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 then eliminated in our urine. The mechanism behind this electron transfer process can be found here.
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).
In our diet, the consumption of vitamins such as Vitamin C and Vitamin E also provide some form of antioxidant support. It helps to reduce pro-oxidant activity to provide a better redox balance within the body.
Unfortunately, our cells can produce quite a fair bit of reactive pro-oxidants (or 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.
In addition to these insults, the mitochondria in our cells can also produce ROS during energy generation:
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.
How does the cell produce antioxidants internally?
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.”
The nrf2 pathway therefore regulates the cell’s internal production of GSH antioxidants. 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.
Two molecules of GSH can accept electrons and be oxidised into a single molecule of oxidised glutathione (which we term as GSSG). GSSG can be reduced back into GSH within the cell via the activity of the glutathione reductase (GR) enzyme. Hence, these 2 molecules of GSH can be constantly cycled back and forth between their reduced GSH and their oxidised GSSG states, and deal with the transfer of hundreds of electrons.
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.
Therefore, the production of GSH internally trumps the consumption of Vitamin C. There are also some nutrients that are known to upregulate the nrf2 pathways in the cells, some of which were included in a composition for US Patent 20180007945 — METHODS AND COMPOSITIONS FOR SUPPORTING ENDOGENOUS SYSTEMS RELATED TO LIFE SPAN:
alpha lipoic acid
resveratrol
curcumin
epigallocatechin gallate (EGCG)
rutin
quercetin
hesperetin
In that patent, it was claimed that
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.
Application wise, what would we be looking at?
Definitely, protection from oxidative stress is one big thing we’d be looking at.
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?
Where is that patent being used right now? It was formulated by Usana Health Sciences, and Usana Health Sciences is using the patent in this product - the CellSentials, which contains the patented composition known as the InCelligence Complex for cell signalling.
Interested in trying it out? The purchase page can be found here.
This article was originally published in Medium.
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