Antioxidants - the Fact and the Fiction

Updated: Jun 10, 2019

At University, a Phytotherapist studies hundreds of herbs with their actions and indications. For each herb, “antioxidant” would invariably be an action. And so, when I wrote my Materia Medica exams I always knew that, if I forgot an answer to an “action” question, I could rely on antioxidant as a back-up.


Although the antioxidant action was a “get out of jail free” card during university, it has become a lot more interesting to me in practice. Phytotherapy relies mainly on plants for vitamins, minerals and other constituents, such as antioxidants. But I started to wonder… if a healthy diet contains antioxidants, why are people supplementing with additional antioxidants?


There has been a big “boom” in antioxidant supplements in health shops. According to Allied Market Research in America, the antioxidant industry brought in 2.9 billion dollars in 2015 and is expected to reach 4.5 billion by 2022. The consumer seems to believe that these supplements will encourage longevity and abate cancer.


Is this substantiated?


Those of you who read my “Fooled by Fibre” post, know that I like to start at the origin of any health discovery. And this seems to be a case of history repeating itself. Here we will see one man postulating a theory and decades of false marketing being perpetuated from it.


This man was called Denham Harman and he was named “the father of the free radical theory of aging”. In 1954 he proposed the following hypothesis...


The free radical theory of aging states that organisms age because cells accumulate free radical damage over time.

"A free radical is any atom or molecule that has a single unpaired electron in an outer shell.

While a few free radicals such as melanin are not chemically reactive, most biologically relevant free radicals are highly reactive. For most biological structures, free radical damage is closely associated with oxidative damage. Antioxidants are reducing agents that limit oxidative damage to biological structures by passivating them from free radicals.”

The theory seems simple enough. A negatively charged particle (free radical), incorrectly binds to other molecules (oxidation) in the body and causes damage to them. This damage leads to the general aging of the body. Based on his theory, Denham Harman used super-doses of antioxidant supplementation to increase lifespan. However, after many years he surrendered to the fact that this did not work.

He then came to a new conclusion. Harman believed that mitochondria were producing, as well as being damaged by, free radicals and that exogenous antioxidants wouldn't enter the mitochondria. And that it is mitochondria that determine lifespan. Therefore, using high doses of antioxidants wouldn’t increase lifespan. He published his ideas on what he called the "mitochondrial theory of aging" in the April 1972 issue of the Journal of the American Geriatrics Society. This is a rather simplistic view and assumes that the body is not complex enough to have its own defense mechanisms within the mitochondria. Modern research suggests a different explanation for aging…but I’ll discuss that later in this post.


Oxidation and Reduction

It is important to note that, although our focus lies on oxidation, there is also a process called reduction. Together they from “redox reactions” and these reactions are vital for existence. Oxidation is the loss of electrons by a molecule, atom or ion. While reduction is the addition of an electron by a molecule, atom or ion. You might come across the mnemonic ‘OIL RIG’, which helps students to remember the correct order of the loss and gain of electrons.


This "give and take" of ions is happening around and inside us constantly. A great visual reference for redox reactions is a rusting car. Inside the body, these redox reactions can occur anywhere; however, an important "redox-dense" area is within the mitochondria. Here, a cellular process called “The Kreb Cycle” converts glucose into energy. This cycle functions via a series of redox reactions and the process leads to various negatively charged ions (free radicals).


This might lead you to think that the more energy we produce (cellular respiration), the more free radicals develops and the more risk we incur for various associated diseases. Whenever you exercise you increase cellular respiration and, since we can’t stop exercising, you might be tempted to reduce the free radical load with antioxidant supplementation post-workout. Take a look at the following paragraphs to find out if this works…


Free Radicals

As Harman stated, a free radical is any atom or molecule that has a single unpaired electron in an outer shell. They are now more appropriately called “reactive oxygen species” (ROS). ROS causes oxidation within a cell. If oxidation occurs in higher rates than what is “natural” it can lead to damage of cellular machinery and increase risk of disease.


As we saw earlier, exercise, respiration and the natural process of converting glucose to ATP creates ROS.


Endogenous (internal) causes of ROS include the processes governed by the following enzymes: xanthine oxidase, lipoxygenase, glucose oxidase, myeloperoxidase, nitric oxide synthase, cyclo-oxygenase.

Other exogenous sources of ROS include; excessive alcohol consumption, cigarette smoke, drugs, xenobiotics, pollutants, refined or deep-fried foods, glycation, radiation and increased cortisol levels (to name a few). Indulging in these lifestyle habits pushes the formation of ROS to a level that cannot be neutralised by endogenous antioxidants.


However, in “normal” doses, ROS is not bad for the body. It plays an important role in telling a cell that it needs to activate defense mechanisms against an attack to cell integrity or to activate the expression of a range of protective genes. Jeffrey Blumberg, (PhD, director of the antioxidants lab at Tufts University) further states that “immune cells will shoot free radicals onto invading bacteria to kill them. They’re an important part of the body’s defences.”


Scientists are now finding that the oxidative stress triggered by exercise promotes insulin sensitivity and weight loss, and possibly reduces risk of diabetes. D Bailey et al. found that supplementation with Vitamin C and E for 6 weeks prior to an exercise test left the participants with increased cortisol and Interleukin-6 an hour into recovery. Neither did it reduce oxidative stress, nor did it facilitate recovery of muscles.


“In fact, we proposed that exercise itself can be considered as an antioxidant because training increases the expression of classical antioxidant enzymes such as superoxide dismutase and glutathione peroxidase and, in general, lowering the endogenous antioxidant enzymes by administration of antioxidant supplements may not be a good strategy when training.”


(M Gomez-Cabrera et al., 2015… check this article out in the references, it is a good read.)


Slowly but surely it is becoming more well-known that Reactive Oxidation Species, in small doses, are vital for cellular homeostasis.


Antioxidants - The good and the bad

Did you know that we make our own (endogenous) antioxidants within our cells? An important one is called “glutathione”. Furthermore, antioxidants and cellular defence mechanisms can be broken down into various classifications. They are certainly not the simplistic molecules we’ve been taught.


1. There are the non-enzyme endogenous modulating compounds that I have mentioned. These endogenous antioxidants include; Glutathione, Coenzyme Q10, Lipoic acid, Thioredoxin, Uric acid, Bilirubin and more.

2. Antioxidant enzymes are by far more important than exogenous antioxidants. Antioxidant enzymes break down ROS molecules. Some examples include; superoxide dismutase (manganese superoxide dismutase in mitochondria), glutathione peroxidase and catalase. These enzymes require various cofactors or coenzymes such as selenium, copper, iron and zinc. Consequently, the focus in dietary advice for ROS management is shifting towards fruit and vegetables that contain cofactors and coenzymes rather than antioxidants themselves.

3. Once ROS molecules have been broken down by these various antioxidants enzymes it is important for by-products and other toxins to be excreted from the cell and potentially recycled in the body. This process of antioxidant detoxification requires various enzymes including: Glutathione-S-transferase, Quinone reductase and UDP-glucuronosyl trasnerase

4. Most exogenous antioxidants come from our daily diet. Dietary antioxidants are merely a support to the ones we create ourselves. They may encourage the modulation of redox reactions. Below is a list of common antioxidants found in herbal and food sources.


Highly antioxidant foods: Berries, Grapes, Cocoa, Spinach, Sweet potato, Carrots, Prunes, Raisins, Kale, Pomegranate juice and Goji berries.

Highly antioxidant herbs: Green Rooibos, Green tea, Moringa, Cloves, Oregano, Rosemary, Thyme and Ginger root.


Modern man has added supplementary exogenous antioxidants to this list. Examples include: vitamin A, vitamin C, vitamin E, beta-carotene, lycopene, lutein, selenium, manganese, n-acetyl-cysteine.

The problem with many of these supplements is that they are not always bioavailable, and so, they are not entirely absorbed. They can also be toxic in high doses; a key example is the effects of high doses of selenium. The research that has been conducted on antioxidant supplements seems to work in vitro but not in vivo. Furthermore, research dating back to the mid 80’s (and perhaps earlier) has shown detrimental health effects of supplementing with antioxidants. The following table shows some shocking results from a review done in 2012 by Hart C et al.




Telomeres - The current theory of aging


“Geneticist Richard Cawthon and colleagues at the University of Utah found shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

While telomere shortening has been linked to the aging process, it is not yet known whether shorter telomeres are just a sign of aging, like grey hair or actually contribute to aging.”

To read more about Telomeres and the current theory of aging follow the link below.

https://learn.genetics.utah.edu/content/basics/telomeres/


To conclude...

Reactive Oxidation Species occur in the body and they lead to oxidation. Excess oxidation leads to damage of “cellular machinery” and may contribute to aging and disease but is not the sole or key factor. ‘Natural’ levels of oxidation are, in fact, beneficial to the body and can be neutralised through endogenous antioxidants. Endogenous antioxidants are merely supported by dietary antioxidants found in fruit, vegetables and herbs and not reliant upon them. However, these fruits, vegetables and herbs are also supplying important mineral cofactors and vitamin coenzymes. Supplementing with exogenous antioxidants is not only unnecessary but can also be harmful. (A caveat might be those who have been tested and found to severely lack certain antioxidants due to chronic lifestyle behaviours or genetic predispositions. A second consideration may in male infertility, again, testing would be required before supplementation commenced.) Rather, turn to alterations in diet and lifestyle practices to reduce oxidative stress. Additionally, you can have your genome tested for various SNPs to discern if you are at risk for various genetic factors that foster poor cellular defense mechanisms.


References

  • Bailey, D., Williams, C., Betts, J., Thompson, D. and Hurst, T. (2010). Oxidative stress, inflammation and recovery of muscle function after damaging exercise: effect of 6-week mixed antioxidant supplementation. European Journal of Applied Physiology, 111(6), pp.925-936.

  • Berger, R., Lunkenbein, S., Ströhle, A. and Hahn, A. (2012). Antioxidants in Food: Mere Myth or Magic Medicine?. Critical Reviews in Food Science and Nutrition, 52(2), pp.162-171.

  • Gomez-Cabrera, M., Salvador-Pascual, A., Cabo, H., Ferrando, B. and Viña, J. (2015). Redox modulation of mitochondriogenesis in exercise. Does antioxidant supplementation blunt the benefits of exercise training?. Free Radical Biology and Medicine, 86, pp.37-46.

  • Gutteridge, J. and Halliwell, B. (2010). Antioxidants: Molecules, medicines, and myths. Biochemical and Biophysical Research Communications, 393(4), pp.561-564.

  • Hart, C., Cohen, R., Norwood, M. and Stebbing, J. (2012). The emerging harm of antioxidants in carcinogenesis. Future Oncology, 8(5), pp.535-548.

  • MatÉs, J., Pérez-Gómez, C. and De Castro, I. (1999). Antioxidant enzymes and human diseases. Clinical Biochemistry, 32(8), pp.595-603.

  • https://www.alliedmarketresearch.com/anti-oxidants-market

  • https://en.wikipedia.org/wiki/Free-radical_theory_of_aging


This article is for educational purposes only and is not intended to treat or diagnose readers.





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