Antioxidants: A Scientific Outlook
Most of us have heard of antioxidants and their flabbergasting health properties. Since the onset of early scientific findings linking antioxidants to better health the supplement industry has lured consumers who want a life with fewer health complications and an increase in overall wellness. But beyond the hype of crunchy granolas, Toms, and antioxidants what should we all know about these compounds? What do they protect against and how is this accomplished? What is their relation to aging and disease? Can we trust the fad diet claims or more specifically, those in the supplement industry? If you are interested in the answer to any of these questions and more just stick around, I promise your time will be well spent.
In short, antioxidants do exactly what their name implies, i.e., they protect against oxidative stress and damaged caused by reactive oxygen species (ROS) otherwise known as free radicals, but a foundational knowledge of these ROS is essential to understand the role of antioxidants in body dynamics. To begin we need to understand what free radicals are and where they come from. Concisely free radicals are highly reactive molecules with an unequal number of electrons that have the potential to create chain reactions to further “radicalized” other molecules (this is exactly how plastics are made) and cause cellular damage, for our discussion it is appropriate to focus solely on oxygen. Molecular oxygen (O2) accounts for approximately 20 percent of the air we breathe. This form of oxygen is used metabolically as the ultimate electron acceptor in the mitochondrial electron transport chain (ETC) of cellular respiration. If you recall, cellular respiration is the process by which every cell in our body converts food into energy, oxygen in need to accomplish this. During this process oxygen is ultimately converted to water, this requires 4 electrons. The problem is the reactivity of molecular oxygen with electrons that “leak” from the electron transport chain. Add one electron and you get a superoxide radical (this radical does not interact with DNA or proteins, but can create more dangerous compounds), add two electrons and you get hydrogen peroxide (although not a radical, hydrogen peroxide can pass through membranes and cause damage throughout the cell), add three electrons and you get a very, very reactive form called a hydroxide radical, add four electrons and you get innocuous water. This conversion of oxygen to water is part of normal metabolism and energy production, we all do it and in fact it is part of our symbiotic relation to plants. Plants make the compounds we need, i.e., carbohydrates and oxygen, in return we do what they need, which is water and carbon dioxide.
As discussed above all of this happens in the mitochondria so it is now believed that mitochondrial metabolism is the major source of these reactive oxygen species (90%) endogenously. However, our cells have a programmed pathway to eliminate free radicals by creating antioxidants, in biology, we refer to this pathway as the Nrf2-keap1 endogenous pathway, these antioxidants work by counteracting free radicals, thus inhibiting short-lived chain reactions that damage cellular structures, the accumulation of which is thought to contribute to the aging process. Antioxidants accomplished this by providing the electrons necessary to stabilize the radical molecules rendering them nonreactive. The consumption of fruits and vegetables is an “exogenous” method of obtaining these antioxidants. But just how laws govern physics, it appears that the field of biology is governed by exceptions, this is highlighted in a recent article published by Newcastle University school of medicine, department of dermatology in The International Journal of Cosmetic Science, which says the following,
“ROS are not always detrimental, as they act as important signaling molecules in processes such as apoptosis [cell death]…a vast array of additional papers have also shown possible beneficial effects of antioxidants; however, conflicting results have also been received in terms of [exogenous] antioxidants, with some past work showing little or no benefit, possibly due to the antioxidant being unable to get to the appropriate location in the body, an inefficient dose of antioxidant with possible toxicity at high levels, and differences in the genetic backgrounds of individuals.”
In other words, free radicals may be beneficial in some contexts and dangerous in others. An important point is that despite all the goodness antioxidants provide us with there is such a thing as too much of a good thing. In fact, too much vitamin E is linked to prostate cancer in males. Other antioxidants have been found to exacerbate the proliferation of cancerous cells once an individual is affected. On the positive end consumption of lycopene, found in tomato paste, has been shown to protect human skin against the effect of ultraviolet radiation mediated by oxidative stress. Blueberries have been shown to decrease oxidative DNA damage, improve memory, arterial stiffness and blood pressure.
Stepping aside from the damage caused by reactive oxygen species created during normal metabolism, it is important to note that environmental factors and lifestyle also play important roles. It has been well known for some time that ultraviolet radiation can induce oxidative stress. If you look at any sunscreen bottle you will see that these creams protect against UV-A and UV-B but not UV-C, this is because the ozone filtrates almost all UV-C. Though UV-A penetrates deeper into tissues, UV-B is more damaging to the skin, this is why the regular use of sunscreen is recommended by professionals. Furthermore, cigarette smoke contains superoxide radicals, hydrogen peroxide, and hydroxide radicals within it, leading to premature aging of the skin, hair (graying of hair) and other forms of cancer, along with alcohol it reduces the availability of antioxidants in the body making us more susceptible to oxidative stress. It has been studied that alcohol raises iron levels in the body thus contributing to a reaction that results in hydroxide radicals (the Fenton reaction). Environmental pollution is yet another cause of reactive oxygen species, here ultra-fine particles mainly from automobile emissions have been found to localize in epithelium and immune cells (macrophages) causing oxidative damage in these.
Finally, I will leave you with the most widely accepted theory of why we age, it is called “the mitochondrial free radical theory of aging” or MFRTA for short. In essence, it states that the cumulative sustained damage cause by free radicals leads to the gradual functional decline of cells, thus making us more susceptible to diseases like cancer, heart disease among others. The support of this theory lies in the fact that older tissue has higher concentrations of oxidative damage. Animal studies have shown that pigeons outlive rats astoundingly by a 9-fold increase despite their similar mass and metabolic rates. Furthermore, studies have found that pigeons’ rate of hydrogen peroxide production was much lower when compared to rats’, “suggesting” that lower ROS generation results in a longer lifespan. Criticism of this theory is very well founded with some researchers claiming that aging is not a monolithic entity with a single cause and a single cure.
In dealing with people in the business of selling supplements you can’t possibly get an accurate answer whether the supplement actually does anything. Many of these supplements are not FDA approved and information regarding effectiveness, including bioavailability (how much of it actually gets to the target) is scant and difficult to quantify. Making matters worst, it appears that conventional knowledge across common supplementation junkies lingers around the idea that if something is good, you can’t possibly have too much of it, as it turns out the body always strives to remain in a balanced state known as homeostasis, that is neither too much nor too little. In a 2013 editorial published in the Annals of Internal Medicine, researchers at the John Hopkins Bloomberg School of Public Health concluded that “the case is closed - supplementing the diet of well-nourished adults with (most) minerals and vitamin supplements has no clear benefit and might even be harmful.” It appears the best option to receive exogenous antioxidants is a well-balanced diet in fruits and vegetables but protecting against environmental factors and life-style perils is of equal importance to health.
As always I hope you’ve enjoyed this blog, I know it is a lot of science to digest in one read, but I hope you take the big picture with you, which is that antioxidants protect against free radicals that damage cells by stabilizing these reactive species. Though aging is a lost battle for all of us you can age well by taking good care of yourself. As always, if you enjoyed this blog make it known, by leaving your kudos, sharing it with others and subscribing. This is a spam-free platform so I promise you won’t receive rubbish in your inbox. Thank you and until next time!
Mounir C. Cejin