Oxaloacetate for long COVID
OXALOACETATE
What is oxaloacetate?
Oxaloacetate is a substance found in every cell in our bodies and is crucial for metabolism, cellular function, and energy production and use. It also helps meet glucose needs in the brain and, potentially, the cerebellum, giving it a potential role in cognition and mood [[1]]. Oxaloacetate also affects cellular metabolism in several biochemical reactions [[2]]. For example, oxaloacetate gives rise to the amino acid aspartate, which acts as a neurotransmitter in the brain. Oxaloacetate also serves as a precursor for glucose production in the liver [[3]].
What does oxaloacetate do in the body?
Oxaloacetate plays a variety of roles in the body. An animal study showed that oxaloacetate played different roles, including improving the insulin pathway, reducing inflammation, and stimulating neurogenesis, which is the growth of new brain cells [[4]].
How can oxaloacetate help alleviate certain Long COVID symptoms and pathophysiology?
Oxaloacetate has been shown to reduce fatigue associated with Long COVID [[5]]. In one study of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID patients, both patient groups experienced a reduction in fatigue after six weeks of treatment with oxaloacetate [[6]]. Because fatigue is a major feature of Long COVID and ME/CFS, which can develop from Long COVID, oxaloacetate can be of import to these sufferers of chronic illness [[5]].
Oxaloacetate’s neuroprotective and anti-ischemic effects may also be relevant for Long COVID patients, who are at greater risk for brain inflammation and stroke. Oxaloacetate’s neuroprotective capability stems from its ability to reduce levels of glutamate in the brain and blood. Glutamate is an excitatory neurotransmitter that can be toxic to brain cells at high levels, causing neuronal death and debris that can contribute to a stroke in the brain. Therefore, oxaloacetate’s glutamate-regulating capacities may help prevent ischemic stroke in Long COVID patients, who are at greater risk of ischemic events than non-Long COVID patients [[7]].
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Meclizine for long COVID
MECLIZINE
What is meclizine?
Meclizine is a first-generation antihistamine and antiemetic commonly used for motion sickness or vertigo (a sensation that you or your surroundings are spinning). It can be taken in 12.5 to 25 mg doses every six to eight hours as needed. If motion sickness is anticipated for a certain activity, taking meclizine 30-60 minutes prior is best. The maximum dose is 100 mg per day.
How can meclizine help alleviate certain long COVID symptoms?
While rare, there have been reports of new-onset vertigo associated with a COVID infection as well as other neurological symptoms such as persistent dizziness.1 It is known that the SARS-CoV-2 virus can infiltrate the central nervous system and directly invade the brain. The mechanism of its association with vertigo is still unclear. Still, it is thought to be due to the effect of the virus on neural networks impacting our hearing and balance or cytokine storm that occurs when immune cells become hyperactivated and trigger an excess release of inflammatory mediators.2 Dizziness can also be due to multiple factors such as dehydration, headache, and lightheadedness due to stress from the infection.
Meclizine blocks certain receptors in the vomiting center and chemoreceptor trigger zone in our brain, which are responsible for causing feelings of nausea and dizziness. This allows for relief of vertigo and dizziness from neurological long-term COVID symptoms.
What evidence supports meclizine’s use for long COVID?
There are currently no studies exploring the use of meclizine specifically for new-onset vertigo or dizziness after a COVID infection. However, there have been multiple case reports of patients with post-COVID vertigo using meclizine for management.
In a patient with vertigo attacks lasting two weeks following the resolution of his COVID symptoms, he was given meclizine 25 mg tablets in addition to prescription medications (ondansetron and diazepam intravenously). While his nausea resolved, his vertigo was ongoing.3
In another patient’s case of acute vertigo associated with nausea and vomiting following a COVID infection, the patient was given meclizine 25 mg three times a day and ondansetron (a prescription anti-nausea medication) as needed after use of an anti-nausea medication betahistine which is currently not available in the US.1 The patient experienced complete resolution of vertigo and nausea after seven days.
While the data for the use of meclizine for post-COVID vertigo is mixed, it is a reasonable option to improve dizziness. It can be trialed with other prescription medications to improve vertigo, nausea, and vomiting.
What are some things to watch out for with meclizine?
Meclizine should not be used chronically as it can cause side effects such as urinary retention, dry mouth, and blurry vision. It can also cause drowsiness and memory impairment; therefore, it should not be taken before driving or operating heavy machinery. These side effects can worsen with older age and higher doses of the medication. If you are taking this medication more frequently, let your doctor know, as it can contribute to the side effects of other medicines as well.
References:
Beetroot for long COVID
BEETROOT JUICE
What is beetroot juice?
Beetroot juice is, as its name implies, juice from the red beetroot (also called a beet), Beta vulgaris. It has garnered much attention due to its potential health effects on the cardiovascular and pulmonary systems, as well as metabolism and inflammation. These health effects stem from its status as the juice of a vegetable with a high nitrate content [[1]].
What does beetroot juice do in the body?
Beetroot juice, like other foods high in nitrates, such as leafy green vegetables, makes nitric oxide more available to the body’s cells. This, in turn, can boost physical performance and improve endothelial function, which is also reliant upon nitric oxide. Those at risk of dysfunction in the endothelial system, such as older adults, people with peripheral artery disease, pregnant women, and people with high cholesterol and high blood pressure, can benefit from beetroot juice [[1]]. Research from animal studies shows that the nitrate content of beetroot juice may also reduce the inflammatory response by acting directly on pro-inflammatory cells. It may also increase the availability of nitric oxide in the lungs, improving respiratory defenses and potentially protecting against respiratory infections [[1]].
In addition to its nitrate content, beetroot juice boasts other compounds with antioxidant and anti-inflammatory properties, such as polyphenols, carotenoids, and other inflammation-busting compounds. These compounds can scavenge free radicals in the body and regulate the immune response.
How can beetroot juice help alleviate certain Long COVID symptoms and pathophysiology?
Because a feature of Long COVID is endothelial dysfunction, and another is inflammation, consuming beetroot juice could potentially help improve endothelial function and reduce the body’s inflammatory response in Long COVID. According to the above research, the endothelial health benefits may be significant for people with high cholesterol and high blood pressure who are already at higher risk of endothelial dysfunction.
Rhexical Plus Tablet Benefits – Vitamins, Minerals & Health Support
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Rhexical Plus Tablet is a supplement that treats nutritional deficiencies while promoting overall health. It is a blend of essential vitamins and minerals that include Elemental Calcium, Vitamin D3, L-5-Methyltetrahydrofolate, Methylcobalamin, Pyridoxine-5-Phosphate, and Vitamin K2-7.
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Naproxen for long COVID
NAPROXEN
What is naproxen?
Naproxen is a non-steroidal anti-inflammatory (NSAID) medication commonly used to relieve pain and reduce fevers. Unlike acetaminophen, naproxen has anti-inflammatory properties and can be used for inflammatory diseases such as osteoarthritis and rheumatoid disorders. It is typically taken as 500 mg followed by 250-500 mg every 12 hours as needed for the immediate-release formulation or 1 g once daily for the extended-release formulation.
How can naproxen help alleviate certain long COVID symptoms?
Naproxen 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, naproxen 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 with acetaminophen or NSAIDs like naproxen.2 Compared to ibuprofen, naproxen acts longer and can be taken every 8-12 hours, while ibuprofen acts faster and can be taken every four to six hours.
What evidence supports naproxen’s use for long COVID?
Early on in the pandemic, anecdotal reports suggested that NSAIDs could 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 study in which hospitalized COVID patients were randomized to either naproxen 500 mg twice a day or placebo for five days along with standard treatment demonstrated improvement in cough and shortness of breath.5 This result requires additional studies to confirm these findings, but naproxen has also been found to improve headache, malaise, myalgia, and cough in a study of patients with rhinovirus.6
A survey of 696 COVID patients in Italy reported that the use of standard analgesics such as naproxen in the post-acute phase of COVID had a temporary reduction in pain severity.5 NSAIDs can be effective in managing migraines and are commonly used for headaches as well.2
What are some things to watch out for with naproxen?
Naproxen 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 GI bleeding or ulcers. Do not take naproxen for more than 10-15 days per month for headaches. Naproxen should be taken with food, and you should let your doctor know if you are taking it regularly for long COVID symptoms.
References:
3) Kushner, P., McCarberg, B.H., Grange, L. et al. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19. npj Prim. Care Respir. Med. 32, 35 (2022). doi: 10.1038/s41533-022-00300-z
Bromelain for long COVID
BROMELAIN
What is bromelain?
Bromelain is a combination of different enzymes naturally found in pineapple, both in the fruit and in the stem. Its job is to break down proteins [[1]].
What does bromelain do in the body?
Bromelain has many useful clinical properties. It is anti-edema, anti-cancer, anti-inflammatory, and anti-thrombotic. It is also pro-fibrinolytic, which can dissolve blood clots [[1]]. As an anti-inflammatory agent, bromelain exerts activity widely throughout the body in the respiratory, digestive, immune, and circulatory systems [[2]]. Bromelain controls inflammation through its effects on biological pathways that regulate the synthesis of the immune system’s inflammatory molecules, cytokines.
Clinical applications of bromelain include treating cardiovascular disorders, bronchitis, sinusitis, surgical trauma, thrombophlebitis, wound healing, osteoarthritis, and diarrhea [[1]]. Researchers hypothesize that bromelain may also help with chronic fatigue, joint pain, and myalgia [[2]]. Bromelain shortened symptom duration in one study of children with sinusitis [[3]].
How can bromelain help alleviate certain Long COVID symptoms and pathophysiology?
Because bromelain can help treat several disorders, it could be promising for Long COVID patients, who often face multi-organ system challenges. Bromelain’s effects are documented on the cardiovascular, circulatory, musculoskeletal, immune, vascular, and digestive systems. It also has the capacity to impact cancer cells directly and change molecular pathways of cancer malignancy. While it has several benefits, the exact mechanisms by which these benefits are conferred remain unclear. However, its multifaceted effects could benefit Long COVID patients [[1]].
Inflammation is a problem for Long COVID patients, and bromelain directly modulates inflammatory cytokine pathways. Another issue faced by Long COVID patients is difficulties with clotting and circulation, and bromelain’s effects in preventing thrombosis and breaking down clots can be helpful. Bromelain also may have analgesic effects by regulating the synthesis of pain mediators such as bradykinin. Lastly, bromelain may have inhibitory effects on SARS-CoV-2, which causes COVID-19, by its enzymatic activity breaking down its various proteins and receptors [[2]].
Composition CALCIUM CITRATE-250MG + L 5 METHYLFOLATE-1MG + METHYLCOBALAMIN-1500MCG + PYRIDOXAL 5 PHOSPHATE-5MG + VITAMIN D3-2000IU + VITAMIN K2 7-45MCG
Nasal Saline Irrigation for long COVID
NASAL SALINE IRRIGATION
What is nasal saline irrigation?
Nasal saline irrigation, often done with a neti pot, is a non-medicated alternative that can be used as an additional treatment to relieve nasal congestion from allergies or upper respiratory tract infections. To perform nasal saline irrigation, wash and completely dry the neti pot or a similar device before use. Prepare the saline rinse with preferably distilled or sterile water. Lean over a sink and tilt your head sideways and downward to keep the saline rinse from flowing into your mouth. Breathe through your mouth while inserting the neti pot into your upper nostril so the saline can drain from the other nostril. Then repeat on the other side.
How can nasal saline help alleviate certain long COVID symptoms?
The primary target of the SARS-CoV-2 virus starts initially in the nasal epithelium and spreads to the throat and airways. It is believed that nasal saline irrigation can help to remove and limit the viral load in the nasal passages and throat. When added to standard-of-care measures, nasal saline irrigation has been shown to clear viral loads faster in more severe or hospitalized COVID patients.1 In vitro, saline has also been reported to reduce viral replication by 50-98%.1 Also, earlier studies have shown that nasal saline may even help reduce household transmission of COVID.2 Given its ability to clear the nasal passages, nasal saline may help in the reduction of nasal symptoms post-COVID as well as smell or taste dysfunction.
What evidence supports the use of nasal saline for long COVID?
In a study of 140 patients with 68 participants who performed daily nasal saline irrigations for 12 days, there was an average reduction of 24.7% in nasal congestion, a runny nose, and sneezing.3 Smell or taste dysfunction may take 10-40 days to resolve with nasal saline irrigation, and the evidence is somewhat mixed in effectiveness.1 In the previously mentioned study, lack of smell and taste did not vary significantly between the treatment and control groups.3 However, other studies have found significant differences in loss of smell between patients who used nasal saline irrigation and gargling and those who did not.4 Another study found that using nasal saline irrigation in combination with triamcinolone acetonide nasal spray (a topical corticosteroid available over the counter) significantly improved the sense of smell compared to nasal saline irrigation alone.5
What should you be aware of when using nasal saline?
Nasal saline irrigation appears to be safe with no reported serious adverse events with proper administration. Remember to thoroughly wash your neti pot before and after each use. Some may experience nasal irritation and stinging. Reducing the amount of salt in the solution or adjusting the temperature of the water may help. It is important to use distilled or sterile water to prevent potential infection from tap water.
References:
L-Carnitine for long COVID
L-CARNITINE
What is Carnitine?
Carnitine is a generic term for several highly related compounds, such as L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine. As a nutrient, carnitine is comprised of two essential amino acids, lysine and methionine [[1]]. We get carnitine from foods, especially animal products, and we can also get it from supplements [[2]]. Carnitine deficiency creates fatigue, tiredness, and lethargy [[1]].
Within the cell, L-carnitine and acetyl-l-carnitine are virtually identical, as one can be converted to the other easily. Acetyl-carnitine has better gut absorption than carnitine and can cross the blood-brain barrier, which gives it some advantages from a drug delivery standpoint [[3]].
What does carnitine do in the body?
L-carnitine and a similar compound, acetyl-l-carnitine, both work to improve mitochondrial function [[4]]. Mitochondria are the cell’s powerhouse, generating chemical energy to fuel the cell’s processes. Mitochondrial damage is linked to early aging and neurodegeneration. Carnitine and acetyl-l-carnitine have an important mitochondrial function [[5]].
How can carnitine help alleviate certain Long COVID symptoms and pathophysiology?
Fatigue is a feature of Long COVID, and previous studies of carnitine have shown that it can reduce fatigue in people with chronic diseases such as cancer and multiple sclerosis [[1]]. This leads researchers to believe carnitine can also help relieve fatigue in Long COVID [[6]].
Carnitine’s antioxidant properties are also relevant to Long COVID. Supplementing carnitine, CoQ10, and lipoic acid can lower inflammatory markers, which can be elevated in Long COVID. Lastly, carnitine can boost anti-inflammatory and antioxidant mechanisms along with its anti-fatigue characteristics. Potentially, carnitine can also regulate the formation of acetylcholine, a substance in the brain that is involved in memory [[1]].
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