I've found out this article on Eurekalert http://www.eurekaler...p-aom080307.php that states that despite the well know benefits of the various antioxidants, excess antioxidants can cause reductive stress that may lead to disease.
Their study, wich i've not yet read, focus on mice and heart failure caused by excess glutathione.
I've searched the forum for something related to this and I could not find anything so I decided to post.
Does anyone knows anything about more studies about this? Are there any well conducted studies on reductive stress on human?
See you around 
Good work, evilthinker; I haven't seen this yet. I have an excuse though; I've been really busy!
Eurekalert is reporting on a study published in the journal Cell. Some introductory information regarding the primary source that seems to be accurate as of August 9, 2007:
Cell is a biweekly peer-reviewed scientific journal which publishes novel research in any area of experimental biology that is significant outside its field. Cell is a well-regarded journal and it had a 2005 Impact Factor of 29.431, which makes it one of the most cited scientific journals. Cell is published by Cell Press a division of Elsevier.
Content over 12 months old is available free of charge.
Here is the study abstract:
Copyright © 2007 Cell Press. All rights reserved.
Cell, Vol 130, 427-439, 10 August 2007
Article
Human αB-Crystallin Mutation Causes Oxido-Reductive Stress and Protein Aggregation Cardiomyopathy in Mice
Namakkal S. Rajasekaran,1 Patrice Connell,2 Elisabeth S. Christians,2,3 Liang-Jun Yan,2 Ryan P. Taylor,1 András Orosz,1 Xiu Q. Zhang,1 Tamara J. Stevenson,1 Ronald M. Peshock,2,4 Jane A. Leopold,5 William H. Barry,1 Joseph Loscalzo,5 Shannon J. Odelberg,1 and Ivor J. Benjamin1,2,
1 Center for Cardiovascular Translational Biomedicine, Division of Cardiology, Department of Internal Medicine, University of Utah School of Medicine, 30 North 1900 East, Room 4A100, Salt Lake City, UT 84132, USA
2 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
3 Centre for Developmental Biology UMR5547, 118 route de Narbonne, 31062 Toulouse, France
4 Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
5 Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur Boston, MA 02115, USA
Corresponding author
Ivor J. Benjamin
ivor.benjamin@hsc.utah.edu
Summary
The autosomal dominant mutation in the human αB-crystallin gene inducing a R120G amino acid exchange causes a multisystem, protein aggregation disease including cardiomyopathy. The pathogenesis of cardiomyopathy in this mutant (hR120GCryAB) is poorly understood. Here, we show that transgenic mice overexpressing cardiac-specific hR120GCryAB recapitulate the cardiomyopathy in humans and find that the mice are under reductive stress. The myopathic hearts show an increased recycling of oxidized glutathione (GSSG) to reduced glutathione (GSH), which is due to the augmented expression and enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase, and glutathione peroxidase. The intercross of hR120GCryAB cardiomyopathic animals with mice with reduced G6PD levels rescues the progeny from cardiac hypertrophy and protein aggregation. These findings demonstrate that dysregulation of G6PD activity is necessary and sufficient for maladaptive reductive stress and suggest a novel therapeutic target for abrogating R120GCryAB cardiomyopathy and heart failure in humans.
This appears to be a study on mice that may extrapolate onto humans.
However, yes, wouldn't you agree that it would be sort of "too good to be true" to assume that a blanket assessment such as "everyone take x multivitamin" for optimum health? What if certain individuals already are in "optimum" health and get all the essential nutrients in their well balanced diet?
Let's assume you are such an individual (one that eats a balanced diet and gets all the essential vitamins and minerals without any pills). You would then probably have already reached an equilibrium of sorts in your body. In that case, taking additional vitamins and minerals could throw you out of balance; in such a case, taking extra anti-oxidants could possibly have a reverse effect and may INCREASE oxidative stress. That might be part of the reason objective analyzes of literature on vitamin and mineral consumption come out with such unexpected poor results such as those presented in peer-reviewed Medical Journals such as the Journal of the American Medical Association; an excellent example being:
JAMA: Vitamin E, A, beta-caro increases mortality, however, vitamin C and selenium -- ? . The bottom line is -- when you take a look at the data as a whole, it seems highly unlikely that blanket prescriptions for entire populations to take supplemental vitamins and minerals is a safe prescription.
To achieve optimum health, you should work with YOUR doctor -- one that is aware of what you do (or don't) eat in your diet. Anything else is simply dangerous. Especially self-prescribing drugs and supplements based on potentially biased information provided by firms that may profit (or have profited) from the sales of such products. It's best to get the opinion of a licensed health care professional; (hopefully one not part of a supplement firm!) all else is gambling with your most essential asset: your health.
Here's one of the references cited in the Cell paper cited above (I took a look at the full text). It appears that humans can self-induce heart failure due to: "decreased translation or processing, or a posttranslational modification of MnSOD" -- due to out of balance enzymes. It appears too little is
just as dangerous as too much of particular vitamins or minerals. Achieving balance is essential.
J Card Fail. 2005 Aug;11(6):473-80.
Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium.
Sam F, Kerstetter DL, Pimental DR, Mulukutla S, Tabaee A, Bristow MR, Colucci WS, Sawyer DB.
Myocardial Biology Unit, Boston University School of Medicine, Boston Medical Center, MA 02118, USA.
BACKGROUND: The nature of oxidative stress and the activity of antioxidant enzyme systems are incompletely characterized in the failing human heart. METHODS AND RESULTS: We obtained ventricular myocardium from failing, explanted human hearts in patients with nonischemic dilated cardiomyopathy at the time of heart transplant to examine whether reactive oxygen species (ROS) production and antioxidant enzyme activity or expression were altered in end-stage human heart failure. Nonfailing myocardium was obtained from organ donors who were not eligible for transplantation. Electroparamagnetic resonance (EPR) with the O(2)(-) spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide demonstrated that formation of superoxide anion was increased more than 2-fold in the failing (P < .001 vs. nonfailing) myocardium. Manganese superoxide dismutase (MnSOD) mRNA and catalase mRNA expression were increased by 52% (P=.05) and 116% (P < .05), respectively, in failing vs. nonfailing hearts. Copper-zinc superoxide dismutase (CuZnSOD) mRNA and glutathione peroxidase-1 (GPx-1) mRNA were unchanged. The expression of MnSOD, CuZnSOD, and catalase mRNA showed moderate correlation, suggesting coordinate regulation of gene expression. Activity was no different with regard to catalase, GPx-1, and glucose-6-phosphate dehydrogenase. MnSOD activity accounted for approximately 90% of total SOD activity, and was markedly decreased in failing hearts (by 61%, P < .05). MnSOD protein expression by western blot analysis was decreased in the failing group (P < .05 vs. nonfailing). CONCLUSION: The decrease in MnSOD activity in failing myocardium, in the setting of increased mRNA expression, may reflect decreased translation or processing, or a posttranslational modification of MnSOD. The increase in MnSOD mRNA in failing hearts is consistent with the thesis that there is increased oxidative stress in failing myocardium that leads to increase transcription of antioxidant enzymes. The source of this direct measure of ROS is likely superoxide. These observations have implications for the pathophysiology and treatment of heart failure.
PMID: 16105639 [PubMed - indexed for MEDLINE]
For individuals that are most vigilant and care the most about their health, I think they can have possibly their doctor perform quantitative assays to assess the status of certain vitamins and minerals in your bloodstream (this might get expensive though). I remember once when my B12 levels were so low (because I am vegetarian) my state of mind was altered. Some modern tests supposedly test your urine too for presence of certain neurotransmitters.
Again, the bottom line issue is as follows: many individuals -- instead of seeking advice from a Board Certified, licensed physician -- go online and trust advice provided by firms that profit from sales of certain products (
conflict of interest). Now it seems clear the largest body of assembled MDs on this planet convened and appear to conclude outright that the evidence is inconclusive and there may be no benefit from certain anti-oxidant therapies (or perhaps some potential danger). I am still trying to get a close enough of a look at the data myself where I can see some benefit from vitamin E. It's me & the supplement industry vs. the AMA. Do you think we have a chance?
The only person who is qualified to hold the answers to these questions pertaining your health is your doctor. Not me, not the guy next door -- your doctor. The one that knows your whole medical history; what you eat, what you ate, what you take, and what you took.
