Oxidative Stress

I have been curious about this subject for an extremely long time, and I had yet to sit down and educate myself on the subject, but now I have; and, because I have you will be, as well. This subject is huge, I certainly won’t lie to you there, but it is extremely interesting. One of the primary theories for our aging comes from oxidative stress, and while everyone has come to understand free radicals as a purely negative thing, what if they weren’t? Without further ado, let’s examine what oxidative stress is, how free radicals factor into this, and a bit about anti-oxidants.

What is Oxidative Stress?
It wouldn’t be an Omni Focus Fitness article without some understanding of the basics, so what do we mean when we talk about oxidative stress?

Well, oxidative stress is the imbalance between healthy molecules and free radical molecules in favor of the free radicals. Surely, this brings about further questions like, what are free radicals?


What are Free Radicals?
Free radicals are, in the simplest terms, molecules with an unpaired (single) electron [4].

That probably still doesn’t mean much to you, because how do electrons play into this? Let’s gain some perspective.

Atoms, Elements, Molecules
Don’t worry, I’m only going to give you the basics here – just enough to understand the rest of the article. The order in size is (smallest to largest) atoms -> elements -> molecules, so let’s examine it based on that stratification.

Atoms, the most basic make up of matter, are made up of three particles, but as we are simplifying this, just understand that two of these particles (neutrons and protons) are found in the nucleus of the atom. Meanwhile, electrons orbit outside of the nucleus. The number of electrons determines, in a way, the “shape” of the atom as electrons can orbit closer to the nucleus or further from the nucleus [1][2].

Elements are, simply, a grouping of similar atoms. So, all the atoms with 4 (2 pairs of) electrons would be grouped together to create an element. You are familiar with elements already, because of the periodic table. The periodic table is just a large list of similar atom groups that, in enough density, make up the elements listed [3][6].

Meanwhile, molecules are various configurations of elements. So, something like H2O (water, duh) is made up of the elements hydrogen and oxygen (two hydrogens and one oxygen). Carbohydrates are made up of a particular combination of elements, fats as well, proteins as well, etc.


How does this relate to free radicals, however?

Well, we absolutely need to understand how electrons play a role in all this. A healthy, stable molecule (made up of elements, which are made up of atoms, which are partly made up of electrons) typically has a number of dual electrons in its elemental atoms. This is called an electron pair and is considered, for this purpose, “healthy”. In the section before, it was explained that a free radical had an unpaired electron, so if an electron is unpaired, it must be an odd number (poor, lonely one).
 

In the above example, the molecule chlorine loses its electron (oxidation) to the methyl free radical. Chloromethane is created, which is stable, but potentially useless due to its random change in molecular structure in a system that used chlorine for some function. As only one chlorine was used to form chloromethane, the other chlorine from the previous chlorine molecule now only has one electron and is now a free radical chlorine.

Many, many atoms of the same configuration (single atom displayed left) make up each single element (displayed below in the periodic table). Elements make up molecules (displayed below the periodic table).

Why does any of this matter?
Well, now that we have identified two states of being; one, the “healthy” state with an even number of electrons partitioned in pairs, and two, free radical state with an odd number of electrons with lone, unpaired electron(s), we can examine why any of this matters. Oxidative stress, if you’ll recall, is made of having a greater amount of free radical molecules than the body can handle.

Why is having an unpaired electron so detrimental?

When molecules are made up of stable elements, the molecules remain as they are, so a healthy fat molecule will stay a fat molecule. When a free radical (molecule with unpaired electron(s)) is presented to an environment, it is highly reactive. Let’s explain this in a way that we will almost all understand – relationship drama. Soap opera enthusiasts, get ready.

Our players:
Molecule A (John)
Molecule B (David)
Energy (Insecurities)
Electrons (Relationship status/girlfriend)


 

The story:
Insecurities (energy) has been applied to the environment that John (Molecule A) lives in. While John was in a relationship (having paired electrons), the insecurities affected John and he is single now (a free radical, unpaired electron). Because insecurities have affected John so much, he is frantic to find a girlfriend (highly reactive molecule A), so he tries to get with the nearest girl (electron) he can find. Sadly, although John is successful at getting a girlfriend and is now happy again, the girl he got was David’s girlfriend (the plot thickens)! Now, David (Molecule B) is single and upset, so he becomes frantic (reactive, free radical) to find a new girlfriend and puts the moves on one of his friends’ girlfriends. And so the cycle continues.

Is there more, Nic? Of course there is!

Annoyingly, John used to be interested in lifting with his first girlfriend by his side and was a damn good personal trainer, but ever since she left him, he hasn’t been the same. Even with a new girlfriend, he can’t seem to function nearly as well as a personal trainer. Similarly, David was a great mechanic with his previous girlfriend by his side, and although eventually he finds a new girlfriend (most likely by stealing another dude’s girlfriend), things just aren’t the same. Bottom line, everyone is miserable. Moral of the story? Don’t let insecurities get to you.

Scientific translation:
Although Molecule A finds a new electron to fill its electron pair and is technically stable, because the electron could have linked Molecule A to a different element to get its electron, its molecular structure is slightly different. As a result, Molecule A will function less like its previous self. The same is true of every molecule that encounters a free radical molecule. More on this later.

Birth and Mechanism of Free Radical Lifecycle
Now, let’s understand the details of how free radicals occur from a biochemical stand point and understand the three steps that have been identified as it relates to free radical impact on cells.

The Birth/Initiation [5]
Sounds like a chapter from Alien.

Free Radicals occur when molecules are introduced to heat and/or light in a way that stimulates (makes them “shake”) with enough vigor to break free from their bonds. Once this occurs, free radicals are formed from previously stable (electron paired) molecule, each free radical takes one of its electrons.


Propagation [5]
Okay, we have, at least, two molecules that have split from their previously bonded, larger molecule. These split molecules are free radicals as they both took one electron from the split. These new free radicals now frantically bump around until they attach to another molecule (or each other – extremely rare) and spread the reaction onward by creating a new free radical while satisfying the electron “hunger” of one of the initial free radicals.


Termination [5]
When free radicals run into one another, the free radicals “terminate” the reactive chain by neutralizing one another.


 

What causes Free Radicals?
There are many things that cause free radical number to increase, but in general, it is safe to assume that most stressors cause free radical numbers to grow.

A few of the things that cause free radicals:


Exercise
Might as well hit you with an interesting one right off the bat. Apparently, exercise does cause greater oxidative stress [7][18]. However, that is not the end of the story, because this is not a “buzz” article (we deal with facts, damn it!). Although it is true that exercises causes greater oxidative stress, it seems this is due to stress put on the body throughout exercise (because, believe it or not, exercise is stress on the body), but the body enhances its ability to then neutralize the formed free radicals as bodily adaptations occur [7][18]. So, exercise will not, taking into account the creation of free radicals and the neutralization of free radicals, lead to detrimental effects.

But wait, there’s more. The above is applicable for trained individuals as the body slowly adapts to the stress and deals with it accordingly. This is not the case for untrained individuals (beginners) as the body of a beginner is unused to the stress, so the harder one attacks the gym in the early stages of exercise, the more unaccounted free radical accumulation occurs [7].

Radiation
Why is direct sunlight possibly detrimental? For this exact reason. The added heat/light makes it easier for free radicals to form (we will look at this in detail)[8].

Poor Diet
We will discuss antioxidants in greater detail later on, but antioxidants have been proven to neutralize free radicals and as antioxidants come from our diet, having a poor diet can certainly elevate the number of free radicals in our system [7][8].

Aging/Metabolism
There is a good amount of research on this subject, and seems to be one of the dominating theories as to why we age. According to the research, during the metabolism of Adenosine Tri-Phosphate (ATP) through the Electron Transport Chain (ETC) for our survival, the body makes small amounts of free radicals in the mitochondria of each cell [9][10]. Likely, I will write an entire article dedicated to this topic as it is extensive.

There are, of course, many stressors in this world (smoking, alcohol, pollution, etc.), but these are a few of the ones I’ve highlighted.


What can be done against Free Radicals?
Apart from avoiding stressors, it would be prudent to maintain a healthy lifestyle by these two means:

Exercise
Sure, earlier we discussed how exercises causes free radicals, but we also mentioned that exercise increases the body’s ability to combat free radical production, as well. So, it would go without saying that moderate exercise would not only not lead to oxidative stress, but lead a better ability to deal with free radicals.

In future articles, we will see discuss exactly how the body clears free radicals, in detail. Until then, just know that moderate exercise that one’s body can handle and adapt to in reasonable fashion (no 5 hour gym sessions with ridiculous intensity) will lead to a better defense system against free radicals.

Nutrition
Exercise has its own benefits, but everything is more potent in favor of one’s health with a combination of good nutrition. Sure, saying the generic “eat a balanced nutrition” is accurate, but specifically, we need to dedicate a whole section to one particular nutritional white knight: antioxidants.



 

Antioxidants
To understand antioxidants, we need to understand a slightly deeper definition of oxidative stress. The term “oxidative” comes from chemistry’s oxidation, which means to “give up an electron”. Stress is created by the giving up of an electron to a free radical, creating further free radicals, as we know.

Antioxidants are, in simple terms, molecules that stop the oxidation of other molecules. These antioxidants fulfill this protective role by donating an electron of their own to free radicals. So, instead of the free radicals “ripping” an electron away from a happy, stable, useful molecule, these antioxidants step in and donate their own electrons to render the free radicals inert and effectively stopping the chain reaction of destruction and chaos [11].

 

What are the antioxidants?

There are many, many antioxidants that each react with different free radicals, but among the most well-known are [11]:

Vitamin E
Vitamin A
Vitamin C
Manganese
Among many others.


How much antioxidant?
While it is true that antioxidants absolutely aid in clearing free radicals and getting the appropriate amount is advised, it may seem prudent to overconsume (a little is good, more must be better?). However, quite a bit of research has shown that an overconsumption of antioxidants can have negative health effects [11]. More research needs to be done to accurately attain the fullest understanding of each antioxidant, but staying within the Recommended Daily Allowance (RDA) would, most likely, be beneficial.

So, all in all, from a nutritional stand point, be sure to consume a balanced diet with vegetables and fruits that enhance the amount of antioxidants running through your system that will then react positively with free radicals that may be present. However, do not overconsume.

 

Damage from Free Radicals?
Although not everything is understood about free radicals, from what we understand, free radicals have an impact in many areas. They may be the chief point of concern in many diseases extending from Alzheimer’s to cancer [12][13][14]. Let’s examine how free radicals could have such a profound impact to lend in a hand in the generation of these devastating diseases.

As we know, free radicals take electrons from the nearest molecule it can find and successfully take. We also know (at least I hope we do, by now), that although the initial free radical may be satisfied, the effected molecule becomes a free radical. Now, imagine if that molecule, before a free radical brutally took an electron from it, was part of a cell membrane? Maybe you know this, but in case you do not, cells are enveloped in a membrane that is made up of, largely, fat molecules. So, with this scenario, let’s examine how free radicals could kill a cell.

 

You have a healthy cell, a healthy, strong cell membrane made up of fat molecules. Then, a free radical approaches and gravitates to the cell membrane. The free radical takes an electron from a previously healthy fat molecule. Now, the fat molecule is reactive as it becomes a free radical and takes an electron from another molecule. This fat molecule could acquire a new electron from a different element, rendering it less like its previous self. If it is less than its previous self, it is unlikely to function as well. So, if this process occurs over and over again, the cell membrane, with all of its affected fat molecules that are now bastardized versions of their original selves, does not work nearly as well [16]. If this happens, what needs to stay inside the cell no longer has a barrier to keep it in place, and things that are supposed to be kept outside of the cell can move freely into the intercellular space. Eventually, the body either elects to destroy the damaged cell, or the damaged cell implodes or explodes of its own condition.

Granted, if this happens to one cell, no big deal – cells come and go all the time, but imagine if this happens to millions? Or, worse yet, free radicals can not only impact fatty lipid layers, but protein; specifically, protein that is used in DNA, for example. If DNA sequencing is somehow interrupted, the possibilities are endless for what could happen [15].


Can Free Radicals resolve themselves?
Well, now that we understand how free radicals cause damage across a system through their reactiveness, their disruption of normal processes, structures, and their potent chain reaction, we can answer this question with some clarity. We also know that oxidative stress is a state in which the body can no longer handle the number of free radicals created – this is especially true when the number of free radicals increases.

It is this increase in free radicals that leads to free radicals balancing themselves out. When we only have a few free radicals initially, the odds of them colliding together to satisfy (share electrons to create electron pairs) each other is quite slim. However, as free radicals increase in number, the chances of them colliding together increases, and as they collide into one another more often, the higher likelihood they resolve themselves by sharing single electrons to make electron pairs between molecules [5]. Another way of saying this is, the greater the oxidative stress, the more often free radicals satisfy themselves.


Does this matter?

Not really. By the time your body is in such a high state of oxidative stress, getting the occasional free radical resolution is not much of a hope to bank on.


Can Free Radicals do good?
So, we’ve covered to death how free radicals absolutely wreak havoc, cause diseases, and absolutely wreck our physiology, but would you believe it if told that free radicals can also be used for your health?

Surprisingly, free radicals are produced by the body, and although some of this will have to wait until a more detailed article is released, it is true that our cells make free radicals with which to combat viruses and bacteria that invade our system. Vicious as oxidative stress is, and as uncontrollable it is, our cells use this weapon, a bit like a nuclear bomb, and drop it on pathogens with great effectiveness [17].




 

SUMMARY

An overview for this is pretty difficult to do, but here is the best shot: Oxidative stress is having more free radicals than healthy molecules in a particular area. Free radicals are molecules with an unpaired electron and are highly reactive and disruptive to healthy molecules. We can mitigate the damage of free radicals by exercising moderately, avoiding stressors, and consuming up to the RDA in a variety of antioxidants (no more than RDA). Oxidative stress is a main culprit for many disease states, but our cells also use it to destroy invading pathogens.

Writer: Nicolas Verhoeven

Special thanks to Dr. Hines and Dr. Bell of the Physiology/Nutrition and Chemistry departments at East Carolina University for their guidance on this topic.

                                                                                                                                                Citations
 

[1] Theory of Atoms in Molecules: What is an Atom?. (n.d.). Retrieved from http://www.chemistry.mcmaster.ca/aim/aim_1.html
 

[2] What is an Atom? | Parts of an Atom. (n.d.). Retrieved from http://www.livescience.com/37206-atom-definition.html
 

[3] Questions and Answers - What is the simplest way of explaining what atoms, elements, compounds and mixtures are?. (n.d.). Retrieved from http://education.jlab.org/qa/atom_02.html
 

[4] Understanding Free Radicals and Antioxidants. (n.d.). Retrieved from http://www.healthchecksystems.com/antioxid.htm
 

[5] Free Radicals. (n.d.). Retrieved from http://www.4college.co.uk/as/atm/freeradicals.php
 

[6] Atoms and Elements. (n.d.). Retrieved from http://hyperphysics.phy-astr.gsu.edu/hbase/chemical/atom.html
 

[7] Antioxidants and Free radicals. (n.d.). Retrieved from http://www.rice.edu/~jenky/sports/antiox.html
 

[8] Free Radicals. (n.d.). Retrieved from http://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/radicals.html
 

[9] Murphy, M. P. (2009). How mitochondria produce reactive oxygen species. Biochemical Journal. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605959/
 

[10] Cadenas, E., & Davies, K. J. (2000). Mitochondrial free radical generation, oxidative stress, and aging 1 1 This article is dedicated to the memory of our dear friend, colleague, and mentor Lars Ernster (1920–1998), in gratitude for all he gave to us. Free Radical Biology and Medicine. doi:10.1016/S0891-5849(00)00317-8
 

[11] Antioxidants: Beyond the Hype | The Nutrition Source | Harvard T.H. Chan School of Public Health. (n.d.). Retrieved from http://www.hsph.harvard.edu/nutritionsource/antioxidants/
 

[12] Tuppo, E. E. (2001). Free radical oxidative damage and Alzheimer's disease. Journal of American Osteopathology Journal. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11794746
 

[13] Retz, W. (1998). Free radicals in Alzheimer's disease. Journal of Neural Transmission. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9850931
 

[14] Dreher, D. (1996). Role of oxygen free radicals in cancer development. European Journal on Cancer. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8695238

 

[15] Dizdaroglu, M., Kirkali, G., & Jaruga, P. (2008). Formamidopyrimidines in DNA: Mechanisms of formation, repair, and biological effects. Free Radical Biology and Medicine. doi:10.1016/j.freeradbiomed.2008.07.004
 

[16] Cell Membranes. (n.d.). Retrieved from http://vet.uga.edu/ivcvm/courses/VPAT5200/02_injury/cellmemb/cellmem01.html
 

[17] Knight, J. A. (2000). Review: Free radicals, antioxidants, and the immune system. Clinical Lab Science. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10807157

[18] Ji, L. L. (1999). Antioxidants and Oxidative Stress in Exercise. Society of Experimental Biology and Medicine, 222. Retrieved from http://www.mwphealth.com/wp-content/uploads/2013/07/Antioxidants_and_Oxidative_Stress_in_Exercise.pdf

Illustrations (In order):


1) http://www.ducksters.com/science/the_atom.php

2) http://www.bpc.edu/mathscience/chemistry/history_of_the_periodic_table.html
3) http://pixcooler.com/diagram+molecule
4) https://www.cliffsnotes.com/study-guides/chemistry/organic-chemistry-i/reactions-of-alkanes/alkanes-halogenation
5) http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/Chapter_17%3A_Radical_reactions/Section_17.2%3A_Radical_chain_reactions
6) http://authoritynutrition.com/antioxidants-explained/
7) http://www.h2-h2o.com/health.html
8) http://diehardbrain.blogspot.com/2012/03/free-radicals-and-antioxidants.html

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