Long Covid – a nutritional perspective
For two years or so we’ve been focused on the progression of SARS Covid-19, wondering when it would hit our shores and how we would be impacted. As a remote island nation, we were able to watch what happened to the rest of the world and we remained largely unaffected in terms of the disease outbreak. Until Omicron. For the majority of people this variant is much milder than earlier variants. Now that Omicron has well and truly made it into the community in New Zealand, we are facing another challenge, that of “Long Covid”.
While we have some data from other countries, there is still a lot unknown about long covid, this is not helped by the fact that studies have used different measurement and inclusion criteria, so they cannot be reliably compared. What we do know however is that it affects a lot of people, The National Institute for Health Innovation (NIHI, New Zealand) state that as of January 2022 more than 50% of people who have had Covid-19 in New Zealand have experienced symptoms six months after recovery from infection.[i]
With so many people impacted by long covid the New Zealand government have established an expert advisory group (March 2022) to find out more information about the impact on our health, and to provide GPs with advice on how to help people.
Let’s have a look at what is currently known about long covid. It is characterized by symptoms that continue for more than 4 months post covid infection and recovery, the most common being:
- Fatigue and weakness 52%
- Joint and muscle pain 48%
- Sleep disorders 47%
- Memory and cognitive function decline 36%
To research which nutrients might help we need to first attempt to gain some insight as to what is driving the ongoing symptoms. Now we’re not going to dive deep into this as it is pretty heavy, but we’ll dip our toes in the water to look at some of the main drivers, no doubt you’ve heard some of these terms over the past two years.
One of the terms you have likely heard is ‘cytokine storm’. This is an acute response by the immune system with various immune cells and cytokine levels raising high and fast.
Spike protein is another term you may be familiar with, it’s the portion that protrudes from its surface and allows the virus to latch on to and enter our cells and cause infection.
Supporting your immune system function clearly is important It would seem that helping the body to combat oxidative damage may be your best defense[ii]
The good news here, is that there are lots of nutritional compounds with antioxidant properties. Many have been studied for their impact on symptom management, while we await more studies on interventions for long covid, there is a lot we can draw on from this research on earlier phases.
Some of the most commonly discussed nutrients in natural minded circles have been vitamins C and D, the mineral zinc, the plant extract quercetin and the amino acid N-acetyl cysteine (NAC).
Curious about what research there was around covid-19 and some of my favourite anti-inflammatory and antioxidant nutrients I dove into PubMed Central (a database of journal literature) and I was not disappointed. This is not an exhaustive list and if you’re curious about nutrients I’ve not covered, pop along to https://www.ncbi.nlm.nih.gov/pmc/ and simply pop in the nutrient you’re interested in into the search bar and see what comes up, many papers have free full access.
The nutrients we will cover are:
- Vitamin C
- Vitamin D
- Omega 3 fatty acids
- PEA (palmitoylethanolamide)
- NAD+ (nicotinamide adenine dinucleotide)
Vitamins C and D, zinc and selenium are all well-known basic nutrients, common for general health and the first three are synonymous with immune support.
Vitamin C has antioxidant and anti-inflammatory action, it can reduce the incidence and duration of respiratory infections and plays a role in reducing blood clots.
Vitamin D supports many aspects of immune health, specific to covid it has been shown to help reduce lung injury and decrease those inflammatory cytokines.
Zinc is used for both viral and bacterial infections, it also helps to regulate the inflammatory response. Furthermore, the factors that are related to zinc deficiency – obesity, ageing and immunosuppression – are also risk factors for the virus.
Selenium is perhaps not as well known for immunity, but it does have antiviral activity and supports immune cell activity and has anti-inflammatory activity. Perhaps more importantly, selenium reduces oxidative damage generated by viruses.
Deficiencies in these nutrients can be considered a nutritional risk factor for people with covid-19. [iii]
While eating a healthy and varied diet is always a good idea, it’s probably worth taking these nutrients in a supplement if you have or have been exposed to the virus.
Omega 3 fatty acids, PEA & resveratrol
The main application for omega 3 fatty acids and long covid are, probably unsurprisingly, their potent anti-inflammatory activity.
They also activate aspects of our immune system and support the health and structural integrity of our cells wall membranes. While omega 3 fatty acids are available in the diet, studies show time and again that the majority of populations reviewed are not eating sufficient amounts. [iv] Omega 3 fatty acids, commonly from fish oil, have been studied extensively for a myriad of health benefits including general cardiovascular support and healthy blood flow, cognitive function and memory and easing joint discomfort.
They have also been found to be a very safe and relatively inexpensive intervention. So, if you’re trying to combat ongoing cytokine induced inflammation, suffering from joint discomfort, memory and cognitive challenges and cardiovascular issues then high quality omega 3 supplements are worth including in your regime for long covid management.
Palmitoylethanolamide – PEA
PEA is a biologically active lipid (fat) that is both made in our bodies (endogenous) and found in some foods. It is also classed as a cannabinoid, for anyone who’s researched CBD oil you’ll understand how beneficial this is, but we won’t go into that in this article. PEA was first identified in the 1950’s as an active anti-inflammatory. Further research has found that it has a wide range of therapeutic benefits including reducing nerve pain, eczema, neurodegeneration and it is basically devoid of negative side effects.[v] There are a lot of studies and reviews on how PEA can help with covid-19, there are even two clinical trials using PEA to measure the effect on disease progression in Covid-19 positive patients, one of them authorized by the US FDA (Food and Drug Administration).[vi] [vii]
As well as potent anti-inflammatory activity that can protect against cytokine storm, PEA has been studied for its neuroprotective benefit; while the studies to date have focused on this as an early intervention, as we now face high numbers of people with long covid, it would seem logical that these benefits would still apply. PEA works to inhibit mast cell activation (part of the immune response that is involved in inflammation) and has been shown to have a protective effect on the respiratory tract during viral infections.[viii] Given this one nutrient can help with pain, inflammation, immune response and protect your brain, it should really be considered at all stages of covid-19 infection.
This well-known plant extract has a vast amount of research on its biological activity – from antioxidant, anti-proliferation, anti-inflammatory, anti-cancer, anti-fungal and antiviral activities, amongst others.
The antioxidant and anti-inflammatory actions alone are responsible for many of the benefits associated with resveratrol, like heart health, capillary wall integrity, healthy blood flow and joint health. Resveratrol is also known to stimulate a group of proteins called sirtuins which are responsible for healthy ageing, healthy metabolism and brain function.
A report conducted in 2020[ix] found that resveratrol down regulated the release of cytokines (remember they’re a big part of the inflammation problem), stimulated the immune system – specifically cytotoxic T lymphocytes and natural killer cells – they kill pathogens like viruses. The report also found that resveratrol trapped damaging reactive oxygen species (these will damage your cells if left unchecked) and it regulated the renin-angiotensin system (RAS) and expression of angiotensin-converting enzyme 2 (ACE2).
ACE2 is an enzyme as well as a receptor on cell walls, they are especially concentrated on the cells of our heart, kidneys and lungs. Now this is the important bit, it is via these receptors that viruses can enter our cells and can lead to progression.[x] The RAS is an important regulator of cardiovascular system health. If you have any heart related lingering symptoms, or risk factors, then it is probably a good idea to make sure that resveratrol is part of your regime.
Quercetin, NAD+ & Astaxanthin
Quercetin – possibly this plant extract is more important when looking at acute covid, but as far as managing disease progression and severity and how those aspects play into long covid, it’s worth looking into how it may help. That and it’s very popular amongst the alternative health crowd. One of the most significant benefits of quercetin for covid-19 seems to be the effect it has on regulating ACE2, as above with resveratrol, this is important at regulating the invasion of the virus into the host (our!) cells.[xi] Furthermore, reviews have found that quercetin has the potential to block covid-19 replication via two of the main viral proteins (3-chymotrypsin-like protease and papain-like protease if you really wanted to know!). The anti-inflammatory and anti-thrombotic (reduces blood clots) activity should be remembered too.[xii]
NAD+ (nicotinamide adenine dinucleotide)
Nicotinamide riboside (NR), the precursor to NAD+ and the more common form available as a supplement, has been found beneficial for the treatment of many cardiovascular, neurodegenerative and metabolic disorders. Now I think this could be one of the most important nutrients for long covid. Covid-19 is associated with mitochondrial dysfunction, metabolic abnormalities, glutathione metabolism and NAD+ deficiency. This is the stuff right in your cells and basically affects how they function which impacts all areas of your health. NAD+ is a metabolic activator and it can restore metabolic function – great for healthy ageing and of course covid recovery! A clinical trial using NAD+ and other metabolic activators found their use led to a more rapid, symptom free recovery in covid-19 patients from 9.2 days to 5.7 days.[xiii]
Replenishment of NAD+ levels could restore energy levels and impaired sirtuin function, help reduce cytokine storm and possibly rebalance the maladaptive immune response to covid-19 infection.[xiv]
If you are experiencing lingering symptoms post covid-19 infection, even if you’re not at the official four month mark to call it long covid yet, you really should try taking some nicotinamide riboside (NR) to boost your body’s levels of NAD+.
Astaxanthin is a carotenoid commonly sourced from algae. It has a clinically proven safety profile and has antioxidant, anti-inflammatory, and immunomodulatory properties. It regulates many pro-inflammatory pathways in the body and could be a therapeutic agent against the cytokine storm of covid-19. Unlike most antioxidants that work either in the space outside of cells or inside the cells themselves, astaxanthin can stretch through the cell membrane and work both inside and outside the cell. The antioxidant activity of astaxanthin is approximately 6,000 time higher than that of vitamin C, 800 times that of coenzyme Q10, and 550 times that of vitamin E. Astaxanthin also supports cardiovascular health, improves blood flow, offers neuroprotection, protects eye health, it has been a suggested agent for the treatment of gouty arthritis and even cancer.[xv] It is a powerful plant extract and might just help to control the damaging inflammation as well as provide a clean up crew for the cell damaging reactive oxygen species (ROS) that have increased in the presence of the acute covid-19 viral infection.
That’s a lot of nutrients, and it’s not a full list of ones that have been studied for their benefits for supporting immune health during current times.
So, do you need to take them ALL?
I would suggest making sure you definitely have powerful anti-inflammatory activity covered. After that you could base your next choices upon specific symptoms you’re experiencing, say, memory and cognitive challenges or joint pain or protecting yourself in areas you know you are susceptible, such as heart health. You may have noticed that the ten nutrients covered don’t address sleep issues, which can be common in during recovery. The main reason for that is because I wanted to focus on the nutrients that are working on the underlying causes driving the ongoing symptoms. Hopefully by taking nutrients that support your overall metabolic function you will find that sleep and energy improve.
Whether you haven’t had it yet or if you’re still in the early stages of infection, these specific nutrients may be beneficial to boost your body’s innate metabolic pathways, allowing you to better handle both long covid and any other physical challenges that come your way. Many natural supplements are formulated with multiple complimentary ingredients, so you’ll likely find that a number of these nutrients can be found together – zinc, vitamin C and D are a common example of this. See what you can find to cover as many bases as possible in the least number of supplements.
As with anything relating to our health, it is far easier to take preventative steps towards good health than to try to recover from poor health. It is quite clearly known that poor diet and lack of fitness are detrimental to our health in general and our outcomes with covid-19 infection are directly linked to factors such as obesity. So, if you’re not already, then start eating more fresh fruit and vegetables, less processed foods, sugar, alcohol and caffeine; move your body everyday – it doesn’t have to be a marathon, just move regularly to improve your fitness and weight if needed. Psychological health is part of our wellbeing too – emotions like fear can act to suppress immune function, so do your best to stay connected socially and if you need support for your mental wellbeing, be sure to reach out to someone.
Finally, it is vital to rest as much as you can and to not overdo it physically while recovering at any phase.
[ii] Silvia Lucena Lage, Eduardo Pinheiro Amaral, Kerry L. Hilligan, Elizabeth Laidlaw, Adam Rupert, Sivaranjani Namasivayan, Joseph Rocco, Frances Galindo, Anela Kellogg, Princy Kumar, Rita Poon, Glenn W. Wortmann, John P. Shannon, Heather D. Hickman, Andrea Lisco, Maura Manion, Alan Sher, and Irini Sereti ‘Persistent Oxidative Stress and Inflammasome Activation in CD14highCD16− Monocytes From COVID-19 Patients’ Frontiers in immunology. 2021; 12: 799558. Available https://www.frontiersin.org/articles/10.3389/fimmu.2021.799558/full
[iii] Lucia F.C. Pedrosa, Acsa N.A.B. Barros,a and Lucia Leite-Laisb ‘Nutritional risk of vitamin D, vitamin C, zinc, and selenium deficiency on risk and clinical outcomes of COVID-19: A narrative review’ Clinical Nutrition ESPEN. 2022 Feb; 47: 9–27. Available https://clinicalnutritionespen.com/article/S2405-4577(21)01107-4/fulltext
[iv] Donald Hathaway, Krunal Pandav, Madhusudan Patel, Adrian Riva-Moscoso, Bishnu Mohan Singh, Aayushi Patel, Zar Chi Min, Sarabjot Singh-Makkar, Muhammad Khawar Sana, Rafael Sanchez-Dopazo, Rockeven Desir, Michael Maher Mourad Fahem, Susan Manella, Ivan Rodriguez, Alina Alvarez, and Rafael Abreu ‘Omega 3 Fatty Acids and COVID-19: A Comprehensive Review’ Infection & Chemotherapy 2020 Dec; 52(4): 478–495. Available https://icjournal.org/DOIx.php?id=10.3947/ic.2020.52.4.478
[v] Linda Gabrielsson, Sofia Mattsson, and Christopher J. Fowler ’ Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy’ British Journal of Pharmacology. 2016 Oct; 82(4): 932–942. Available https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.13020
[vi] Principal Investigator: Prof.ssa Flaminia Coluzzi, MD Azienda Ospedaliera Universitaria Sant’Andrea di Roma ‘Efficacy of Palmitoylethanolamide, in add-on to Standard Therapy, on Inflammatory Markers of Patients With Interstitial Pneumonia Due to COVID-19. A Pilot Controlled, Randomized, Open Label Clinical Study’ ClinicalTrials.gov identifier (NCT number): NCT04568876 Available https://www.clinicaltrials.gov/ct2/show/NCT04568876
[vii] ‘A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase IIA Study of FSD201 (Ultramicronized PEA) + Standard of Care (SOC) Vs SOC in the Treatment of Hospitalized Patients With COVID-19’ ClinicalTrials.gov identifier (NCT number): NCT04401475 Available https://www.clinicaltrials.gov/ct2/show/NCT04401475
[viii] Antonio Gigante, Alberto Aquili, Luca Farinelli, Alessandro Caraffa, Gianpaolo Ronconi, Carla Enrica Gallenga, Giulia Tetè, Spyros K Kritas, Pio Conti ‘Sodium chromo-glycate and palmitoylethanolamide: A possible strategy to treat mast cell-induced lung inflammation in COVID-19’ Medical Hypotheses. 2020 Oct;143: 109856. Available https://pubmed.ncbi.nlm.nih.gov/32460208/
[x] Stephany Beyerstedt, Expedito Barbosa Casaro, Érika Bevilaqua Rangel ‘COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection’ European Journal of Clinical Microbiology and Infectious Diseases. 2021 May;40(5):905-919. Available https://pubmed.ncbi.nlm.nih.gov/33389262/
[xi] Saiyad Bastaminejad, Salar Bakhtiyari ‘Quercetin and its Relative Therapeutic Potential Against COVID-19: A Retrospective Review and Prospective Overview’ Current Molecular Medicine. 2021;21(5):385-391. Available https://pubmed.ncbi.nlm.nih.gov/32957884/
[xii] Giuseppe Derosa, Pamela Maffioli, Angela D’Angelo, Francesco Di Pierro ‘A role for quercetin in coronavirus disease 2019 (COVID-19)’ Phytotherapy research. 2021 Mar;35(3):1230-1236. Available https://pubmed.ncbi.nlm.nih.gov/33034398/
[xiii] Ozlem Altay, Muhammad Arif, Xiangyu Li, Hong Yang, Mehtap Aydın, Gizem Alkurt, Woonghee Kim, Dogukan Akyol, Cheng Zhang, Gizem Dinler-Doganay, Hasan Turkez, Saeed Shoaie, Jens Nielsen, Jan Borén, Oktay Olmuscelik, Levent Doganay, Mathias Uhlén, Adil Mardinoglu ‘Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19’ Advanced Science (Weinheim). 2021 Sep;8(17):e2101222. Available https://pubmed.ncbi.nlm.nih.gov/34180141/
[xiv] Mario Mehmel, Nina Jovanović, and Urs Spitz ‘Nicotinamide Riboside—The Current State of Research and Therapeutic Uses’ Nutrients. 2020 Jun; 12(6): 1616. Available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352172/
[xv] Jayanta Talukdar, Bhaskar Bhadra , Tomal Dattaroy , Vinod Nagle , Santanu Dasgupta ‘Potential of natural astaxanthin in alleviating the risk of cytokine storm in COVID-19’ Biomedicine & Pharmacotherapy
Volume 132, December 2020, 110886 Available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566765/