Ivabradine for long COVID
IVABRADINE
What is Ivabradine?
Ivabradine is a medication used to treat heart conditions.
What does Amantading do in the body?
Ivabradine slows the electrical conduction in the heart which subsequently slows the heart rate.
How can Ivabradine help alleviate certain long COVID symptoms and pathophysiology?
The use of ivabradine in long COVID (post-acute sequelae of SARS-CoV-2 infection, PASC) is based on limited but emerging scientific evidence. According to the 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 by the American College of Cardiology, ivabradine has been used in patients with severe fatigue exacerbated by beta-blockers and calcium-channel blockers.
This recommendation is based on a small trial involving 22 patients with postural orthostatic tachycardia syndrome (POTS). The trial found that ivabradine improved heart rate and quality of life over one month[1]. Additionally, a perspective article suggests that ivabradine may be helpful in managing COVID-19-related cardiovascular complications due to its heart rate-lowering effects and various additional benefits, such as anti-inflammatory and anti-oxidant actions[2]. However, these findings are preliminary and derived from small-scale studies or theoretical benefits rather than large, randomized controlled trials specifically targeting long COVID. While there is some evidence supporting the use of ivabradine for managing cardiovascular symptoms in long COVID, it is primarily based on small studies and expert opinion. More extensive clinical trials are needed.
1.Gluckman TJ, Bhave NM, Allen LA, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and other Myocardial involvement, Post-Acute Sequelae of SARS-COV-2 Infection, And return to play. Journal of the American College of Cardiology. 2022;79(17):1717-1756. doi:10.1016/j.jacc.2022.02.003
2.Baka T, Repova K, Luptak I, Simko F. Ivabradine in the Management of COVID-19-related Cardiovascular Complications: A perspective. Current Pharmaceutical Design. 2022;28(19):1581-1588. doi:10.2174/1381612828666220328114236
Amantadine for long COVID
AMANTADINE
What is Amantadine?
Amantadine is a medication used to treat abnormal movements in conditions such as Parkinson’s disease.
What does Amantadine do in the body?
Amantadine has mild effects on dopamine neurons, but we’re not sure exactly how it works for Parkinson’s. It also seems to stop a virus from infecting cells, but we don’t fully understand how it works. While Amantadine has some antiviral properties, it is no longer recommended as an antiviral in clinical practice. [1]
How can Amantadine help alleviate certain long COVID symptoms and pathophysiology?
When it comes to long COVID, especially post-COVID-19 fatigue, there’s limited but hopeful evidence for using amantadine. One study found that patients who took amantadine for two weeks had less fatigue compared to those who didn’t, as measured by the Visual Analog Fatigue Scale (VAFS) and Fatigue Severity Scale (FSS). [2] However, other studies looked at different aspects of COVID-19 and how amantadine is used to treat it.
For example, one study found no significant improvements in fatigue among unvaccinated patients with early, mild to moderate COVID-19. [3] Another study emphasized the need for more standardized and robust studies on long COVID.[4]. The treatment has also been considered for fatigue in other conditions, such as Multiple Sclerosis. A Cochrane Database of Systematic Reviews found that amantadine is generally well-tolerated. However, the evidence supporting its effectiveness in reducing MS-related fatigue is still limited and inconsistent [5]. While Amantadine has the potential to reduce post-COVID-19 fatigue, but we need more large-scale, well-controlled studies to confirm its effectiveness and safety in this context.
1.Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa. Clinical Infectious Diseases. 2018;68(6):e1-e47. doi:10.1093/cid/ciy866
2.Harandi AA, Pakdaman H, Medghalchi A, et al. A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue. Scientific Reports. 2024;14(1). doi:10.1038/s41598-024-51904-z
3Rejdak K, Fiedor P, Bonek R, et al. Amantadine in unvaccinated patients with early, mild to moderate COVID‐19: A randomized, placebo‐controlled, double‐blind trial. European Journal of Neurology. 2023;31(1). doi:10.1111/ene.16045
4.Chee YJ, Fan BE, Young BE, Dalan R, Lye DC. Clinical trials on the pharmacological treatment of long COVID: A systematic review. Journal of Medical Virology. 2022;95(1). doi:10.1002/jmv.28289
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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]].
Quercetin for long COVID
QUERCETIN
What is quercetin?
Quercetin is a flavonoid, a group of plant pigments that give fruits, vegetables, and flowers their colors. As a flavonoid, quercetin is a potent antioxidant. Along with the other members of the flavonoid family, quercetin reduces the risk of heart and metabolic disorders and certain cancers. Flavonoids work to combat oxidative stress in the body [[1]].
What does quercetin do in the body?
Quercetin lowers coagulation and reduces hyperglycemia, inflammation, and hypertension. Quercetin supplementation is used to prevent and treat chronic diseases including, but not limited to, cardiovascular issues [[2]].
How can quercetin help alleviate certain Long COVID symptoms and pathophysiology?
As antioxidants, quercetin and other flavonoids prevent oxidative stress and buffer against the effects of aging [[2]]. Quercetin is the most promising flavonoid to help deal with Long COVID because it has shown the ability to inhibit tumor necrosis factor alpha [[3]]. Tumor necrosis factor alpha is one of the most important cytokines involved in the intense and severe chronic inflammation in Long COVID [[4]].
While much remains to be known about Long COVID, an increasingly clear picture is emerging about its underlying mechanisms, and tumor necrosis factor alpha plays a role. Individuals with Long COVID have higher levels of tumor necrosis factor alpha and other types of immunoreactive cells than people who recovered fully from acute COVID infection [[4]].
What else should I know about quercetin?
Quercetin supplementation via over-the-counter supplements is common, but significant drug interactions exist [[5]]. According to WebMD, several drugs interact with quercetin, such as antibiotics, cyclosporin, warfarin, or drugs changed by the liver [6]].
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]].
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