Thursday, November 7, 2013

Aging, exercise, and diet: Are free radicals to blame?

Many people have heard of antioxidants and free radicals, but few understand their importance to health.  Much like most health topics, antioxidants and free radicals have been reduced to the simplistic "antioxidants are good and free radicals are bad" explanation.  People certainly like simplicity, but what's the point in a simplistic explanation if it's outright wrong?  This has led to many people wasting money on supplements that they don't need at best, or could be potentially harmful at worst.  When we take a look at how the human body works and what research shows us, we can get a good idea of what we should be doing about antioxidants and free radicals.

It's not a controversial thing to say that eating in excess and limiting physical activity tends to have negative effects on the body.  Physical activity is a good thing whether it's via an exercise program or just regular, everyday chores.  Of course, this is all dependent on other things in that person's life as well as the dosage of physical activity.  A person who isn't sleeping or eating properly is adding to the amount of stress their body is under, so it's important to apply a level stress in the form of physical activity or exercise that is manageable to that person.  If exercise was as simple as more=better, people who run marathons and triathlons would live longer than the rest of us...They don't.  There is a fine balance between diet and exercise that is optimal, and letting that get out of balance may be one of the keys to this antioxidant/free radical relationship.

Free radicals and antioxidants

Free radicals are molecules that have an unpaired electron in their outer shell.  This makes that molecule reactive so it goes around reacting with stable molecules, pulling an electron from them.  While this stabilizes the free radical, it causes the other molecule to become a free radical.  Antioxidants work by donating electrons to free radicals, but this makes the antioxidant a free radical.  So, ingesting antioxidants such as Vitamins C or E really don't reduce the number of free radicals in your body, it just passes the buck from the free radical to the antioxidant.  In this way, antioxidants that you get from your diet really aren't that helpful on their own, they need help from the antioxidants your body makes on it's own, also called endogenous antioxidants.

The 4 endogenous antioxidants are superoxide dismutase(SOD), alpha lipoic acid(ALA), coenzyme Q10(CoQ10), and glutathione peroxidase(GPX).  These master antioxidants work by completely taking care of free radicals rather than just donating an electron and passing the buck down the road.  ALA, CoQ10, and GPX also have the ability to recharge the exogenous antioxidants you get from your diet by donating an electron to them, making them more stable.  Having a fully operational endogenous antioxidant defense system is very important to health, and it's fairly easy to accomplish when armed with the proper information.

Human metabolism and free radicals

It may come as a surprise to you, but one of the natural byproducts of human metabolism is free radical production.  Free radicals aren't all bad, they actually help perform some vital cellular processes so eliminating them is not something you should be looking to do.  Your primary goal should be to develop a balance between your endogenous antioxidant defense system and free radical production, not eliminate free radicals altogether.  This can be accomplished very easily, let's look at the relationship between energy production and free radicals.

Your mitochondria are organelles within your cells that are responsible for most of the energy production.  Mitochondria create energy aerobically which means they require oxygen.  One of the ways mitochondria make energy is via the electron transport chain.  The electron transport chain makes energy by passing electrons between complexes within the electron transport chain.  No machine operates at 100% efficiency, so as a natural byproduct of this process electrons can leak out and react with oxygen to make the free radical superoxide, which is very toxic and highly reactive.

Physical activity and the endogenous antioxidant defense system

When we are physically active, the endogenous antioxidant defense system within our cells is activated.  Gravity has a profound effect on the endogenous antioxidant defense system because when our muscles are activated, so is the endogenous antioxidant defense system.  Looking at astronauts in microgravity, research shows that a lack of or lower amounts of gravity lead to an increase in free radical damage(1).  This isn't from an increase in free radical production, it's from a downregulation of genes that produce endogenous antioxidants.

Other research sheds some light on how this effect occurs.  A study on breaking up periods of sedentary time by getting up and moving around showed that breaking up periods of sedentary behavior led to upregulation of genes responsible for antioxidant production when compared to remaining sedentary(2).  Another study found that exercise increases endogenous antioxidant defense system activity and capacity(3).  Therefore, the positive effect from exercise on free radicals more than likely occurs as a direct effect of exercise on stimulating the antioxidant defense system as well as increasing that system's capacity to deal with free radicals over time by increasing it's output.

Obesity and it's relationship to aging and free radicals

It should come as no surprise that there is a strong relationship between obesity and disease, and for the most part leaner people tend to look younger.  However, the relationship between obesity and disease is just that, a relationship. The fact that there is a relationship between them does not mean that obesity causes disease or that disease causes obesity, only that the two share something(s) in common.  It's quite possible that an imbalance between free radical production and the endogenous antioxidant defense system could be what links the two together.

Obese people tend to overconsume calories and have lower physical activity levels than their lean counterparts.  Despite having lower levels of physical activity, obese people tend to burn more calories than lean people.  In fact, total daily energy expenditure for humans is pretty static when you control for body size.  One study looked at the daily energy expenditure of modern day hunter gatherers and compared it to that of the more sedentary western lifestyle and found the same total energy expenditure when you control for body size.  While the hunter gatherers burned more calories from physical activity, Westerners burned more calories through an increase in metabolic rate(4).

One would have to think that, despite generating the same amount of energy, the hunter gatherers would have had a better balance between free radical production and endogenous antioxidant production than the more sedentary Westerners.  They also tend to have much better health outcomes and lower to non-existent rates of Type 2 diabetes, obesity, cancer, and heart disease, all of which share a relationship with an imbalance between free radical production and endogenous antioxidant production.

Perhaps obesity is simply the outward manifestation of putting an excess number of calories through the mitochondria without the beneficial effects of physical activity on endogenous antioxidant production in people prone to obesity.  Cancer, Type 2 diabetes, and heart disease all share the common trait of high free radical levels as well.  The relationship between obesity and  poor health could simply be a mismatch between free radical production and endogenous antioxidant production.  Obesity is what this looks like in people prone to it, but poor health is the outcome for all whether they are prone to obesity or not.  In other words, obese people tend to be less healthy because obesity shows that this process is going on, but some people don't have the forewarning that this is going on because they aren't prone to obesity.


The human body functions best when it is physically active and given a nutrient dense diet that has a moderate amount of calories.  It would be inappropriate to say that excess free radical generation is directly to blame for increased aging, obesity, and poor health outcomes.  It seems more likely that an imbalance between free radical production and endogenous antioxidant production brought about by a lifestyle that is not conducive to our physiology is to blame.  Taking antioxidant supplements or even eating tons of vegetables to provide the body with antioxidants will not put someone on the path to better health.  As I discussed here, certain vegetables can stimulate your body to produce endogenous antioxidants, but even then I wouldn't expect a revolutionary benefit.  A holistic approach that incorporates a nutrient dense, calorically moderate diet with high levels of general physical activity will do a much better job of improving your health while at the same time slowing down the aging process, or at the very least making it look like the process is slowing down.

Next Thursday I will discuss how free radical production and mitochondrial dysfunction, two factors in many of the diseases we see today, can speed up the disease process.

Part 2