or most of us, the chemical process of oxidation was quickly forgotten after escaping from high school chemistry class. But, even if the definition eludes us, we cannot ignore the effects of oxidation in our everyday lives. Sometimes, oxidation occurs quickly, and is easy to observe. The use of bleach to lighten fabric, or the browning of a cut apple are oxidation processes which can take place right before our very eyes. And yet, other times, the oxidation process takes much longer, and only when it has reached an advanced stage, are the results evident. We’ve all encountered a weather-beaten, rusty padlock, a tarnished copper penny, or an old car whose paint-job has lost its original showroom luster. These oxidation processes may take years to develop to a noticeable degree, and are largely preventable if certain protective measures are taken.

And because of the role oxygen plays in our metabolism, oxidation reactions occur constantly within our bodies as well. Ironically, these reactions are the ones upon which both our life - and our death - may be ultimately dependent. On one hand, oxidation, the chemical dance of electrons taking place continually in every cell of our body, is the essence of life itself. Oxidation is an integral part of energy production, and is the chemical basis for every beat of our heart, every movement we make, or every thought that we think. On the other hand, an excess of oxidation, especially involving oxidation reactions which damage our physical structure, are the essence of aging and disease. As we age, our cells can become more susceptible to the “collateral damage” of energy production caused by harmful byproducts of cellular function known as free radicals.

We may not tarnish like a penny, or rust like a padlock, but over the years, excessive oxidation takes its toll on us in a different way. As we age, we find ourselves under the burden of increasing levels of what scientists call oxidative stress. As more and more of our bodies’ cells and structures begin to wear down under the lifelong effects of oxidative damage, our skin begins to wrinkle, our joints, and arteries become hard and stiff, and our memory and energy levels begin to fade.

Is this gradual descent into frailty and disease inevitable, or are there ways to dramatically slow, or even reverse the ravages of father time? While many questions remain to be answered in our fight against aging, the scientific literature is exploding with reasons for us to be optimistic about our future. Many scientists believe that, buried in scientific journals right now, are all of the clues we need to begin countering the degenerative effects of aging. In understanding what oxidative stress is, and how it affects our cellular function, we can then take steps to minimize its damage; and by making the intelligent dietary and lifestyle choices needed to build and maintain strong, healthy and adaptive bodies, we may finally be able to achieve an energy, vitality, and lifespan reflecting our full human potential.

What is Oxidative Stress?

Oxidative stress is a term used to indicate a relative excess of free radicals, or damaging pro-oxidant molecules, versus antioxidants in the body. Those familiar with nutritional supplements, will probably know that antioxidants, compounds like vitamin C, vitamin E, selenium, and even a mind-boggling array of herbal components, may help to protect the structure of the body by short-circuiting excessive free radical reactions.

When all is functioning well, our cells are able to utilize oxygen properly, and function as efficiently as finely tuned engines. In our youth, especially, our bodies can easily repair and rebuild any cells which are minimally damaged in the natural process of producing energy. But as we age, damage to our cells accumulates and overwhelms our bodies’ innate antioxidant and cellular repair systems. Over time, damaged and faulty cells begin to produce energy ever more inefficiently and produce greater and greater levels of free radicals.

This “catastrophic vicious cycle” as biologists call it, makes oxidative stress the hallmark of all cellular degeneration, and therefore, all degenerative disorders. Everything from the seemingly benign characteristic of aging such as wrinkles, graying hair, and “liver spots,” to the modern scourges of our day - cancer, diabetes, atherosclerosis, and Alzheimer’s disease, are all characterized by progressively failing antioxidant defenses, and increasing levels of oxidative stress. The downward spiral of diminished cellular energy production, and increased cellular damage is not only characteristic of, but is itself - on a molecular and cellular level - the aging process.

Three Factors Contributing To Oxidative Stress

Oxidative stress can be characterized by three interrelating factors:

1. An increase in harmful pro-oxidant molecules

These pro-oxidant molecules could be anything from byproducts of our own metabolism, to certain oils in our diet, to harmful environmental chemicals like PCBs, pesticides, or heavy metals. Even certain viruses and bacteria could be called pro-oxidants because they trigger an inflammatory reaction by our immune system which causes oxidative damage not only to the invading pathogenic organism, but to our cells as well. Inflammation, pro-oxidants, and disease states are always very much related.

2. Lowered Antioxidant Protection

Going hand in hand with an increase in pro-oxidants, is a lowered level of antioxidant protection. When looking at recommended daily intakes for certain vitamins, it’s very easy to underestimate the amount of antioxidants our body truly needs. The amount of a nutrient needed to effectively deal with oxidative stress may be tens, or even a hundred times larger than the amount dictated by the RDA to prevent classical nutrient deficiency diseases. And in addition to antioxidants from our food and supplements, like vitamin C and E, our body can produce its own antioxidants as well. One of these antioxidants, called glutathione, is perhaps the single most important compound responsible for protecting our cells from oxidative damage:

Study Link - Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress.

3. The Inability To Repair Cells Damaged By Oxidative Stress

Usually, when cells are damaged, our immune system is called into action to get rid of them. But when cells and certain cell structures (especially the “power plants” of the cell, the mitochondria) are seriously damaged, they can sneak under the radar of our immune system. These damaged cells and their mitochondria can then continually produce more and more free radicals, and can even reproduce thus multiplying the damage they cause. As we age, the level of these mutated cells increases and, as one theory goes, even a small amount of these damaged cells then have the ability to cause serious increases in oxidative stress. Mitochondria damaged due to oxidative stress have been implicated in the development of cancer, atherosclerosis, Alzheimer’s disease, and diabetes.

Study Link - Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetes.

Study Link - Role of oxidative stress from mitochondria on aging and cancer.

Step 1 in Reducing Oxidative Stress – Minimize PUFAs To Protect Your Cells

It may seem logical that the first step in reducing oxidative stress would involve consuming high amounts of antioxidants. But antioxidants, while helpful, may not be enough to adequately protect our cells if we don’t make some other dietary changes first.

While most people think of “fat” as a fuel source which we all want to burn more of, fats and lipids are also structural components of every single cell in our body. Healthy, well functioning cells mean healthy, well functioning organs, and healthy, well functioning organs mean a healthy well functioning body. We all know that “we are what we eat,” so let’s first zoom in to the cellular level and see how the types of fats we eat contribute to the functioning of our cells - in particular our cell’s ability to produce energy efficiently and properly respond to stress.

We mentioned previously that as our cells produce energy, they also produce what’s known as free radicals in the process. Like sparks shooting from a campfire, free radicals are chemically unstable, reactive molecules which can cause damage to our cellular structure, lipids, proteins, and DNA. On a chemical level, free radicals can “steal” electrons from other molecules thus making them free radicals in the process. This chain reaction is precisely what makes free radicals so dangerous. Just as one wayward spark from a campfire can be enough to cause a raging forest fire, just one free radical molecule has the ability to damage millions of others before the chain reaction of oxidative damage is halted.

In the November 2007 edition of the Integrated Supplements Newsletter, we warned against consuming processed, heated, or excessive amounts of polyunsaturated fatty acids (PUFAs) in the diet, or from supplements. We showed you how too many of these fats could increase levels of oxidative stress, because they contain several free radical-producing double bonds in their structure. Not only are these double bonds in polyunsaturated fatty acids prone to oxidize in foods (when foods go rancid), but because fatty acids make up a major part of our cellular structure, they’re prone to oxidize once they become part of our cells as well. As our cells produce energy, the free radicals which are naturally produced in the process are more prone to damage cells which contain high levels of PUFAs in their structure:

Study Link - Ingestion of high doses of fish oil increases the susceptibility of cellular membranes to the induction of oxidative stress.

Study Link - Induction of lipid peroxidation in biomembranes by dietary oil components.

Study Link - Aging-related oxidative stress. depends on dietary lipid source in rat postmitotic tissues.

Study Link - Influence of dietary oils on liver and blood lipid peroxidation.

Study Link - Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans.

Study Link - Effect of the degree of fatty acid unsaturation of rat heart mitochondria on their rates of H2O2 production and lipid and protein oxidative damage.

And it is very well accepted in scientific circles that animals which have a lower level of PUFAs in their cells and tissues generally have significantly longer life spans than those whose cells and tissues contain more PUFAs:

Study Link - Oxidation-Resistant Membrane Phospholipids Can Explain Longevity Differences Among the Longest-Living Rodents and Similarly-Sized Mice.

Study Link - Modification of the longevity-related degree of fatty acid unsaturation modulates oxidative damage to proteins and mitochondrial DNA in liver and brain.

Study Link - On the importance of fatty acid composition of membranes for aging.

Study Link - Extended longevity of queen honey bees compared to workers is associated with peroxidation-resistant membranes.

Study Link - Membrane Fatty Acids as Pacemakers of Animal Metabolism.

Study Link - Oxidative Stress and Calorie Restriction in aging.

Study Link - Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil.

Quote:

“These results indicate that polyunsaturation of n-3 fatty acids is the most important target for lipid peroxidation. This suggests that the ingestion of large amounts of DHA oil enhances lipid peroxidation in the target membranes where greater amounts of n-3 fatty acids are incorporated, thereby increasing the peroxidizability and possibly accelerating the atherosclerotic process.”

And because free radical generation occurs in a chain reaction, high levels of PUFAs have also been shown to cause cholesterol to oxidize, the first step in the plaque build-up of heart disease. So while PUFAs may lower cholesterol levels, they may also hasten its conversion into the toxic, oxidized form.

Study Link - Effects of Fish Oil on Oxidation Resistance of VLDL in Hypertriglyceridemic Patients.

Quote:

“We conclude that fish oil supplementation strongly reduces serum concentrations of total triglycerides, VLDL triglycerides, and VLDL cholesterol. However, in HTG patients fish oil supplementation increased the serum LDL cholesterol concentration and the susceptibility of VLDL and LDL to oxidation.”

While only required by our body in very small amounts each day, polyunsaturated oils can be found everywhere in our food supply-from junk foods to health foods alike. Many people refer to the polyunsaturated fatty acids as EFAs, or essential fatty acids, because it is widely believed that they must be supplied from the diet. Defining these oils as “essential” often serves to give people the impression that more of these oils should be consumed, often through fortified foods or nutritional supplements. But because most of us consume far too many polyunsaturates as it is, perhaps the acronym EFA should more aptly stand for excessive fatty acids.

Most of us take in significantly more PUFAs than the 1-4% of calories needed to prevent deficiency. Four percent of calories in a 2000 calorie diet correlates to 9 grams of PUFA per day - an amount which most of us exceed in our diet without even trying. While once recommended for cholesterol reduction, PUFA fats are now being downplayed by nutritional “experts” because of the potential harm they can cause. Even the American Heart Association’s nutrition committee admits that “nothing is known about the long-term effects of a diet high in polyunsaturates.”

New York Times Article

Study Link - Dietary intakes of polyunsaturated fatty acids and indices of oxidative stress in human volunteers.

Yet, through very little fault of our own, consuming polyunsaturated oils in excess is exactly what most of us have been doing our entire lives. According to the EPA, Soybean oil, which contains approximately 61% polyunsaturated fats, accounts for a staggering 79% of all edible oil consumed in the United States, and soybean oil alone has been estimated to account for 10% of the calories in the average American diet.

EPA Data

James South writes about the free radical-generating effects of modern PUFAs:

One of the biggest dietary revolutions of the 20th century was the shift away from saturated fats, (such as lard, coconut oil, meat and dairy fat, etc.) to polyunsaturated fat (primarily linoleic acid) - rich margarines and vegetable oils. While monosaturated fats (olive oil), cholesterol, and even saturated fats are subject to free radical damage, it is polyunsaturated fatty acids (PUFA) that are most susceptible to free radical damage. PUFA lipid peroxides “have toxicities comparable to the radical species produced by [X-ray] irradiation.”  Lipid peroxides and their breakdown products (e.g. MDA) can cross-link proteins, phospholipids, nucleic acids and cellular DNA. They can inactivate enzymes. While all cellular components are subject to free radical attack, it is membranes, usually PUFA-rich, that are most susceptible to peroxidative free radical damage. Also, more unsaturated PUFA (such as EPA and DHA) are more free radical-damage prone than less unsaturated PUFA, (e.g. linoleic acid). Thus a prudent antioxidant measure is to avoid all margarines and PUFA-rich vegetable oils, such as safflower, sunflower, corn, soy and canola oil. Foods fried in PUFA-rich oils are especially good sources of (unwanted) lipid peroxides.

While many people within the natural health industry these days currently recommend “balancing” our Omega-6 PUFA intake with the less inflammatory Omega-3 PUFAs, it’s important to remember that Omega-3 fatty acids, while they may reduce inflammation in the short term, are even more chemically reactive and are even more prone to increase oxidative stress in the long term. While we as a nation certainly do take in far to many PUFAs from the Omega-6 series, taking in more Omega-3s may not be the answer. These Omega-3 oils readily oxidize even before they reach the bloodstream, and as indicated in some of the studies cited in this article, some Omega-3 fats, when incorporated into our cells make the cells very susceptible to oxidative damage.

It has even been shown that increasing our intake of the fat-soluble antioxidant, Vitamin E, may not be enough to counter the production of lipid peroxides, and oxidative damage caused by excessive intake of the currently popular Omega-3 fish oils:

Study Link - Lipid peroxidation during n−3 fatty acid and vitamin E supplementation in humans.

Study Link - Effect of Long-Term Fish Oil Supplementation on Vitamin E Status and Lipid Peroxidation in Women.

Study Link - Effect of fish-oil and vitamin E supplementation on lipid peroxidation and whole-blood aggregation in man.

Because of the harmful effects of excess PUFAs from both the Omega-6 and Omega-3 series, we should probably aim to reduce our consumption of both of these fats to levels just high enough to prevent deficiency (if, in fact, a deficiency can exist – despite the textbook definition of these fatty acids as essential, these fatty acids are so common in our diet, there exists some scientific debate as to whether an “essential fatty acid deficiency” is even a valid concept).

Conservatively, the Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy in Europe suggests that the minimum requirement for Omega-6 Linoleic Acid (LA) is approximately 1% of caloric intake, and that the minimum requirement for Omega-3 linolenic acid (LNA) is 0.2% to 0.5% of caloric intake.

Study Link - Polyunsaturated Fatty Acids: Biochemical, Nutritional and Epigenetic Properties.

This represents approximately 2 grams of Omega-6 LA (most of us consume much more than this per day) and 400mg to 1000mg of Omega 3 (LNA) per day for an individual consuming a 2000 calorie diet.

While Omega-3s can be more difficult to come by in the standard American diet, the trend in recent years towards rampant Omega-3 supplementation has blinded many people to the harmful nature of these oils when they are consumed in excess. The fact is that most of us can easily meet our Omega-3 requirements if we simply choose a healthy diet. A single salad meal containing half of a head of romaine lettuce and two ounces of feta cheese (seasoned with lemon juice and not oil-based dressings) will contain approximately 500 mg of total Omega-3s, and a whole host of other antioxidants and phytonutrients.

Nutrition Data

Nutrition Data

Dietary unsaturated fats and their breakdown products represent, by far, the greatest burden on our bodies’ immune system and antioxidant defenses. Knowing how significantly these lipids add to oxidative stress, and how delicate their balance in the body really is, the haphazard recommendation of nutritional oil supplements, like flax and fish oils, is irresponsible. If these oils are useful for certain people, under certain conditions, their intake should never be undertaken without major alterations in the fatty acid composition of the diet (i.e. reducing total PUFAs), and those taking these supplements should always be carefully monitored in the long term to watch for increasing markers of oxidative stress.

Once we’ve ensured that our intake of dietary fats isn’t contributing to our oxidative burden, we are then ready to go to work strengthening our antioxidant defenses.

Step 2 In Reducing Oxidative Stress – Support The Production of Glutathione with Whey Protein Isolate

As we mentioned, glutathione is the workhorse of our bodies’ antioxidant system. It is glutathione which is responsible for “mopping up” the damage produced by oxidized fats. But the effects of glutathione don’t stop there. This tripeptide molecule is also responsible for detoxifying other free radical-generating substances like pesticides and environmental toxins.

Representing a constant drain on our glutathione status, all of us living in industrialized nations are sure to have high levels of environmental toxins (pesticides, PCBs, and other organochlorines) in our bodies, even if we don’t exhibit outward symptoms of toxicity. Our fatty tissue is the preferred storage site for these chemicals, and if our bodies’ tissues contain high levels of PUFAs, the damage which these toxins do may be exacerbated. Women with breast cancer, for example have been shown to harbor particularly high levels of pesticide chemicals in their breast tissue:

Study Link - [Serum organochlorines pesticides level of non-occupational exposure women and risk of breast cancer:a case-control study]

And high PUFA vegetable oils have been associated with breast cancer development in many studies:

Study Link - Postmenopausal breast cancer is associated with high intakes of omega6 fatty acids (Sweden).

Study Link - Fat from different foods show diverging relations with breast cancer risk in postmenopausal women.

And studies have indicated that when our glutathione status is compromised, our cells are more susceptible to the damaging effects of oxidative stress in a variety of tissues:

Study Link - Glutathione deficiency leads to mitochondrial damage in brain.

Study Link - Mitochondrial damage in muscle occurs after marked depletion of glutathione and is prevented by giving glutathione monoester.

So, while our body can produce glutathione, factors in our diet and environment, factors to which none of us are immune, no matter how well we eat, can constantly compromise our glutathione status.

Luckily, certain nutritional substances can lead to a significant increase in glutathione production. For example, undenatured (and only undenatured) whey protein has been shown to be one of the best nutritional supplements for boosting glutathione and reducing oxidative stress.

Study Link - Therapeutic applications of whey protein.

Integrated Supplements CFM® Whey Protein Isolate is unique among whey proteins in containing the highest level of active, undenatured protein available. Our flavored versions also contain the amino acid glycine which may further support glutathione synthesis.

Step 3 In Reducing Oxidative Stress – Consume More Fiber

In the last issue of the Integrated Supplements Newsletter, we told you about a strange phenomenon we’ve noticed in the nutritional supplement and health food industry in recent years. We’ve found that many companies have taken to producing fiber supplements (and just about every other “health food” you can think of) with flaxseed meal. In at least one study, flaxseed meal had been associated with increasing levels of oxidative stress, probably due to the relatively high level of PUFAs which it contains.

Since we formulated our Fiber Balance™ fiber supplement to support all aspects of our customers’ health – including reducing oxidative stress, we obviously chose to avoid flax meal in the product.

We chose instead to base our Fiber Balance™ formula around a particular type of oat bran containing high levels of beta glucan fiber. Oat bran has been shown to reduce oxidative stress induced by a high-fat diet (coincidentally, the researchers behind the following study chose to use flax/linseed oil to induce oxidative stress - another reason to perhaps think twice before believing all of the health claims of the flax oil sellers):

Study Link - Wheat Bran and Oat Bran Effectively Reduce Oxidative Stress Induced by High-Fat Diets in Pigs.

For many reasons, including its effects on regulating blood sugar, and reducing blood lipids like cholesterol and triglycerides, fiber may play a very important role in reducing oxidative stress.

Vitality – The Essence Of Life

The effects of reducing oxidative stress can be summed up in one word – vitality. Vitality has been well defined as the combination of our ability to produce energy, along with our ability to adapt to stress. The less damage inflicted on our cells during energy production, the more efficient and resilient our cells remain. As we gain confidence in our body’s innate ability to adapt, the unavoidable stresses of life then become less of a burden, and more of an opportunity for growth.

Healthy muscle cells, for example, will adapt to the stress of exercise by growing stronger, larger, and more efficient. Unhealthy muscle cells, on the other hand, responding to the same workout stress, can leave us sore, worn out and predisposed to injury and illness.

But adaptive, efficient, high energy cells can help us adapt better to any stress be it physical or psychological. True vitality manifests not only in a high level of energy, and resistance to disease, but in an enthusiasm for existence and a sense of strength in the face of all of life’s challenges.

Imagine the possibilities if you knew, for example, that your mind would be as sharp as that of a 20 year-old when you were 70. Would this open up avenues for you to constantly enrich your life? Would you consider starting a new career in middle age, maybe in engineering or the sciences? Or would you engage in intellectual pursuits purely to satisfy your own curiosity? Most importantly, what do you think your mood would be like if you had the energy and vitality to seek these new and greater horizons of personal development well into your golden years, instead of constantly worrying about your declining health?

Contemplating the answers to these questions should give even the marginally health-conscious person sufficient motivation to make healthy choices today and for a lifetime. In its essence, the promise of combating oxidative stress is boundless vitality - not merely an extended life, but an enriched one as well.