Special edition: inflammation

Suppliers make case to go to the source with supplementation of endogenous antioxidants

By Hank Schultz

- Last updated on GMT

Image: iStockPhoto
Image: iStockPhoto

Related tags Antioxidant Inflammation

Managing inflammation is something the body does naturally, without inputs, via a complex system of endogenous antioxidants. What’s the case for trying to boost this activity by supplementing the body directly with these substances?

Chronic inflammation is thought to form the slippery slope that can lead to a variety of disease states. And the waning of the body’s natural antioxidant defenses has been postulated to be a key factor in the aging process. Free radicals are ever more free to zip around the body’s tissues, the thinking goes, causing damage and degrading the function of organs over time and gradually depleting the body’s ability to regenerate itself.

As the measurement of ORAC values (Oxygen Radical Absorption Capacity) first became de rigueur, marketers sought supplement ingredients, many within the sphere of polyphenols, to put into supplements aimed at quelling inflammation. You got a radical oxygen species spill on aisle 3? Here’s a sponge!

But questions have arisen about the relationship of the seemingly ever-higher ORAC values being quoted for new ingredients and the performance of those ingredients in the body.  Were they doing in vivo what they purported to do in vitro, and, with the truly astounding figures being put forth for some new ingredients toward the end of this craze, the question became, could this become too much of a good thing?

Working with what’s there

Another tack that researchers took alongside the quest for antioxidant ingredients out in nature was finding a way to boost the body’s natural ability to handle oxidation. There are many endogenous components of the body’s natural antioxidant defenses. Among those which have been isolated and developed as dietary supplement ingredients are glutathione and superoxide dismutase (SOD). Another is CoQ10, an ingredient which has demonstrated activity with mitochondria but whose antioxidant supplementation bona fides are less robust.

Glutathione has been known for more than 125 years. The accumulated body of research continues to elucidate this molecule’s wide-ranging activities in the body, said Karen Todd, RD, director of global brand marketing at Kyowa Hakko, which supplies a stabilized form of glutathione called Setria.


“Glutathione is sometimes called “ the master of all antioxidants” as it is the most abundant endogenous antioxidant and it is a critical regulator of oxidative stress and immune function. But, for many reasons including age, prescription and OTC medication intake, health conditions, lifestyle, diet, weight and even time of day, the body’s stores of glutathione may be in short supply. An optimal diet rich in glutathione or oral supplementation has shown to be effective at enhancing body stores of glutathione and supporting the immune system,” ​Todd told NutraIngredients-USA.

The issue with glutathione, as with others of the endogenous antioxidants, is that these molecules are naturally reactive and don’t survive life on the shelf or the passage through the GI tract well. Kyowa Hakko’s manufacturing process for Setria presents the glutathione in a stabilized, reduced form, she said.

“Our most recent science has shown that Setria glutathione combined with Citrulline sustains the Arginine and Nitric Oxide levels better than when compared to just taking Citrulline or Arginine alone.  This finding is important for blood flow for heart health and performance athletes.  Our recent study showing the increase in body stores of glutathione and supporting the immune system has helped overcome the myth that it is destroyed in the GI tract,”​ she said.


Cheryl Myers, RN, chief science officer for supplement firm EuroPharma, which supplies its own form of stabilized glutathione in a technology licensed from a French company, said glutathione is perhaps the most important of the antioxidant ingredients overall.

“It is the most incredible antioxidant. I hesitate to use that term because it has been so overused. But hydroxyl free radicals don’t have much of a response to anything beyond glutathione,”​ she said.

Glutathione presents in two types in the body, Myers said. The reduced form, which is still active, and the oxidized from, which has already taken part in a reaction and is “used up.” Recent compelling research shows that the differences in the ratios of these forms might be associated with significant medical condition, Myers said.

“In healthy adults more than 90% should be in the active form. But they do see that ratio shift markedly in a wide variety of diseases. In healthy kids, more than 99% is in the active form, but they’ve found that in autistic kids, that level is only 60%. Why that is the case is something of a chicken-and-egg question,”​ she said.

Closer to the beginning?


Barbara Davis, PhD, vice president of scientific and regulatory affairs for branded ingredient supplier PLT Health Solutions, said there is an even more basic case to be made for SOD. It occupies a basic tier in the body’s antioxidant defenses. PLT supplies GliSODin, a branded form of SOD that is bound to gliadin, a protein from wheat that stabilizes the molecule.

“It acts at the beginning of the transformation of the molecular oxygen cascade. The logic is that you are stopping the generation of reactive oxygen species right at the beginning of the process,”​ Davis said. It’s a process that includes glutathione and catalase and results in the release of oxygen and hydrogen.

“Getting SOD through the GI system is difficult, with the low pH and the proteolytic enzymes would usually rending another enzyme inactive,”​ Davis said.“GliSODin combines the SOD with gliadin that protects the molecule and helps maintain it in the GI tract.” 

Davis said the molecular oxygen cascade of which she spoke is part of a complex series of reactions, some of the details of which are still not completely understood. The company’s research shows that SOD levels and activity go up with GliSODin supplementation, but the reason why is not entirely clear.

“We don’t understand the mechanism completely.  But what has been shown is that you get increases in SOD levels and in SOD activity with GliSODin supplementation.  DNA damage is reduced and CRP (C-reactive protein, a common inflammation marker) levels in the blood are reduced.  Whether that is because the SOD that survives in the GI tract is up regulating the mechanism or because it is crossing into the blood and raising levels directly we’re not sure of,” ​she said.

Beyond energy support

Scott Steinford, president of the CoQ10 Association, an industry group that supports the marketing and research efforts for the ingredient, said that ingredient, even though it occupies a position as one of the body’s resident antioxidant molecules, has more research in the supplement sphere in its support of energy production in the mitochondria.  Indeed, one of the strongest cases for supplementation with this ingredient lies in support of patients undergoing statin treatment, as this depletes CoQ10 levels in muscle mitochondrial cells and gives rise to complaints of muscle fatigue and soreness. Steinford said some research indicates a correlation between CoQ10 supplementation and anti-inflammatory activity, more much more needs to be done.


“Although there has not been significant research on the effect of CoQ10 supplementation on inflammation; some recent research indicates a positive correlation. In 2013 the journal Nutrition reported a double blind placebo study in Taiwan that demonstrated CoQ10 supplementation at 300 mg/d significantly enhances antioxidant enzymes’ activities and lowers inflammation in patients who have coronary artery disease during statins therapy. Another study in the same journal in 2012 reported CoQ10 supplementation at a dosage of 150 milligrams appears to decrease the inflammatory marker interleukin-6 in patients with coronary artery disease. CoQ10 supplementation, concomitantly with other ingredients such as aged garlic extract and vitamin E, has been clinically studied to provide reduction of C-reactive protein indicating a positive impact on inflammation,” h​e said.

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1 comment

Yes even drug companies are looking into NRF2 Activation"

Posted by Pat DeLorenzo,

Because of my research into helping my daughter fight her Autism and Epilepsy I have studied Oxidative Stress and its impact on endogenous antioxidants extensively. We use Protandim, an herbal supplement proven to boost SOD, Catalase and Glutathione so much so that it outperformed 3 drugs in a clinical treatment trial on MS and the study was paid for by one of the drug company's not the maker of Protandim!

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