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Supporting clients with post-viral fatigue has long been an important focus for functional medicine and complementary healthcare practitioners. With many different possible underlying factors and no one-size-fits-all solution, it is a complex and chronic health problem for which conventional medicine has limited answers. A personalised approach that connects all the dots together is absolutely key. In this article we take a closer look at what post-viral fatigue is and highlight some of the therapeutic possibilities we may have in our toolkits.

What is post-viral fatigue?

The term ‘post viral fatigue’ describes a condition that can happen weeks or months after the initial onset of a viral infection. Any viral infection can trigger post viral fatigue; such as influenza, SARS-CoV-2 or the herpes family of viruses which includes Epstein Barr Virus (EBV). Post-viral fatigue or post viral fatigue syndrome is completely different to normal tiredness, can affect people of different ages and does not always relate to the severity of the initial viral infection. In addition to fatigue, other symptoms may include brain fog, headaches, joint pain, muscle soreness, sleep problems, depression and even recurring symptoms of viral infections such as sore throat and swollen lymph nodes.

What influences susceptibility?

There is no single known cause, no unifying theory as to why symptoms may persist in some people and not others, and limited understanding of why the presentation of post-viral fatigue can be so different from one person to the next. It is likely however that factors such as the specific virus involved, which organ system(s) are affected, viral load, inflammation, mitochondrial function, blood brain barrier integrity and oxidative stress may all influence susceptibility. There have also been similarities noted between post-viral fatigue and mast cell activation syndrome (MCAS) in some people.

It’s complex - so where do you begin?

• Inflammation
• Mitochondrial function
• Antioxidant status
• Blood brain barrier integrity
• Mast cell stabilisation

Let’s take a closer look at our post-viral fatigue toolkit:

Glutathione

It’s no coincidence that glutathione sits right at the top of this list. As world renowned naturopathic doctor and Institute of Functional Medicine (IFM) Chair Dr Joseph Pizzorno has said, “it is hard to overstate the importance of glutathione”. Mitochondrial dysfunction, oxidative stress and blood brain barrier alterations may all be significant factors contributing to post-viral fatigue. Mitochondria are often referred to as the energy-producing powerhouse of the cell yet they are highly vulnerable to damage from oxidative stress. In addition, factors such as infection, oxidative stress and inflammation can negatively impact the blood brain barrier – a crucial structure which separates and protects the central nervous system from peripheral tissues and restricts the entry of peripheral inflammatory mediators into the brain. Glutathione is often referred to as the body’s master antioxidant and provides essential protection for both mitochondria and the blood brain barrier against oxidative damage. Our bodies can make glutathione from the amino acids cysteine, glycine and glutamic acid, however cysteine is often considered to be a rate-limiting step. Supplementing with N-acetyl cysteine may thus help to support the body’s production of glutathione. Common genetic polymorphisms may mean some people are less effective at producing glutathione and they may benefit from supplementing with glutathione directly. It is important to note however that oral glutathione is known to have poor bioavailability and whilst research is limited, liposomal forms may be more effective.1,2

Alpha lipoic acid

Is a naturally occurring compound that we can synthesise ourselves and can be taken in supplement form. Alpha lipoic acid is both water and fat soluble and is an essential co-factor for several mitochondrial enzymes involved in energy production. Alpha lipoic acid is also an important antioxidant, has the potential to regenerate other key antioxidants such as glutathione, vitamin C and Co-enzyme Q10 and is involved in the activation of key antioxidant signalling pathways. Alpha lipoic acid has been shown to increase both intra and extra-cellular levels of glutathione3 and is widely regarded as a useful support for chronic health problems associated with oxidative stress.

Co-enzyme Q10 (CoQ10)

Is a fat-soluble ‘vitamin-like’ compound that is found in virtually all cell membranes, including mitochondrial membranes. CoQ10 plays an important role in mitochondrial function, ATP production and is an important antioxidant. Levels of CoQ10 tend to decline with age. Supplemental CoQ10 has been shown to have potential to impact markers of inflammation such as C-Reactive Protein (CRP) and Tumour Necrosis Factor- alpha (TNF-α).4 Deficiency of CoQ10 has been well documented in chronic fatigue syndrome and research has shown that supplementation with CoQ10 may help to improve symptoms such as fatigue and depression.5-7

Magnesium

Is often referred to as ‘nature’s tranquiliser’ for the key roles it has to play in supporting calm, relaxation and a balanced stress response, yet magnesium is also essential for energy production and muscle function. Magnesium is needed both for the production and utilisation of the body’s energy currency – ATP, and for proper mitochondrial function. In simple terms, without magnesium, the body can neither make nor use energy. Experimental evidence shows that magnesium deficiency can disrupt mitochondrial function,8,9 and it has been suggested that magnesium may have an important role to play in fatigue-related health problems such as chronic fatigue and fibromyalgia.10,11 It can be challenging to consume enough magnesium and it is used up rapidly during times of stress. It is interesting to note also that a deficiency of magnesium has been shown to induce the emergence of mast cells.12 Supplementation may be required to support optimal intake. Magnesium can be taken effectively in higher doses in the form of magnesium glycinate without unwanted gastrointestinal side effects. Magnesium malate is another effective form of magnesium which may be particularly useful for supporting muscle function.

Curcumin

Is the main active component of turmeric and is best known for powerful and widespread anti-inflammatory and antioxidant activity. Research has shown that curcumin has the ability to modulate many inflammatory pathways in the body and it has demonstrated significant antioxidant activity in vitro.13-15 As well as direct antioxidant activity, curcumin may also function indirectly by enhancing the synthesis of glutathione; studies have shown that curcumin increases cellular glutathione levels.16-18

Green tea

Is well known for its powerful antioxidant activity. One of the main bioactive molecules of green tea is epigallocatechin-3-gallate (EGCG), and in addition to its role as a powerful antioxidant, it has been shown to positively influence multiple inflammatory pathways.19

Quercetin

Is a bioflavonoid found in plants such as onions, berries, apples and capers. It has received much attention for its powerful potential to modulate inflammation. It also has direct antioxidant activity and is able to activate cellular defences against oxidative stress. Quercetin is considered to be able to cross the blood brain barrier making it a particularly valuable compound for neuronal protection against oxidative stress and inflammation. Several studies have demonstrated neuroprotective effects of quercetin, either against neurotoxic chemicals or in models of neuronal injury or neurodegenerative diseases. Quercetin may inhibit the release of histamine, prostaglandins and leukotrienes; three of the most common inflammatory mediators found in MCAS.20-22

Sulforaphane

Is a bioactive compound derived from cruciferous vegetables such as broccoli. It has been widely studied for its incredible ability to activate many different antioxidant pathways in the body. These antioxidant pathways are crucial for protecting mitochondria and the blood brain barrier against oxidative stress, and for keeping inflammation in check. Sulforaphane is not very stable and is highly reactive, whereas its immediate precursor glucoraphanin is very stable. Glucoraphanin requires an enzyme called myrosinase to enable its conversion to sulforaphane. Glucoraphanin derived from broccoli seeds is available in supplement form and this may be best supplied with a source of myrosinase such as mustard seed powder to support this conversion. Read more about the benefits of sulforaphane.

Omega-3

Fatty acids Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) have long been appreciated for the vital roles they play in supporting balanced inflammation. Ensuring optimal daily intake is therefore key, and especially for chronic health problems such as post viral fatigue where inflammation may be a significant underlying factor. Our bodies can use omega-3 fatty acids EPA & DHA as building blocks to produce incredible chemical mediators called Specialised Pro- Resolving Mediators or SPMs. SPMs are essential for switching inflammation off when it is no longer needed and are often described as inflammation’s ‘stop signals’. A daily supplement of omega-3 rich fish oil providing EPA & DHA may help to support the production of SPMS, or for more targeted support you may consider an omega 3 fish oil supplement enriched with additional support for the production of SPMs. Read more about SPMs.

B Complex

And last but most certainly not least it is important to ensure regular intake of the full range of B vitamins as essential co-factors for many different aspects of energy production, storage and utilisation processes throughout the body. Read more about this here. B complex vitamins are water soluble and thus it is important to ensure they are regularly included in the diet. B complex vitamins are also important for supporting a balanced stress response.

Post viral fatigue toolkit

• Glutathione
• N-Acetyl Cysteine
• Alpha Lipoic Acid
• Co-enzyme Q10
• Magnesium
• Curcumin
• Green tea
• Quercetin
• Sulforaphane
• Omega-3s
• B Complex

Read More
How to look after your blood brain barrier

5 ways to protect your mitochondrial health

Why SPMs are an important consideration for long Covid

The impact of specialised pro-resolving mediators on inflammation

Navigating our way through Long Covid

References:
1. Richie Jr. JP, Nichenametla S, et al. Randomised controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition. 2015 Mar; 54(2): 251-63.
2. Sinha R, Sinha I, Richie JP, Jr. et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur. J. Clin. Nutr. 2018, 72, 105–111
3. Han D, Handelman G, Marcocci L, et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997; 6: 321-338
4. Marc P & McRae DC Coenzyme Q10 supplementation in reducing inflammation: an umbrella review. Journal of Chiropractic Medicine. Volume 22, Issue 2, June 2023, Pages 131-137
5. Maes M, Mihaylova I, et al. 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.
6. Maes M, Mihaylova I, et al. Lower plasma Coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness. Neuro Endocrinol Lett. 2009;30(4):462-9
7. Mantle D, Parry Hargreaves IP, et al. Mitochondrial dysfunction and coenzyme Q10 supplementation in post-viral fatigue syndrome: an overview. Int J Mol Sci 2024, 25(1), 574
8. Killilea DW, Killilea AN. Mineral requirements for mitochondrial function: A connection to redox balance and cellular differentiation. Free Radical Biology and Medicine. Volume 182, March 2022, Pages 182-191
9. Pilchova I, Klacanova K, et al. The involvement of Mg2+ in regulation of cellular and mitochondrial functions. Oxid Med Cell Longev. 2017; 2017: 6797460.
10. Cox IM, Campbell MJ et al. Red blood cell magnesium and chronic fatigue syndrome. Lancet 1991 Mar 30; 337(8744): 757-60
11. Abraham GE & Flechas ID. Management of fibromyalgia: a rationale for the use of magnesium and malic acid. J Nutr Med 1992; 3: 49-59
12. Takemoto S, Yamamoto A, et al. Magnesium deficiency induces the emergence of mast cells in the liver of rats. J Nutr Sci Vitaminol, 59, 560-563, 2013.
13. Sreejayan, Rao MN. Nitric oxide scavenging by curcuminoids. J Pharm Pharmacol. 1997;49(1):105-107
14. Sreejayan N, Rao MN. Free radical scavenging activity of curcuminoids. Arzneimittelforschung. 1996;46(2):169-171.
15. Garcea G, Jones DJ, Singh R, et al. Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer. 2004;90(5):1011-1015
16. Dickinson DA, Levonen AL, Moellering DR, et al. Human glutamate cysteine ligase gene regulation through the electrophile response element. Free Radic Biol Med. 2004;37(8):1152-1159.
17. Dickinson DA, Iles KE, Zhang H, Blank V, Forman HJ. Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate- cysteine ligase gene expression. Faseb J. 2003;17(3):473-475.
18. Zheng S, Yumei F, Chen A. De novo synthesis of glutathione is a prerequisite for curcumin to inhibit hepatic stellate cell (HSC) activation. Free Radic Biol Med. 2007;43(3):444-453.

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