Recent scientific article

Discussion in 'Fibromyalgia Main Forum' started by znewby, May 26, 2009.

  1. znewby

    znewby Member

    Posted May 14, 2009 at Heirs international research blog

    You may be wondering what chronic fatigue syndrome, fibromyalgia and Mediterranean-style soup have in common. I hope after reading the following studies this will be more clear…..

    The first study I would like to note is a very recent study on CFS. According to the researcher’s findings he demonstrates,

    “Patients with CFS do not have altered plasma levels of IL-6, sIL-6R or sgp130 either at rest or following exercise. F(2)-isoprostanes, however, were consistently higher in CFS patients.” (Robinson)

    The second study was published last year and was performed to determine different biological markers in fibromyalgia. According to the abstract of the published article the researchers found,

    “Fibromyalgia has a genetic component and that MCP-1 and eotaxin (a major regulator of allergic reactions – Guitierrez-Ramos) may contribute to their symptoms and were also raised in their family members. In addition, the author notes that myoblasts can secrete MCP-1, eotaxin and IP-10. IP-10 is a chemokine produced in response to interferon-gamma. (Wipedia) They concluded that fibromyalgia has direct effects on the migration of eosinophils and monocytes in the presence of mast cells and skeletal muscle may secrete it.” (Zhang)

    Taking these two studies into account, let us now review some of the research information that we have discussed about MCP-1. Last week we explained that activation of the MCP-1/CCL2/CCR2 pathway inhibits insulin-stimulated glucose uptake as well as the expression of different genes including those for GLUT4 and PPAR-gamma and can be initiated by TNF-a. In addition, it also has a role in peripheral neuropathic pain by increasing sensitivity and inducing hyperalgesia. Eotaxin has been identified as a mediator of allergic reaction in several different organ systems. Diesel exhaust and its particles have been shown to upregulate eotaxin. For this reason and because of the findings above, particulate matter becomes a concern for individuals with fibromyalgia. (Takizawa)

    Next let us review the press release that explains how:

    “brain cells called microglia to produce CCL2, a chemical that attracts monocytes. When the researchers blocked CCL2 signaling, monocytes did not enter the brain despite ongoing inflammation in the liver. Liver inflammation also stimulated cells in the blood to make an immune chemical (TNF?). When the researchers blocked the signaling of this immune chemical, microglia produced less CCL2, and monocytes stayed out of the brain. In the mice with inflamed livers, preventing the entry of monocytes into the brain reduced sickness behaviors; mice showed more mobility and social interaction.”

    In patients with chronic inflammation, the researcher commented, sickness behaviors severely impact quality of life. The recent studies that show that MCP-1 is elevated in fibromyalgia and the above studies provide evidence for the symptoms associated with fibromyalgia including skeletal muscle ache, fatigue, sleep disorders, headache, etc.

    As for the study that found elevated levels of F2-isoprostane in chronic fatigue syndrome. This is interesting because it provides evidence that CFS is a condition caused by oxidative stress from lipid peroxidation. F2-isoprostance are formed from catalyzed products of arachidonic acid and is now considered to be a marker for lipid peroxidation, are inflammatory mediators which augments (increase) the perception of pain. (Wipedia) Arachidonic acid also causes an increase in vascular permeability which depends on the formation of free radicals and lipid peroxidation. (Easton) Incidentally, F2-isoprostanes are also found to be elevated in people who smoke. (Morrow) This makes sense since many people who have been diagnosed with CFS have commented on their sensitivity to smoke. According to one researcher,

    “Measurement of F(2)-IsoPs (F2-isoprostance) is the most reliable approach to assess oxidative stress status in vivo, providing an important tool to explore the role of oxidative stress in the pathogenesis of human disease. Moreover, F(2)-IsoPs and other products of the IsoP pathway exert potent biological actions both via receptor-dependent and independent mechanisms and therefore may be pathophysiological mediators of disease. Measurement of F(2)-IsoPs may provide a uniquely valuable approach to understanding of the clinical pharmacology of antioxidants.” (Montuchi)

    At this point, I need to draw your attention to a press release of discoveries made in Gulf War Syndrome (GWS). Recently a press release was made that found that brain function problems in GWS may stem from chemical exposure. In this press release the leader of the research team was quoted as saying about these patients,

    “What we found was that some of the brain areas we previously suspected responded abnormally to the cholinergic challenge. Those areas were in the basal ganglia, hippocampus, thalamus and the amygdala.” (

    In addition, he goes on to say,

    “Changes in functioning of these brain structures can certainly cause problems with concentration and memory, body pain, fatigue, abnormal emotional responses and personality changes that we commonly see in ill Gulf War veterans.” (

    If one scrutinizes the changes that occur in GWS and those that occur from sickness syndrome and others in CFS and fibromyalgia they seem quite similar. Several studies have demonstrated in the past that these conditions often occur together. PON1 is an enzyme synthesized by the liver and polymorphisms have been implicated as having a causal role in the development of GWS. In the report, Gulf War Illness and the Health of Gulf War Veterans – Scientific Findings and Recommendations (GHGW), it explains on page 251 that the amounts of PON1 production in individuals differ and as a result these individuals may be more or less able to neutralize toxic compounds. “Five of six studies identified significant PON1 differences that were associated with Gulf War Illness or, more generally, with Gulf War service. However, specific findings have varied according to the experimental questions raised and it has been concluded more investigation is needed before the exact nature of a link between PON1-GWS can be determined.” In addition, the report mentions the incidence levels of ALS and Parkinson’s is higher in those with gene varients of PON1. Another study has demonstrated PON1 has a protective effect against inflammation, PPAR-delta and fibrosis and (Judit) a decrease in PON1 gene expression is accompanied by an increase in MCP-1 which is the same pathway that causes symptoms and could be used as an immunological marker for fibromyalgia.

    The CCL2/MCP-1 pathway has also been shown to have an effect on brain structures. It has now been suggested its activity may have an impact on cholinergic and dopaminergic transmission and related disorders. (Banisadr) While these findings do not exclude other genetic vulnerabilities, the effects on dopaminergic transmission may help to explain the high incidence of Parkinson’s disease after certain environmental exposures. Pyridostygmine potentiated by stress has also been implicated in GWS. One study has shown the effects are not mediated by passage of the chemicals through an opening in the blood brain barrier but that it exerts its influence through a peripheral pathway. Tnf-a and other inflammatory mediators are produced as part of the stress response and as we mentioned above Tnf-a does activate the CCL2/MCP-1 pathway. In other blogs we have described how microglia can initiate neuroinflammation. Dr. Blaylock describes the fact that peripheral immune stimulation has been shown to activate CNS microglia which could explain neurodegeneration and cognitive defects associated with GWS.

    As promised, I am now going to discuss why I mentioned Mediterannean Soup in the title of this blog. If you are a regular reader of the HEIRS Blog, you know that I believe nutrition is extremely beneficial in controlling some of the symptoms related to environmental illness. In addition, I have suffered from several conditions that are included under the umbrella environmental illness for years and so have several members of my family and it appears some of my ancestors. When one studies food and nutrition in-depth they learn alot about how diets effect physiology and also about the culture of diets. In many populations, food is considered medicinal and I, like my grandmother who was also my mentor believed this to be true. My beliefs parallel the hormetic response of food which Mattson defines as an adaptive ability for food compounds such as phytonutrients etc. to generate favorable responses” and alter genetic expression (or cell signaling) even though the compounds may be considered toxins or environmental stressors at higher levels.(Mattson) Scientists have believed for quite some time there is a link between illness and diet change and it is now accepted that more health problems occur where an individual’s food intake leads them father away from their ancestral or paleo-diet.

    In relation to the environmental illnesses I speak about most, I also have provided research on the nutritional benefits of food. I have posted several blogs on the health benefits of the Mediterranean Diet and if you have read a nutritional magazine, have watched a recent news or newspaper report on benefitcial diets, they all say the same thing…. that following a Mediterranean Diet is good for you. The Mediterranean Diet consists of the consumption of a lot of vegetables, fruits, breads, nuts, beans, seeds, olive oil, etc. (American Heart Association) The reason that I mentioned Mediterranean Soup (MS) is that I recently found a study in which participants were given MS consisting of tomatoes, peppers, cucumbers, etc. (YUM!) In this study, researchers set out to determine the availability of vitamin C and its effect on inflammatory markers from the ingestion of the soup. The researcher’s concluded at the end of the study that MS increases plasma concentrations of vitamin C and significantly decreases F2-isoprostanes, prostaglandin E and also MCP-1.

    As you now know, two of these markers F2-isoprostanes and MCP-1 are markers found in studies on patients with CFS, Gulf War Syndrome or fibromyalgia. One author says under normal or oxidative stress conditions intracellular stores of vitamin C may be lower but certain levels are necessary to attenuate F2-isoprostane and MCP-1 production when cells are exposed to oxidative stress. (Loke) This study may suggest that by supplying vitamin C, the soup has an effect on the production of both F2-isoprostanes and MCP-1 both of which can stimulate Tnf-a (Timmerman) and therefore are important when exploring causal influences on inflammatory processes in environmental illness. Because MS has shown reductions in both of these inflammatory mediators it may have a positive influence on symptoms related to fibromyalgia, CFS, and GWS although no studies would imply this presently. In addition, previous studies have shown that catechins have an inhibitory effect on the formation of arachidonic acid. (Neiva) Catechins and procyanidins are flavonoids that have shown protective effects against heart disease and other health conditions. Traditional foods associated with the Mediterranean diet contain alot of them and incidentally, they activate the Nrf2 pathway.

    Lastly, just in case your wondering I have tried a tried Mediterranean soup recipe — and it is pretty tasty. Personally, I added more tomatoes and more herbs because of their nutritional and anti-inflammatory value and properties according to many research studies that have been published.


    Nrf2 is a regulator of antioxidant proteins and paraoxonases are antioxidant proteins which would suggest that Nrf2 can regulate their expression. This assumption is supported by the fact that resveratrol induces the induction of the PON1 gene (Gouedard) and also increases the level of Nrf2 and induces its translocation to the nucleus. (Rubiola)
    MCP-1 contributes to macrophage infiltration in adipose tissue, insulin resistance and liver steatosis in obesity. (MedNews Today)
    There is interaction between MCP-1 and CCR2 that effect monocyte adhesion in TNF-a activated pulmonary artery endothelium after shear stress. (Maus) One author describes shear stress as the dragging force created by blood flow and is important because it stimulates vasoactive processes that can regulate and change gene expression. (Maus)
    In past blogs, we have discussed how controlling insulin and glucose levels may be of benefit for environmental illness. In addition, we have also noted that endotoxin is now considered a pathway for CFS. It has been demonstrated that inflammatory mediators Tnf-a and Il-6 increase dramatically when insulin is administered with endotoxin and the the former may increase inflammation in the central nervous system and elevates oxidative stress. (Fishel)
    Insulin can positively modulate norepinephrine in the brain and other proteins which can in turn down-regulate the inflammatory cascade. (Fishel)
  2. znewby

    znewby Member

    Just thought it might be of interest to a few who do.
  3. AuntTammie

    AuntTammie New Member

    all I got out of it is that vit c could be helpful to us, and that Mediterranean soup can supply vit c....of course, the author did also recommend adding extra tomatoes, which for many can be problematic (nightshade can cause more pain)....other than that, though, it might as well have been written in another language....and I am usually pretty good at figuring out medical text
  4. sweetbeatlvr

    sweetbeatlvr New Member

    (in a small, small nutshell, as that is all i'm capable of producing =) )...

    there has been research that shows that some biological markers have been found in people with CFS, FM, and GWS.

    two of these markers are F2 isoprostanes and MCP-1.

    supposedly, following a Mediterranean style diet (alot of vegetables, fruits, breads, nuts, beans, seeds, olive oil, etc (from American Heart Association))... can significantly decrease F2 isoprostanes and MCP-1, in turn, lessening symptoms.

    sounds interesting, especially the part of the genetic markers they found in these studies for those with these illnesses.

    hope this helps.
  5. kjfms

    kjfms Member

    I found this to be a very interesting article.

    Thanks for posting it.