Introduction
This post deals exclusively with Long Covid. That is, the debilitating symptoms associated with an overactive immune response that persist for months after the active infection.
Long Covid can be visualised on the image below. In Long Covid the grey line (the hyper-inflammatory stage) stays elevated instead of reducing in response to virus present (purple line).
The below is what should happen. There is not necessarily virus present in Long Covid, rather the issue is the bodies excessive and continuing immune response.
Long Covid can be a severely debilitating disease. It is also on the rise, the latest science indicates up to 1 in 8 of those infected develop at least one Long Covid symptom. Critically, Long Covid risk increases with each subsequent infection.
There are three categories of people who appear to be more at risk:
Those with high oxidative stress / impaired antioxidant systems
Those with a predisposition an over-excited immune system - think allergies, IBS etc (often called Mast Cell Activation Syndrome - MCAS)
Those with cortisol issues, often associated with chronic stress
The diagram below outlines key relationships. In summary - NAD+, Mast Cells, Gut Health and Inflammation/Oxidative Stress all play key roles. The reason Long Covid has been tricky to solve is because of the inter-relationships between these things.
The medical cross indicates where supplementation can correct imbalances. The apples indicate where diet and lifestyle change can correct imbalance.
Part 1: The Key Pieces of the Puzzle
ACE2
ACE2 is an important receptor cell found throughout the body but especially concentrated in the heart, lungs and small intestine. ACE2 has a number of important roles including:
· Converting pro-inflammatory ANG-II to the anti-inflammatory/antioxidant ANG1-7 during energy production
· Degrading bradkykinin (the enzyme that drives inflammatory "storms")
· Enabling absorption of tryptophan
· Protecting the heart and lungs from injury
· Helping regulate homeostasis of the gut biome
Covid-19 accesses the body by binding to ACE2. Both the virus and inflammation damage ACE2 receptors.
A short note on Angiostensin II (ANG II) and Bradykinin
These two inflammatory mediators are at the heart of Covid impacts.
ANG II:
Narrows blood vessels and causes blood clots
Initiates & promotes inflammation
Promotes oxidative stress by increasing free radical production.
Bradykinin: Facilitates continuation of the inflammatory cascade Increases blood vessel permeability (ultimately releasing fluid on the nerves which causes the loss of taste and smell) Increases permeability of the blood-brain-barrier, contributing to brain fog
Tryptophan
There are two critical paths for the amino acid tryptophan in the body:
1. Production of serotonin & melatonin
3. Kynurenine Pathway (protein synthesis and NAD+)
The serotonin pathway is extremely important. Serotonin is a critical neurotransmitter and master regulator, especially in the gut. Serotonin is also the raw ingredient of melatonin, necessary for sleep and the most powerful antioxidant within mitochondria.
Whenever mitochondria make energy they need melatonin to quench the free radicals produced as a side effect. Without sufficient melatonin the cell is destroyed. Synthesis of melatonin within mitochondria is stimulated by infra-red radiation, primarily from daytime sunshine.
Problems arise when too much tryptophan is sent down the kynurenine pathway. This pathway is increased in response to:
1. The IDO enzyme, released in response to infection and inflammation
2. The TDO enzyme, released in response to stress
3. Depleted NAD+. Tryptophan (through the kynurneine pathway) is the bodies backup system for low NAD+. This is very important to understand. The body will always prioritise NAD+ manufacture as it absolutely critical for survival.
Too much diversion of tryptophan down the Kynurenine pathway:
· Depletes serotonin/melatonin
· Converts to the neurotoxin quinolinic acid (causing Alzheimer’s, dementia etc)
· Induces muscle atrophy, bone loss and neurodegeneration
· Increases oxidative stress
· Increases anxiety
Covid-19 diverts tryptophan down the kynurenine pathway through multiple mechanisms including triggering massive inflammation, burning up antioxidants and rapidly depleting NAD+.
Tryptophan can be supplemented directly, however dietary sources are generally sufficient. The best dietary sources are turkey, chicken, beef, pork, lamb, salmon, tuna, milk and eggs. 5HTP and melatonin are other supplementation options. Sunshine, or alternative sources of infra-red radiation, are critical for triggering cells to make the antioxidant melatonin.
NAD+
NAD+ has two primary functions which can be summarised as anti-aging and energy creation. NAD+ levels decline with age which correlate with associated declines in energy and immune function.
NAD+:
·Catalyses electron transfer in mitochondria to produce ATP (i.e. starts the energy creation process)
Significantly boosts mitochondrial mass, muscle strength & endurance
Protects against oxidative stress, DNA damage and aging
Together with zinc, activate sirtuins which kill viruses, regulate inflammation and protect against excessive mast cell activation.
NAD+ can be depleted by oxidative stress or any demands on the sirtuin system, such as viral infection. Covid-19 rapidly depletes NAD+ resulting in fatigue, brain fog etc.
NAD+ can be synthesised in the body from Vitamin B3 (Niacin, Nicotinamide, Nicotine etc) or the far less efficient tryptophan (via kynurenine pathway). Supplementing Vitamin B3 is a simple way to restore healthy NAD+ levels and free up tryptophan.
The gut
The gut harbours a microbiome that plays a fundamental role in:
Supplying all kinds of enzymes, neurotransmitters and vitamins to the body
Reducing intestinal permeability
Protecting against pathogens
Talking to and regulating the gut immune system, including mast cells
There are thousands of potential triggers for gut imbalance. At the heart of gut problems are three issues, which have a tendency to worsen each other:
Inflammation
Dysbiosis (disrupted microbiome)
Increased intestinal permeability
A healthy diet is the cornerstone of gut health. Options to improve gut health include:
Supplementing L-Glutamine (preferred fuel to renew and power gut cells)
Approaching diet with the intent of supporting a healthy microbiome (i.e. feed good gut bacteria)
Taking taurine to reduce intestinal permeability
Taking 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)
Mast cells are an important part 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, commonly experienced 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 make Covid-19 impacts much more severe and long lasting. Mast cells, once over-activated, can remain over-activated for a long time.
The intervention is to disrupt the ongoing immune response through natural and/or pharmaceutical mast cell stabilisers and immune modulators. Options include:
Pharmaceutical anti-histamines and anti-inflammatories
Quercetin
Luteolin
Rutin (buckwheat is the best source)
Resveratrol
Vitamin C
Black seed oil
CBD oil
Nettle, chamomile
Nearly all spices including ginger, garlic, turmeric, black pepper, cinnamon and cardamom
Oxidative Stress
“Oxidation” occurs when a molecule (called a free radical) hungry for an electron steals one from a neighbour. That neighbour is damaged and will steal an electron from another neighbour, creating a damaging chain reaction only neutralised when an “antioxidant” intervenes to supply a spare electron.
Some oxidants are created internally, for example as a by-product of energy creation, vision or immune response. External sources of oxidants include vegetable oils, UV radiation, electronics, pollution, chlorine, cigarette smoke and pesticides. The body is always trying to ensure it has enough antioxidants to quench oxidising free radicals.
Those with existing conditions caused by oxidative stress, such as diabetes, cardiovascular disease or dementia, are predisposed to suffer severe impacts or death from Covid-19. Why? Because NAD+ is already low and Covid-19 rapidly depletes what remains.
Covid-19 also sharply increases oxidative stress load on the body through numerous mechanisms. One is by disrupting ACE2 which changes the chemistry of the process used to create energy; the superoxide free radical is produced instead of the antioxidant nitric oxide.
The following can help:
Infra-red radiation, especially from the sun but also naked flame, infra-red saunas etc.
“Negative ions” from the environment. Negative ions is simply another word for “antioxidant”. Good sources include being barefoot on the ground (lightning negatively charges the earth), plants, forests and water molecules hitting something (surf, waterfalls, fountains)
Vitamin’s A, C, E & selenium
Avoiding tap water and chlorinated swimming pools. Chlorine is an oxidant. This is how it kills microorganisms.
Reducing cortisol. Cortisol sharply increases oxidative stress. Cortisol can rise in response to both inflammation and stress:
Conclusion
Long Covid is complex. The science is difficult to grasp, even for scientists. Treatment however need not be as complex, in fact it is comparatively straight-forward. Major interventions include:
Restoring NAD+ by supplementing B3 (niacin/niacinamide etc)
Ensuring sufficient supply of tryptophan through diet or supplementation
Calming mast cell activation (excessive immune response) by mast cell stabilisers
More generally, improving gut health and reducing stresses on the bodies anti-oxidant system will help significantly.