Mexidol for long COVID
MEXIDOL
What is Mexidol?
Emoxypine succinate, also known by its commercial name Mexidol, is a chemical resembling Vitamin B6 (pyridoxine). Mexidol has many effects on the nervous and vascular systems. While available in Russia, Mexidol is generally unknown elsewhere [[1]].
What does Mexidol do in the body?
Mexidol’s effects are diverse because its mechanism of action involves both antioxidant effects and actions at cell membranes. Some actions of Mexidol include that it protects against hypoxia (oxygen deficiency) and ischemia (inadequate blood supply to organs and other body parts, especially heart muscles). Mexidol is also anti-stress, anti-anxiety, anti-convulsant, anti-aging, neuroprotective, cardioprotective, and protective against forming fatty plaques in the arteries [[1]]. Lastly, Mexidol has been met with some success in treating mental disorders without any significant side effects [[2]].
How can Mexidol help alleviate certain Long COVID symptoms and pathophysiology?
As a multitasking compound, Mexidol can act on many aspects of COVID-10 pathogenesis, including Long COVID. Researchers believe Mexidol can reduce brain inflammation and free radical oxidation [3]]. Long COVID has post-viral brain symptoms often referred to as “brain fog,” which involves heightened free radical activity in the brain, as well as decreased blood flow in the brain due to activation of the brain’s resident immune cells, as well as altered blood flow more generally [[4]]. Mexidol’s anti-inflammatory and neuroprotective properties may help combat these issues.
Features of acute and chronic COVID-19, such as endothelial dysfunction, increased blood clotting, accumulation of angiotensin 2, endothelial problems, overactivation of inflammatory cytokines, and too much inflammation, are issues that Mexidol can improve. Mexidol improves outcomes after ischemic stroke, which may be useful for Long COVID and its associated endothelial, cardiovascular, and pulmonary inflammatory issues [[2]].
Diclofenac Sodium (Voltaren Gel) for long COVID
DICLOFENAC SODIUM (VOLTAREN GEL)
What is diclofenac?
Diclofenac sodium or Voltaren gel is a non-steroidal anti-inflammatory drug (NSAID) that was previously only available as a prescription medication but is now available over the counter. It is a topical gel formulation that can be applied to joints such as the knees, ankles, feet, elbows, and wrists to relieve pain from arthritis and osteoarthritis.
It is important to apply a sufficient amount to the affected joint to reach its full effectiveness. For lower extremities, 4 g can be used for each affected area up to four times daily with a maximum dose of 16 g per joint. For upper extremities, 2 g can be applied to each affected area up to 4 times a day for a maximum dose of 8 g per joint. The maximum total body dose for all combined joints should be 32 g daily. A dosing card on the product’s box should be used when applying this medication.
How can diclofenac help alleviate certain long COVID symptoms?
Diclofenac works by reversibly inhibiting enzymes in our body called COX-1 and COX-2 that help reduce pain and inflammation topically. 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 Multiple possible mechanisms behind post-COVID pain exist. The virus may cause pain by 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.
COVID can cause various types of pain, such as headaches, neuropathic pain, musculoskeletal pain, and fibromyalgia. Inflammatory arthritis has also been reported in post-COVID patients, with symptoms similar to rheumatoid arthritis (RA) that commonly affects the knee, ankle, and wrist.2 Diclofenac is specifically useful in cases of inflammatory arthritis or musculoskeletal pain focused on the joints post-COVID.
What evidence supports diclofenac’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 common analgesics such as ibuprofen temporarily reduced pain severity in the post-acute phase of COVID.5 More studies are needed, specifically investigating the use of the NSAID diclofenac for post-COVID pain. Still, diclofenac has been shown to effectively relieve joint pain and is a reasonable option to consider for post-COVID symptoms like inflammatory arthritis. Chronic use of NSAIDs, however, should be discussed with a healthcare provider.
What are some things to watch out for with diclofenac?
Because Voltaren gel is a topical NSAID, it has a better safety profile than other oral NSAIDs with limited absorption into the body. Some side effects can include skin irritation or itching, skin dryness or redness, and numbness or tingling.
References:
5) Galluzzo V, Zazzara MB, Ciciarello F, Tosato M, Bizzarro A, Paglionico A, Varriano V, Gremese E, Calvani R, Landi F on behalf of Gemelli against COVID-19 Post-Acute Care Team. Use of First-Line Oral Analgesics during and after COVID-19: Results from a Survey on a Sample of Italian 696 COVID-19 Survivors with Post-Acute Symptoms. J Clin Med. 2023; 12(8):2992. https://www.mdpi.com/2077-0383/12/8/2992
Low Histamine Diet for long COVID
LOW HISTAMINE DIET
What is a low histamine diet?
A low histamine diet aims to restrict foods that are high in histamine. This typically starts with a two to four-week trial period. High-histamine-content foods can then be slowly reintroduced one at a time to test histamine tolerance. Foods high in histamine include alcohol, cured meat, salmon, tuna, bananas, oranges, grapes, fruit juices, dried fruits, and fermented foods, including yogurt. However, histamine content is highly variable in various food products.1 Alternatives low in histamine include non-citrus fruits, fresh meat, fresh fish, and dairy substitutes such as almond milk.
How can a low histamine diet help alleviate certain long COVID symptoms?
Histamine is a chemical that is released by mast cells during an infection and leads to an inflammatory response. It is suggested that COVID causes mast cells to over-release histamine, resulting in inflammatory effects that can lead to long COVID symptoms. Histamine is naturally present in various foods, and by ingesting foods with less histamine, it is believed that this can reduce the inflammatory effects from long COVID.2
What evidence supports the use of a low histamine diet for long COVID?
More research is being done to investigate the benefit of low histamine diets for long COVID symptoms; however, more studies currently need to be supporting its use. Anecdotally, several case reports have noted success and improvement of long COVID symptoms with a low histamine diet.3 It is important to note that this may only be the case for some long COVID patients. Given its difficulty in application, a doctor or dietitian should carefully consider a low histamine diet to weigh the risks and benefits for an individual.
What are some things to watch out for with a low histamine diet?
It is recommended that you have a dietitian provide support while starting a low-histamine diet and ensure that you are safely following it without the risk of nutritional deficiencies. The low-histamine diet is time-consuming and difficult to follow for many; thus, you should not start one if it may cause greater fatigue or negative impacts on your mental health.
References:
1) Diet & long COVID recovery: anti-inflammatory vs low histamine. Vitality360. Accessed November 3, 2023. https://www.vitality360.co.uk/blog/2022/04/05/diet-amp-long-covid-recovery-anti-inflammatory-vs-low-histamine
2) Anderson E. Caution advised with low histamine diets for long COVID. BDA: The Association of UK Dietitians. May 20, 2021. Accessed November 3, 2023. https://www.bda.uk.com/resource/caution-advised-with-low-histamine-diets-for-long-covid.html
Biotin for long COVID
BIOTIN (VITAMIN B7)
What is biotin?
Biotin, also known as vitamin B7, is a water-soluble vitamin in the B vitamin family. As a member of this family, biotin helps convert the food we eat into energy. More specifically, biotin helps enzymes break down carbohydrates, fats, and proteins [[1]].
What does biotin do in the body?
In humans, biotin helps make possible reactions that break down amino acids, synthesize fatty acids, and make glucose [[2]]. In other words, biotin helps our bodies use food to power our cells.
Biotin regulates gene expression, including metabolism genes that promote blood sugar regulation. It also decreases levels of enzymes that stimulate the liver’s glucose production [[3]].
Beauty lovers know biotin as a vitamin that, when deficient, affects hair, skin, and nails [[4]].
How can biotin help alleviate certain Long COVID symptoms and pathophysiology?
Long COVID patients who suffer from hair, skin, and nail changes may benefit from biotin supplementation [[5]].
Proper biotin supplementation plays a role in the health of hair, skin, and nails, which can all be affected in a bout with COVID-19. COVID-19 affects hair, leading to hair loss, brittle hair, and hair that is too fine. Skin and nail changes can also be part of COVID-19 [[6]]. In the case of nails, microvascular injuries may be to blame, with the body in an inflammatory response similar to what is seen with “COVID toes.” Nail issues may especially appear after the COVID-19 acute phase has passed [[7]].
Biotin has dual roles in skin and nervous system health, including neuropathic pain [[8]]. A combination of biotin, alpha-lipoic acid, calcium pantothenate, ferrous gluconate, and vitamin B3 helped reduce neuropathic skin pain in a patient with Long COVID [[9]].
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.
Guanfacine for long COVID
GUANFACINE
What is guanfacine?
Guanfacine is a medication commonly used for blood pressure and attention-deficit/hyperactivity disorder (ADHD). Immediate-release (IR) tablets are used for blood pressure, whereas extended-release (ER) tablets are used for ADHD, often in combination with other medications. Guanfacine is a centrally acting alpha2A-adrenergic receptor agonist. Guanfacine treats high blood pressure by decreasing heart rate and relaxing the blood vessels so blood can flow more easily. Guanfacine ER tablets may treat ADHD by affecting the part of the brain that controls attention and impulsivity, the prefrontal cortex [1]. Guanfacine is not a stimulant, unlike most medications prescribed for ADHD; therefore, it lacks addictive qualities. Coupled with its relatively affordable nature, it could be a very appealing option to many patients.
How does guanfacine relate to long-COVID?
Sufferers of long-COVID often deal with “brain fog,” a persistent cognitive defect resulting in memory problems, poor focus, and decreased ability to concentrate. Through its supposed effects on the prefrontal cortex, guanfacine could be helpful in those suffering from “brain fog.”
Although a lengthy clinical trial has yet to be completed, one researcher from Yale found evidence of guanfacine decreasing “brain fog” in long COVID patients. [2]. He completed a small study with 12 patients all experiencing “brain fog” post-COVID. Patients were given guanfacine and N-acetylcysteine (NAC), an antioxidant with anti-inflammatory properties. Of those 12 patients, eight experienced relief from “brain fog.” Two patients were lost to follow-up, and two stopped the treatment due to side effects [2]. Guanfacine is an attractive medication option to help with memory and concentration problems for those suffering from long-COVID. Although no formal recommendations have been made regarding its use, it shows promise to patients.
References:
1https://medlineplus.gov/druginfo/meds/a601059.html
Mirtazapine for long COVID
MIRTAZAPINE
What is mirtazapine (Remeron)?
Used for depression, mirtazapine is a medication belonging to the tetracyclic antidepressant drug class. Mirtazapine is different than other antidepressants in that it works on alpha-2 adrenergic receptors. Inhibition of these receptors results in an increased availability of both serotonin and norepinephrine. Serotonin is a molecule in the body that aids in mood, sexual desire, sleep, digestion, wound healing, bone health, and blood clotting [1]. It is often referred to in psychology as the “happy” chemical. Norepinephrine is thought to play a role in the body’s stress response and helps to regulate sleep, alertness, and blood pressure [2].
How can mirtazapine be used in long-COVID?
Mirtazapine may also benefit the long-COVID patient population. Many of those diagnosed with long-COVID suffer from “brain fog,” memory problems, difficulty concentrating, and forgetfulness. The proposed reason is that during a COVID-19 infection, the body’s immune response becomes activated, causing heavy amounts of inflammation, including in the central nervous system (CNS) [3]. Those with long-COVID live in a state of inflammation, manifesting as the symptoms associated with “brain fog.”
In addition to aiding in several bodily processes, serotonin also protects against viral inflammation by blocking certain viruses (like HIV-1) from entering the cells. It can also decrease cytokine production, promoting the immune response [3]. Currently, its use is limited to depression. There is no evidence to support the use of mirtazapine in treating COVID-19 itself. However, it may be beneficial if more studies are conducted to examine its effects.
References:
1 https://my.clevelandclinic.org/health/articles/22572-serotonin
2https://americanaddictioncenters.org/antidepressants-guide/ndris
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