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Novel Associations of F2-Isoprostanes, F3- Isoprostanes and Isofurans in Older Adults with CFS

A.B.

Senior Member
Messages
3,780
Novel Associations of F2-Isoprostanes, F3-Isoprostanes and Isofurans in Older Adults with Chronic Fatigue Syndrome: An Exploratory Study

Plasma levels of F2-isoprostanes (F2-IsoPs), a whole body oxidative stress marker, have been noted to be elevated in populations with chronic fatigue syndrome (CFS). We hypothesized that the oxidative stress biomarkers of F2-isoprostanes (F2-IsoPs), isofurans (IsoFs) and F3-isoprostanes (F3-IsoPs) are related to hypothalamic-pituitary-adrenal (HPA) axis dysregulation in chronic fatigue syndrome (CFS) subjects assessed by plasma dehydroepiandrosterone (DHEA) and cortisol and gene expression of sirtulin-1 (SIRT1). Plasma samples were obtained from nine CFS individuals aged 65 years or older. The mean levels of plasma F2-IsoPs (M=178 pg/ml, SD=100) and IsoFs (M=266 pg/ml, SD=205) were several-fold higher than previously reported in healthy subjects. F2-IsoPs:F3-IsoPs and SIRT1 were negatively associated (r=– .674, p<.05) whereas F3-IsoPs were inversely correlated with DHEA (r=– .586, p<.05) and positively associated with SIRT1 (r=.733, p<.05). After correction for age and sex, the F2-IsoPs:IsoFs ratio was positively correlated to DHEA:cortisol (r=.758, p<.05).The findings indicate that plasma IsoFs and F2-IsoPs are elevated in older subjects with CFS and that isoprostane and isofuran ratios are associated with HPA dysregulation.

https://sciforschenonline.org/journals/clinical-research/article-data/CLROA-1-103/CLROA-1-103.pdf
 

A.B.

Senior Member
Messages
3,780
Would anybody care to translate what that means and it's implications into really simple English?

From the study text and the references one can gather the following:

They're observing elevated markers of oxidative stress in CFS patients. The isoprostanes are considered good markers for oxidative stress.

CFS patients are known to often have HPA axis dysregulation.

A study by a different author has suggested that oxidative stress specifically leads to HPA axis dysregulation.

Therefore they checked whether there was a relationship between these markers of oxidative stress and HPA axis function, and there was.

The authors also found "The exceptionally high levels of IsoFs could be of relevance in view of
elevated IsoFs levels noted in diseases with mitochondrial dysfunction such as Parkinson’s disease [24]."

However, the study was small, used older patients, and there was no control group (they had to use reference published elsewhere), and there were unable to account for some factors that could affect the results (smoking, etc).
 

Research 1st

Severe ME, POTS & MCAS.
Messages
768
Would anybody care to translate what that means and it's implications into really simple English?

Hello, here is your answer, as requested:

This 'CFS' research builds on prior findings, F2 Isoprostanes have been shown elevated before ( there's likely other studies out there).

Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms
'Patients had significantly increased levels of isoprostanes'
Kennedy et al, 2005

Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome.
'F(2)-isoprostanes, however, were consistently higher in CFS patients'.
Robinson et al, 2010.


As it's in older patients, it's even more relevant as this age group are at risk of adverse cardiac/brain events, especially (sadly) as PWME (who are severely affected at least), have to sit still all day, cannot move around, and are thus heart attacks waiting to happen in older life to be quite frank. (Obesity, No exercise, Inflammation = bad news).

Here is why:

F2 isoprostanes are a marker of oxidative stress (free radials that damage cells), and thus associated to many inflammatory states such as infection and autoimmunity.

The long term prospect of high levels of oxidative stress in a human over time, are bad:

*Increased risk of heart attack/stroke and death. Endothelium can get plaque with inflammation, plague blocks arteries and can break away = disaster. One way to test for this is also to test for Oxidised LDL (not just HDL/LDL ratio, but Oxidised LDL) and do a LP- PLA2. LP-PLA-2 test is potentially worth a shot as it shows the actual enzyme released by plaque, not just the theoretical risk because you might have high cholesterol.

*Increased risk of vascular dementia *if associated to evidence of other brain markers (glial cell activation)* also found in PWME.

*Increased risk of cancer. We already know that PWCFS are at increased risk of cancer from a few papers and rare cancers (from Dan Peterson's findings), and more importantly, PWCFS dying online with cancer and this sad news turning up on Facebook and patients forums.

So we have the problem here of metabolic inflammation in ME that is uncontrolled. We all die, from ageing. Our DNA gets damaged, our organs get damaged (over a life time) and then the organs fail. It's luck if we grow old, if we don't get spectacular failures (stroke, heart attack), even if we are healthy! Life is itself a lottery and chronic ill health with infection/autoimmunity will reduce life expectancy.e.g. even something perceived to be harmless to cardiac health (like rheumatoid arthritis) reduces life span, as of course, it's associated to inflammation! Inflammation is a huge killer. Diabetes, for example, is associated to inflammation, via Cytokines. (Cytokines are very high in severe ME and Lyme or Lyme Like illness (Chronic Lyme).

Some attempts can be made to reduce inflammation but you can't reverse it to normal in active untreated disease:
We can reduce effects of oxidative stress in health, by eating healthy (Mediterranean diet), not becoming obese (easier said than done in ME) and by avoiding exposure to lifestyles that are known to increased free radical attack (smoking!). Unfortunately, being chronically ill, with low grade inflammation for decades, is going to effect your longevity even if you do everything you should. No one can argue about this as ME is clearly a chronic disease state. What matters is luck, and some genetic factors (family history) that determine how bad your oxidative stress damage is, and what happens to you because of this. Yet again. life is a lottery in terms of longevity. You can get a 90yr old who smokes since a teenager, and a 35yr old dying from smoking related disease. You can have severe ME patients who are 50 and severe ME patients who are dead in their 30's. Genes and luck.


Ageing via DNA damage, happens to us all, but we can accelerate it, through excessive exercise. Why is this relevant to us? A significant problem for severe ME, is they can have levels of oxidative stress when not exercising, than people who are healthy, who do exercise. Think about that for a second. Some with severe ME are going through the same metabolic damage, as someone who exercises in a short burst, when laying in bed! Long term, not short term, but long term, this is very bad for you.

You can reduce this damage, a little, by checking all your nutrient levels (Significant vitamin deficiency increases rates of oxidative stress and thus cellular ageing). Thus, you could be unwittingly damaging your body (as I was), without knowing and presuming it's all bad. This situation isn't good (no treatment exists for ME), but it can be helped with the right approach. E.g. never smoke with ME, reduce all forms of psychological stress when possible, sleep as well as possible, and maximise your nutritional levels.

High levels of oxidative stress damage, proven via testing, (when sitting still and not exercising) is 'evidence' your are experiencing excessive metabolic inflammation, at rest: You can test for oxidative stress markers in urine, mine is very high at rest. There are many markers, not just F2 Isoprostanes. I always test over time, and keep testing, keep recording.

Lastly, imagine what is happening to your brain during all this, long term, free radical damage. This is an unfortunate truth no one wants to consider who denies a Myalgic Encephalopathy, or an actual low grade encephalitis (as the Japanese neuroimaging study potentially shows and Dr Komaroff (Harvard) has confirmed would confirm Myalgic Encephalomyelitis is thus a correct term after all).

I hope that helps.
 

Snowdrop

Rebel without a biscuit
Messages
2,933
Thanks for that reply @Research 1st . I'll have to read it a few times to take it in.
I do have one question so far: Is vascular dementia different from senile dementia or Alzheimer's? If so how does it differ in terms of expression.