Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

Antioxidants may do you more harm than good

with 3 comments

Chris just sent me a great link!

ANTIOXIDANT overload may underlie diseases such as congenital heart failure and Alzheimer’s, a study has shown.

Research on mice suggests that antioxidants, generally seen as beneficial to health, may sometimes do more harm than good.

Vitamins C and E and numerous compounds found in fruit and vegetables act as antioxidants.

They are generally regarded as healthy since they neutralise free radicals which are destructive groups of atoms that damage cells and DNA.

Many serious disorders, ranging from heart disease to cancer, are wholly or partly blamed on free radicals.

But there is another side to the coin – reductive stress, which some experts believe can be triggered by antioxidants.

Reductive stress, paradoxically, causes atoms to gain electrons, thereby acquiring a more negative charge.

The new research confirms that it can have damaging effects, too, and may have been overlooked as a cause of human disease. The Scotsman

I’m not a chemist – I’ve a good grasp of the concepts but what I know about chemistry is self-taught. But the emphasis on oxidative stress as the cause of everything that goes wrong in the body has always struck me as a bit weird and wrong as I’ve stumbled across so many examples of oxidation being beneficial under the right circumstances, for example, the body deliberately creates free radicals to fight off infections. Oxidation is in fact essential to life and a normal bodily process. It also strikes me as pretty interesting that most of the chemicals that make me feel so ill are antioxidants.

There was a paper published on reductive stress in 2002 but unfortunately this isn’t available online. I found a letter agreeing with the paper that is very telling:

We are writing to agree with Dr B Lipinski’s perceptive comments (Lipinski, 2002) and to suggest that they are of wide relevance. In particular, the importance of reductive stress should be more widely recognized. The prevailing view is extraordinarily blinkered. In PubMed (2001) there are 8957 citations to oxidative stress and none to reductive stress. This reflects not reality, but the mistaken but widely held ideas that oxidative stress is common, that it is the main source of biological free radicals, and that it is (or should be) susceptible to correction with antioxidants. In fact, extensive clinical and experimental work over the past 30 years has failed to reveal a single abnormal clinical state which could be confidently ascribed to oxidative stress or, more importantly, which has convincingly benefited from antioxidants. One reason is probably the initial difficulty of grasping the concept of reductive stress: another the relative paucity of experimental methods for demonstrating and measuring it. Evidence in support of a concept of reductive stress: Reply

Sounds like another case of The Emperor’s New Clothes, doesn’t it? I also found this press release:

Science Daily — Antioxidants are widely considered an important defense against heart disease, but University of Utah researchers have found excessive levels of one antioxidant–reduced glutathione–actually may contribute to the disease.

The findings, published in Cell, indicate a new class of drugs can be developed to treat or even prevent heart disease caused by “reductive stress,” according to Ivor J. Benjamin, M.D., Christi T. Smith Chair of Cardiovascular Research, division chief of cardiology at the U School of Medicine and the study’s principal author.

The protein alpha B-Crystallin, termed a molecular chaperone, normally helps long strips of other proteins fold inside cells. When it works properly, the cell produces the correct amount of reduced glutathione, which is healthy for the body. Unfortunately, when the gene that makes alpha B-Crystallin is mutated in humans, the protein unfolds improperly into aggregrates, the hallmark of the condition in different organs, including the heart. When that happens, reduced glutathione is produced in such excessive levels that it harms the heart, Benjamin said. The resulting condition is called reductive stress.

In a study of laboratory mice with failing hearts caused by mutant alpha B-Crystallin, Benjamin and several U of U colleagues found increased activity of the biochemical pathway leading to high levels of reduced glutathione in the animals.

Glutathione, one of the body’s most powerful antioxidants, is regulated at multiple steps principally by the G6PD enzyme. To establish the connection between reduced glutathione and heart failure, Benjamin mated mutant alpha B-Crystallin mice that carried too much G6PD with mice that had far lower levels. The resulting offspring had normal levels of reduced glutathione and did not develop heart failure.

“Lowering the level of reduced glutathione dramatically changed the survival of these mice,” Benjamin said. “Basically, we prevented them from getting heart failure.”

Heart, Alzheimer’s, Parkinson’s, and other deadly diseases are associated with oxidative stress, in which “free radical” molecules are produced in reaction to oxygen intake. Free radicals travel the body, triggering chemical reactions that damage proteins and causing them to form aggregates. Many people take antioxidants to prevent heart and other protein-aggregate diseases, but there actually is scant evidence to prove they work, according to Benjamin.

Until now, reductive stress has not been looked at in the context of disease. “This is a case of too much of a good thing,” Benjamin said. “Our findings indicate reductive stress warrants a more thorough investigation.”

By lowering the levels of reduced glutathione without the altering mutant gene encoding thee alpha B-Crystallin, , the study shows reductive stress can be addressed through new drugs that target the genetic pathway causing the problem, according to Benjamin.

“This field of medicine has not appreciated reductive stress and its influence on disease,” he said. “This is about balance needed in the environment of our cells, and it can have profound consequences on the treatments of heart disease and other serious disorders.” Too Many Vitamins? One Antioxidant Linked To Heart Disease, Study Shows

Which is an interesting take on glutathione, isn’t it?

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Written by alienrobotgirl

11 August, 2007 at 9:39 am

3 Responses

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  1. Long ago I became rather obsessed with all the kinds of antioxidants around. Luckily it didn’t last long. Or I would’ve become a freak like those you find at the sci.life-extension google group.I wonder how they’ll take it: http://groups.google.com/group/sci.life-extension/browse_thread/thread/bec3791772a14bbf/62176950e8ec25e7#62176950e8ec25e7I remember reading that preventing oxidation from happening (i.e. good food) is a better measure against aging than taking more antioxidants to clean up the mess from eating bad foods.I wonder about fluoride and reductive stress, as fluoride is the most negatively charged element in the periodic table. And heparin has reportedly the highest negative charge density of any known biological molecule. Both apparently aren’t really good for your bones in high doses: heparin: “Rarer side effects include alopecia and osteoporosis with chronic use.”

    Brecht

    12 August, 2007 at 1:45 am

  2. Actually, this study is not convincing because there is no evidence that reductive stress plays an important role in human disease or aging. All this study shows is that one can manipulate rodent genes in such a way as to cause an imbalance between antioxidants and oxidant that mimics heart disease. But that is far cry from actually showing that heart disease is caused by such an imbalance. Indeed, we know that arterial plaque is caused by oxidation of LDL. That is not controversial. One way of understanding why oxidation is so seductive as an explanation for aging is to look at what happens to the body’s three antioxidant defenses (glutathione, SOD, and catalase) as the body ages. Well, they all fall dramatically and oxidative stress rises dramatically. So the logical bet is that it is the decline in the body’s ability to resist oxidative stress that is either causes aging or contributes in an important way to it.

    Roderick S. Beck

    12 August, 2007 at 10:24 pm

  3. There is no evidence, because no one has looked for it. Part of the purpose of the study was to start looking for evidence that reductive stress is harmful.In the context of heart disease, plaque build up is a lot more complicated than mere oxidation of LDL. Plaque does not build up in the first place without the presence of an underlying inflammatory disorder. The oxidation of the LDL could well be quite irrelevant compared to the underlying inflammation, so treating heart disease with antioxidants could be rather like fending off a helicopter with a fly swat. Anything that is statistically only as useful as statins is not very useful at all.Again with ageing, what we see is a correlation, not evidence of causation. The oxidative stress theory of ageing is one of at least nine major theories of ageing. Just because it is the most fashionable theory (appealing to our society’s sense of food-guilt, pleasure-guilt and everything else guilt), does not mean it is the most well thought out, rigorously tested theory.

    Alien Robot Girl

    14 August, 2007 at 4:16 pm


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