Free Radicals: Is the fear exaggerated? (SQ-21)

Free radicals – nasty toxic molecules that have long been known to damage DNA, proteins, lipids and other essential biological molecules. Their contribution to premature aging and chronic degenerative illness is well-established. But is it the only way to perceive free radicals? As we are about to find out, the fear of free radicals may actually be exaggerated. While free radicals ride on a lot of negative hype, the truth is they are a crucial part of life and play an important role in many biological functions in small amounts.

So what are these free radicals really?

Free radicals: A by-product of cellular metabolism

Our cells need oxygen to produce energy needed to carry out important bio-chemical reactions that keep us alive. As cells process oxygen, highly reactive molecules known as free radicals are produced as a toxic by-product. How do free radicals damage our genetic make-up?

A free radical is a molecule with one or more unpaired electrons. In its attempt to stabilize itself, it is always on the look-out for more electrons – a property that makes a free radical highly unstable and reactive. It reacts with nearby stable molecules such as DNA, lipids, proteins and cell membranes to steal their electrons and in turn makes the attacked biological molecule unstable. This triggers a chain reaction heralding the production of more and more free radicals. Free radicals cause oxidative damage to fragile cellular structures – compromising the structure and functions of tissues and organs. This oxidative stress is known to play a dominating role in the onset of many chronic and degenerative diseases such as premature aging, cancer, autoimmune disorders, arthritis, cardiovascular disease, Parkinson’s, Alzheimer’s and vision loss.

However, our body works hard to maintain an elaborate, complex defensive mechanism to counter the effects of free radicals. With the help of an endogenous and exogenous supply of anti-oxidant enzymes, nutrients from food, and its self-repair mechanism, our body is generally able to keep this oxidative stress under control. But an overload of free radicals can be a tremendous problem. Many environmental triggers stimulate the body to produce more free radicals that it can keep pace with. Chronic stress, chemicals in food such as pesticides, processed food, sunlight, metal exposure and medications are a few examples that causes excessive accumulation of free radicals in the body which release a trail of destruction.

Beneficial role of free radicals in the body

Well, one thing is certain. Free radicals are an inevitable part of life. And though commonly perceived as toxic waste thrown off during cellular reactions, our body actually requires free radicals in small amounts to carry out certain important functions.

Weapons in immune system arsenal

Our immune system purposefully creates free radicals to kill viruses and bacteria. Immune cells such as neutrophils, monocytes and macrophages increase the uptake of oxygen from the bloodstream, taking away an electron – creating a range of free radicals such as superoxide anion, nitric oxide and hydrogen peroxide. These powerful free radicals blast the invading pathogens with their toxic oxidative burst – a key step in immune defense. In this way, our immune cells ride on the destructive power of some of the most potent free radicals to kill and engulf pathogens.

Relaying intracellular signals

Free radicals are also an integral part of the cellular signalling system – a complex, integrated system through which cells speak to each other, sense and process their micro-environment, co-ordinate their actions and respond to it in a variety of ways such as activating immune cells or repairing tissue damage. Depending on the cell, this response triggers a change in the cell’s ability to divide, gene expression and metabolism in order to maintain the required balance. Hormones, neurotransmitters and cytokines are all examples of signalling molecules that help the body to respond to a great number of external and internal stimuli. Perceiving and responding accurately to the environmental triggers is the key to homeostasis in the body – necessary for survival and good health. Any error in the way cells process this information may result in diseases such as cancer, diabetes and auto-immunity.

What role do free radicals play in relaying intracellular signals? Very important roles it seems.

• Certain free radicals regulate the intracellular signalling pathways in many cells besides phagocytes. For example, production of free radicals by non-phagocytes versions of NADPH oxidase, an enzyme complex found in plasma membranes “plays a key role in the regulation of intracellular signalling, and cascades in various types of nonphagocytic cells including fibroblasts, endothelial cells, vascular smooth muscle cells, cardiac myocytes, and thyroid tissue. For example, nitric oxide (NO) is an intercellular messenger for modulating blood flow, thrombosis, and neural activity.” [1].
  
  
• A 2011 study published in The Journal of Physiology showed that free radicals serve as signalling molecules that, in stressful situations, make the heart beat with the required force [2]. When our body is in any type of stress, the sympathetic nervous system activates specific receptors, beta-adrenergic receptors, on the surface of heart muscle cells. This triggers a cascade of bio-chemical changes within the cardiac cells. One such specific reaction results in stronger contractions of heart muscle cells – making the heart beat with greater force. The scientists showed that activation of beta receptors increases free radicals production in the mitochondria and contributes to stronger contractions. "Free radicals play an important role, since they contribute to the heart being able to pump more blood in stress-filled situations," says Håkan Westerblad, the study lead. "On the other hand, persistent stress can lead to heart failure, and chronically increased levels of free radicals may be part of the problem here." [3]
  
  
• In another 2001 study [4] published in Nature Medicine the researchers found that overeating results in increased production of free radicals in the hypothalamus - a section of the brain responsible for the production of many of the body's essential hormones. These free radicals behave as signalling molecules and activate certain neurons that suppress appetite and promote satiety – basically signalling the brain to regulate the food intake. However, when the body is chronically exposed to the torrent of free radicals, it causes cellular damage and aging. In a feedback loophole, the body kicks in a cellular mechanism to stop the production of free radicals. Did you notice the irony here? While this mechanism acts to protect cells from oxidative damage, it is also limiting the body’s ability to feel full after a meal. The study unmasked the role of free radicals in regulating energy metabolism and found that cellular mechanisms that kick in to control free radicals “are at the heart of increased appetite in diet-induced obesity.” [5]
  
  
• Another insightful study conducted by biologists at the University of California found that free radicals may play an important role in healing skin wounds [6]. In the study conducted on laboratory roundworm C. eleganshe, researchers found that free radicals “generated in the mitochondria not only are necessary for skin wound healing, but that increased levels of reactive oxygen species, or ROS, can actually make wounds heal faster.” According to Andrew Chisholm, one of the researchers "It appears you need some optimal level of ROS signaling……..Too much is bad for you, but too little is also bad. We discovered in our experiments that when we knocked out the genes that produced ROS in the mitochondria and eliminated antioxidants, the roundworms had trouble closing up their wounds. We also found that a little more ROS helped the wounds close faster than normal." The researchers believe that such effects may apply to ‘higher’ animals as well.

Useful Cellular Adaptions during moderate exercise

Researchers in this field assert that moderate exercise generates healthy amounts of oxidative stress, healthy to an extent that it serves as anti-oxidant [7]. There is strong evidence that during mild to moderate exercise, production of free radicals helps in activation of signaling pathways and signals muscle cells to make useful adaptive changes to exercise. These adaptions are important to achieve increased blood flow to muscles and new patterns for fuel consumption in generating energy. The point is that in small amounts some oxidative stress makes cells stronger and increases their resistance to stressors. So much so that “interfering with free radical metabolism with antioxidants may hamper useful adaptations to training” .While moderate exercise is actually known to up-regulate the immune system [8], intense exercise for longer durations appears to produce more free radicals that beats our body’s antioxidant defences – leading to tissue and immune function damage.

Good or bad?

What do all these studies point to? An excess of free radicals can damage DNA, proteins and other fragile cellular structures, promoting cellular damage and aging. But at low concentrations, free radicals play an important function in biological processes and in fact exert positive effects on immune functions and cellular responses. In addition, our body has an amazing self-defence mechanism that responds to the free radical challenge in quite a fascinating and much more organized manner than we can even imagine. It just needs to strike the right balance.

It is true that cells have only a limited pool of anti-oxidants, and with that comes a limited ability to neutralize overwhelming concentrations of free radicals. That brings us to anti-oxidants. Is saturating the body with anti-oxidants the solution? No. Especially when we are taking them out of their natural context. In the absence of other helper nutrients supporting their role, isolated antioxidants are not capable of fixing the free radical problem.

The whole idea is to pack a nutritional punch from a wholesome diet – containing natural and whole foods. Brightly coloured vegetable and fruits are abundant in a wide spectrum of anti-oxidants, enzymes and nutrients that add heft to the body’s natural arsenal. To think that a processed pill of supplement will offer the same benefits is simply not accurate.

References:

1. Lien Ai Pham-Huy, Hua He and Chuong Pham-Huy. Free Radicals, Antioxidants in Disease and Health. International Journal of Biomedical Science. 2008.
2. Andersson DC, Fauconnier J, Yamada T, Lacampagne A, Zhang SJ, Katz A, Westerblad H. Mitochondrial production of reactive oxygen species contributes to the β-adrenergic stimulation of mouse cardiomycytes. The Journal of Physiology. April 2011
3. Free radicals may be good for you. ScienceDaily. March 1, 2011
4. Diano et al. Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nature Medicine. 28 August 2011
5. Free radicals crucial to suppressing appetite. Science Daily. August 29, 2011
6. Kim McDonald. Moderate Levels of ‘Free Radicals’ Found Beneficial to Healing Wounds. UC San Diego News Center. October 13, 2014
7. Gomez-Cabrera MC, Domenech E, Viña J. Moderate exercise is an antioxidant: upregulation of antioxidant genes by training.Free Radical Biology & Medicine. January 15,2008.
8. Radak Z, Chung HY, Koltai E, Taylor AW, Goto S. Exercise, oxidative stress and hormesis. Ageing Research Reviews. January 2008.

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