Vitamin B3 for long COVID
NIACIN (VITAMIN B3)
What is Niacin?
Niacin, also called vitamin B3, belongs to the B vitamin family. Niacin helps convert the food we eat into energy to power our cells. We can get niacin from the food we eat or from supplements.
What does niacin do in the body?
In our bodies, vitamin B3 helps create nicotinamide adenine dinucleotide, or NAD+ for short, which is used in many metabolic reactions [[1]]. NAD+ affects cellular functions beyond energy metabolism, such as DNA repair, cellular aging, and immune system function [[2]]. NAD+ also reduces the inflammatory response, so by synthesizing NAD+, vitamin B3 helps temper inflammation.
How can niacin help alleviate certain Long COVID symptoms and/or pathophysiology?
The immune response to COVID-19 and the inflammation that may follow and persist in Long COVID, threatens NAD+ metabolism. COVID-19 severity and persistence of symptoms after acute infection rely upon the robustness of the patient’s NAD+ salvage pathway [[2]]. Long COVID, in many ways, resembles pellagra, or vitamin B3 deficiency, similarly characterized by increased inflammation. Therefore, vitamin B3 supplementation may help restore the NAD+ balance in Long COVID [[2]].
What else should I know about niacin?
Niacin supplements are known for an acute flush reaction, which can worsen when taken with other vitamins, such as zinc. Also, niacin can increase the risk of bleeding events when combined with selective serotonin reuptake inhibitors or non-steroidal anti-inflammatory drugs and increase the risk of rhabdomyolysis when taken together with statins [[3]].
Glutamine for long COVID
GLUTAMINE AND BRANCHED CHAIN AMINO ACIDS (BCAAs)
What are amino acids, including glutamine and branched-chain amino acids?
Amino acids are the building blocks of proteins and play essential roles in biological processes, including inflammation, glucose balance, and more, that may be involved in Long COVID. Amino acids contribute to intermediate molecules involved in energy-producing pathways. Glutamine, in particular, is used by the cell metabolism pathways and the immune system [[1]]. Glutamine is the most abundant amino acid in the body, and it is naturally produced in the body [[2]]. Other amino acids, such as branched-chain, are not made in the body and must be obtained from dietary sources.
BCAAs include leucine, isoleucine, and valine, which are involved in protein synthesis and glucose balance in the body. BCAAs may also directly and indirectly affect immune function [[1]]. Both glutamine and BCAAs aid muscle recovery, especially after exercise in healthy individuals [[3]].
What do glutamine and the branched-chain amino acids do in the body?
Glutamine is a source of TCA cycle intermediates that play a role in energy metabolism and may serve immune functions [[1]]. Glutamine replenishes the intermediates used up in biological processes in immune cells such as T cells and macrophages. BCAAs can be used by immune cells and are needed for lymphocytes to create proteins and nucleotides in response to stimulation. BCAAs also serve as a source of molecules that enter the TCA cycle to support mitochondrial health [[1]].
How can glutamine, branched-chain amino acids, and other amino acids help alleviate certain Long COVID symptoms and pathophysiology?
Amino acids, including glutamine and BCAAs, are essential for the immune response and mechanisms involved in acute and chronic COVID-19. Especially in older adults, the changes associated with aging, such as inflammation and anabolic resistance, as well as the risk of immune dysfunction and sarcopenia, make adequate amino acid supplementation necessary. Given these considerations, researchers recommend focusing on amino acid intake in COVID-19 survivors, especially in older patients with Long COVID who might be at greater risk of malnutrition [[1]].
Lumbrokinase for long COVID
LUMBROKINASE
What is lumbrokinase?
Lumbrokinase is a substance that is naturally found in earthworms. Lumbrokinase comes from the scientific name for earthworms, which is Lumbricus. Lumbrokinase has been used as a traditional medicine in China, Japan, and other Asian countries for centuries to support the body’s healthy circulation. To harvest lumbrokinase and other healthy compounds present in earthworms, the earthworms can be dried and powdered, then taken as an oral supplement to support healthy circulation [[1]].
What does lumbrokinase do in the body?
Lumbrokinase refers to a collection of enzymes isolated from the earthworm. There are two ways lumbrokinase supports healthy blood circulation. It can break down a protein called fibrin, which is an insoluble protein that forms during blood clotting. It can also create plasmin, a substance that breaks down blood clots. As a result, lumbrokinase shows promise in reducing the aggregation of blood clots, dissolving the blood clots, and making blood less viscous and more able to flow. Lumbrokinase does not adversely affect organ systems or body tissues [[1]].
How can lumbrokinase help alleviate certain Long COVID symptoms and/or pathophysiology?
Lumbrokinase is already being used to treat stroke, heart disease, deep vein thrombosis, and diabetes. It is also used to help the cardiovascular system stay healthy. Given the heightened risk for blood clotting disorders in Long COVID, lumbrokinase can be used to maintain healthy cardiovascular function [[1]]. Most of interest to Long COVID, lumbrokinase’s anticoagulant and fibrin degrading properties make it an ideal choice to help patients with improved circulation [[2]].
Ginkgo Biloba for long COVID
GINKGO BILOBA
What is ginkgo biloba?
Ginkgo biloba is one of the oldest trees. Its leaves are used for supplements [[1]].
What does ginkgo biloba do in the body?
Ginkgo biloba, a vast source of antioxidants, is well-known for its health-promoting effects on the brain and vasculature, significantly increasing blood flow throughout the body [[2]]. It has been used to treat memory impairment, cognitive function, edema, inflammation, oxidative stress following traumatic brain injury, neurodegeneration, stroke, and vasooclusive disorders. It has also been used as an anti-aging supplement. Based on these uses, scientists propose that ginkgo biloba may work through antioxidant, neurotransmitter modulatory, and anticoagulant properties [[3]].
How can ginkgo biloba help alleviate certain Long COVID symptoms and pathophysiology?
Researchers believe gingko biloba’s effects as an antioxidant and anti-inflammatory and its role in preventing cell death make it helpful in treating Long COVID. Oxidative stress and inflammation drive cell death in Long COVID, resulting in a cycle of cell and tissue damage [[4]].
Ginkgo biloba’s actions in the nervous system to reduce oxidative stress may make it worthwhile to reduce cognitive and neurological symptoms ranging from mild to severe [[4]].
What else should I know about ginkgo biloba?
Scientists urge caution for patients taking coagulants who want to take ginkgo biloba. Therefore, you should check with your doctor before starting a ginkgo biloba regimen if you take coagulants [[3]].
Nattokinase for long COVID
NATTOKINASE
What is nattokinase?
Nattokinase is a substance found in the Japanese dish natto, a staple in the Asian nation for centuries. Natto is a “vegetable cheese” made of fermented soybeans [[1]]. Eating natto is linked to reduced death from heart disease, owing to natto’s activity reducing coagulation and clotting. Researchers found that a natto extract contains an enzyme that prevents viral infection, such as that from SARS-CoV-2, the virus that causes COVID-19. Lastly, nattokinase, part of natto, degrades the spike proteins of the novel coronavirus without being toxic to cells. Therefore, scientists believe that nattokinase can be used to protect cells [[2]].
What does nattokinase do in the body?
In the body, nattokinase has several functions. It acts as a fibrinolytic, which means that it breaks up blood clots. It is also an anticoagulant, which means that it plays a role in helping prevent blood clots. Lastly, it degrades the spike proteins found in the virus that causes COVID-19, SARS-CoV-2. However, the degradation is not specific to the novel coronavirus, which means that nattokinase may break down other proteins, too [[1]].
How can nattokinase help alleviate certain Long COVID symptoms and/or pathophysiology?
The outstanding aspect of nattokinase is its vascular effects, which are relevant to Long COVID patients. Nattokinase’s role in clotting and preventing clotting can combat post-COVID clotting disorders. Strokes and cardiac incidents are more common post-COVID, and coagulation abnormalities can be part of Long COVID [[3]].
Nattokinase also degrades the spike protein of SARS-CoV-2, the virus that causes COVID-19 [[4]]. This can be useful because the virus can be found in Long COVID patients for some time after the acute disease phase.
What else should I know about nattokinase?
Some people are allergic to nattokinase, which can lead to skin irritation. Also, those patients taking anticoagulants should consult a doctor who can closely supervise their clotting before starting a nattokinase regimen [[5]].
Glutathione for long COVID
GLUTATHIONE
What is glutathione?
Glutathione is a tripeptide of glutamate, glycine, and cysteine [[1]]. It has been called a “mighty little molecule” because of its antioxidant, immune response, antiviral defense, and other functions [[1]].
What does glutathione do in the body?
Glutathione is an antioxidant made in our bodies and found in our cells. It is the most abundant of the endogenous antioxidants found in our cells. Its high concentration reflects its important functions in detoxifying the body’s tissues, folding proteins, defending the body against viruses, and regulating the immune response [[2]].
Glutathione can neutralize reactive oxygen species, molecules involved in chronic inflammatory disorders. Many enzymes, including regulators of blood vessel function, also use glutathione as a co-factor for chemical processes. Glutathione also helps generate nitric oxide, stimulate blood flow, and promote brain and vascular health [[3]].
How can glutathione help alleviate certain Long COVID symptoms and pathophysiology?
COVID-19 creates a severe inflammatory response that leads to the overactivity of immune cells called cytokines in the lungs. This so-called “cytokine storm” can be dangerous and, if not lethal, may linger after the acute infection phase [[3]]. Glutathione has a protective response against this inflammatory response.
Risk factors for severe COVID, such as advanced age, diabetes, and being immunocompromised, are linked to glutathione deficiency as well as increased oxidative stress [[2]].
A study found that hospitalized COVID-19 patients have a glutathione deficiency and increased oxidative stress. Oxidative damage was worse in older people but also present in younger adults, in whom it typically does not happen [[4]]. Given that Long COVID involves oxidative damage, glutathione’s antioxidant effects could potentially help reduce the serious manifestations of post-COVID syndrome.
Sulbutiamine for long COVID
SULBUTIAMINE
What is sulbutiamine?
Sulbutiamine is a manmade version of vitamin B1. It was developed in Japan in the 1960s to treat beriberi, which is vitamin B1 deficiency [[1]]. It is known mainly for its effects on cognition and fatigue.
What does sulbutiamine do in the body?
Sulbutiamine is widely used in endurance sports for its anti-fatigue, cognitive enhancement, and antioxidant effects. It can also have neuroprotective effects [[1]]. Sulbutiamine is used in medicine to treat fatigue, thiamine deficiency, and concentration difficulties. The supplement improves brain function regarding memory, concentration, and mood. In rodent studies, sulbutiamine modulates acetylcholine activity in the hippocampus. Sulbutiamine exerts anti-oxidant and anti-apoptotic properties, which can prevent cells from dying due to oxidative damage. Medical applications of sulbutiamine outside of cognitive enhancement and fatigue include depression, diabetes polyneuropathy, and erectile dysfunction. Sulbutiamine may also be an anti-cancer supplement, as its analog, thiamine, is [[2]].
How can sulbutiamine help alleviate certain Long COVID symptoms and/or pathophysiology?
Sulbutiamine is known for its anti-fatigue effects in healthy populations and those suffering from various diseases [[3]]. Sulbutiamine could be used to reduce fatigue in Long COVID alongside other treatments. In patients with multiple sclerosis, sulbutiamine, supplemented alongside disease-modifying treatment, reduced fatigue symptoms [[4]]. Therefore, sulbutiamine may have particularly restorative and/or regenerative activities relevant to the central nervous system. COVID long-haulers suffer from cognitive issues and debilitating “brain fog” as well as both physical and mental exhaustion, so sulbutiamine could be a way to improve those symptoms via supplementation.
Lastly, as sulbutiamine was developed as a replacement for vitamin B1 or thiamine, the same effects seen for Long COVID with thiamine may generally apply for sulbutiamine, though this hypothesis needs further testing. Thiamine can help reduce inflammation in Long COVID and, in one study, reduced the neurological burden of Long COVID patients [[5]].
Iron for long COVID
IRON
What is iron?
All living organisms need iron. Iron is a mineral required for growth and development by our bodies [[1]]. Iron is used to shuttle oxygen from the lungs all over the body, including to muscles and our brains. Beyond its involvement in oxygen transport, iron also plays a role in the immune response. We also use iron to make hormones [[1]].
What does iron do in the body?
Iron is essential in biological processes such as oxygen transport, energy production, and the synthesis of nucleic acids like DNA. Iron is also involved in the body’s antiviral response; in a viral infection, the quickly-replicating viruses compete for iron with the person’s cells. Iron balance also influences the immune response. Low iron levels are associated with altered growth of immune cells, higher levels of pro-inflammatory molecules, and increased oxidative stress. In COVID-19, markers of low iron status can be both risk factors and prognostic indicators. These iron measures include ferritin, a protein used to store iron that stimulates pro-inflammatory compounds; high ferritin levels are linked to COVID-19 severity and mortality [[2]].
How can iron help alleviate certain Long COVID symptoms and pathophysiology?
Iron deficiency can be expected after COVID-19 and can contribute to long-term outcomes in terms of symptoms [[3]]. Changes in iron balance can linger for at least two months after acute COVID-19 infection. Therefore, monitoring iron levels in patients with Long COVID is essential. Fatigue and difficulty breathing (dyspnea) are symptoms of iron deficiency, so supplementation with iron may help improve these symptoms in Long COVID patients with deficient iron. Iron deficiency is linked to impaired performance as well as non-resolving lung disorders in people who are post-COVID-19. Iron supplementation may also reduce inflammation and improve immune response to COVID-19 vaccination [[2]]. In one study of Long COVID, iron deficiency was not associated with structural lung impairment but was linked to impaired stress resilience [[3]].
Sulforaphane for long COVID
SULFORAPHANE
What is sulforaphane?
Sulforaphane is a plant-derived substance known to possess anti-cancer properties; more recently, its effects in fighting COVID-19 have become known [[1]]. It is found in cruciferous vegetables with exceptionally high concentrations in broccoli. Because it is found in plants we already eat, sulforaphane is generally well-tolerated [[2]].
What does sulforaphane do in the body?
Sulforaphane is an antioxidant and anti-inflammatory compound known to inhibit the effects of pro-inflammatory molecules [[3]]. It is also neuroprotective, meaning it has protective effects on the nervous system, including the brain and spinal cord. As a known anti-cancer agent, sulforaphane reduces the impact of oxidative stress on the body’s cells, inhibiting inflammatory activity. Sulforaphane inhibits the cytokines involved in the cytokine storm of COVID-19 [[2]], which is linked to Long COVID [4]].
How can sulforaphane help alleviate certain Long COVID symptoms and/or pathophysiology?
Animal studies suggest that it can improve endothelial function by blocking oxidative stress [[5]]. A study of broccoli capsules containing sulforaphane to treat COVID-19 concluded that sulforaphane could potentially protect against severe illness [[6]]. A study of sulforaphane in COVID found that it was potentially an anti-inflammatory mediator in COVID-19, reducing the gene expression of inflammatory compounds [7]]. However, laboratory research also suggests that sulforaphane may be less effective in older people than in younger populations [[5]].
Hydroxy-Beta-Methylbutyrate for long COVID
HYDROXY-BETA-METHYLBUTYRATE
What is hydroxy-beta-methylbutyrate?
Hydroxy-beta-methylbutyrate, or HMB, is a substance made during the body’s breakdown of the amino acid leucine [[1]].
What does hydroxy-beta-methylbutyrate do in the body?
HMB has many roles in the body. It is involved in forming proteins from amino acids, insulin activity, increase and growth of muscle cells, and stem cell growth and specialization into mature cells, among other functions [[2]].
HMB reduces muscle damage from exercise, strengthens muscle, improves aerobic performance, and heightens fatigue resistance. In older people, HMB can reduce sarcopenia, or the loss of muscle and strength that occurs when people get older and exercise less. Optimal effects of HMB in older people occur with oral supplementation in conjunction with exercise [[1]].
In frail older people, HMB supplementation helps reduce the decline of muscle mass and preserve muscle function, especially for older patients who are in hospital stays [[2]].
HMB may regulate the immune and inflammatory responses, especially under stress. It was found to exhibit anti-inflammatory effects, protect against muscle breakdown, and improve pulmonary function in patients in the intensive care unit for chronic obstructive pulmonary disease [[2]].
How can hydroxy-beta-methylbutyrate help alleviate certain Long COVID symptoms and pathophysiology?
HMB’s role in supporting muscle mass, its immune and anti-inflammatory properties, and its effects on physiology affected by COVID-19 make it useful for people dealing with Long COVID. HMB may also potentially affect the brain and cognition [[2]].
Butyrates such as HMB may be linked to chronic fatigue disease through “good” intestinal bacteria in the gut-brain axis [[3]]. Since symptoms in chronic fatigue and Long COVID overlap, HMB may play a similar role for long-haulers, though more evidence is needed.
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