Let's look at the ongoing, debilitating symptoms linked with a hyperactive immune response that lingers for months, even after the active infection has subsided.
Long Covid can be visualized as shown below. In this condition, the grey line, representing the hyper-inflammatory stage, remains elevated instead of decreasing in response to the presence of the virus, illustrated by the purple line.
Ideally, what should happen is illustrated below. It's important to note that Long Covid doesn't necessarily mean the virus is still present. Instead, the problem lies in the body's excessive and persistent immune response.
Long Covid can be a profoundly debilitating disease. Worryingly, its prevalence is on the rise, with recent science suggesting that up to 1 in 8 of those infected develop at least one Long Covid symptom. Crucially, the risk of Long Covid increases with each subsequent infection.
There are three groups of individuals who seem to be more susceptible:
- Those with high oxidative stress or compromised antioxidant systems
- Those with a tendency towards an overactive immune system - conditions like allergies, IBS, etc., often associated with Mast Cell Activation Syndrome (MCAS)
- Those with cortisol issues, often linked to chronic stress
The diagram below illustrates key relationships. In essence, NAD+, Mast Cells, Gut Health, and Inflammation/Oxidative Stress are all major players. The reason Long Covid has been a tough nut to crack is due to the interconnectedness of these factors.
The medical cross symbol indicates where supplementation can restore balance. The apples symbolize areas where dietary and lifestyle changes can correct imbalances.
Ace2 Receptor Theory
If you've followed any long covid research you must have heard about ACE-2 receptors. Ivermectin and a lot of other compounds were called Ace-2 blockers, which were meant to stop the virus being able to bind to it. ACE2 is extremely important, and I don't think it's wise to ignore it if you want to heal.
ACE2, a significant receptor cell present throughout our bodies, with a high concentration in the heart, lungs, and small intestine. ACE2 wears many hats, performing essential tasks such as:
- Turning the pro-inflammatory ANG-II into the anti-inflammatory/antioxidant ANG1-7 during energy production
- Dismantling bradykinin, the enzyme responsible for inflammatory "storms"
- Facilitating the absorption of tryptophan
- Providing a shield for the heart and lungs from injury
- Ensuring the balance or homeostasis of the gut biome
Now, here's the kicker - Covid-19 enters the body by attaching itself to ACE2. The virus and inflammation can wreak havoc on ACE2 receptors.
Let's talk about two pivotal inflammatory mediators, Angiostensin II (ANG II) and Bradykinin. They're at the epicenter of Covid impacts.
ANG II is a bit of a troublemaker:
- It narrows blood vessels and triggers blood clots
- It fires up and encourages inflammation
- It promotes oxidative stress by ramping up free radical production
Bradykinin isn't any better:
- It sustains the inflammatory cascade
- It escalates the permeability of blood vessels, leading to fluid release on the nerves causing loss of taste and smell
- It increases the permeability of the blood-brain-barrier, contributing to brain fog
Tryptophan Theory
Turning our attention to tryptophan - this amino acid follows two main paths in our bodies:
- It aids in the production of serotonin & melatonin
- It contributes to the Kynurenine Pathway, crucial for protein synthesis and NAD+
The serotonin pathway is vital. As a neurotransmitter, serotonin is a key player, particularly in the gut. Plus, it's the building block of melatonin, needed for sleep and acting as a potent antioxidant within mitochondria.
This is why so many people I've talked with swore by magic mushrooms helping them heal a significant portion of their LC. Now that I'm healed I will be playing with the effects of psilocybin as well, but I wish I had tried it even earlier.
Every time mitochondria create energy, they rely on melatonin to neutralize the free radicals produced as a byproduct. Insufficient melatonin spells doom for the cell. Melatonin synthesis within mitochondria is triggered by infra-red radiation, primarily from the daytime sun.
Issues crop up when an excess of tryptophan is funneled down the kynurenine pathway, which increases due to:
- The IDO enzyme, released in reaction to infection and inflammation
- The TDO enzyme, released in response to stress
- Depleted NAD+. Tryptophan (via the kynurenine pathway) is the body's fallback system for low NAD+. This is crucial - the body will always prioritize NAD+ production as it's vital for survival.
Excessive diversion of tryptophan down the Kynurenine pathway can lead to:
- Serotonin/melatonin depletion
- Conversion to quinolinic acid, a neurotoxin linked to Alzheimer’s, dementia, etc.
- Induction of muscle atrophy, bone loss, and neurodegeneration
- An increase in oxidative stress
- A rise in anxiety
Covid-19 forces tryptophan down the kynurenine pathway via several mechanisms, including triggering significant inflammation, burning through antioxidants, and rapidly depleting NAD+.
Tryptophan supplementation is an option, though dietary sources are usually sufficient. You can find it in turkey, chicken, beef, pork, lamb, salmon, tuna, milk, and eggs. 5HTP and melatonin can also be supplemented. Don't forget to get your sunshine or other sources of infra-red radiation, as they're critical for triggering cells to produce the antioxidant melatonin.
NAD+ Theory
NAD+, also known as Nicotinamide Adenine Dinucleotide, serves two primary functions in our bodies: anti-aging and energy creation. With age, NAD+ levels naturally decline, often correlating with decreases in energy and immune function.
NAD+:
- Initiates the energy creation process by catalyzing electron transfer in mitochondria to produce ATP
- Substantially enhances mitochondrial mass, muscle strength, and endurance
- Shields against oxidative stress, DNA damage, and aging
- Activates sirtuins, in conjunction with zinc, which kill viruses, regulate inflammation, and protect against excessive mast cell activation
NAD+ can be exhausted by oxidative stress or any demands on the sirtuin system, such as a viral infection. Covid-19, for instance, rapidly drains NAD+, leading to symptoms like fatigue and brain fog.
NAD+ can be synthesized in the body from Vitamin B3 (Niacin, Nicotinamide, Nicotine etc) or the far less efficient tryptophan (via the kynurenine pathway). Supplementing with Vitamin B3 is a straightforward way to rejuvenate healthy NAD+ levels and liberate tryptophan.
The Gut Theory
Our gut hosts a microbiome that plays an essential role in:
- Supplying a variety of enzymes, neurotransmitters, and vitamins to the body
- Reducing intestinal permeability
- Defending against pathogens
- Communicating with and regulating the gut immune system, including mast cells
There are countless potential triggers for gut imbalance. At the core of gut issues are three interconnected problems that tend to exacerbate each other:
- Inflammation
- Dysbiosis (disrupted microbiome)
- Increased intestinal permeability
Maintaining a healthy diet is the foundation of gut health. Options to improve gut health include:
- Supplementing L-Glutamine (the preferred fuel to renew and power gut cells)
- Adopting a diet that supports a healthy microbiome (i.e., feeding good gut bacteria)
- Taking taurine to reduce intestinal permeability
- Using marshmallow root, slippery elm, or aloe vera to heal mucosa
- Avoiding common triggers which may include gluten, alcohol, nightshades, over-eating, high-fat meals, and polyunsaturated vegetable oils
Mast Cell Activation Syndrome (MCAS) Theory
Mast cells are vital components of the immune system. They degranulate (break open) to release inflammatory cytokines, histamine, and serotonin. Mast Cells Activation Syndrome (MCAS) is essentially an overactive immune system, often manifested as IBS, asthma, allergies, psoriasis, dermatitis, hot flashes, endometriosis, etc.
The percentage of the population who develop severe Covid-19 (17.5%) roughly parallels the percentage of the population with a condition known as Mast Cell Activation Syndrome (17%). Researchers have found treating MCAS treats Covid-19 and treating Covid-19 treats MCAS.
Key point: A predisposition for MCAS can intensify and prolong the impacts of Covid-19. Over-activated mast cells can remain in this state for a long time.
The intervention is to disrupt the ongoing immune response using natural and/or pharmaceutical mast cell stabilizers and immune modulators. Options include:
- Pharmaceutical antihistamines and anti-inflammatories
- Quercetin
- Luteolin
- Rutin (buckwheat is the best source - accidental Filonov haiku;)
- Resveratrol
- Vitamin C (this is one of the biggest deficiencies during extended fasting. Some people have even developed symptoms of scurvy. Top it up!)
- Black seed oil
- CBD oil
- Nettle, chamomile (highly recommended during dry fasting refeed, changing out Java Tea)
- Almost all spices including ginger, garlic, turmeric, black pepper, cinnamon, and cardamom
- Activated Charcoal (I have a very important protocol that aggressively uses this to great effect, especially for beginners on the healing journey)