Antioxidant Protection In The Body Begins From Within The Cell.
It’s not too late to find out that the cells in our bodies do produce their own antioxidants.
Our body is constantly in a tug of war between reduction and oxidation (redox), which basically comprises multiple reactions where electrons are being transferred from one component to another.
We oxidise a component when we remove electrons from it, and we reduce another component when we add electrons onto it.
The liver, for example, has to remove 2 electrons from every ethanol (the alcohol that we find in alcoholic drinks) during the detoxification process:
The removal of the one electron from ethanol oxidises ethanol to acetaldehyde. The subsequent removal of another electron from acetaldehyde oxidises it into acetate, or vinegar.
The acetate is the final product that is eliminated in our urine.
More about antioxidants and pro-oxidants
The 38 trillion cells in our body are all capable of producing pro-oxidants (components that can oxidise other biochemicals) and antioxidants (components that reduce other biochemicals).
Pro-oxidants can be generated by the cell’s power plants (also known as the mitochondria), when their regulation of the electron transport chain isn’t going on as efficiently as it ought to be. These pro-oxidants are also known as reactive oxygen species (ROS):
As it is said in this article,
Reactive oxidants are produced from numerous sources in multiple compartments within the cell, either normally or as a result of exposure to toxic or pathologic insults.
Meaning that when we are exposed to materials that our body deems toxic, the cells in the body will produce ROS in response to that toxic insult.
Meaning that when we are exposed to anything that can cause physical or mental disease, the cells in the body will produce ROS in response to that pathologic insult.
But that article also comments that:
The mitochondria are considered a primary site of ROS production from aerobic respiration under physiological and many pathophysiological conditions. Nonetheless, nearly all enzymes that utilize molecular oxygen as a substrate, including plasma membrane–bound NADPH oxidase (NOX), microsomal cytochrome P450 (CYP), and cytoplasmic xanthine oxidase, produce ROS either intentionally or as by-products.
Does that mean that all ROS molecules are bad? No, we do need to have some for signalling purposes, but in a controlled manner for the regulation of various biochemical cascades and processes in our body:
In normal cells, reactive oxidants are produced in a controlled manner and some serve useful purposes. Oxidants formed in response to physiological cues act as important signaling molecules to regulate such processes as cell division, inflammation, immune function, autophagy, and stress response. Uncontrolled production of oxidants results in oxidative stress that impairs cellular functions and contributes to the development of cancer, chronic disease, and toxicity. From prokaryotes to humans, reactive oxidants seemingly function as important regulators of both physiological and pathophysiological outcomes.
When the production of these ROS species is uncontrolled, cellular functions aren’t going to work as well as they ought to be, and problems associated with cancer, chronic disease and toxicity can be encountered in the body.
But we have the internal antioxidant production to balance things out
The nuclear factor-erythroid 2 p45-related factor 2 (or nuclear respiratory factor 2, nrf2) transcriptional pathway in the body is one of the major regulators of antioxidant production.
It is said to be “the primary transcription factor protecting cells from oxidative stress by regulating cytoprotective genes, including the antioxidant glutathione (GSH) pathway.”
Meaning, then, that the nrf2 pathway regulates the cell’s internal production of GSH antioxidants, which helps to protect cells from getting into an unwanted state of oxidative stress.
GSH is able to neutralise the pro-oxidants that are formed from aerobic respiration, disease, or exposure to toxins, and in doing so, can aid in delaying the onset of oxidative stress in the body — provided that the rate of GSH production is sufficient to counter the rate of pro-oxidant formation.
We’re looking at a dynamic equilibrium issue here.
Two molecules of GSH can accept electrons and be oxidised into a single molecule of oxidised glutathione (which we term GSSG).
GSSG can be reduced back into GSH within the cell via the activity of the glutathione reductase (GR) enzyme.
So we’d be looking at an internal recycling mechanism that keeps GSH in its active state, such that the transfer of electrons within the mitochondria during the energy generation process can be better regulated.
This continuous GSH cycling allows for the neutralisation of many ROS molecules over the cell’s lifespan.
In comparison, dietary antioxidants such as Vitamin C (ascorbic acid) can only deal with the transfer of 2 electrons (where it gets oxidised into dehydroascorbic acid)… unless there is adequate GSH to deal with the regeneration of Vitamin C back into its reduced ascorbic acid form.
However, while GSH can reduce dehydroascorbic acid, ascorbic acid cannot reduce GSSG, because their redox potentials are different.
Hence, we cannot rely on Vitamin C to regenerate GSH, but alpha-lipoic acid can do so.
Application-wise, what would we be looking at?
Definitely, protection from oxidative stress is one big thing we’d be looking at — because oxidative stress begets mild chronic inflammation, and these two things work in an amplification loop where they feed off each other to intensify the production of pro-inflammatory cytokines.
And when there are too many pro-inflammatory cytokines floating about in the blood, the dynamic equilibria of various biochemical processes within the body will hit snags — as it is in the case of obesity, for instance.
But we’d also have other considerations, such as how we can regulate our immune systems.
We definitely wouldn’t want our cells to be overproducing ROS during situations of pathologic/disease insults.
The potential of cytokine storms occurring, especially with what we’re seeing in this COVID-19 climate, can be traced back to the onset of excessive ROS production, as it is mentioned in this article covering avian influenza infections:
A number of factors are thought to contribute to overall cytokine dysregulation, one of which is the expression of reactive oxygen species (ROS). Previous studies have demonstrated that infection with influenza A viruses induces a rapid influx of inflammatory cells into lungs resulting in the production ROS. ROS are essential, potent microbicidal agents that are known to kill ingested microorganisms within phagosomes. Excess production of ROS, however, has been associated with acute lung injury contributing significantly to morbidity and mortality following avian influenza virus infection.
GSH production counters ROS activity. Vitamin C production also counters ROS activity.
However, as GSH is able to regenerate Vitamin C but not the other way round, I’d say that GSH production is more useful than Vitamin C consumption, wouldn’t you think?
Especially when it comes down to supporting our immune system against infections?
Some nutrients are known to upregulate the nrf2 activity in our cells. These include:
alpha lipoic acid
resveratrol
curcumin
epigallocatechin gallate (EGCG)
rutin
quercetin
hesperetin
A patent made use of that composition in a formulation, and the inventors also made this claim in that patent:
the composition comprises an upregulating compound mixture configured to upregulate an endogenous antioxidant system, an exogenous antioxidant mixture configured to inhibit oxidation of biomolecules by reactive oxygen species, and a mineral mixture configured to provide one or more cofactors to a endogenous antioxidant enzyme. The endogenous antioxidant system includes regulation of mitophagy through mTOR mediated regulation, and a Nrf2 transcription factors that promotes transcription of antioxidant genes.
The endogenous production of antioxidants within the cell is much more powerful than the consumption of dietary exogenous antioxidants.
Who woulda thunk that?
A blend of these nutrients were formulated into a patented composition known as the InCelligence Complex for cell signalling. That patent is currently being used in this product.
Which, of course, is
Cheaper than other patented drugs out there.
Supposed to help support one’s health, and not make it worse.
If you are interested in trying out that product:
The purchase page can be found
A pre-packaged formulation can be found
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