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]].
Pollen-Based Herbal Extracts for long COVID
POLLEN-BASED HERBAL EXTRACTS
What is a pollen-based herbal extract?
Pollen is a powder produced by flowers when they are reproducing. Flowers reproduce when the pollen spreads around to fertilize other plants. You may know pollen from its status as a springtime allergen. The exact mixture of bioactive substances in pollen depends on its plant source, the activity of bees (who pollinate flowers), climate, and other agricultural variables. However, pollen typically contains nutrients such as amino acids, carbohydrates, and minerals [[1]].
One type of pollen-based herbal extract is purified cytoplasm of pollen. The cytoplasm of a cell, such as pollen, refers to the material within it, excluding the nucleus—in other words, the different components found within the cell. Purified cytoplasm of pollen, or PCP, is one pollen-based herbal extract used to support menopausal women’s health [[2]].
What does pollen-based herbal extract do in the body?
The exact mechanisms behind PCP are not understood. Still, researchers believe it may act as a selective serotonin reuptake inhibitor (SSRI) to increase the availability of the neurotransmitter serotonin in the brain, particularly in the hypothalamus cells. Indeed, precursors to serotonin can be found in PCP. The hypothalamus regulates the brain, controlling temperature perception, sleep-wake cycles, appetite, and overall balance of the body’s functioning. Studies of PCP supplements improved sleep quality and quality of life, reducing hot flashes, fatigue, and other menopause symptoms in women [[2]].
How can pollen-based herbal extract help alleviate certain Long COVID symptoms and pathophysiology?
Researchers believe PCP could be used to reduce some of the common symptoms experienced by COVID long-haulers. Symptoms commonly experienced by people with Long COVID include fatigue, muscle weakness, and difficulty sleeping, as well as anxiety or depression. PCP, given its successes in treating these symptoms in menopausal women without the side effects of SSRIs.
Benfotiamine for long COVID
BENFOTIAMINE
What is benfotiamine?
Benfotiamine is derived from thiamine or vitamin B1. While vitamin B1 is water-soluble, benfotiamine is fat-soluble and can be naturally found in roasted garlic [[1]].
What does benfotiamine do in the body?
Benfotiamine is a powerful antioxidant and anti-inflammatory compound relevant to several diseases. Benfotiamine has helped prevent complications from diabetes as well as inflammatory complications of diabetes. Conditions that benefited from benfotiamine include a type of eye inflammation called uveitis and endotoxemia. Endotoxemia is involved not only in diabetes but also in other chronic diseases. It may contribute to low-grade inflammation that affects people with diabetes, dysregulating inflammation and triggering weight gain and diabetes [[1], [2]].
How can benfotiamine help alleviate certain Long COVID symptoms and/or pathophysiology?
Relevant to COVID-19, benfotiamine could potentially reduce neurological complications by reducing amyloid beta deposition and tau activity, which are markers of neurodegeneration. Inflammatory complications that can be improved with benfotiamine include reductions in the activation of immune cells such as cytokines, as well as genes and molecular cascades upregulated during inflammation. Metabolic activity can be improved with benfotiamine through improvements and efficiencies gained in the Krebs cycle. Overall, for COVID-19, these effects reduce immune cell activation and decrease the cytokine storm. They also reduce oxidative stress and other complications associated with diabetes for COVID-19 patients. While it is unclear which of these improvements occur during the acute versus chronic phase of COVID-19, benfotiamine is a promising compound in this realm [[3]].
Selenium for long COVID
SELENIUM
What is selenium?
Selenium is an essential trace element, meaning our bodies only need a small amount [[1]]. We can get selenium from the foods we eat or from supplements [[2]].
Selenium intake is essential to ensure the proper function of selenoproteins, which get their name, in part, from selenium [[3]]. Selenium is a crucial aspect of selenoproteins, which help make DNA and are involved in the antiviral response. More generally, selenoproteins protect against cell damage [1]]. Selenium supplements support the innate immune system and help regulate the secretion of pro-inflammatory molecules [[2]].
What does selenium do in the body?
Selenium is involved in the brain, hormones, heart, blood vessels, and immune functions. Our bodies also need selenium for antioxidant processes. Selenium deficiency increases susceptibility to COVID-19. Dietary selenium is necessary for proper immune function and may protect against certain diseases, such as cancers, asthma, and heart disease [[4]]. Selenium is thought to prevent cancer cells from growing and spreading due to its ability to shut down the cancer cell cycle, promote cell death of tumor cells, and initiate DNA repair [[5]].
How can selenium help alleviate certain Long COVID symptoms and pathophysiology?
Low selenium levels in COVID-19 are linked to increased tissue damage and Long COVID symptoms [[2]]. Low selenium levels may increase susceptibility to COVID-19, influence disease severity, and contribute to post-acute COVID symptoms, such as Long COVID. Many studies show that selenium concentration in COVID-19 patients is lower than in people who do not have COVID-19. Selenium concentration in COVID-19 is also linked to the severity and mortality of the disease [[2]].
[3] https://journals.lww.com/co-lipidology/abstract/2008/02000/selenium_intake_and_cardiovascular_risk__what_is.9.aspx
Vitamin B1 for long COVID
THIAMINE (VITAMIN B1)
What is thiamine?
Thiamine, also called vitamin B1, belongs to the group of vitamins known as the B vitamins. Like the other B vitamins, thiamine converts food into fuel for our cells. More specifically, thiamine helps break down carbohydrates we eat into energy [[1]].
What does thiamine do in the body?
Thiamine is essential for nervous system function because it helps brain cells communicate better, both in terms of the insulation needed for brain cells to communicate and the propagation of neural signals itself. Thiamine deficiency can lead to neurological issues such as memory problems, seizures, delirium, and more. Thiamine also has antioxidant properties; the body needs more during a viral illness. Continual dietary supplementation is vital because the body can only store a limited amount of thiamine and has a relatively short half-life [[2]].
How can thiamine help alleviate certain Long COVID symptoms and/or pathophysiology?
Research shows that thiamine depletion occurs in critical illness, including acute COVID-19 [[2]], and that this depletion is associated with an almost 50% increase in mortality [[1]]. One study found that the lower a patient’s vitamin B1 is, the larger the systemic inflammatory response, which is linked to adverse clinical outcomes in COVID-19 and is a risk factor for developing Long COVID [[3]].
Beyond thiamine’s role in dampening inflammation in acute illness, Long COVID symptoms resemble those of beriberi, or thiamine deficiency [[4]]. Many of the symptoms of beriberi involve the nervous system, which can be affected by long COVID. Therefore, sufficient thiamine intake may be essential to treat Long COVID symptoms, and potentially, especially those Long COVID symptoms that affect the nervous system.
Systemic Proteolytic Enzymes for long COVID
SYSTEMIC PROTEOLYTIC ENZYMES
What are systemic proteolytic enzymes?
We previously discussed bromelain’s utility in reducing inflammation. Bromelain, discussed in this guide, belongs to a larger class of systemic proteolytic enzymes, or SPEs. SPEs break down proteins to help facilitate normal body processes such as digestion or pain relief. They can also be used to reduce swelling and help with wound healing cleanup [[1]].
Other SPEs include lysozyme, catalase, and papain. SPEs break down proteins into smaller fragments and, ultimately, into amino acids, which are the building blocks of proteins and other vital molecules the body uses for various purposes [[2]].
What do systemic proteolytic enzymes do in the body?
SPEs can be taken as oral supplements or applied to the skin. Applied to the skin, they can aid in cleaning up tissue from wounds to support healthy wound healing [[1]].
As a supplement, SPEs can work in the body to perform a variety of processes related to immune health, digestion, and more. Regarding COVID-19 and its impact on the immune system in Long COVID, SPEs are known immune system modulators. SPEs work to combat oxidative stress and prevent cell and tissue damage [[2]].
How can systemic proteolytic enzymes help alleviate certain Long COVID symptoms and pathophysiology?
SPEs may be able to break down the spike proteins in SARS-CoV-2, the virus that causes COVID-19 [[2]]. They may also be able to unfold coronavirus proteins. SPE’s antiviral properties can be helpful because the virus can persist in Long COVID patients after the acute phase.
Ibuprofen for long COVID
IBUPROFEN
What is ibuprofen?
Ibuprofen is a nonsteroidal anti-inflammatory (NSAID) medication commonly used to relieve pain and reduce fevers. Unlike acetaminophen, it also has some anti-inflammatory properties and can be used for inflammatory diseases such as osteoarthritis and rheumatoid disorders.
How can ibuprofen help alleviate certain long COVID symptoms?
Ibuprofen works by reversibly inhibiting enzymes in our body called COX-1 and COX-2 that help reduce fever, pain, and inflammation. It is also believed to reduce pro-inflammatory substances called cytokines and inhibit the activation of other immune cells that can cause inflammation.
The prevalence of post-COVID pain is estimated to be up to 63.3%, and patients with chronic pain can have exacerbated symptoms after COVID.1 There are multiple possible mechanisms behind post-COVID pain. Post-COVID pain may be caused by the virus entering and attacking musculoskeletal and nervous systems, including the brain. Persistent inflammation from overactivated inflammatory pathways and excessive activation of blood clotting can also contribute to pain. Various types of pain can also be caused by COVID, such as headaches, neuropathic pain, musculoskeletal pain, chest pain, arthralgia, and fibromyalgia.
While other prescription medications are typically used to treat headaches, neuropathic pain, chest pain, and fibromyalgia, ibuprofen can be used to relieve short-term headaches, musculoskeletal pain, arthralgia, and myalgias that persist or worsen after COVID; however, it should not be used to treat COVID or to reduce the duration of COVID symptoms. Post-COVID headache can also be treated first-line with acetaminophen or NSAIDs like ibuprofen.2
What evidence supports ibuprofen’s use for long COVID?
Early on in the pandemic, anecdotal reports suggested that NSAIDs could potentially increase susceptibility to COVID due to their ability to increase expression of ACE2 receptors that are targeted by the SARS-CoV-2 virus.3 However, several studies have since debunked this theory and have shown that the use of NSAIDs is not associated with increased COVID severity or risk of all-cause mortality.4
A survey of 696 COVID patients in Italy reported that the use of standard analgesics such as ibuprofen in the post-acute phase of COVID had a temporary reduction in pain severity.5 NSAIDs can also be effective in managing migraines and are commonly used for headaches as well.6 While there are few studies investigating the use of ibuprofen for long COVID pain, the use of NSAIDs for pain is well-established and can be used safely in many patients post-COVID. Chronic use of NSAIDs, however, should be discussed with a healthcare provider.
What are some things to be aware of when taking ibuprofen?
Ibuprofen is not recommended in people at risk for or with existing cardiovascular disease, GI disease, kidney impairment, chronic liver disease, or people at higher risk of bleeding. Use of NSAIDs is associated with an increased risk of serious cardiovascular events such as heart attacks and strokes. New-onset hypertension can also occur with NSAIDs and can exacerbate heart failure. There is also a higher risk of gastrointestinal adverse events such as gastrointestinal bleeding or ulcers. Do not take ibuprofen for more than 10-15 days per month for headaches. Ibuprofen should be taken with food, and you should let your doctor know if you are taking ibuprofen regularly for long COVID symptoms.
References:
Folic Acid for long COVID
FOLIC ACID (VITAMIN B9)
What is folic acid?
Folic acid is a water-soluble B vitamin. It is also known as vitamin B9 [[1]].
What does folic acid do in the body?
Folic acid belongs to the B vitamin family. All B vitamins help the body break down and derive energy from macromolecules such as carbohydrates, proteins, and fats. B vitamins also play a role in nervous system function [[2]].
Folic acid has many functions in human biochemistry. It is essential for proper balance in our cells [[3]].
Folic acid helps the body grow new cells and prevent changes in DNA that may cause cancer. Deficiency in folic acid is associated with a variety of health conditions, including cancer [[1]].
Folic acid works with vitamins B6 and B12 to regulate the levels of homocysteine in the blood [[4]]. Homocysteine is an amino acid linked to arteriosclerosis, cancer, aortic aneurysm, hypothyroidism, and end-renal stage disease, among other conditions [[5]].
How can folic acid help alleviate certain Long COVID symptoms and pathophysiology?
Folic acid can help curb inflammatory processes in Long COVID by regulating homocysteine levels.
Low levels of folic acid can also predispose to Long COVID [[6]]. Folic acid may also help reduce respiratory involvement in the acute phase of COVID-19, especially in the early phase [[1]]. Folic acid blocks the function of a protein called furin, which is involved in the viral replication of SARS-CoV-2, the virus that causes COVID-19 [[1]]. Decreased folic acid levels are expected in hospitalized COVID-19 patients, and scientists believe that lower folic acid levels are seen in more severe patients [[7], [8]]. Since more severe COVID-19 patients are more likely to develop Long COVID, folic acid levels should be measured in the acute phase of COVID-19 [[9]].
Probiotics for long COVID
PROBIOTICS
What are probiotics?
Probiotics are helpful microorganisms that can benefit the body when eaten or applied. They include bacteria, such as those from the group Lactobacillus, or other microorganisms, such as yeasts, including Saccharomyces boulardii [[1]].
What do probiotics do in the body?
Probiotics are a range of different microorganisms, so each probiotic may work differently. They can affect the immune system, help one’s body have a normal level of gut microorganisms, or even produce compounds beneficial for the body [[1]]. Probiotics can have immunomodulatory, antioxidant, and antiviral effects. They can improve cognitive function, reduce physical and mental fatigue, regulate brain health, improve sleep quality, and boost mood [[2]].
How can probiotics help alleviate certain Long COVID symptoms and pathophysiology?
The acute COVID-19 phase is associated with gastrointestinal systems such as diarrhea, nausea, vomiting, and loss of appetite. Furthermore, SARS-CoV-2 RNA can be found in stool samples even after the virus clears the respiratory tract [[3]]. Changes in gut microorganisms are linked to COVID-19 severity, possibly resulting from a post-COVID-19 “leaky gut” [[3]].
The gastrointestinal system is implicated in acute COVID-19 infection and Long COVID [[4]]. The severity of gut and lung microbiomes in COVID-19 and the effect of probiotics on these microbiomes remain under investigation by researchers. A systematic review showed that COVID-19 altered the microbiome, making opportunistic pathogens more prevalent. Furthermore, stress, hospitalization, and the actions of the SARS-CoV-2 virus directly on receptors in the gastrointestinal system are linked to gut microbiome imbalance. The altered microbiome may also change the lungs’ response to respiratory infections by modulating immune responses, and these changes may persist way after acute COVID-19 infection. Therefore, improving or supplementing the gut-lung microbiome axis is of interest in Long COVID. Probiotics such as Bifidobacteria and Lactobacilli may modulate immune function in the gut-lung axis [[5]].
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