Lactoferrin for long COVID
LACTOFERRIN
What is lactoferrin?
Lactoferrin is a mammalian protein found in milk, whether from an animal or human. It is also found in saliva. As an iron-binding protein, lactoferrin is used to balance iron levels in the body. While too little iron can lead to anemia, too much iron can be toxic, so lactoferrin helps keep the balance [[1]]. When lactoferrin binds to iron, this reduces the iron’s bioavailability so that the body’s iron concentration remains balanced [[2]].
What does lactoferrin do in the body?
Scientists have called lactoferrin a “miracle molecule” because it has many different properties. It is antimicrobial, antiviral, antioxidant, and immunostimulatory and can regulate DNA activity [[3]]. Lactoferrin can act defensively against microbes, and it also has antiviral activity, which it can perform in multiple ways, including binding to viruses or virus receptors. Lactoferrin’s antiviral activity extends to SARS-CoV-2, the virus that causes COVID-19; lactoferrin can bind to the spike protein and cell surface components. Lactoferrin may also dampen the inflammatory cascade by directly acting upon inflammatory cascades and its actions related to iron levels [[2]].
How can lactoferrin help alleviate certain Long COVID symptoms and pathophysiology?
Lactoferrin can be helpful for patients with acute COVID-19 and patients with Long COVID [[2]]. It can interact directly with the virus that causes COVID-19 to neutralize it. It can also inhibit inflammatory activity, characteristic of Long COVID [[4]]. Lactoferrin can also degrade blood clots, activate growth factors to support the healthy function of the body’s tissues, and remove excess proteins that collect in the body. Human lactoferrin, from human tissues, is known to reduce the problem of coagulation that can be characteristic of patients who have experienced COVID-19 [[4]].
Sulbutiamine for long COVID
SULBUTIAMINE
What is sulbutiamine?
Sulbutiamine is a manmade version of vitamin B1. It was developed in Japan in the 1960s to treat beriberi, which is vitamin B1 deficiency [[1]]. It is known mainly for its effects on cognition and fatigue.
What does sulbutiamine do in the body?
Sulbutiamine is widely used in endurance sports for its anti-fatigue, cognitive enhancement, and antioxidant effects. It can also have neuroprotective effects [[1]]. Sulbutiamine is used in medicine to treat fatigue, thiamine deficiency, and concentration difficulties. The supplement improves brain function regarding memory, concentration, and mood. In rodent studies, sulbutiamine modulates acetylcholine activity in the hippocampus. Sulbutiamine exerts anti-oxidant and anti-apoptotic properties, which can prevent cells from dying due to oxidative damage. Medical applications of sulbutiamine outside of cognitive enhancement and fatigue include depression, diabetes polyneuropathy, and erectile dysfunction. Sulbutiamine may also be an anti-cancer supplement, as its analog, thiamine, is [[2]].
How can sulbutiamine help alleviate certain Long COVID symptoms and/or pathophysiology?
Sulbutiamine is known for its anti-fatigue effects in healthy populations and those suffering from various diseases [[3]]. Sulbutiamine could be used to reduce fatigue in Long COVID alongside other treatments. In patients with multiple sclerosis, sulbutiamine, supplemented alongside disease-modifying treatment, reduced fatigue symptoms [[4]]. Therefore, sulbutiamine may have particularly restorative and/or regenerative activities relevant to the central nervous system. COVID long-haulers suffer from cognitive issues and debilitating “brain fog” as well as both physical and mental exhaustion, so sulbutiamine could be a way to improve those symptoms via supplementation.
Lastly, as sulbutiamine was developed as a replacement for vitamin B1 or thiamine, the same effects seen for Long COVID with thiamine may generally apply for sulbutiamine, though this hypothesis needs further testing. Thiamine can help reduce inflammation in Long COVID and, in one study, reduced the neurological burden of Long COVID patients [[5]].
Melatonin for long COVID
MELATONIN
What is melatonin?
Melatonin is a hormone produced by the brain’s pineal gland in darkness. Melatonin synthesis relies on the amino acid tryptophan [[1]].
What does melatonin do in the body?
Melatonin helps regulate the sleep-wake cycle and helps us sleep. Light exposure at nighttime can block the production of melatonin [[2]]. While it is known as a sleep-promoting molecule, it also activates a molecule called NRF2, which plays an antioxidant role and prevents macrophages from acting in pro-inflammatory ways [[3]].
At high doses, melatonin can be a robust scavenger of free radicals, a feat accomplished by interacting with enzymes that boost the body’s antioxidant defenses [[1]].
Relevant to SARS-CoV-2, the virus that causes COVID-19, researchers believe melatonin has a variety of helpful functions: impairing COVID-19 infection; anti-oxidant, anti-inflammatory, and immunoregulatory properties; restoring and maintaining a sleep-wake cycle (also known as the circadian rhythm); treating comorbidities of COVID-19 including metabolic syndrome, diabetes, and cardiovascular issues; neuroprotection; boosting function of COVID-19 vaccines [[4]].
How can melatonin help alleviate certain Long COVID symptoms and pathophysiology?
Because of its antioxidant, anti-inflammatory, and immune-modulatory properties, melatonin can reduce symptoms associated with COVID-19. It also activates molecular activities inside the body’s cells that increase the expression of enzymes that make the potent antioxidant glutathione, which is another powerful supplement for Long COVID [[4]].
Brain inflammation is thought to lead to lesions in the brain, which can contribute to Long COVID symptoms such as “brain fog.” Melatonin can treat delirium and can also help improve sleep-wake cycles for COVID patients in the ICU and Long COVID patients who have circadian rhythm problems [[4]].
Lastly, in its role in protecting cells, melatonin can help prevent conditions that make COVID-19 outcomes worse, such as diabetes, metabolic syndrome, and cardiovascular diseases [[4]].
Melatonin can potentially serve as a neuroprotective supplement to help Long COVID patients with “brain fog” – the cognitive dysfunction experienced by many Long COVID patients. It may also be useful to control pain in Long COVID patients [[4]].
Sulforaphane for long COVID
SULFORAPHANE
What is sulforaphane?
Sulforaphane is a plant-derived substance known to possess anti-cancer properties; more recently, its effects in fighting COVID-19 have become known [[1]]. It is found in cruciferous vegetables with exceptionally high concentrations in broccoli. Because it is found in plants we already eat, sulforaphane is generally well-tolerated [[2]].
What does sulforaphane do in the body?
Sulforaphane is an antioxidant and anti-inflammatory compound known to inhibit the effects of pro-inflammatory molecules [[3]]. It is also neuroprotective, meaning it has protective effects on the nervous system, including the brain and spinal cord. As a known anti-cancer agent, sulforaphane reduces the impact of oxidative stress on the body’s cells, inhibiting inflammatory activity. Sulforaphane inhibits the cytokines involved in the cytokine storm of COVID-19 [[2]], which is linked to Long COVID [4]].
How can sulforaphane help alleviate certain Long COVID symptoms and/or pathophysiology?
Animal studies suggest that it can improve endothelial function by blocking oxidative stress [[5]]. A study of broccoli capsules containing sulforaphane to treat COVID-19 concluded that sulforaphane could potentially protect against severe illness [[6]]. A study of sulforaphane in COVID found that it was potentially an anti-inflammatory mediator in COVID-19, reducing the gene expression of inflammatory compounds [7]]. However, laboratory research also suggests that sulforaphane may be less effective in older people than in younger populations [[5]].
Olive Polyphenol for long COVID
HYDROXYTYROSOL (OLIVE POLYPHENOL)
What is hydroxytyrosol?
Hydroxytyrosol is a substance found in olive oil. It is a polyphenol, which means it is a plant-based compound known to protect against cell damage due to inflammation and oxidative stress [[1]].
What does hydroxytyrosol do in the body?
Hydroxytyrosol has anti-oxidant and anti-inflammatory properties. It reduces the activity of cytokines, which are part of the immune response, especially in severe COVID, and can lead to Long COVID. It also prevents oxidative stress and inflammation in cells infected with SARS-CoV-2, the virus that causes COVID-19 [[2]].
How can hydroxytyrosol help alleviate certain Long COVID symptoms and pathophysiology?
Given that Long COVID is characterized by oxidative stress and inflammation, hydroxytyrosol can help via its actions preventing oxidative stress and inflammation in cells infected with COVID-19.
Research suggests, furthermore, that lingering SARS-CoV-2 virus can contribute to the pathophysiology of Long COVID and that these effects can be counteracted by antioxidants, including hydroxytyrosol, which reduce oxidative stress in cells [[3]].
Olive leaf extract improved the clinical status of hospitalized acute COVID-19 patients, improving respiratory rate and oxygen saturation [[4]]. Because olive polyphenols can improve acute COVID outcomes, they may show clinical promise for Long COVID, although more research is needed.
Combined with the amino acid arginine, hydroxytyrosol could deter the formation of harmful pro-inflammatory substances such as peroxynitrite, which is implicated in COVID-19-related organ dysfunction. Lessening inflammation, supporting immune function, protecting against damage from free radicals, and preventing blood vessel injury are just some things that arginine and hydroxytyrosol can do together [[2]].
Cistanche Tubulosa Extract for long COVID
CISTANCHE TUBULOSA EXTRACT (CTE)
What is cistanche tubulosa extract or CTE?
Cistanche tubulosa extract, or CTE, is a traditional Chinese herbal medicine that protects the gut [[1]]. CTE comes from the cistanche tubulosa plant, a perennial parasitic herb found in the Chinese desert. Cistanche tubulosa is a bright yellow and beige desert plant that is parasitic in that it obtains all or part of its nutrition from other plants [[2]].
What does cistanche tubulosa extract or CTE do in the body?
Over 120 bioactive ingredients have been found in cistanche tubulosa [[3]]. CTE can have neuroprotective, immune function, antioxidant, anticancer, and liver protective effects. One study of CTE in mice found that, via restoring gut microbiota balance, CTE produced antidepressant-like effects and elevated the level of brain-derived neurotrophic factor, a significant growth factor in healthy brain function [[4]].
How can cistanche tubulosa extract or CTE help alleviate certain Long COVID symptoms and/or pathophysiology?
A compound isolated from cistanche tubulosa called echinacoside was found to stimulate the production of immune cells called T cells, which attack foreign particles in the body [[3]]. It was also found to boost levels of growth hormone. Hormonal insufficiencies are an aspect of Long COVID. Growth hormone deficiency, in particular, is linked to fatigue in Long COVID patients [[3], [5]]. Cistanche tubulosa’s many immune-supporting, neuroprotective, anticancer, and liver-protective effects can also potentially help improve cognitive symptoms and reduce inflammation in long COVID patients dealing with those issues.
Fluticasone Nasal Spray for long COVID
FLUTICASONE NASAL SPRAY
What is fluticasone?
Fluticasone is a nasal corticosteroid used for symptoms of seasonal allergies such as sneezing, nasal congestion, a runny nose, and inflamed sinuses. There are two formulations of fluticasone that you can find over the counter: fluticasone propionate (Flonase Allergy Relief) and fluticasone furoate (Flonase Sensimist). Fluticasone propionate can be used twice daily, while fluticasone furoate should be used once daily because of its longer duration of action. The recommended maximum dose can be given as two sprays in each nostril once daily. Fluticasone furoate may be preferred for some because of its aftertaste compared to fluticasone propionate.1
How can fluticasone help alleviate certain long COVID symptoms?
The SARS-CoV-2 virus is known to enter ACE2 receptors in the nasal mucosa, which activates an inflammatory response that can lead to olfactory dysfunction. An estimated 19-68% of COVID patients may present with olfactory dysfunction that can linger after the infection has passed.2 Nasal corticosteroids like fluticasone may help improve loss of smell and taste from COVID. The mechanism behind this is not fully known, but it may be due to reduced inflammatory swelling of the nasal passage to allow for the increased penetration of odors.3
What evidence supports fluticasone’s use for long COVID?
Several reports have recommended an intranasal corticosteroid such as fluticasone for patients with post-COVID olfactory dysfunction symptoms lasting longer than two weeks.2 In a study done with 120 patients that looked at the use of fluticasone propionate nasal spray with a triamcinolone paste for loss of smell, they found significant improvement in the ability to smell five tested odors and taste four different flavors within a week of use.4 However, there are some concerns with the study methods used in the trial, such as an unstandardized test of assessing odors and tastes and using the nasal spray at the onset of olfactory symptoms rather than after two weeks of symptoms.5
A systematic review of 21 studies found that an intranasal corticosteroid such as triamcinolone or fluticasone helped COVID patients regain their sense of smell 23 days earlier than with an oral corticosteroid or another intranasal corticosteroid called mometasone furoate.6 It is also recommended that this be done with olfactory or smell training, which exposes patients to four different odors twice a day for at least 24 weeks.
What should you be aware of when taking fluticasone?
Some side effects of fluticasone include headache, nose bleeds, and throat irritation. When using fluticasone, consider applying it contralaterally by spraying your right hand in your left nostril and vice versa. This directs the medication away from your nasal septum to prevent nasal septal perforations or ulcerations. This product should be avoided after recent nose ulcers, nasal trauma, or nose surgery until the nostril is healed. Because fluticasone is a steroid nasal spray, it should not be used chronically. It should also be used with caution in people with cataracts and glaucoma.
For children 11 years old or younger, fluticasone should not be used more than one spray per nostril daily, as it may suppress their growth if used chronically. Flonase Allergy Relief (fluticasone propionate) should not be used in children under four, and Flonase Sensimist (fluticasone furoate) should not be used in children under two.
References:
Triamcinolone Acetonide Nasal Spray (Nasacort) for long COVID
TRIAMCINOLONE ACETONIDE NASAL SPRAY
What is triamcinolone?
Triamcinolone is available as an over-the-counter nasal corticosteroid spray (Nasacort) used to relieve symptoms of seasonal and year-long allergies such as sneezing, nasal congestion, and a runny nose. It can be applied as two sprays (or 110 mcg) in each nostril once daily and then one spray once daily in each nostril once symptoms are more controlled. Triamcinolone should not be used if there is no relief after three weeks.
How can triamcinolone nasal spray help alleviate certain long COVID symptoms?
The SARS-CoV-2 virus is known to enter ACE2 receptors in the nasal mucosa, activating an inflammatory response that can lead to olfactory dysfunction. An estimated 19-68% of COVID patients may present with olfactory dysfunction that can linger after the infection has passed.1 Nasal corticosteroids like triamcinolone may be used to improve loss of smell post-COVID. The mechanism behind this is not fully known, but it may be due to reduced inflammatory swelling of the nasal passage that allows for the increased penetration of odors.2
What evidence supports the use of triamcinolone nasal spray for long COVID?
Several reports have recommended an intranasal corticosteroid such as fluticasone for patients with post-COVID olfactory dysfunction symptoms lasting longer than two weeks.1 In a study of 120 patients that looked at the use of fluticasone propionate nasal spray with a triamcinolone paste for loss of smell, there was significant improvement in the ability to smell five tested odors and taste four different flavors within a week of use.3 However, the effects of triamcinolone paste may not be the same as those of a triamcinolone nasal spray due to differences in how the drug is absorbed through different routes of administration.
A systematic review of 21 studies found that the use of an intranasal corticosteroid such as triamcinolone or fluticasone was able to help COVID patients regain their sense of smell 23 days earlier than with an oral corticosteroid or another intranasal corticosteroid called mometasone furoate.4 It is also recommended to be combined with olfactory or smell training, which exposes patients to four different odors twice a day for at least 24 weeks.
What should you be aware of when using triamcinolone nasal spray?
Triamcinolone can have some local effects, such as a burning or stinging sensation in the nose. It can also cause nosebleeds and may have a bitter aftertaste for some people. If you are experiencing mucous crusting around your nostrils, you can consider rinsing with a nasal saline spray before applying triamcinolone.
When using triamcinolone, consider applying it contralaterally by spraying it in your left nostril with your right hand and vice versa. This directs the medication away from your nasal septum to prevent nasal septal perforations or ulcerations. This product should be avoided after recent nose ulcers, nasal trauma, or nose surgery until the nostril is healed. Because triamcinolone is a steroid nasal spray, it should not be used chronically. It should also be used with caution in people with cataracts and/or glaucoma.
References:
Tollovid for long COVID
TOLLOVID
What is Tollovid?
Tollovid is a blend of plant extracts. It is in clinical studies to treat both COVID-19 and Long COVID. Having shown promising data in acute COVID-19, studies are underway to assess its use for Long COVID [[1]].
What does Tollovid do in the body?
Tollovid works by inhibiting the activity of an enzyme known as the 3CL protease. This enzyme is involved in the replication of coronaviruses inside our cells. Once the virus synthesizes its RNA into a long polyprotein, the protease breaks down the proteins, helping form the coronavirus molecules [[2]]. By inhibiting the 3CL protease, Tollovid stops coronaviruses’ ability to replicate. Tollovid may also have anti-cytokine properties [[3]].
How can Tollovid help alleviate certain Long COVID symptoms?
Evidence suggests that, in some patients with Long COVID, the SARS-CoV-2 virus that causes COVID-19 persists in their bodies even after their bout with COVID-19. Therefore, Tollovid may help neutralize the effects of the lingering virus in these patients. The virus may persist, especially in the gut, leading to persistent inflammatory responses. In a non-peer-reviewed study conducted by the manufacturers of Tollovid, the supplement decreased symptoms, including fatigue and congestion, in both acute COVID and Long COVID. 46.2% of Long COVID patients reported reduced symptoms in the study [[4]]. The company also recently published a non-peer-reviewed case study in which one Long COVID patient with microclots benefitted after taking Tollovid [[5]].
[1] https://www.biospace.com/article/releases/todos-medical-announces-positive-biomarker-data-from-phase-2-trial-of-tollovir-in-hospitalized-covid-19-patients/
[3] https://www.researchgate.net/profile/Andrew-Blumenthal/publication/362791461_VALUE_OF_3CL_PROTEASE_INHIBITOR_SUPPLEMENTATION_1_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Syndrome_Patients_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Sy/links/62ff607daa4b1206fabfa146/VALUE-OF-3CL-PROTEASE-INHIBITOR-SUPPLEMENTATION-1-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Syndrome-Patients-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Sy.pdf
[4] https://www.researchgate.net/profile/Andrew-Blumenthal/publication/362791461_VALUE_OF_3CL_PROTEASE_INHIBITOR_SUPPLEMENTATION_1_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Syndrome_Patients_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Sy/links/62ff607daa4b1206fabfa146/VALUE-OF-3CL-PROTEASE-INHIBITOR-SUPPLEMENTATION-1-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Syndrome-Patients-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Sy.pdf
Heart Rate Variability (HRV) Biofeedback for long COVID
HEART RATE VARIABILITY (HRV) BIOFEEDBACK
What is HRV biofeedback?
Heart Rate Variability (HRV) biofeedback is a non-invasive method of matching your breathing to heart rate patterns. Your heart rate speeds up as you inhale and slows down as you exhale. During HRV biofeedback, patients can visually see their beat-by-beat heart rate data and try to slow down their breathing to match their heart rate patterns.1 The patient receives immediate feedback from the device throughout this process. Patients are trained to breathe from their diaphragm to reduce their respiration rate to about six breaths per minute. Slowing down the heart rate activates the parasympathetic nervous system, which conserves our energy and allows our body to rest and relax.
HRV biofeedback has been used for asthma, depression, anxiety, stress, and muscle relaxation. For individuals looking for non-pharmacological ways of alleviating these symptoms, HRV biofeedback is a reasonable therapy to try first before other methods, such as neurofeedback.
How can HRV biofeedback help alleviate certain long COVID symptoms?
The SARS-CoV-2 virus can lead to heart damage through multiple mechanisms. The binding of the virus to ACE2 receptors can have negative downstream impacts on the cardiovascular system. Direct myocardial damage from vascular inflammation and indirect damage from lack of oxygen, stress-induced heart abnormalities, and increased risk of clotting can all result in cardiovascular dysfunction.
Patients with long COVID have persistent dysfunction of the autonomic nervous system, which is the component of our peripheral nervous system that regulates our heart rate, respiration, and other functions.2 This persistent autonomic dysfunction can lead to long COVID symptoms such as fatigue, breathlessness, palpitations, dizziness, and brain fog. As a result, HRV biofeedback can help activate the parasympathetic nervous system and increase cardiac homeostasis, which can reduce the release of inflammatory markers.
What evidence supports the use of HRV biofeedback for long COVID?
Investigations conducted by the European Society of Cardiology evaluated 434 COVID survivors three months after hospital discharge and found alterations in heart rate variability likely explained by autonomic dysfunction.3 HRV biofeedback training improved autonomic functioning and generated better cardiovascular regulation.
There is an ongoing trial in the UK assessing the use of a four-week HRV biofeedback training intervention for long COVID symptoms.4 Overall, HRV biofeedback has been utilized since the 1990s and is a reasonable treatment alternative for long COVID symptoms triggered by autonomic dysfunction.
What should you be aware of with HRV biofeedback?
HRV biofeedback is a safe training method with no serious adverse events reported. Individuals may experience stress when given negative feedback in a session, but there are no other known side effects of HRV biofeedback. HRV biofeedback can also serve as an option for pregnant women who would like a non-pharmacological treatment option for certain long COVID symptoms. Results from a randomized controlled trial indicated a statistically significant beneficial effect on psychological well-being and anxiety for both pregnant and non-pregnant women.5
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