Olive Polyphenol for long COVID
HYDROXYTYROSOL (OLIVE POLYPHENOL)
What is hydroxytyrosol?
Hydroxytyrosol is a substance found in olive oil. It is a polyphenol, which means it is a plant-based compound known to protect against cell damage due to inflammation and oxidative stress [[1]].
What does hydroxytyrosol do in the body?
Hydroxytyrosol has anti-oxidant and anti-inflammatory properties. It reduces the activity of cytokines, which are part of the immune response, especially in severe COVID, and can lead to Long COVID. It also prevents oxidative stress and inflammation in cells infected with SARS-CoV-2, the virus that causes COVID-19 [[2]].
How can hydroxytyrosol help alleviate certain Long COVID symptoms and pathophysiology?
Given that Long COVID is characterized by oxidative stress and inflammation, hydroxytyrosol can help via its actions preventing oxidative stress and inflammation in cells infected with COVID-19.
Research suggests, furthermore, that lingering SARS-CoV-2 virus can contribute to the pathophysiology of Long COVID and that these effects can be counteracted by antioxidants, including hydroxytyrosol, which reduce oxidative stress in cells [[3]].
Olive leaf extract improved the clinical status of hospitalized acute COVID-19 patients, improving respiratory rate and oxygen saturation [[4]]. Because olive polyphenols can improve acute COVID outcomes, they may show clinical promise for Long COVID, although more research is needed.
Combined with the amino acid arginine, hydroxytyrosol could deter the formation of harmful pro-inflammatory substances such as peroxynitrite, which is implicated in COVID-19-related organ dysfunction. Lessening inflammation, supporting immune function, protecting against damage from free radicals, and preventing blood vessel injury are just some things that arginine and hydroxytyrosol can do together [[2]].
Cistanche Tubulosa Extract for long COVID
CISTANCHE TUBULOSA EXTRACT (CTE)
What is cistanche tubulosa extract or CTE?
Cistanche tubulosa extract, or CTE, is a traditional Chinese herbal medicine that protects the gut [[1]]. CTE comes from the cistanche tubulosa plant, a perennial parasitic herb found in the Chinese desert. Cistanche tubulosa is a bright yellow and beige desert plant that is parasitic in that it obtains all or part of its nutrition from other plants [[2]].
What does cistanche tubulosa extract or CTE do in the body?
Over 120 bioactive ingredients have been found in cistanche tubulosa [[3]]. CTE can have neuroprotective, immune function, antioxidant, anticancer, and liver protective effects. One study of CTE in mice found that, via restoring gut microbiota balance, CTE produced antidepressant-like effects and elevated the level of brain-derived neurotrophic factor, a significant growth factor in healthy brain function [[4]].
How can cistanche tubulosa extract or CTE help alleviate certain Long COVID symptoms and/or pathophysiology?
A compound isolated from cistanche tubulosa called echinacoside was found to stimulate the production of immune cells called T cells, which attack foreign particles in the body [[3]]. It was also found to boost levels of growth hormone. Hormonal insufficiencies are an aspect of Long COVID. Growth hormone deficiency, in particular, is linked to fatigue in Long COVID patients [[3], [5]]. Cistanche tubulosa’s many immune-supporting, neuroprotective, anticancer, and liver-protective effects can also potentially help improve cognitive symptoms and reduce inflammation in long COVID patients dealing with those issues.
Omega-3 Fats for long COVID
OMEGA-3 FATS, SUCH AS DHA AND EPA
What are omega-3 fats?
Omega-3 fats are polyunsaturated fatty acids found in foods like fish and flaxseed. They can also be obtained from supplements, such as fish oil capsules [[1]]. Omega-3s can also be found in some plant sources, such as flaxseed [[2]].
Two types of omega-3 fats that have beneficial properties for Long COVID are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [[3]]. Because they have anti-inflammatory properties, they might be relevant to immune dysfunction and inflammation inherent in Long COVID.
What do omega-3 fats do in the body?
Omega-3s have anti-platelet effects and can lower the levels of fibrinogen, thrombin, and factor V, proteins involved in clotting [[4]].
Omega-3s are also well-known for being anti-inflammatory, especially those from EPA and DHA. They also have anti-clotting properties [[5]]. The omega-3s in fish oil have been found to reduce disease activity in inflammatory and autoimmune conditions and reduce the need for anti-inflammatory drugs [[3]].
Omega-3 fats, especially EPA, have shown promise in treating mood disorders by reducing pro-inflammatory cytokine activity, acting on the HPA axis, and regulating neurotransmitters [[7]].
How can omega-3 fats help alleviate certain Long COVID symptoms and pathophysiology?
Omega-3 fats’ anti-clotting properties can be useful for Long COVID patients, who are at greater risk of clotting events due to cellular death and debris, which lead to thickening of blood and “brain fog” [[8]]. Omega-3’s anti-inflammatory properties can also help reduce inflammation in Long COVID patients.
Omega-3s can improve Long-Term COVID by treating brain damage and inflammation (including brain inflammation), reducing long-term central nervous system damage, and repairing oxidative stress due to cytokine storms and blood clotting.
N-Acetylcysteine for long COVID
N-ACETYLCYSTEINE
What is N-acetylcysteine or NAC?
N-acetylcysteine, or NAC, is often used to treat acetaminophen overdose. It is a precursor of L-cystine, which boosts the formation of L-cysteine. NAC is a powerful antioxidant. It protects mitochondria, which are the energy powerhouses of cells. It can treat diseases by itself or in conjunction with other medications. Bronchitis, colitis, liver cancer, hemodialysis, asthma, concussions [[1]], and neurodegenerative diseases are some therapeutic targets that are evidenced to be improved with NAC [[2]].
What does NAC do in the body?
NAC is a potent antioxidant and anti-inflammatory compound [[3]].It is considered a mucolytic, which means it breaks up mucus in the lungs to make breathing easier [[4]]. As an antioxidant, NAC reduces levels of inflammatory substances [[3]]. It can scavenge free radicals as an antioxidant, protecting the lungs from stressors such as infections and pollution [[4]]. It also can improve brain damage produced from ischemic events, reduce pain in an infection, and reduce the inflammatory response in the thyroid [[3]].
How can NAC help alleviate certain Long COVID symptoms and/or pathophysiology?
Research shows that COVID-19 can benefit from NAC in the acute phase. NAC led to decreased C-reactive protein levels, a marker of inflammation, and a significant oxygen saturation increase, reducing COVID-19 mortality [[5]].
Long COVID patients can also benefit from NAC. NAC lowers homocysteine levels, a marker of cardiovascular stress, reducing heart risks for long COVID patients, who are already at greater risk of clotting events than those not long-haulers [[6]].
In one study combining guanfacine with NAC, patients saw a decrease in Long COVID “brain fog.” Eight out of twelve patients participating in the study experienced improvements in working memory, concentration, and executive function. Some patients were able to go back to their normal workloads [[7]]. While more research is needed to elucidate other benefits of NAC and how its antioxidant and cellular health mechanisms work in different conditions, the cognitive benefits of NAC for long COVID are promising. The fact that NAC has good safety, absorption, and bioavailability, and is available cheaply, is another advantage for people suffering from Long COVID [[3]].
[1] https://medicine.yale.edu/news-article/potential-new-treatment-for-brain-fog-in-long-covid-patients/
[4] https://karger.com/res/article-abstract/50/Suppl.%201/26/286806/Acetylcysteine-A-Drug-with-an-Interesting-Past-and?redirectedFrom=PDF
Palmitoylethanolamide for long COVID
PALMITOYLETHANOLAMIDE (PEA)
What is palmitoylethanolamide or PEA?
Palmitoylethanolamide, also called PEA, is part of a fatty acid found in the body. The body makes PEA on demand [[1]]. Oddly enough, PEA can be found in legumes, peas, beans, vegetables, tomatoes, and potatoes. PEA is also found in milk, egg yolks, soy oil, and corn [[2]].
PEA is a cannabimimetic compound, which means that it affects the endocannabinoid system. Cannabimimetic substances are not endocannabinoids [[3]]. However, they can regulate animals’ and plants’ physiological and pathological functions [[4]].
What does PEA do in the body?
PEA is synthesized by the body on demand. It works to balance cell and tissue processes needed to maintain the health of the nervous system and reduce neuroinflammation [[2]].
PEA has anti-inflammatory, immune-modulating, neuroprotective, and pain-relieving properties. It performs various functions, including combatting chronic pain and inflammation [[5]]. Because it has a protective response that occurs in response to cellular injury, PEA levels are often higher in disease states [[6]].
PEA acts on cannabinoid receptors and inhibits the breakdown of the endocannabinoid anandamide, boosting its activity via the “entourage effect” [[7]].
How can PEA help alleviate certain Long COVID symptoms and pathophysiology?
Relevant to Long COVID, PEA can combat chronic pain and inflammation.
PEA can be used to treat the consequences of the COVID-19 cytokine storm, which is a problem in severe COVID-19 and can also be a problem in Long COVID [[5]]. In severe COVID-19, a cytokine storm can give rise to additional issues, such as an antiphospholipid syndrome secondary to viral infection. In one study, PEA was used to successfully treat a 45-year-old female who developed antiphospholipid syndrome secondary to COVID-19 [[5]].
Magnesium Threonate for long COVID
MAGNESIUM THREONATE
What is magnesium threonate?
Magnesium threonate is a form of magnesium that is more easily absorbed by the body than magnesium. The compound threonate is a supplement that makes magnesium more bioavailable in the body. Magnesium is an essential mineral in the body that is required to synthesize all B vitamins except vitamin B7 (biotin).
What does magnesium threonate do in the body?
Mitochondrial activity depends on B vitamins [[1]]. The body uses magnesium for physiologic functions and biochemical reactions. Magnesium may have anti-inflammatory, anti-oxidant effects. Magnesium supplements prevent damage to organs and tissues through multiple means; they are also anticholinergic, antihistamine, and anti-inflammatory. Magnesium supports lung function by reducing airway hyperreactivity and wheezing and promoting bronchodilation [[2]]. Magnesium plays a role in respiratory symptoms, reducing inflammation and restoring electrolyte abnormalities in COVID-19 [[2]].
How can magnesium threonate help alleviate certain Long COVID symptoms and/or pathophysiology?
Magnesium deficiency can be frequent in the intensive care unit, where it is linked to increased mortality, greater need for a ventilator, sepsis, and more extended hospital stays. Therefore, researchers believe magnesium deficiency could be associated with acute COVID-19 infection severity. In COVID-19 patients, magnesium supplementation prevents lung fibrosis, a rare but severe complication of COVID-19. Magnesium deficiency is also, more generally, associated with low-grade chronic inflammation. It also plays a role in maintaining endothelial and vascular function [[2]]. Magnesium also plays a recovery role in the post-acute phase of COVID-19 [[3]]. Magnesium supplementation in long COVID patients could help improve endothelial and vascular function and help protect against inflammation. Magnesium deficiency is linked to cognitive difficulties, post-exertional malaise, headache, dizziness, myalgia, and asthma in Long COVID [[4]].
Lastly, magnesium metabolism is also linked to vitamin D, which is also often recommended for Long COVID patients, and a vitamin D deficiency-associated problem cannot be corrected without enough magnesium [[4]].
Prebiotics for long COVID
PREBIOTICS
What are prebiotics?
Prebiotics are polysaccharide compounds not digestible in the small intestine, either by the acids or enzymes present there. However, probiotics and gut microorganisms in the large intestine can use prebiotics to support health. Good bacteria in the intestine ferment prebiotics to produce short-chain fatty acids, which can also be used to support health. Prebiotics also serve sensory functions to improve the taste and texture of food. For example, they can improve the stability of foams and improve mouthfeel in dairy products, bread, and other foods [[1]].
What do prebiotics do in the body?
Prebiotics, which are found in several vegetables and fruits, have health benefits, including cutting cancer risk and increasing calcium and magnesium absorption. Prebiotics also boost mineral absorption and immunity, lower cholesterol, and prevent gastrointestinal conditions such as colon cancer [[2]].
How can prebiotics help alleviate certain Long COVID symptoms and pathophysiology?
Studies show that gut imbalance is linked to the severity of COVID-19 infection and persisting multi-organ and multi-system complications after the acute phase is over. The gut influences additional systems, such as the liver and brain, in COVID-19, which means that improved gut health can also improve the health of other organ systems [[3]].
Studies of prebiotics in Long COVID patients bear out this hypothesis. In one study in which Long COVID patients were given a mix of a probiotic and three different prebiotics, called SIM01, adverse health outcomes decreased, and elderly and diabetic patients exhibited restored gut dysbiosis [[4]]. In another study of SIM01, Long COVID patients’ SARS-CoV-2 virus levels decreased, as did their opportunistic pathogen levels, after week four of SIM01 supplementation [[5]]. While SIM01 is not a purely prebiotic supplement, these studies show that prebiotics, provided alongside probiotics, may improve Long COVID outcomes for patients.
NAD/NADH for long COVID
NAD/NADH
What is NADH?
NAD, nicotinamide adenine dinucleotide, is a coenzyme within our cells. It helps enzymes by transporting electrons. NAD, NAD+, and NADH are variations of the same molecule. NAD+ is an oxidized form of NAD. When NAD+ gains an electron, it becomes NADH. When it loses an electron, it turns back into NAD+.[1]
What does NADH do in the body?
NAD+ is important for energy metabolism, DNA repair, aging of cells, and the immune system. [2] The balance between NAD+ and NADH is called the NAD+/NADH ratio. Ideally, this ratio should favor NAD+, but a good balance is important. This ratio helps regulate the inside of cells, especially in the mitochondria and the nucleus.[3]
How can NADH help alleviate certain Long COVID symptoms and/or pathophysiology?
NADH helps the body create energy. One study found that patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experienced less mental fatigue and improved quality of life when they took oral coenzyme Q10 (CoQ10) with NADH. These improvements might also benefit people with Long COVID.[5].
Research shows that while NAD+ levels were only slightly lower in COVID cases, there was a significant increase in how quickly NAD+ was used.[6]
In clinical trials, a team found that using metabolic activators, including NAD+ precursors, helped people recover faster from mild-to-moderate COVID and improved metabolic and inflammatory markers. [7] However, another study found no significant improvement in blood cell counts or clinical outcomes when using nicotinamide for COVID-related low lymphocyte counts. This suggests that the benefits of NAD+ might vary based on individual circumstances and may not work for everyone.[8]
Mixed Phospholipids for long COVID
MIXED PHOSPHOLIPIDS
What are mixed phospholipids?
Phospholipids are lipids or fats found in human cell membranes on the outer edge and within the cell. The phospholipid membrane protects the cell from intruders and helps compartmentalize it into separate units where cell processes take place [[1]].
Many phospholipids exist in the human cell membrane, including phosphatidylcholine, phosphatidylethanolamine, phosphatic acid, and cardiolipin [[1]].
What do mixed phospholipids do in the body?
Research shows that lipid replacement therapy can improve mitochondria function and cell health more generally. In lipid replacement therapy, a person takes a nutritional supplement with antioxidants and a mix of many phospholipids, such as phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine. The lipids obtained through dietary means are then replaced by the damaged lipids in the cells [[2]]. Phospholipids also have an emerging role in the aging process [[1]].
How can mixed phospholipids help alleviate certain Long COVID symptoms and pathophysiology?
Phospholipids are the most important class of lipids that are dysregulated in both acute COVID-19 infection and Long COVID. Levels of phospholipids such as phosphatidylcholine are elevated in COVID-19 patients admitted to emergency rooms. In a study of hospitalized patients, lipid metabolism was dysregulated in hospitalized COVID-19 patients and remained so for several months after the acute infection phase [[3]].
Lipid replacement therapy can be used in patients with chronic fatigue syndrome to deliver undamaged lipids into cellular organelles, which in humans are enveloped in a membrane. Research studying people with chronic fatigue shows that lipid replacement therapy plus antioxidants helps restore mitochondrial function and also improves fatigue [[2]].
Nicotinamide Mononucleotide for long COVID
NICOTINAMIDE MONONUCLEOTIDE (NMN)
What is nicotinamide mononucleotide or NMN?
Nicotinamide mononucleotide, or NMN, is a molecule involved in cell signaling. It is a crucial part of the communication network that supports another molecule called NAD+ that reduces the body’s inflammatory response. NAD+ is used in many metabolic reactions and in DNA repair, cellular aging, and immune system functioning [[1]].
What does NMN do in the body?
NMN supplementation ensures a steady supply of NAD+, as NMN, taken as an oral supplement, is changed to NAD+ in the body. Structurally, NMN is structurally the closest to NAD+, with only one intermediary step between the two [[2]]. []. NMN, therefore, can increase NAD+ levels in the body, affecting various functions. NMN supplementation can dampen inflammation related to aging, improve the insulin system’s efficiency, support mitochondrial function and brain function, and more [[3]]. In one case study, orally administered NMN was found to reverse the COVID-19 cytokine storm [[4]].
How can NMN help alleviate certain Long COVID symptoms and/or pathophysiology?
Scientists have hypothesized that NAD+ disruption is one mechanism by which Long COVID pathophysiology occurs [[5]]. Because it is only one step away from NAD+ chemically, NMN can replenish the dwindling NAD+ supply seen in Long COVID patients. One doctor wrote the British Medical Journal to state that he tried it on himself with “rapid and long-lasting” improvement [[6]]. In one study examining NMN supplementation in animal models of lung damage, NAD+ and NMN were administered together, reducing cell death and inflammatory cell takeover in the lungs [[5]].
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