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March 29, 2008

Studies Find Antioxidants Harmful. Well, Sort Of.

Vitamin_e_gelssmall_2 In a sense, aging can be very simply defined as the accumulated free radical damage that occurs to our body over a lifetime. It’s a slow process, of course, but the outward manifestations of aging can be pretty obvious at advanced stages: our skin wrinkles and loses the suppleness of youth, the muscles that we’ve worked so hard to build begin to atrophy, and our joints become stiff, inflexible, and painful.

Know Thy Enemy – Oxidative Stress

But in digging a little deeper into the biology, scientists have begun to unlock, on a molecular level, the root causes of all aging and degenerative conditions. Rather than simply stating what we all know, that “As we age we start to fall apart,” scientists have come to describe the aging process by the term known as oxidative stress. These same scientists soon began their fight against oxidative stress using a whole host of chemicals we know broadly as antioxidants.

The Two Faces of Antioxidants

The role of oxidative stress in aging has found its way into the public consciousness largely via the promotion of antioxidant supplements. Even the casual supplement user these days knows that antioxidants neutralize free radicals – the harmful molecules which are the drivers of oxidative stress. In recent decades the use of antioxidant nutritional supplements has exploded; but for all the fanfare and promotion, antioxidants have largely failed to live up to their initial expectations in halting the aging process. In fact, more than a few studies have shown that the relatively indiscriminate use of isolated antioxidants may often stimulate free radical damage - doing more harm than good.

Here’s a fascinating article from New Scientist Magazine:

The Antioxidant Myth – A Medical Fairy Tale

Quote from the above article:

But if free radicals are bad for us, how come coffee and tea might be beneficial? One possibility is that they can help nudge our own internal antioxidant systems into action. "There has been a considerable rethink as to what free radicals are doing," says Malcolm Jackson, a biochemist at the University of Liverpool, UK. He believes that in the right quantities radicals can be positively health-enhancing, prompting our cells to fire up their own internal defence machinery: a battery of radical-busting enzymes such as catalase and superoxide dismutase. "Cells are very good at protecting themselves against minor stresses, as long as they are not excessive," says Jackson. "The question is: should we be quenching free radicals at all?"

If it turns out that antioxidants in food work because they generate health-promoting quantities of free radicals, that would be an ironic turnaround. It may also explain why supplements and extracts don't seem to work or may even be dangerous: the doses are too high, and produce too many free radicals.

The researchers interviewed for the above article all note that while a diet full of antioxidant-rich foods is well-documented to prevent disease, the effects of isolated antioxidant supplements have been more than a bit discouraging.

But exactly why do the antioxidants from foods “work” while those from isolated supplements fall short in study after study?

The theory of the researchers quoted above is that the chronic low doses of antioxidants we ingest through foods may actually stimulate our bodies’ own antioxidant systems. But the way in which they do this may be the exact opposite of what you’d expect. When antioxidants quench free radicals by donating an electron from their structure, they too become free radicals - and it may actually be the chronic and subtly harmful nature of antioxidants which is responsible for their beneficial effects. This is why some high-dose antioxidants from supplements, when taken in isolated form, may actually make oxidative stress worse.

Hormesis – Dose Is Everything

In biology, it’s often the case that low-level exposure to a compound or external “stress” stimulates our bodies’ protective mechanisms - thus conferring long-term health benefits. Conversely, high levels of exposure to the same stress often prove to be decidedly harmful.

Scientists call this phenomenon hormesis.

We’ve written previously about the most common example of hormesis – exercise. We’ve seen how exercise actually increases our level of oxidative stress markers in the short term, but in adapting to this stress, our body is able to up-regulate its own production of very powerfully protective enzymes and proteins.

We’ve also seen how exercise, when performed to excess, can overwhelm our bodies ability to protect us, and can actually hasten the degenerative process.

And, if you think to take notice, you’ll see other examples of hormesis everywhere you look.

When our skin is exposed to sunlight, our body responds by producing melanin to protect us. The result? A protective suntan, of course. But if we overdo our sun exposure, a harmful sunburn will be the result.

Or we can see the principle of hormesis at work in vaccines (or more controversially, homeopathy) in which a small dose of a “harmful” substance is introduced into the body specifically to stimulate our protective mechanisms.

And surprisingly, even low-level radiation is thought by some to impart health benefits. Researchers have noted that the waters of many “healing spas” around the world contain particularly high levels of naturally radioactive minerals.

Long-term efficacy of radon spa therapy in rheumatoid arthritis—a randomized, sham-controlled study and follow-up

So, one wonders, what exactly are these “harmful” things stimulating in our body?

As it turns out, similar to exercise, many nutritional components may be causing low-level damage to our cells, thus stimulating glutathione production. As we mentioned in our blog on exercise recovery, glutathione is the most powerful cellular antioxidant produced by our body – and its production can be up regulated in accordance with our bodies’ demands.

Polyphenols – Exercise You Can Eat?

Surprisingly, plant chemicals known as polyphenols (found in health-promoting foods such as red wine, cocoa, and green tea) have been found to have little antioxidant activity in our body. But here’s the kicker - they do stimulate glutathione production.

Check out this study:

Polyphenols and glutathione synthesis regulation

So, it’s not too far-fetched to wonder if maybe the “antioxidants” in our food may not really be neutralizing free radicals as has been assumed. Instead, they may be imparting their health-benefits by stimulating our bodies’ production of protective substances like glutathione. And because (in proper doses) they stimulate many of the same protective mechanisms as exercise, on a cellular level, it’s tempting to think of food-based antioxidants like polyphenols as “exercise you can eat.”

But if this is true, then like excessive exercise, excessive amounts of antioxidants could be decidedly harmful. This perspective certainly would help to explain a lot of conflicting research. Like why high-dosed antioxidant extracts (the kind commonly sold as nutritional supplements) are able to quench free radicals in the test tube like nobody’s business - while often offering no such protection in our bodies.

This would even explain why high dose antioxidants are sometimes shown to be mildly harmful in published studies, and why some of the herbal extracts commonly sold as nutritional supplements have been shown to have a much greater toxicity than was initially expected. Reports have indicated several occurrences of acute liver toxicity in people taking dietary supplements containing concentrated sources of green tea antioxidants, for example.

http://www.annals.org/cgi/reprint/144/1/68.pdf

(The relevant abstract begins on page four of the above document).

Quote from the study:

Although Chinese green tea is widely touted as a cytoprotective antioxidant and panacea, we believe that large amounts or concentrated preparations of C. sinensis [green tea] are dangerous and should be avoided.

Supporting Glutathione Production Is The Answer

Whey_single_natural_wSo, perhaps the real answer to the antioxidant conundrum lies in supplying our body with antioxidant-rich foods, along with the raw materials it needs to make healthy amounts of glutathione.

We know that glutathione is produced from the amino acids cysteine, glutamic acid, and glycine.

And it just so happens that whey protein is among the richest sources of dietary cysteine, and glutamic acid (and where undenatured whey protein contains these amino acids in their native protein-bound form, undenatured whey is free of the toxicity concerns associated with L-cysteine and N-Acetyl Cysteine supplements, or free glutamic acid).

Whey protein is even one of the very few sources of a protein peptide known as glutamylcysteine. As its name suggests, glutamylcysteine is cysteine and glutamic acid bound together. When ingested, this peptide, which is two-thirds of glutathione already, is very easily absorbed, and is converted to glutathione in the cells readily - just one reason why undenatured whey protein isolate outshines all other supplements when it comes to boosting glutathione safely and effectively.

Note: Straight glutathione supplements do exist, but they are not terribly well-absorbed, and don’t seem to boost glutathione levels as efficiently as undenatured whey protein.

And of course, the flavored versions of Integrated Supplements CFM Whey Protein Isolate contain added glycine as well – specifically to enhance whey protein’s already remarkable glutathione-boosting ability.

So, in putting the pieces of the antioxidant puzzle together, we may very well find boosting glutathione production too be a much more important anti-aging strategy than anyone previously realized. I suspect that we at Integrated Supplements will have much more to say about nutritional hormesis, exercise, and the glutathione-boosting action of undenatured whey isolate in the very near future – stay tuned.

Related Articles:

Blog: Is Exercise More Harmful Than You Think?  How To Protect Yourself With Whey Protein Isolate

Blog: Oxidative Stress And Exercise - Too Much of a "Good Thing"

Newsletter: Rancid Fats and Oxidative Stress - Strategies To Reverse Aging - Part 1

Newsletter: Combating Oxidative Stress - Strategies To Reverse Aging - Part 2

Newsletter: The Anti-Aging Diet Part 1 - Can Some Foods Accelerate Aging?

Newsletter: The Anti-Aging Diet Part 2 - The Dark Side of Iron

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