Wine Compound Improves Symptom of CFS - Study

Wine Compound Improves Symptom of CFS - Study

National CFIDS Foundation Announces Link between CFS and Low Level Radiation

Radon exposure is probably the most prevalent source of low level radiation while far infrared therapy may be another source.

"The National CFIDS Foundation Inc., of Needham Mass, has announced its formal disease model for Chronic Fatigue Syndrome (CFS) also known as Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) as well as Myalgic Encephalomyelitis (ME). According to the NCF, a subgroup of patients with CFS fit a unique disease profile based on a model for a radioactive toxin"

Read more: National CFIDS Foundation (NCF) Announces Link between Chronic Fatigue Syndrome and Low Level... -- NEEDHAM, Mass., Aug. 20 /PRNewswire-USNewswire/ --:

New Research on Viral Cause & Successful Treatment of Chronic Fatigue Syndrome

"This study provides compelling evidence for the role of herpesviruses in chronic fatigue syndrome and also for treatment with anti-viral medications that target herpesviruses. Many doctors don't test for EBV, HHV6 and CMV, so you may want to alert your doctor to these findings."

New Research on Viral Cause & Successful Treatment of Chronic Fatigue Syndrome:

SNP in Gene Associated W/ Autism Present in CFS, Study Says!

DISC1 Ser704Cys might be a functional variant that affects one of the mechanisms implicated in the biology of CFS.

"Fukuda, S., Hashimoto, R., Ohi, K., Yamaguti, K., Nakatomi, Y., Yasuda, Y., Kamino, K., Takeda, M., Tajima, S., Kuratsune, H., Nishizawa, Y., and Watanabe, Y. (2010). A functional polymorphism in the disrupted-in schizophrenia 1 gene is associated with chronic fatigue syndrome. Life sciences."

CiteULike: A functional polymorphism in the Disrupted-in schizophrenia 1 gene is associated with chronic fatigue syndrome.:

Glutamine Synthetase, PFOS and Neurotransmission

PFC are chemicals that are ubiquitous in the environmental and can or could be found in products including building materials, fabrics, packaging, clothing, protective gear etc. Recent studies show that these chemicals have the capacity to regulate or impair gene expression including those that regulate the excretion of toxic waste products that may result in alterations of neurotransmission and contribute to their toxicity. In addition, genetic problems may aggravate this inhibition and augment the physical consequences of exposure. Glutamine synthetase is one enzyme that is important for regulation of toxins such as ammonia in the brain as well as production of glutathione. In addition, certain conditions, such as in endotoxemia and implicated as a causal factor is CFS, the activity of this enzyme is further reduced. Nrf2 is protective against PFOS through the generation of HO-1 and reductions in its production may augment oxidative stress damage from PFOS.


Yang, X., Wang, L., Sun, W., and Xue, Z. (2009). [effects of perfluorooctane sulfonate on amino acid neurotransmitters and glutamine synthetase in rats]. Wei sheng yan jiu = Journal of hygiene research, 38(1):19-21. http://www.citeulike.org/user/HEIRS/article/6999108
Häussinger, D. and Schliess, F. (2007). Glutamine metabolism and signaling in the liver. Frontiers in Bioscience, 12:371-391.
http://www.citeulike.org/user/HEIRS/article/7208003
Shi, X. and Zhou, B. (2010). The role of nrf2 and mapk pathways in pfos-induced oxidative stress in zebrafish embryos. Toxicol. Sci., 115(2):391-400.
http://www.citeulike.org/user/HEIRS/article/6761678

Il-6 Modulates CRF in the Hypothalamus in Response to Different Signals.

Module: 5/22/2010

Background: CRF can regulate signaling in response to different odors. In those cases, it can lead to an anxiolytic or elevation and other responses typical of the stress response including pain generation, immune regulation, itch, rash and other changes such as gastric function alterations. Of course, these are symptoms characteristic of chemical sensitivity and also some symptoms characteristic of other environmentally influenced conditions such as CFS and sickness syndrome.

A major regulator of sickness syndrome is Il-6 which can be functionally modulated through Il-10 and ultimately most probably HO-1 which has been shown in other studies to increase during exercise. Interestingly, one can identify similarities in cancer-related fatigue to some chronic symptoms of CFS and sickness syndrome including the exhausting fatigue and cachexia that is exhibited in the latter, in animals and humans. Preliminary studies suggest cytokine Il-6/Il-8 may modulate the severity of cancer-related fatigue and others show cancer-related fatigue is common with serotonin dysregulation. Coincidentally, in the trout corticotrophin activation by ammonia is associated with alterations in neurotransmitter levels including dopamine and serotonin. So here again, we see potential especially with periods of aberrant corticotrophin signalling, where symptoms of environmental illness such as anxiety, depression, weakeness and fatigue may present itself. These findings supports past studies that suggest that fatigue in CFS may be in part due to serotonin dysregulation and elevations in Il-6.(Ryan)

CiteULike: Transcriptional regulation of hypothalamic corticotropin-releasing factor gene.: "Glucocorticoid-dependent repression of cAMP-stimulated CRF promoter activity is mediated by both nGRE and SRE in hypothalamic cells. Interleukin (IL)-6 produced in the hypothalamus stimulates the CRF gene. Suppressor of cytokine signaling-3, which is induced by a cAMP stimulant and IL-6, is involved in the negative regulation of CRF gene expression in hypothalamic cells. Such complex mechanisms would contribute to stress responses and homeostasis in the hypothalamus."

Related: Hummel, M., Cummons, T., Lu, P., Mark, L., Harrison, J. E., Kennedy, J. D., and Whiteside, G. T. (2010). Pain is a salient ßtressor" that is mediated by corticotropin- releasing factor-1 receptors. Neuropharmacology.
http://www.citeulike.org/user/HEIRS/article/7177466
Coric, V., Feldman, H. H., Oren, D. A., Shekhar, A., Pultz, J., Dockens, R. C., Wu, X., Gentile, K. A., Huang, S.-P. P., Emison, E., Delmonte, T., D'Souza, B. B., Zimbroff, D. L., Grebb, J. A., Goddard, A. W., and Stock, E. G. (2010). Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder. Depression and anxiety, 27(5):417-425.
http://www.citeulike.org/user/HEIRS/article/7193107
Theoharides, T. C., Singh, Boucher, W., Pang, X., Letourneau, R., Webster, E., and Chrousos, G. (1998). Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. Endocrinology, 139(1):403-413.
http://www.citeulike.org/user/HEIRS/article/7207688
Mustian, K. M., Fisher, S., Adams, J., Janelsins, M., Palesh, O., Darling, T., Peppone, L., Heckler, C., Williams, J., and Morrow, G. (2009). Cytokine-mediated changes associated with improvements in cancer-related fatigue induced by exercise: Results from a randomized pilot study of cancer patients receiving radiotherapy. Journal of Clinical Oncology, 27(15s).
http://www.citeulike.org/user/HEIRS/article/7207720
Ryan, J. L., Carroll, J. K., Ryan, E. P., Mustian, K. M., Fiscell, K., and Morrow, G. R. (2007). Mechanisms of cancer-related fatigue. The Oncologist, 12(1 supp):22-34.
http://www.citeulike.org/user/HEIRS/article/7207823

Dark Chocolate for Fibromyalgia & Chronic Fatigue Syndrome

Dark Chocolate for Fibromyalgia & Chronic Fatigue Syndrome: "Dark Chocolate for Fibromyalgia & Chronic Fatigue Syndrome"

The Not So FINE Trial Study for CFS.

A million and a half dollars, two hundred fifty patients and seven years later the UK government's best hope for locking in its twisted approach to ME/CFS permanently, fell to earth with a crash.

Chronic Fatigue Syndrome (ME/CFS) News From Phoenix Rising - FINE: "A million and a half dollars, two hundred fifty patients and seven years later the UK government's best hope for locking in its twisted approach to ME/CFS permanently, fell to earth with a crash."

Thought for the Day: Hyperammonemia and Environmental Illness...

Does anyone see these as being familiar symptoms? To me, they seem like some common symptoms in CFS or exposures????

The symptoms and blood ammonia values of mild to moderate chronic hyperammemia (CH) are similar to those observed during physical exhaustion with ‘exercise-induced hyperammonemia’ (EIH). These include confusion, hyperventilation, and muscular dysfunction.....Treatments for lowering CH and EIH are similar, and include: 1) restriction of dietary
protein, 2) increasing carbohydrate (%) intake, 3) administration of amino acids (AA’s)that enhance ammonia clearance into (the less toxic) urea, and 4) correction of the underlying metabolic etiology

HEIRS Library Tags: Hyperammonemia
Blog Tags: Hyperammonemia, ammonia

Edwards, W. ARM CRANK POWER AND HYPERAMMONEMIA IN RESPONSE TO L-ASPARTIC ACID SUPPLEMENTATION. PhD thesis, Louisiana State University.
http://www.citeulike.org/user/HEIRS/article/7111333

Preliminary Study Shows Polymorphism in Different Loci of Autism/Aspberger's Gene in Chronic Fatigue Syndrome.

Preliminary Study Shows Polymorphism in Different Loci of Autism/Aspberger's Gene in Chronic Fatigue Syndrome.

A preliminary study suggests that a polymorphism in the DISC1 gene is associated with chronic fatigue syndrome. These findings, if found to be true, have important implications for the conditon, as well as, may have an influence on research findings of other environmental illnesses. DISC1 is also known as Disrupted in Schizophrenia and has been associated with a number of mental health conditions including schizophrenia, bipolar disorder and major depression. Just recently the gene has also been implicated in playing a role, in addition to other genes, in autism. We have noted before that some experts believe that conditions such as ADHD and certain types of MCS are in fact, autism spectrum disorders. As one author points out, DISC1 is responsible for a number of physiological activities including the production of new neurons during brain development and adult neurogenesis. A defective DISC1 gene which has been demonstrated in schizophrenia could lead to a reduction in dendritic spines and also influence nerve cells to maintain weaker connections with neighboring neurons and for the purpose of simplification, reduce the "cross-talk" between neurons by influencing dopamine production. If similar disruptions through mutation in DISC1 were to occur, it does make sense it may be involved in the development of autism because of its effect on the central nervous system. (Tsai)


Of course, the idea that it plays a role in chronic fatigue syndrome is a novel finding. From my standpoint, the idea that DISC1 may play a role in CFS makes a lot of sense. As I have described in other blogs, a protein called GSK-3b is an on/off switch for Nrf2 which provides a protective role against endogenous threats that may negatively influence neurotransmission  in autism. Recently, it was demonstrated that the Wnt pathway is a pathway involved in ammonia and urea excretion that also involves the activities of GSK-3b. Biochemically, one researcher writes that DISC1 inhibits GSK-3b and therefore, this pathway has been suggested to play the important role in a number of mood disorders which we noted earlier. Like most anything in cell biology, too much activity or too little can have dramatic effects on function. In the case of GSK-3b, blocking its abherrant signaling has been associated with symptomatic benefits in MS, colitis, sepsis and arthritis and conditions involving inflammation. The latter implicates an inhibitory role of GSK-3b signaling on Nrf2. Elevations of GSK-3b activity are also present in patients with Parkinson's disease and Alzheimer's. A recent report from MIT demostrates that DISC1 knock-out present with behaviors including hyperactivity, a characteristic of schizophrenia and GSK-3b inhibitors reversed these behaviors. The author suggests that the scewed balance of neural cell development and alterations in signaling may lead to compromised cognition and behavior alterations. (Halber) A polymorphism in DISC1 that has been suggested in CFS could very well lead to abherrant signaling from GSK-3b, elevations in oxidative stress and uncontrolled expression of inflammatory proteins and changes in redox because of subsequent loss of Nrf2 signaling. Of course, other factors such as genetic SNPs in Nrf2 and suppression of gene expression should also be considered.

Citations and Original Document

Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome.

In CFS, cytokine activity may vary directly with SF, which may explain prior inconsistent findings.

CiteULike: Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome.: "White, A. T., Light, A. R., Hughen, R. W., Bateman, L., Martins, T. B., Hill, H. R., and Light, K. C. (2010). Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome. Psychophysiology."

Ammonia, ASIC Channels and Mental Health

We recently have been discussing how the biological accumulation of ammonia may be an important condition related to a number of environmental illnesses. In fact, several studies suggest that accumulation of ammonia may contribute to autism and others note it plays a very important role in hepatic failure. As we noted, elevated levels of homocysteinemia may impair the urea cycle - which helps the body get rid of excess ammonia and glutamine synthetase genes of the Wnt/Catenin pathway, also regulate  ammonia concentrations in the body. Interestingly, several "so-called therapies" for MCS also have the capacity to reduce ammonia. Also, it is well-known that psychological disturbances are co-morbid with a number of environmental conditions, in addition to those mental effects associated with autism and liver disease.

In light of the potential for elevated ammonia levels to influence the psychological and physical effects of environmental disease, I thought I would point out two interesting studies. The first is a study that suggests that ASIC channels contribute to the health consequences where hyperammonemia becomes an issue. As the author points out, this may include hepatic encephalopathy, cirrhosis and neuronal disorders. This study discusses how these types of channels have been implicated in neuronal death after their activation. Incidentally, nociceptive behavior is associated with acidic environments that develop from injury and inflammation and therefore could play a role in the pain generation in environmental illnesses including  MCS (Pall) and chronic fatigue syndrome (Light).  Pidoplichko provides evidence the involvement of these channels may contribute to the loss of dopamine neurons in Parkinson's disease because these channels are associated with those neurons and "ammonium sensitivity is a widely distributed ASIC characteristic in the CNS, including the hippocampus." The second study seems to suggest that these same channels have an important role in the development of depression-related behavior by demonstrating genetically altered -/- mice presented with anti-depressant-like behaviors even while put under experiemental stress. In addition, the dysruption of these channels interfered with an important "biomarker of depression" which is a decrease of levels of BDNF in the hippocampus. In past blogs, we have explained how BDNF is important for "olfactory neurogenesis" and may be important consideration in the development of MCS.  Coryell concludes by saying that his "findings of ASIC1 signaling in the amydala in mood regulation support others and that pharmaceutical approaches that target ASIC1 signaling may be therapeutic for this kind of depression. We might propose that investigating therapies that reduce ASIC signaling may be beneficial for a number of environmentally-related conditions may be of value.

Notes:

• A recent study shows that HO-1 activates bilirubin and CO to modulate BDNF/GDNF in neurons and astrocytes. This provides a protective effect on dopaminergic neurons.

Coryell, M. W., Wunsch, A. M., Haenfler, J. M., Allen, J. E., Schnizler, M., Ziemann, A. E., Cook, M. N., Dunning, J. P., Price, M. P., Rainier, J. D., Liu, Z., Light, A. R., Langbehn, D. R., and Wemmie, J. A. (2009). Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior. J. Neurosci., 29(17):5381-5388. http://www.citeulike.org/user/HEIRS/article/6607146
Pidoplichko, V. I. and Dani, J. A. (2006). Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage. Proceedings of the National Academy of Sciences of the United States of America, 103(30):11376-11380. http://www.citeulike.org/user/HEIRS/article/6607127
Light, A. R., White, A. T., Hughen, R. W., and Light, K. C. (2009). Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. The journal of pain : official journal of the American Pain Society. http://www.citeulike.org/user/HEIRS/article/5370052
Ugawa, S., Ueda, T., Ishida, Y., Nishigaki, M., Shibata, Y., and Shimada, S. (2002). Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors. The Journal of clinical investigation, 110(8):1185-1190. http://www.citeulike.org/user/HEIRS/article/2942104
Pall, Martin (2007). Explaining Ünexplained Illnesses": disease paradigm for chronic fatigue syndrome, multiple chemical sensitivity, fibromyalgia, post-traumatic syndrome, Gulf War syndrome, and others. Harrington Park Press:Hawthorne Press, 10 Alice Street Binghampton NY 13904. http://www.citeulike.org/user/HEIRS/article/3042479
Hung, S.-Y. Y., Liou, H.-C. C., and Fu, W.-M. M. (2010). The mechanism of heme oxygenase-1 action involved in the enhancement of neurotrophic factor expression. Neuropharmacology, 58(2):321-329. http://www.citeulike.org/user/HEIRS/article/6196852

Neuroinflammation,Diabetes and GSK-3b in Environmental Illnesses

Background: In other blogs, we have described how different proteins interact in molecular pathways to achieve specific metabolic processes. Most often we focus on the Nrf2-PGC-1a-SIRT1 pathway because activation or non-activation will effect cell survival. Recently, we spent quite a bit of time discussing the importance of PGC-1a for metabolic homeostasis and energy metabolism. Friedrich's ataxia is a neurodegenerative conditions that strikes early in life and have used FA as an example for comparison of complications of diseases that arise from Nrf2 dysfunction. Newer studies show that some of the complications in FA arise from dysregulation of PPAR-gamma and PGC-1a and symptoms associated with this dysfunction includes insulin resistance, cardiomyopathy and diabetes. Generally, dysregulation of the PPAR-gamma pathway which is anti-inflammatory leads to abherrant signaling from NF-kappaB. NF-kappaB increases mediation of inflammatory cytokines and in addition to inflammation and other health-related consequences, overexpression of NF-kappaB may alter drug metabolism including CYP3A4 which is responsible for the detoxification of over 50% of the drugs currently marketed.


Some of the most severe complications of environmental illnesses occur from neuroinflammation from inflammatory signals initiated through TLR and NF-kappaB. Under normal conditions, a number of different proteins interact to provide protective mechanisms to prevent inhibition of cellular function. It has been shown that GSK-3b overactivation is a major contributor to neuroinflammation through its role in the disruption of the blood brain barrier (Ramirez) and is at least in part, responsible for complications of a number of neurodegenerative diseases including PD. The activation of GSK-3 increases the production of a number of cytokines including IL-6 and inhibits IL-10. Both PPAR-gamma and another anti-inflammatory Il-10 that modulates sickness syndrome cytokines can inhibit GSK-3b. The over expression of the latter using a kind of "feedback mechanism". In addition to preventing neuroinflammation, GSK-3b inhibition also stabilizes PGC-1a and important regulator of normal mitochondrial biogenesis and energy metabolism. Other studies have showed that GSK-3b also inhibits glycogen synthase that regulates long term energy storage and may account for some of the weight problems reported in those with EI. This hormone is also inhibited by epinephrine and therefore, one may suggest that stress and overactive expression of GSK-3b may potentiate the effects of each other and further exacerbate complications of energy metabolism. In addition, this protein has been implicated as a factor contributing to a number of what are suspected to be neural inflammation-induced mental health conditions including autism, bipolar disorder, other mood disorders, Alzheimer's disease and others.  Incidentally, studies have demonstrated that both endotoxin may influence the activation of GSK-3b. Endotoxin has been implicated as a factor in environmental illness including chronic fatigue syndrome and it has been shown that endotoxin infection-induced GSK-3b by Tnf-a leads to a "synergistic effect" of increasing nitric oxide and reduction of IL-10 while promoting IL-6. GSK-3b, although a necessary protein, has potential for being a therapeutic target for a number of health conditions, including several that are under the "umbrella" of environmental illness. Several months ago we blogged about the evolutionary development of IGF-1 and its relationship to the olfactory system as well as DAF-16 and SKN-1 in lower organisms. Heavy metals may inhibit IGF-1 during the methionine cycle and is a common constituent of air pollution and particulate matter. Bondy explains how IGF-1 has an inhibitory effect on GSK-3b and has direct effects on neural growth and survival during brain development. She further explains how GSK-3b contributes to the loss of olfactory and dentate neurons when IGF-1 is underexpressed which may be important considering that environmental illnesses often present with loss of olfactory function and /or dysregulation.(Bondy) On the other hand , reductions in IGF-1 expression promote longer lifespans and reduce effects of endotoxemia while abherrant IGF-1 signaling may contribute to neuropathic pain, especially in diabetes. (Pabbidi) During nerve injury {ie lead (Williams), low-level toluene(Fujimata)}, NGF (Nicols) can activate both GSK-3b and nociceptors generating inflammatory pain.(Gould) Nociceptive behaviors have been implicated in MCS. (Pall)

Notes:

• EGCG, a compound in green tea, can suppress neurotoxicity by inhibiting GSK-3b.
• Exercise may positive influence the expression of glycogen synthase by inhibiting GSK-3b in skeletal muscle.
• Aging influences increased expression of GSK-3b. (Mercado-Gomez)

For Further Reading:

• GSK-3beta inhibition/beta-catenin stabilization in ventral midbrain precursors increases differentiation into dopamine neurons
• Promoters & Inhibitors of the Metabolic & Antioxidative Pathway of PGC-1a and Its Role in Environmental Illness

Original article and citations located here.

Sleepiness in CFS and Fibromyalgia May Be a Form of Narcolepsy!

In our recent blog discussed how orexin(hypocretin) effects sleep patterns and may have an important role in CFS and sickness syndrome. A new study using a pharmaceutical called sodium oxybate showed significant improvement in patients in fatigue with both chronic fatigue syndrome and fibromyalgia and point to the "real possibility" that sleep problems in these conditions are similar to narcolepsy. In addition, the study suggests, even though further study is warranted that both CFS and FM are similar or not the same condition because of the improvements seen in patients with them.  We have noted similarities to sickness syndrome in these conditions and have emphasized that sickness syndrome also occurs in animals and importantly, narcolepsy also is not exclusive to humans and in often seen in dogs. Some breeds more commonly than others.

Other recent discoveries indicate that the major pathophysiology of human narcolepsy "is the loss of lateral hypothalamic neurons that produce the neuropeptide hypocretin (orexin). Approximately 90% of people diagnosed as having narcolepsy with cataplexy are hypocretin ligand deficient." Narcolepsy is thought to be an autoimmune related disorder and can alter regulation of cortisol and influence steroid production which also may initiate panic.  In our recent blog, we wrote how streptococcus pneumoniae may be an important trigger of orexin-influenced narcoleptic sleep behavior. This is important because this pathogen effects the severity of H1N1 and may mean that patients with EI may be more susceptible to both. Parkinsonism is also associated with alterations in hypocretin and future therapies in PD may involve treatments involving orexin. Some suggest that narcolepsy and Parkinson's disease have a common and therefore, one must begin to hypothesize that CFS and fibromyalgia may have the same or similar causal factors as PD and and narcolepsy.

For Further Reading About Orexins in CFS, Sickness Syndrome and Fibromyalgia, see

• How Changes in Neurons May Lead to Altered Cortisol in CFS/ME & Sickness Syndrome. HEIRS, January 1, 2010.
• Hormone Linked to Panic Attacks Also Linked to Endotoxin and Sickness Behavior

Spitzer, A. R. and Broadman, M. (2010). Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Practice, 10(1):54-59. http://www.citeulike.org/user/HEIRS/article/6512085
Zeitzera, J. M., Nishinob, S., and Mignotc, E. (2006). The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. Trends in Pharmacological Sciences, (27):368-374. http://www.citeulike.org/user/HEIRS/article/6512089
Thannickal, T. C., Lai, Y.-Y., and Siegel, J. M. (2007). Hypocretin (orexin) loss in parkinson's disease. Medscape Today. http://www.citeulike.org/user/HEIRS/article/6512132

Impairments in Muscle Function After Cigarette Exposure and Environmental Illness

PGC-1a a protein factor necessary for mitochondrial function and may be reduced with exposure to LPS as well as, from impairments in Nrf2. This study demonstrates that TNF-a (already identified as a factor in CFS and Parkinson's) is generated from exposure to cigarette smoke (and lots of other environmental contaminants) and has been shown to down-regulate PGC-1a that may lead to vascular and myocyte dysfunction. PGC-1a also regulates a number of glucose transporters such as GLUT1 and GLUT4 which trasport glucose into cells.  When one looks at a condition related to glucose uptake from impairment of glucose transporters such as in GLUT1 deficiency, there are recognizable patterns of impairment one may recognize in other environmental illnesses including CFS and fibromyalgia and also described as Parkinsonism and ataxia-like symptoms.  Because Nrf2 contributes to PGC-1a expression, a deficiency in Nrf2 may also present with these types of symptoms impaired after cigarette exposure and particulate matter from diesel exhaust. Of course, other factors such as accumulation of ammonia and genetic SNP may also pose potential cellular threats. PGC-1a can be increased through exercise but this will be dependant on the availabity of NRF1 (another protein) regulated by Nrf2/HO-1. Sauna and Waon therapy have been shown to elevate PGC-1a and Nrf2. Deficiencies of PGC-1a may exacerbate the autoimmune-type presentation of environmental illness in Nrf2 deficiencies which produce less HO-1. Lack of PGC-1a and Nrf2 may contribute to the development of chronic diabetes in addition to other metabolic complications and numerous other conditions, such as cardiovascular disease.


For review:

• Chemical Sensitivity and Th2 Autoimmune Disease: The Loss of Treg Cells As Referee!
• Immunosuppression in Environmental Illness By High Fat and Cytokines: Ameliorated By Green Tea Compound!?
• Nrf2 Expression Is Regulated by Epigenetic Mechanisms in Prostate Cancer
• T Regulatory Cells and Vitamin D - Their Importance to Environmental Illness Including Chemical Sensitivity.

CiteULike: TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure.: "Tang, K., Wagner, P. D., and Breen, E. C. (2010). Tnf-alpha-mediated reduction in pgc-1alpha may impair skeletal muscle function after cigarette smoke exposure. Journal of cellular physiology, 222(2):320-327."





Lihua CHE, N. and Chiwai WON, G. Estrogen-related receptor a inverse agonist enhances basal glucose uptake in myotubes through reactive oxygen species. Biological Pharmacology Bulletin, 32(7):1199-1203. http://www.citeulike.org/user/HEIRS/article/6512026
Arany, Z., Foo, S.-Y. Y., Ma, Y., Ruas, J. L., Bommi-Reddy, A., Girnun, G., Cooper, M., Laznik, D., Chinsomboon, J., Rangwala, S. M., Baek, K. H. H., Rosenzweig, A., and Spiegelman, B. M. (2008). Hif-independent regulation of vegf and angiogenesis by the transcriptional coactivator pgc-1alpha. Nature, 451(7181):1008-1012. http://www.citeulike.org/user/HEIRS/article/2406298
Pons, R., Collins, A., Rotstein, M., Engelstad, K., and De Vivo, D. C. (2009). The spectrum of movement disorders in glut-1 deficiency. Movement Disorders, 9999(9999):NA+. http://www.citeulike.org/user/HEIRS/article/6512017
Piantadosi, C. A., Carraway, M. S., Babiker, A., and Suliman, H. B. (2008). Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res, 103(11):1232-1240. http://www.citeulike.org/user/HEIRS/article/4617070?show_msg=already_posted
Glucose Transporter. Wipedia. Retrieved January 10, 2009.

How Changes in Neurons May Lead to Altered Cortisol in CFS/ME & Sickness Syndrome.

Background: Many research experts believe that endotoxin is a causal factor in the development of chronic fatigue syndrome. (Maes) In addition and as we have discussed on this blog, many of the symptoms may be attributed to sickness behavior or sickness syndrome. Generally, this is regarded as a reflection of immune responses that alter normal functions of hormones, neurotransmitters, etc. resulting in changes in behavior in humans and other animals.

We recently discussed how dysregulation of the hormone, ghrelin, may effect sickness behavior. A study just published provides more details about how another hormone may contribute to sickness syndrome and related alterations in behavior. According to the study, LPS endotoxin suppresses the neuronal circuitry in orexin and histamine neurons. As the abstract describes, the orexin neurons in the brain are important for behaviors including waking, feeding and reward-related behaviors and can be regulated by dopamine (Bubser), provide antinociceptive protection (Mobarakeh) and may reduce gastrointestinal injury through several mechanisms including injury from TLR signaling. In other blogs, we describe in detail how LPS from gram-negative bacteria and other environmental contaminants such as ozone can initiate inflammatory effects through TLR signaling and that genetic or environmental dysruption of the Nrf2 system will enhance the inflammatory effects.

Outside the brain, orexin neurons stimulate the production of cortisol in the adrenal glands and another studies shows orexin can time-dependantly raise cortisol levels as well as, influence steroidogenesis. Orexin studies have also revealed it regulates histamine release in the brain. Interestingly, narcolepsy which is suspected to be an autoimmune-related condition is associated with orexin deficiency. Aran proposes that streptococcus is an environmental trigger of narcolepsy. For this reason, the results of these studies in combination suggest that both gram-negative and gram-positive bacteria may contribute to sickness syndrome by altering orexin levels. In addition, orexin is a sexually-dimorphically expressed hormone which may help to explain the gender differences in the rates of environmental illness. (Johren)

Click to view original document and citations.

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Chronic Fatigue Syndrome is an Metabolic Inflammatory Condition w/ Heart Consequences

Summary: "ME/CFS is a multisystemic metabolic-inflammatory disorder. The aberrations in IO&NS pathways may increase the risk for cardiovascular disorders."


CiteULike: Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS.: "Maes, M. and Twisk, F. N. N. (2009). Why myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (io&ns) pathways may explain cardiovascular disorders in me/cfs. Neuro endocrinology letters, 30(6"

CoQ10 deficiency is related to fatigue, autonomic and neurocognitive symptoms in chronic fatigue syndrome.

Summary: The author suggests that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome. They also propose that earlier mortality from CHF in CFs may be a consequence of coQ10 deficiency. They do note that statins may be contraindicated because they reduce Q10.


Maes, M., Mihaylova, I., Kubera, M., Uytterhoeven, M., Vrydags, N., and Bosmans, E. (2009). Coenzyme q10 deficiency in myalgic encephalomyelitis / chronic fatigue syndrome (me/cfs) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in me/cfs due to cardi. Neuro endocrinology letters, 30(4). http://www.citeulike.org/user/HEIRS/article/6414392

HEIRS Library: Q10

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Microbial infections in eight genomic subtypes of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME)

Microbial infections in eight genomic subtypes of chronic fatigue syndrome / myalgic encephalomyelitis (cfs/me).

Summary: Clustering of combined gene data in CFS/ME patients for this and our previous study (n=117 CFS/ME patients) revealed genomic subtypes with distinct differences in SF-36 scores, clinical phenotypes, severity and geographical distribution. Antibody testing for Epstein-Barr virus (EBV), enterovirus, Coxiella burnetii and parvovirus B19 revealed subtype-specific relationships for EBV and enterovirus, the two most common infectious triggers of CFS/ME.


Zhang, L., Goudh, J., Christmas, D., Mattey, D., Richards, S., Main, J., Enlander, D., Honeybourne, D., Ayres, J., Nutt, D. J., and Kerr, J. (2009). Microbial infections in eight genomic subtypes of chronic fatigue syndrome / myalgic encephalomyelitis (cfs/me). pages jcp.2009.072561+. http://www.citeulike.org/user/HEIRS/article/6306231

XMRV and Chronic Fatigue Syndrome on ABC News

A new study links chronic fatigue syndrome with a retrovirus, XMRV which was discussed on ABC News today.