(18)

Karen Lee Richards is ProHealth’s Editor-in-Chief. A fibromyalgia and ME/CFS patient herself, she co-founded the nonprofit organization now known as the National Fibromyalgia Association (NFA) in 1997 and served as its vice-president for eight years. She was also the executive editor of Fibromyalgia AWARE magazine. After leaving the NFA, Karen served as the Guide to Fibromyalgia and Chronic Fatigue Syndrome for the New York Times website About.com, then worked for eight years as the Chronic Pain Health Guide for The HealthCentral Network before coming to ProHealth. To learn more about Karen, see “Meet Karen Lee Richards.”



1. Bjørklund, G., Dadar, M., Pen, J., Chirumbolo, S. and Aaseth, J. (2019). Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach. Biomedicine & Pharmacotherapy, 109, pp.1000-1007. doi: 10.1016/j.biopha.2018.10.076

2. Qian L, Pan N, Gong J. [Change of NOS activity in hypoxia and cold-induced blood vessels damage and its biological significance]. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. Jan 2001;35(1):57-60.

3. Bryer SC, Goldfarb AH. Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise. International journal of sport nutrition and exercise metabolism. Jun 2006;16(3):270-280. https://www.ncbi.nlm.nih.gov/pubmed/16948483

4. Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Alt Med Rev 2000;5:93-108. https://www.ncbi.nlm.nih.gov/pubmed/10767667

5. Ali M. Ascorbic acid reverses abnormal erythrocyte morphology in chronic fatigue syndrome. Am J Clin Pathol 1990;94:515.Abstract #117.

6. Maric D, Brkic S, Mikic AN, Tomic S, Cebovic T, Turkulov V. Multivitamin mineral supplementation in patients with chronic fatigue syndrome. Med Sci Monitor 2014;20:47-53. doi: 10.12659/MSM.889333

7. Streeten DHP, Bell D. “Circulating blood volume in chronic fatigue syndrome.” Journal of Chronic Fatigue Syndrome (1998) Vol 4(1). http://www.ncf-net.org/library/Bell.htm

8. Rowe PC. “General Information Brochure on Orthostatic Intolerance and its Treatment.” Dysautonomia International (March 2014) p. 4-5. http://www.dysautonomiainternational.org/pdf/RoweOIsummary.pdf

9. Cox IM, et al. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991 Mar 30;337(8744):757-60. https://www.ncbi.nlm.nih.gov/pubmed/1672392

10. Maes M, Mihaylova I, De Ruyter M. Lower serum zinc in chronic fatigue syndrome (CFS): Relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. J Affective Disorders 2006;90:141-147. doi: 10.1016/j.jad.2005.11.002

11. Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis 1994;18(supplement 1):S62-S67. https://www.ncbi.nlm.nih.gov/pubmed/8148455

12. Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology 1995;32:132-138. https://www.ncbi.nlm.nih.gov/pubmed/8544970

13. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsychobiology 1997;35:16-23. doi: 10.1159/000119325

14. Blankfield A, A Brief historic overview of clinical disorders associated with tryptophan; The relevance to chronic fatigue syndrome (CFS) and fibromyalgia (FM). International Journal of Tryptophan Research. 2012; 5: 27–32. doi: 10.4137/IJTR.S10085

15. Maes M, Mihaylova I, Leuris JC, In chronic fatigue syndrome, the decreased levels of omega-e poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Neuro Endocrinol Lett. 2005 Dec;26(6):745-51. https://www.ncbi.nlm.nih.gov/pubmed/16380690

16. Myhill S, Booth NE, McLaren-Howard J, Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med (2009) 2, 1-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/

17. Booth NE, Myhill S, McLaren-Howard J, Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med 2012;5(3):208-220. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403556/

18. Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett. 2009;30(4):470-6. https://www.ncbi.nlm.nih.gov/pubmed/20010505

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By ProHealth-Editor

Karen Lee Richards is ProHealth’s Editor-in-Chief. A fibromyalgia patient herself, she co-founded the nonprofit organization now known as the National Fibromyalgia Association (NFA) and served as its vice-president for eight years. She was also the executive editor of Fibromyalgia AWARE, the very first full-color, glossy magazine devoted to FM and other invisible illnesses. After leaving the NFA, Karen served as the Guide to Fibromyalgia and Chronic Fatigue Syndrome for the New York Times website About.com, and then for eight years as the Chronic Pain Health Guide for The HealthCentral Network.To learn more about Karen, see "Meet Karen Lee Richards."

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