Factors associated with severe oxidative stress in CFS

[mellster]

Hi fla,

I think it all depends on your current overall condition, generally you should be able to improve protection through exercise or cold-water swimming, but up to a certain point where you start overtraining and then decline (there are striking similarities between CFS an overtraining syndrome). That could well be true for the brain as well. Being a SW developer, I think it is fairly brain intensive but I don't think it is dangerously brain intensive and overall beneficial However I think that certain extremely brain intensive activities such as parallel blind-folded chess tournaments have been outlawed before due to possible detrimental effects on the brain (exhaustion etc.), maybe just a tale but a quick google search should be able to verify that

 

[August59]

Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins.

That was a mouth full!!! Thanks for the info though

 

[biophile]

Snow Leopard asked: Are there any published studies which actually show the in-vivo effect of Opuntia ficus indica extract?

Most of what I've seen about claims of effectiveness for Tex-OE lead back to anecdotes and marketing material from companies that sell it and therefore is highly suspicious. However, I did find potential leads from a paper on a human trial, "Effect of Opuntia ficus indica on Symptoms of the Alcohol Hangover" (http://archinte.ama-assn.org/cgi/reprint/164/12/1334.pdf). I have not investigated these cited sources in detail, after a quick look I'm not getting my hopes up, but here are the relevant quotes:

"An extract from the skin of the prickly pear fruit, Opuntia ficus indica (OFI), has been shown to accelerate the synthesis of heat shock proteins and to decrease oxidative injury.[40-42]"

"The OFI extract has been shown to accelerate the production of heat shock proteins (especially heat shock proteins 27, 68, and 72) during stress.[39,40,46]"

I also found several animals studies on PubMed but here is a human study on whole fruit: "Supplementation with cactus pear (Opuntia ficus-indica) fruit decreases oxidative stress in healthy humans: a comparative study with vitamin C" (http://www.ncbi.nlm.nih.gov/pubmed/15277160 | http://www.ajcn.org/content/80/2/391.full.pdf).

Marco wrote: A cold shower would be cheaper!

I don't respond well to cold showers, which seems to be because of both reduced circulation and an increased sensitivity to cold sensations. Last time I had one out of necessity during summer when the hot water system broke down, at the end my muscles temporarily ceased up with excruciating pain. On that particular day it was only about 90 degrees, but on the previous days when it was 100 degrees it wasn't as bad, but I don't remember experiencing any benefits from it.

PS - I'm also weary of anything that stimulates anything in CFS because the body may under-express it for good reason.

 

[fla]

Being a SW developer, I think it is fairly brain intensive but I don't think it is dangerously brain intensive and overall beneficial

I am a SW developer too. I've noticed quite a few [former] SW developers on these forums so I just wondered if it could be a contributing factor to oxidative stress and thus M.E..

 

[searcher]

I was a software developer too. Maybe we spend too much time indoors in moldy places? I know a lot of the buildings in which I worked in San Francisco were pretty old and not in great condition. I guess VItamin D could be an issue too, although I currently think low Vit D levels are downstream of other causes.

I think the more likely explanation, though, is that the contributors on Phoenix Rising are a self-selected group that is interested in science and analyzing the variables that cause/exacerbate ME/CFS, so are more likely than average to have had analytical jobs. I don't have any friends from university that I know of who have ME/CFS, and almost all of them work in brain intensive jobs like software or research. They have no idea what I am talking about when I try to describe brain fog...

I tried to work a part-time job this summer and found I could only concentrate for about an hour or two (and even that was at a reduced rate.) I then had to lay down for an hour to recover, so I know something is wrong, and it may be due to increased oxidative stress. Maybe I should experiment and try programming a variant of "Hello World" after a big dose of antioxidants and see if I can program for longer

 

[mellster]

Yeah, leaning towards searcher's explanation here. For all we know today, training and using your brain is all good, esp. in preventing senility and dementia So I think the worst part of this job is sitting in a chair all day, I started getting up every 1-2 hours (could even contribute to OI/POTS) and walk around and do some light exercise. Next come the air, esp. in airtight/AC buildings and the mold, VOCs (from printers etc.) and the EMF, the fluorescent lights and the lack of sun exposure. And yes, the self-selected group wanting analysis and answers can explain the dominance of SW engineers on this forum very well

 

[Marco]

And yes, the self-selected group wanting analysis and answers can explain the dominance of SW engineers on this forum very well

As could a common etiology with autism spectrum?:innocent1:

Marco (MSc Computing)

 

[searcher]

good point Marco There does seem to be a lot in common between autism and ME/CFS, and people on the spectrum are often more mathematically inclined. This is something I have thought about before, but I never could get my head around a possible mechanism. Do you have a theory on what could underlie autism, CFS, and a propensity toward mathematical skill? With autism/Asperger's I could imagine that there is extra development in certain areas of the brain, but our mathematical abilities were usually well established before we got ill. I do think there could be something there, though.

It would be great if we had good demographic information on all ME/CFS patients so we had a better understanding of the backgrounds and professions of sufferers, but even then we would be missing a lot of people who are undiagnosed or have diagnoses such as adrenal fatigue and Lyme (which I think are often names for the same illness process.) And I think us techies are more likely to keep pushing until we get a diagnosis, even one as frustrating as ME/CFS.

 

[mellster]

Yes, good point. Interestingly for me - although I could always occupy myself at a very deep level for a long time - the shift towards being more autistic (and also better at math) occurred gradually and some of the autistic features did not develop before the onset of IBS and then FM/CFS. It makes relationships much much harder, let me tell you There is definitely a connection between general feeling of well-being and energy and the level of being a social person. But not all of the turning inwards is bad IMO, it makes you reflect about things on a much deeper level and also decouples you from today's consumerist, external-simulation driven society ad lets you appreciate mental balance and tranquillity.

 

[fla]

Of course physical and mental exertion is good for everyone up to a limit. For us, those limits have lowered tremendously. Someone who trains for triathlons is constantly pushing the physical limit and in some genetically predisposed cases the limit comes crashing down and some athletes get M.E.. I see high level software development as constantly pushing the mental limit and in some genetically predisposed cases the limit comes crashing down and some developers get M.E..

Perhaps genetically predisposed to get M.E. means genetically predisposed to excel at math/problem solving...(autism spectrum as you called it)?

In M.E., PENE is triggered by physical or mental exertion. If oxidative stress explains the lowered physical limit then what explains the lowered mental limit or are they the same? Glutathione levels?

There appears to be the concept of repeated pushing of the limit causing the limit to pathologically lower. It's not usually amateur athletes that make a single extreme push but serious athletes doing repeated pushing. It's not students cramming overnight for an exam but SW developers doing repeated pushing.

 

[biophile]

MitoQ for oxidative stress?

MitoQ is a modified form of ubiquinone (CoQ10) which selectively targets mitochondria. In a recent study on mice genetically engineered to develop Alzheimer's disease, this antioxidant compound showed promising results (http://www.sciencedaily.com/releases/2011/12/111214094851.htm).

[fla] wrote: In M.E., PENE is triggered by physical or mental exertion. If oxidative stress explains the lowered physical limit then what explains the lowered mental limit or are they the same? Glutathione levels?

You may find this statement from the above article interesting: "The brain consumes 20 percent of the oxygen in the body even though it only makes up 5 percent of the volume, so it's particularly susceptible to oxidative stress," said Franklin, coauthor of the study along with Meagan McManus, who received her Ph.D. in neuroscience from UGA in 2010."

 

[u&iraok]

Yes, good point. Interestingly for me - although I could always occupy myself at a very deep level for a long time - the shift towards being more autistic (and also better at math) occurred gradually and some of the autistic features did not develop before the onset of IBS and then FM/CFS. It makes relationships much much harder, let me tell you There is definitely a connection between general feeling of well-being and energy and the level of being a social person. But not all of the turning inwards is bad IMO, it makes you reflect about things on a much deeper level and also decouples you from today's consumerist, external-simulation driven society ad lets you appreciate mental balance and tranquillity.

That's interesting, mellster, that you say autisic features didn't develop until after IBS and FM/CFS. I've wondered after seeing some similar symptoms with Autism and ME/CFS if some people who were on the Autistic spectrum before ME/CFS, maybe mild Aspergers or High Functioning Autism or Non-Verbal Learning Disorder, maybe some who didn't know it, were more susceptible towards developing ME/CFS. Or maybe the people who are math and/or science focused or engineers who sometimes are the parents of Autisic kids are more susceptiple to ME/CFS. Now you make me wonder if there's some who develop autistic traits after ME/CFS.

 

[aprilk1869]

I don't know if this will be of any use to anyone but I was reading up on the herb peony and found that it contains paeoniflorin which is supposed to have an effect on heat shock proteins.

Paeoniflorin, a novel heat shock proteininducing compound
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1065277/

Identification of genes responsive to paeoniflorin, a heat shock protein-inducing compound, in human leukemia U937 cells.
http://www.ncbi.nlm.nih.gov/pubmed/17952766

Protective effect of a molecular chaperone inducer, paeoniflorin, on the HCl- and ethanol-triggered gastric mucosal injury.
http://www.ncbi.nlm.nih.gov/pubmed/21167840

Involvement of Multitargets in Paeoniflorin-Induced Preconditioning
http://jpet.aspetjournals.org/content/319/1/165.full

 

[richvank]

In M.E., PENE is triggered by physical or mental exertion. If oxidative stress explains the lowered physical limit then what explains the lowered mental limit or are they the same? Glutathione levels?

Hi, fla.

I think the answer to that is yes. Work involving either the brain or the muscles generates oxidizing free radicals, and the glutathione depletion problem in ME/CFS is a systemic problem. The organs that have a complete transsulfuration pathway and can thus convert methionine to cysteine are able to protect themselves better by being able to make glutathione more readily. These include the liver, pancreas, kidneys, intestine, and lens of the eye. They do not include the muscles, and the brain has only a minimal transsulfuration capacity. So I do think this fits pretty well.

As I've posted (probably ad nauseum) before, the solution to this problem is to lift the partial methylation cycle block, which we have found will cause glutathione to rise automatically, in most PWMEs.

Rich

 

[fla]

As I've posted (probably ad nauseum) before, the solution to this problem is to lift the partial methylation cycle block, which we have found will cause glutathione to rise automatically, in most PWMEs.

Being stubborn is a quality not a fault when you're right. Stick with it!

 

[u&iraok]

How about Fermented Payapa:


- FPP Papers on DNA damage and Anti-oxidation -
?Click the titles of the papers, and a new window will open to read the summary.


?Anti-oxidant effect

1). Nutraceutical Supplementation: Effect of a Fermented Papaya Preparation on Redox Status and DNA Damage in Healthy Elderly Individuals and Relationship with GSTM1 Genotype
F. MAROTTA, M. WEKSLER, Y. NAITO, C. YOSHIDA, M. YOSHIOKA, AND P. MARANDOLA,
Ann. N. Y. Acad. Sci. 1067, 400-407 (2006)
The study was conducted on 54 elderly patients without major invalidating diseases for 3 months. The fermented papaya preparation (FPP)-supplemented group showed a decrease in 8-OHdG, which is a marker of lymphocyte DNA damage, and improvement in DNA adduct, which is a marker of cancer-causing risk. Especially a subgroup without GSTM1 gene, under FPP treatment, showed a significant decrease in 8-OHdG and DNA adduct.

2). Oxidative-inflammatory damage in cirrhosis: Effect of vitamin E and a fermented papaya preparation
Francesco Marotta, Chisato Yoshida, R Barreto, Yasuhiro Naito, E Fesce and Lester Packer,
J. Gastroenterol. Hepatol. 22, 697-703 (2007)
The study was conducted on 50 patients with HCV-related cirrhosis for 6 months. The fermented papaya preparation (FPP)-supplemented group showed improvement in GSH?GPx?GSSG?MDA?serum TNF-??lymphocyte 8-OHdG and became close to the concentration level of a healthy person. Cirrhosis patients would develop liver cancer with continuous oxidative stress. The present data seem to suggest a potential supportive role of antioxidants/immunomodulators as FPP in cirrhosis patients.

3). Assessment of the effect of fermented papaya preparation on oxidative damage in spontaneously hypertensive rat brain using electron spin resonance (ESR) imaging and L-band ESR spectroscopy
Fumihiko Yoshino, Masaichi-Chang-il Lee, Kyo Kobayashi, Yuki Hayashi, Okezie I. Aruoma,
Journal of Functional Foods 1 , 375-380 (2009)
We measured free radicals in spontaneously hypertensive rat brain by using electron spin resonance (ESR) imaging and L-band ESR spectroscopy and got a result that FPP-supplemented rats showed quicker elimination of free radicals.

4). Amelioration of Oxidative Stress in Red Blood Cells from Patients with ?-thalassemia Major and Intermedia and E-?-thalassemia Following Administration of a Fermented Papaya Preparation
Eitan Fibach, Ee-Shien Tan, Saumya Jamuar, Ivy Ng, Johnny Amer and Eliezer A. Rachmilewitz,
Phytother. Res. 24, 1334-1338 (2010)
The study was conducted on ?-thalassemia patients, who have genetic defects in blood, for 6 months. FPP treatment increased the content of reduced glutathione (GSH) in red blood cells (RBC), and decreased their reactive oxygen species (ROS) generation. We got the same results in the clinical trials in Israel, Singapore and Thai as well. It seems to suggest that FPP improves the oxidative states in the diseases mediated by oxidative stress such as thalassemia.




?Anti-inflammatory effect

1). Nutraceutical Strategy in Aging Targeting Heat Shock Protein and Inflammatory Profile through Understanding Interleukin-6 Polymorphism
F. MAROTTA, K. KOIKE, A. LORENZETTI, Y. NAITO, F. FAYET, H. SHIMIZU, AND P. MARANDOLA,
Ann. N. Y. Acad. Sci. 1119, 196-202 (2007)
The study was conducted on 40 elderly, generally healthy subjects for 3 months. FPP treatment normalized the inflammatory parameters with a decrease of inflammatory markers such as IL-6 and TNF-? and a rise of protective Heat Shock Protein such as Hsp70.

2). Improved Function of Diabetic Wound-Site Macrophages and Accelerated Wound Closure in Response to Oral Supplementation of a Fermented Papaya Preparation
Eric Collard and Sashwati Roy,
Antioxid. Redox Signal. 13, 599-606 (2010)
Eight weeks of oral FPP supplementation to diabetic(db/db) mice resulted in attenuation in the gain of blood glucose without any effects on body weight gain, including lower LDL, TGL and Total cholesterol levels and an increase in HDL levels. FPP-supplemented mice showed a significant increase in the rate of wound closure and wound angiogenesis. Also, the iNOS and VEGF gene expression were markedly upregulated in the wounds. These results suggest that FPP could activate the macrophage function which is associated with wound closure and accelerate time to recover from the wound.




?Gene Expression

1). Regulating Redox Balance Gene Expression in Healthy Individuals by Nutraceuticals: A Pilot Study
Francesco Marotta, Keiko Koike, Aldo Lorenzetti, Shalini Jain, Paola Signorelli, Yussef Metugriachuk, Pierre Mantello, and Nicola Locorotondo,
Rejuvenat Res. 13, 175-178 (2010)
The study was conducted on 11 healthy, nonsmoking, teetotaler individuals who do not take any vitamins or supplements for 4 weeks. The redox status was assessed by expression level of genes which produce GPx?SOD?hOGG1. At 2-week observation, FPP brought about a significant upregulation of all gene expressions in leucocyte related to immune system, and remained stable during the rest of testing time. This may suggest that FPP can regulate the functions of immune system and anti-oxidant action.




?Reference Review Article

1). Applications and bioefficacy of the functional food supplement fermented papaya preparation.
OI. Aruoma, Y. Hayashi, F. Marotta, P. Mantello, E. Rachmilewitz, L. Montagnier
Toxicology. 2010 Nov 28;278(1):6-16. Epub 2010 Sep 24.
Fermented papaya preparation (FPP) (a product of yeast fermentation of Carica papaya Linn) is a food supplement. Studies in chronic and degenerative disease conditions (such as thalassemia, cirrhosis, diabetes and aging) and performance sports show that FPP favorably modulates immunological, hematological, inflammatory, vascular and oxidative stress damage parameters. Neuroprotective potential evaluated in an Alzheimer's disease cell model showed that the toxicity of the ?-amyloid can be significantly modulated by FPP. Oxidative stress trigger apoptotic pathways such as the c-jun N-terminal kinase (JNK) and p38-mitogen activated protein kinase (MAPK) are preferentially activated by pro-inflammatory cytokines and oxidative stress resulting in cell differentiation and apoptosis. FPP modulated the H?O?-induced ERK, Akt and p38 activation with the reduction of p38 phosphorylation induced by H?O?. FPP reduces the extent of the H?O?-induced DNA damage, an outcome corroborated by similar effects obtained in the benzo[a]pyrene treated cells. No genotoxic effect was observed in experiments with FPP exposed to HepG2 cells nor was FPP toxic to the PC12 cells. Oxidative stress-induced cell damage and inflammation are implicated in a variety of cancers, diabetes, arthritis, cardiovascular dysfunctions, neurodegenerative disorders (such as stroke, Alzheimer's disease, and Parkinson's disease), exercise physiology (including performance sports) and aging. These conditions could potentially benefit from functional nutraceutical/food supplements and fermented papaya preparation) exhibiting anti-inflammatory, antioxidant, immunostimulatory (at the level of the mucus membrane) and induction of antioxidant enzymes.

 

[pamb]

I'm a late arrival to this thread - thanks Marco for pointing it out to me. Interesting stuff. My ME husband sure could fit into those high level cyclists who came down with ME. 'tis all interesting and I look forward to our appt in May with the only ME/CFS specialist in our city of 1 million people. It is a year wait to see him. I hope he will help John sort through the methylation cycle. We tried it on our own a few years back, but it was tough and without guidance he did not stay the course.

But, I could not resist commenting on the similarities to autism. I have been fascinated by Judy M's inference there was some connection and definitely see John has developed autistic tendencies since ME. He is very self absorbed and I guess due to the brain fog, is usually oblivious as to what is going on around him re: social interaction. And this in a guy who had a very successful b-2-b sales career, requiring him to be very tuned in to social interaction. And the little idiosyncratic behaviors and inability to change focus also quite autistic - and totally understandable on a bad brain fog day. It has been very strange indeed.

I've started working with a software company focused on helping autistic kids and the more I learn about autism the more I see the similarities. I did not know before autistic kids have a lot of digestive issues and my boss' kid reacts to food just the way John does now, right down to the rashes if eating the wrong thing. Interesting indeed.