LONG COVID

Long covid part 2 – the mitochondria

As discussed in part one, long covid is a phenomenon which is multi factorial and symptoms experienced are varied but include breathlessness, a cough that won’t go away, joint pain, muscle aches, hearing and eyesight problems, headaches, loss of smell and taste as well as damage to the heart, lungs, kidneys and gut. However, the most common feature is significant fatigue which occurs following infection with covid19, the coronavirus SARS-CoV2. It is estimated that as many as 1.1 million people in the UK may have long COVID and the National Institute for Health Research (NIHR) released a review suggesting it could be multifactorial.

In part one we discussed the pathogenesis underlying this condition, including inflammation (and neuroinflammation), mitochondrial dysfunction, dormant viruses and the damaged caused by infection of Covid19. It also highlighted interventions which should be considered as well as nutrients associated with ameliorating these dysfunctions.

Skip to Key Takeaways

In part 2 we consider further the role of mitochondrial dysfunction. As mitochondria are the power houses of every cell, not only can damaged mitochondria affect energy levels but also the function of any of the body’s cell type, leading to suboptimal function of organ systems, therefore can contribute to multiple symptoms, as seen in long covid patients.

It has been found that long covid has many manifestations which may differ among individuals. One surprise has been that even with moderate COVID patients there are a number who find it difficult to recover. Their exercise tolerance takes a long time to return — 2 to 3 months or even longer. Some patients have residual palpitations and persistent tachycardia without any residual inflammation in the blood. Other symptoms which include neurological headache, myalgia, dizziness, and fatigue are the most common nonspecific symptoms seen in COVID-19 patients. These symptoms range from 30% to 45.5% and are more common as the disease is severe. We aim to investigate the likelihood that damage to the mitochondria may be a major factor both in the short term and in in the persistence of long covid.

It is known that increased severity of Covid19 infections is associated with a cytokine storm leading to hyperinflammation. One consequence of this is iron dysregulation which leads to hyperferritinaemia (high levels of circulating iron in the blood), caused by exhausted dying cells releasing ferritin. These high iron levels can create oxidative stress leading to an increase in reactive oxygen species (ROS). We know that high levels of oxidative stress from ROS damage mitochondrial membranes leading to mitochondrial dysfunction and or autophagy (as discussed in previous).

Although most mitochondria reside in the cytosol of cells, some are “cell-free” where they are found in non-nucleated platelets, extracellular vesicles and in extracellular space. It is thought that increased oxidative stress to platelet mitochondria may play a role in coagulation and therefore thrombus formation. The presence of thrombi, particularly in the lungs, are a consequence of severe Covid19 infection and may contribute to lung damage associated with long covid.

Inflammatory cytokines associated with covid infections, TNFα and IFγ increase mitochondrial oxidation by increasing calcium dependant mitochondrial ROS and genes which induce mitochondrial ROS generation respectively. Further exacerbating mitochondrial dysfunction.

When the mitochondria are oxidised, dysfunctional and/or apoptotic a myriad of problems occur. Firstly, there is reduced mitochondrial oxygen consumption, leading to lipid peroxidation which is associated with many pathologies including endothelial dysfunction and disrupted glucose signalling. Both may be implicated in fatigue and cardiovascular issues which are experienced in long covid.

It has also been discovered that patients with Covid19 have raised cardiolipin antibodies, which are responsible for supporting the membranes of mitochondria therefore leading to further mitochondrial instability and therefore dysfunction.

Therefore, one of the main interventions for supporting long covid is to reduce oxidative stress and support mitochondrial function and hence energy production.

As iron dysregulation appears to be a driver of oxidative stress in covid19 infection, it is prudent to avoid supplementation with high levels of iron. However, if anaemia is present and iron levels are found to be suboptimal this needs to be addressed.

The presence of poor exercise tolerance, tachycardia and palpitations may also give an indication that the cardiovascular and respiratory system are still under stress. Supporting mitochondrial function and ATP production in cardiac tissue may be useful in ameliorating these symptoms.

How can we support mitochondrial function?

Supporting mitochondrial function involves providing mitochondria with the nutrients required for energy production and health and reducing damage caused by oxidative stress from ROS by providing antioxidant support and reducing factors which can lead to excess oxidation.

Nutrients that support chemical energy production by mitochondria:

Benfotiamine (B1) – Co factor in the essential step which converts pyruvate into acetyl CoA

Riboflavin (B2) – Also known as FAD, accepts electrons and donates to the electron transport chain (ETC) in order to produce ATP (energy)

Nicatinomide Riboside (B3) – Also known as NADH (similar to FAD) accepts and donates electrons to ETC in order to produce ATP.

Pantothenic Acid (B5) – carrier of Coenzyme A, essential for Acetyl CoA and therefore energy production

CoQ10 (Ubiqinol) – utilised as a carrier in complex II of ETC. CoQ10 also has antioxidant properties and is found in high concentrations in the head and mid-piece of the sperm. It is considered to promote motility, foster sperm survival and provide optimal energy.

Alpha Lipoic Acid – a coenzyme of pyruvate dehydrogenase and a-ketoglutarate; enzymes responsible for reactions involved in the breakdown of fat and carbohydrate within the mitochondria

Magnesium – binds to ATP and affects its structure making energy more easily available.

All of the above nutrients are directly involved in metabolism reactions which occur in the mitochondria in order to produce energy, any deficiencies of the above nutrients can affect the rate of energy production.

There are other nutrients that are not directly involved in the chemical pathways of metabolism but are however important for energy production and maintaining mitochondrial function such as;

L-Carnitine – plays a vital role in fatty acid metabolism, transporting fatty acids into the mitochondria to be converted into energy and again a deficiency can lead to reduce energy production. Carnitine concentrations have been found to be very high in the epididymis and testes.  Studies which have compared fertile and infertile men have found that fertile men have statistically significantly more carnitine in their seminal sample than infertile men. Also low levels of plasma carnitine are associated with infertility.

Omega 3 Fatty Acids – can be incorporated into the mitochondrial membrane, which aids fluidity of the membrane and therefore signalling. Omega 3 fatty acids are also very important for cell and mitochondrial membranes and hence their stability.

We can also help to protect our mitochondria by ensuring that we are consuming adequate levels of antioxidants. The antioxidant of particular importance for the mitochondria is glutathione which is our own intrinsic intracellular antioxidant. Although we are normally able to manufacture our own glutathione, when oxidative stress is in excess or if nutrients that are required to manufacture it are deficient, pathways  can become overwhelmed leading to reduced levels of production. Nutrients that support production of glutathione are;

Liposomal Glutathione – this bypasses degradation within the gut and is absorbed directly across the digestive lining and can cross the blood-brain barrier.

N-Acetyl Cysteine (NAC) – regulates synthesis of and is an effective precursor to glutathione. Often used ahead of treatment with liposomal glutathione when there is a high circulating level of ROS, as encourages conjugation and elimination.

Alpha Lipoic Acid – has the ability to induce enzymes required for glutathione synthesis

Selenium – constituent of glutathione and precursor for the production of glutathione peroxidase

Vitamin C – an antioxidant in its own right but also has the ability to regenerate glutathione. Studies have also shown that supplementation can lead to an improvement in viability and motility reduced numbers of abnormal sperm and reduced sperm agglutination.

Other antioxidants have the ability to reduce oxidative stress by neutralising free radicles and could be considered to support mitochondrial function in doing so. These include carotenoids, flavonoids, vitamin E, vitamin A and zinc, this list is not exhaustive. You can ensure that you are obtaining good levels of antioxidants in the diet by:

  • Eating a rainbow (different colours of fruit and vegetables contain differing phytonutrients which have antioxidant properties)
  • Consume herbs and spices including turmeric, garlic and ginger.
  • Include polyphenols found in olives, 70%+ dark chocolate (1-2 squares) and small quantities of red wine.
  • Consume antioxidant containing teas such as green tea and roobosh.

D-Ribose – may be useful is it support ATP production by encouraging re-phosphorylation particularly within muscle including cardia muscle it is used effectively in chronic fatigue patients and scan also improve exercise tolerance.

It is also important to consider the way in which excess oxidative stress and occur and therefore reducing sources of oxidation can be useful.

Factors that contribute to oxidative stress include:

    • Smoking
    • Obesity
    • Inflammation
    • High stress levels
    • High sugar diet
    • Consumption of trans and hydrogenated fats
    • Pollution
    • Chemicals from household products, toiletries and cosmetics

Reduction of exposure to the above can help reduce free radicals and oxidative stress.

Key Takeaways

  • Excess inflammation during severe covid19 infection leads to iron dysregulation which contributes to oxidative stress and mitochondrial dysfunction, this potentially is contributing to the development of long covid.
  • Poor tolerance to exercise, residual palpitations and persistent tachycardia without any residual inflammation therefore highlighting other pathologies may be at play
  • Mitochondrial dysfunction affects every cell in the body and is therefore likely to play a role in long covid, particularly with fatigue as well as neurological dysfunction
  • Interventions to support mitochondrial function includes providing essential nutrients utilised by the mitochondria including CoQ10, B vitamins, L-carnitine an alpha lipoic acid.
  • Interventions also include anti-oxidant support such as zinc, n-acetyl cysteine, vitamin C and glutathione.

If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.

helen@cytoplan.co.uk
01684 310099

Amanda Williams and the Cytoplan Editorial Team


References

  1. Abboud H, Abboud FZ, Kharbouch H, Arkha Y, El Abbadi N, El Ouahabi A. COVID-19 and SARS-Cov-2 Infection: Pathophysiology and Clinical Effects on the Nervous System. World Neurosurg. 2020;140:49-53. doi:10.1016/j.wneu.2020.05.193
  2. Nile SH, Keum YS, Nile AS, Jalde SS, Patel RV (2017) ‘Antioxidant, anti-inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives’, J Biochem Mol Toxicol, 32:e22002.
  3. Textbook of functional medicine. 2008. Institute for Functional Medicine.
  4. inha R, Sinha I, Calcagnotto A, Trushin N, Haley JS, Schell TD, Richie JP Jr. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018 Jan;72(1):105-111. doi: 10.1038/ejcn.2017.132. Epub 2017 Aug 30. PMID: 28853742; PMCID: PMC6389332.
  5. Agrawal M, Ajazuddin, Tripathi DK, Saraf S, Saraf S, Antimisiaris SG, Mourtas S, Hammarlund-Udenaes M, Alexander A. Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer’s disease. J Control Release. 2017 Aug 28;260:61-77. doi: 10.1016/j.jconrel.2017.05.019. Epub 2017 May 24. PMID: 28549949.
  6. Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006 Nov;12(9):857-62. doi: 10.1089/acm.2006.12.857. PMID: 17109576.
  7. Depeint F, Bruce WR, Shangari N, Mehta R, O’Brien PJ. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact. 2006 Oct 27;163(1-2):94-112. doi: 10.1016/j.cbi.2006.04.014. Epub 2006 May 1. PMID: 16765926.

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17 thoughts on “Long covid part 2 – the mitochondria

  1. It’s good that you say what nutrients would help but would be better if you listed which products you have that contain them with a link to buy. Thank

    1. Hi Rachel – Thank you for your comment, although we would like to include supportive products we are not allowed to attach these to public articles. If you would like further information regarding support for long covid please contact our nutritional therapist Helen Drake (helen@cytoplan.co.uk)

  2. What would be helpful after this article is to include links to your products that offer these vitamins and supplements

    1. Hi Claire – Thank you for your comment, although we would like to include supportive products we are not allowed to attach these to public articles. If you would like further information regarding support for long covid please contact our nutritional therapist Helen Drake (helen@cytoplan.co.uk)

  3. Seems to be a very comprehensive article. Thank you. I am doing most of what you suggest already because I had ME following glandular fever approx 40 years ago. Dread getting covid!

  4. Thanks for these articles, which are the first factual discussions of long covid that I’ve read. What would be really useful as a part 3 is a list of foods that people can consume to maximise the nutrients referred to. For example, every day people should aim to consume a few Brazil nuts for selenium, etc. This would give people the tools to support themselves and to identify where they might choose supplementation to support. Otherwise there’s a danger that either people will spend a fortune on supplements and/or that the factual benefits of these articles will be lost on others if they assume the main purpose is to sell supplements. I’ll be sharing this I for 8 widely and would like to be able to say, yes it’s from a supplement company but they are actively encouraging people to get their nutrients from diet where possible.

    1. Hi Angela – Thank you for your comment. Yes diet is always our number one medicine. And we will always start here and diet interventions are essential for reducing inflammation, supporting gut health, balancing blood sugar and supporting a normal stress response. However it is almost impossible to achieve therapeutic levels of nutrient (especially those needed in long covid) from diet alone, this is for multiple reasons; soil depletion, sedentary lifestyle reducing food intake, intensive farming, stress, medication, gut health (this is not an exhaustive list, for more details see our blog the nutrition gap. For example although brazil nuts are suppose to be rich in selenium, the soils are now extremely depleted so they do not have the levels they should in them, there is also a caveat to consuming high amounts of brazil nuts such as excess omega 6 which is pro-inflamamtory and therefore not helpful for long covid. Although we are a supplement company we are charity owned and therefore are not driven by profit making shareholders, however the nutrition gap, caused by nutrient depletion in our foods, is at the heart of our ethos, therefore this may be contradictory to this. We often cite food sources of all nutrients on top but the solution is not completely straight forward. I hope this helps.

      1. Great article ! Thank you ever so much to educate people , even more i this very difficult times .
        I’m very grateful and happy being your customer for long time , and I’m so grateful for this fantastic article to help me as I have MS autoimmune and very scary . I’m following this as much as I could and taking your excellent products .
        Please continue to educate & info us in the future .
        Thank you again

  5. This is an important article also for people with ME as the role of the mitochondria does not seem to have been addressed through supplementation. Are Cytoplan working on a combined supplement, with the components mentioned above? That would be really helpful as my daughter [ who’s had ”medium” ME for 22 years] balks at taking a large number of supplements separately and it’s difficult to work out the amounts !
    Also, my granddaughter, who’s 11, has shown signs of ME for 2 years and already has a disrupted school timetable to accommodate fatigue, muscle weakness and headaches. Could a supplement help her ?

    1. Hi Madeline – thank you for getting in touch. Thank you for your email. Yes many of the drivers of ME are the same as long covid as can both be associated with post-viral fatigue/syndrome.
      All nutrients mentioned support mitochondrial funciton i.e. B vits, CoQ10, NAC, ALA, omega 3 etc. We cant put all of these in one capsule as for example omega 3 does not mix well and you should note we are not allowed to associated specific products with blogs unless they are EFSA approved claims. I would recommend CoQ10 Multi with an Omega 3 such as Krill Oil. For slightly greater support Immune complete 1 or 2 (1 for pre-menopausal women, 2 for men and post-menopausal women) with CytoRenew (high antioxidant and mitochondrial support) and an omega 3 eg. Krill Oil.

      For your Granddaughter I would recommend 1 per day of the Immune Complete, she could also have an omega 3.

      We always send any updates and news about products in our weekly email newsletter. You can sign up here if you’re not already. Thanks, Jo

  6. Most of these symptoms are identical with Hay-fever. Our insects and Bees were becoming extinct due to the overuse of Pharmaceutical Synthetic Toxic substances Sold to Councils for the parks etc and to Farmers who were trying to provide quality food for the public. Grass verges are being left for wild flowers to provide needed pollen so that these vital insects will not become extinct. They are all part of the food chain. Obviously this has increased the Pollen Count which is very high this year, and many people are not aware of it. Prescription drugs are Synthetic Toxic Chemicals exactly the same as those provided to Councils and Farmers that killed our wildlife. The population is suffering with from mass hysteria after being constantly brain washed by the Government and the Media, re Covid. Food for thought, Scotlands Covid Numbers increased dramatically after they were given Covid Vaccination.

  7. Thank you very much. Obviously very highly researched and professional. Well above my head w/ some of the terminology, but OK w/ that. Excellent helpful list of all the nutrients etc. that would/could help. Just at present do not know who can send it to as in the fortunate position of not knowing any one w/ that suffers from Covid or the serious long term consequences for many. But of course will send on if know of someone.
    Thank you again and important reading. Best wishes Carol

  8. Thanks so much for publishing this article. I did wonder if 18 months of vitamins was of absolutely no benefit but it seems my recovery would have been way longer without them.

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