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]].
CoQ10 for long COVID
CoQ10
What is CoQ10?
Coenzyme Q10, or CoQ10, is one of today’s most popular dietary supplements. It is not a vitamin because it is a substance made by the body; however, it is similar in structure to vitamins such as vitamin K [[1]].
CoQ10 is a substance produced naturally by the body that plays a role in cell growth and maintenance. It is fat-soluble, so its absorption is increased with a fatty meal [[2]].
CoQ10 is present in all body tissues. The highest concentrations are seen in tissues with high energy requirements: the heart, kidney, liver, and muscle [[1]]. In tissues with abundant CoQ10, the CoQ10 is focused in the mitochondria, the cell’s energy powerhouse.
What does CoQ10 do in the body?
CoQ10 helps convert food into energy and serves as an antioxidant. Its specific role involves turning energy from carbohydrates and fats into chemicals that can power cells’ machinery to ensure proper cellular function [[3]].
As a scavenger of free radicals, CoQ10 reduces inflammation. As a result, It has been recommended for a variety of inflammatory diseases. CoQ10 ensures the immune response has the proper energy supply and cell types [[2]].
Two common uses of CoQ10 in the clinic are congestive heart failure and statin-associated myopathy syndrome [[4]].
How can CoQ10 help alleviate certain Long COVID symptoms and pathophysiology?
In addition to generating chemical energy for cells, CoQ10 has antioxidant functions in the body. It can recycle other antioxidants to increase antioxidant bioavailability, which can be helpful for COVID long-haulers who may deal with inflammation [[4]].
Studies have found that CoQ10 improves performance, lessens fatigue in healthy individuals, and chronic fatigue syndrome and juvenile fibromyalgia [[2]].
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.
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]].
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]].
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]].
Diphenhydramine for long COVID
DIPHENHYDRAMINE
What is diphenhydramine?
Diphenhydramine is an antihistamine used to relieve symptoms of allergies, hay fever, or a cold, such as red, itchy, or watery eyes, sneezing, runny nose, and cough. It can also prevent nausea and vomiting, motion sickness, and vertigo. Compared to other antihistamines, diphenhydramine is the most sedating and can help you fall asleep. It also has a shorter duration of action and may need to be taken every four to six hours as needed.
How can diphenhydramine help alleviate certain long COVID symptoms?
Histamine is a chemical our immune system releases that causes our allergy symptoms. Cells in our body called mast cells release histamine, and in some patients after COVID, they may release too much, leading to some of the symptoms of long COVID. Long COVID is believed to be a state of prolonged hyper-inflammation that follows the infection. Because diphenhydramine can block histamine type 1 receptors, it has the potential to relieve certain long COVID symptoms and has been reported to improve fatigue and cognitive symptoms specifically.1
What evidence supports diphenhydramine’s use for long COVID?
There has been extensive research on the use of antihistamines in general for long COVID. Unfortunately, no evidence directly supports diphenhydramine’s use for long COVID. Two case reports noted considerable improvement in fatigue, “brain fog” or ability to concentrate, abdominal pain, and loss of smell and taste with diphenhydramine 25 mg or 50 mg.1 The addition of diphenhydramine to a combination of ibuprofen and cimetidine was also found to help treat adult respiratory distress syndrome (ARDS) in a porcine model; however, these results may not extend to humans.2
What are some things to be aware of when taking diphenhydramine?
Diphenhydramine should be used sparingly in older adults. It can cause blurred vision, urinary retention, nausea, and constipation, which may be worsened with other medications. Avoid taking diphenhydramine during the day, as it can cause drowsiness. While diphenhydramine can help with insomnia, it should not be routinely taken for this purpose.
References:
Oxymetazoline (Afrin) for long COVID
OXYMETAZOLINE NASAL SPRAY
What is oxymetazoline?
Oxymetazoline (Afrin) is a decongestant that constricts the blood vessels in your nose to reduce nasal swelling and congestion. It can be applied by spraying 2-3 sprays in each nostril twice a day, with a maximum daily dose of 2 doses in a 24-hour period.
How can oxymetazoline help alleviate certain long COVID symptoms?
Oxymetazoline can be used for nasal congestion that persists after a COVID infection, but it should not be used long-term. Unlike oral decongestants like pseudoephedrine or phenylephrine, which can increase blood pressure in people with high blood pressure, oxymetazoline has fewer effects on blood pressure and can be more beneficial in these patients.
What evidence supports oxymetazoline’s use for long COVID?
Few studies have examined the use of oxymetazoline for long COVID symptoms. While using oxymetazoline with nasal corticosteroids has demonstrated improvement in nasal congestion and lack of smell specifically in patients with nasal polyps,1 oxymetazoline has not been shown to influence loss of smell following a COVID infection.
What should you be aware of when taking oxymetazoline?
If used for more than three consecutive days, oxymetazoline can cause the blood vessels in your nose to swell up again, leading to rebound congestion. Therefore, it is essential to limit use to three to five consecutive days. Side effects of oxymetazoline include temporary burning or stinging and dryness in the nose. Oxymetazoline is not recommended for use in children younger than six.
References:
Tricarboxylic Acid Cycle Intermediates for long COVID
TRICARBOXYLIC ACID CYCLE INTERMEDIATES (Specifically: Malic Acid, Citric Acid, and Succinic Acid)
What are tricarboxylic acid intermediates?
The tricarboxylic acid cycle (TCA), also known as the Krebs or citric acid cycle, is a cyclic reaction used by the body to generate energy from the foods we eat. The TCA cycle occurs in the mitochondria, the cell’s energy powerhouse. The TCA cycle has intermediates, including malic acid, citric acid, and succinic acid, which are known to be involved in energy metabolism in the mitochondria.
What do tricarboxylic acid intermediates do in the body?
While these intermediates used to be thought of as byproducts of cellular metabolism to make lipids, nucleotides, and proteins, they are now known as important molecules with many different functions. Metabolites of the TCA cycle may be involved in remodeling the contents of the chromosome, regulating gene expression, modifying proteins, acting on platelets, and performing immune functions [[1]]. TCA cycle intermediates also regulate the production of reactive oxygen species, a class of free radicals [[2]].
Evidence suggests these intermediates also play a role in maintaining cellular immunity. When cells are in stress conditions, the membrane enclosing the mitochondria within the cell can become compromised, releasing TCA cycle intermediates into the cytosol or the fluid flowing inside the whole cell, directly influencing cellular immunity through its interactions there [[2]].
How can tricarboxylic acid intermediates help alleviate certain Long COVID symptoms and pathophysiology?
Supplementation with TCA cycle intermediates can help boost mitochondrial function and help patients recovering from COVID-19, especially older people. Supplemented along with amino acids, TCA cycle metabolites can play a supporting role in helping prevent mitochondrial damage, oxidative stress, and muscle loss. A combined supplement that includes amino acids and TCA cycle intermediates such as citric, succinic, and malic acids may be relevant to maintaining mitochondrial function. Such a supplement cocktail was studied in a mouse aging model and was found to preserve mitochondrial function, support muscle mass, and preserve physical and cognitive abilities [[1]]. While more work is needed to elucidate the exact role of TCA cycle intermediates in Long COVID pathophysiology, the research seems promising.
Doxylamine for long COVID
DOXYLAMINE
What is doxylamine?
In contrast with other antihistamines typically used for allergy symptoms, doxylamine is a first-generation antihistamine commonly used as a short-term treatment for insomnia. However, it can also be used for allergy symptoms such as nasal congestion, sneezing, runny nose, and itchy nose, as well as nausea and vomiting in pregnancy (when combined with pyridoxine or vitamin B6). For adults or children ages 12 and older, it can be taken as 25-50 mg at bedtime as needed for insomnia.
How can doxylamine help alleviate certain long COVID symptoms?
Sleep-related disturbances are common after COVID and may be present in up to 52% of long COVID patients.1 Insomnia can also contribute to downstream effects such as metabolic and cardiovascular diseases, immune responses, and increased depression and anxiety. While non-pharmacological measures for treating insomnia are preferred, such as maintaining good sleep habits, maximizing exposure to natural daylight, especially in the morning, and following a night routine, pharmacological measures such as doxylamine can improve sleep.
Doxylamine can also be an active ingredient in Nyquil, along with dextromethorphan and acetaminophen (Tylenol). Nyquil helps reduce cough, nasal congestion, a runny nose, and insomnia, but it should not be solely taken to fall asleep. When taken in excess, it can also cause more serious side effects, such as dizziness, dry mouth, headaches, and the potential for liver damage if taken with other acetaminophen-containing products.
What evidence supports doxylamine’s use for long COVID?
There is currently a lack of studies assessing the use of doxylamine for long COVID. Prescription medications used to treat insomnia include benzodiazepines, which are not preferred for long-term use and have a risk of abuse and dependence when used chronically. Thus, doxylamine may be a safer alternative available over-the-counter that can be used to treat short-term insomnia in long COVID patients.
What are some things to watch out for with doxylamine?
Doxylamine should not be taken longer than two consecutive weeks, as it can become less effective. Patients can also build up a tolerance to the medication, so it should not be taken regularly.2
Due to its sedative effects, doxylamine should not be taken during the day before driving or operating heavy machinery. It should not be taken with alcohol or a drug class called monoamine oxidase inhibitors (MAOIs) and should be used with caution when taking other drugs that depress the central nervous system (CNS).
Doxylamine can also cause constipation, urinary retention, and blurred vision, especially when taken with certain other medications. If you are taking this medication more frequently, you should let your doctor know, as it can contribute to the side effects of other medications. Doxylamine is meant as a short-term treatment for insomnia and should not be taken chronically, particularly in older adults. It should also be used with caution in patients with narrow-angle glaucoma, urinary obstruction or gastrointestinal obstruction, and peptic ulcers.
References:
2) Pacheco D and Rehman Anis. Does Nyquil make you sleepy? Sleep Foundation. May 4, 2023. Accessed November 13, 2023. https://www.sleepfoundation.org/sleep-aids/does-nyquil-make-you-sleepy#:~:text=fully%20worn%20off.-,Should%20You%20Take%20Nyquil%20for%20Sleep%3F,for%20more%20than%20two%20weeks.
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