ME/CFS and mitochondrial dysfunction

Source Link

PDF Warning for foggy, spoon (energy) limited individuals - this is a long research piece (16 pages). Warning for you to prepare, rather then opening it, seeing how big it is and being turned off.

In the meantime I will try to find if there is somewhere it is online for those who can't download PDFs.

Abstract: This study aims to improve the health of patients suffering from chronic fatigue syndrome (CFS) by interventions based on the biochemistry of the illness, specifically the function of mitochondria in producing ATP (adenosine triphosphate), the energy currency for all body functions, and recycling ADP (adenosine diphosphate) to replenish the ATP supply as needed. Patients attending a private medical practice specializing in CFS were diagnosed using the Centers for Disease Control criteria. In consultation with each patient, an integer on the Bell Ability Scale was assigned, and a blood sample was taken for the “ATP profile” test, designed for CFS and other fatigue conditions. Each test produced 5 numerical factors which describe the availability of ATP in neutrophils, the fraction complexed with magnesium, the efficiency of oxidative phosphorylation, and the transfer efficiencies of ADP into the mitochondria and ATP into the cytosol where the energy is used. With the consent of each of 71 patients and 53 normal, healthy controls the 5 factors have been collated and compared with the Bell Ability Scale. The individual numerical factors show that patients have different combinations of biochemical lesions. When the factors are combined, a remarkable correlation is observed between the degree of mitochondrial dysfunction and the severity of illness (P<0.001). Only 1 of the 71 patients overlaps the normal region. The “ATP profile” test is a powerful diagnostic tool and can differentiate patients who have fatigue and other symptoms as a result of energy wastage by stress and psychological factors from those who have insufficient energy due to cellular respiration dysfunction. The individual factors indicate which remedial actions, in the form of dietary supplements, drugs and detoxification, are most likely to be of benefit, and what further tests should be carried out.

Co-enzyme Q10 distribution in blood is altered in patients with Fibromyalgia

Source

OBJECTIVE: Co-enzyme Q10 (CoQ(10)) is an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant. Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with fibromyalgia (FM). The aim was to study CoQ(10) levels in plasma and mono nuclear cells, and oxidative stress in FM patients.

METHODS: We studied CoQ(10) levels by HPLC in plasma and peripheral mono nuclear cells obtained from patients with FM and healthy control subjects. Oxidative stress markers were analysed in both plasma and mono nuclear cells from FM patients.

RESULTS: Higher level of oxidative stress markers in plasma was observed respect to control subjects. CoQ(10) level in plasma samples from FM patients was doubled compared to healthy controls and in blood mononucleosis isolated from 37 FM patients was found to be about 40% lower. Higher levels of ROS production was observed in mono nuclear cells from FM patients compared to control, and a significant decrease was induced by the presence of CoQ(10).

CONCLUSION: The distribution of CoQ(10) in blood components was altered in FM patients. Also, our results confirm the oxidative stress background of this disease probably due to a defect on the distribution and metabolism of CoQ(10) in cells and tissues. The protection caused inmononuclear cells by CoQ(10) would indicate the benefit of its supplementation in FM patients.

Normalisation of leaky gut in ME/CFS

Article Source


Normalisation of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria.
Journal: Neuro Endocrinol Lett. 2008 Dec 29;29(6). [Epub ahead of print]
Authors: Maes M, Leunis JC.
Affiliation: M-Care4U Outpatient Clinics, and the Clinical Research Center for Mental Health, Belgium. NLM Citation: PMID: 19112401



BACKGROUND: There is now evidence that an increased translocation of LPS from gram negative bacteria with subsequent gut-derived inflammation, i.e. induction of systemic inflammation and oxidative & nitrosative stress (IO&NS), is a new pathway in chronic fatigue syndrome (CFS).


METHODS: The present study examines the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia Alvei; Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle Pneumoniae in CFS patients both before and after intake of natural anti-inflammatory and anti-oxidative substances (NAIOSs), such as glutamine, N-acetyl cysteine and zinc, in conjunction with a leaky gut diet during 10-14 months. We measured the above immune variables as well as the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale in 41 patients with CFS before and 10-14 months after intake of NAIOSs.


RESULTS: Subchronic intake of those NAIOSs significantly attenuates the initially increased IgA and IgM responses to LPS of gram negative bacteria. Up to 24 patients showed a significant clinical improvement or remission 10-14 months after intake of NAIOSs. A good clinical response is significantly predicted by attenuated IgA and IgM responses to LPS, the younger age of the patients, and a shorter duration of illness (< 5 years).

DISCUSSION: The results show that normalization of the IgA and IgM responses to translocated LPS may predict clinical outcome in CFS.

The results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in CFS and that it is a new target for drug development in CFS. Meanwhile, CFS patients with leaky gut can be treated with specific NAIOSs and a leaky gut diet.

ME/CFS Blood Test On The Horizon

Source
14 December 2008

The Whittemore Peterson Institute for research and treatment of Neuroimmune Diseases located in Nevada USA has announced it is approximately only 12 months away from the clinical establishment of a blood test for ME/CFS.

The major benefit of a blood test that will accurately distinguish even one sub-type of the amorphous and vague CFS illness construct is that scientist can begin to research homogeneous groups of patients all with the same disease. Since 1988 when the US CDC introduced the vague 'fatigue' oriented concept of CFS, and more recently the even less specific Empirical Definition of CFS, advances in understanding of the disease has been severely hindered by research carried out on mixed groups of patients, many of whom most likely didn't or don't have ME/CFS.

The institute's website can be viewed at http://www.wpinstitute.org/.

CFIDS Association Research Grants Raise Hope

The Following Article Was Taken From The ME/CFS Society of WA's Website

By: PR Newswire
Dec. 3, 2008 03:00 PM

CHARLOTTE, N.C., Dec. 3 /PRNewswire/ -- The four million Americans who suffer from chronic fatigue syndrome (CFS) have new reason for hope today with the announcement of an unprecedented research program to help identify biomarkers for the illness and improve diagnosis and treatment of CFS. The announcement was made by the CFIDS Association of America, which is funding the program, called the Accelerate CFS Research Initiative.

As part of this initiative, the CFIDS Association also announced today research grants totaling $647,940 to six research teams in the U.S. and Canada.

"These awards represent a new approach to CFS research," said Suzanne Vernon, PhD, the CFIDS Association's scientific director. "Instead of each investigator working in isolation, we are building a network of researchers and a framework for data sharing and collaboration not only among researchers who receive grants from the CFIDS Association, but among scientists worldwide."

Vernon, a microbiologist who helped pioneer the application of genomics to CFS, is now working to pioneer this new CFS research network and to direct the Accelerate CFS Research Initiative. "We were very impressed with the number and caliber of grant proposals we received this year, which signals a heightened level of interest in CFS research," said Vernon. "CFS, once shied away from by some researchers, is now considered a legitimate and challenging field of scientific inquiry."

The grant recipients are:
-- Gordon Broderick, PhD, of the University of Alberta in Canada, who will study the immune and endocrine response in adolescent patients who became ill with CFS after contracting infectious mononucleosis, which is caused by the Epstein-Barr virus. By studying patients from the time they get infectious mononucleosis to the development of CFS and through the first 24 months of illness, the researchers hope to identify disease progression biomarkers, including those essential for early diagnosis.

-- Kathleen Light, PhD, of the University of Utah Health Sciences Center, who will investigate the mechanisms involved in chronic pain that afflicts 40%-70% of CFS patients. This study will determine whether receptors located on blood cells are increased and overactive in people with CFS and associated with increased pain sensitivity. Light theorizes that increases in specific receptors following exercise may be blood-based biomarkers for CFS and could lead to a medical test to identify CFS patients.

-- Marvin Medow, PhD, of New York Medical College, who will investigate how orthostatic intolerance, seen in many CFS patients, affects brain function. This study will examine if CFS patients have increased pooling of blood in the abdomen that results in reduced cerebral blood flow. Medow will also investigate physiologic and oxidative stress changes associated with disturbance in blood flow. These results will help determine if alterations in blood flow affect brain metabolism.

-- Bhubaneswar Mishra, PhD, of the Courant Institute of Mathematical Sciences at NYU, who will use state-of-the-art bioinformatics and computational biology tools to create a computational model of CFS-a kind of "Google for CFS" that will be part database, part knowledge-base, part research network. This new resource will provide a "systems view" of CFS that accumulates published CFS literature and experimental data to
disentangle complex relationships among reported findings and discover causes of CFS.

-- Sanjay Shukla, PhD, of Marshfield Clinic Research Foundation, who will use metagenomics to determine if the ratio of good to bad intestinal bacteria in CFS patients is altered, and whether this imbalance in gut bacteria may be responsible for triggering CFS symptoms. Recent advances in metagenomics have demonstrated the significance of altered gastrointestinal bacteria in illnesses like HIV, diabetes, Crohn's disease, inflammatory bowel disease and ulcerative colitis. Shukla theorizes that CFS patients also have an imbalance of good and bad intestinal bacteria, resulting in enhanced intestinal permeability-called leaky gut-allowing bacteria to move across the protective intestinal barrier and causing chronic inflammation and immune activation in CFS patients. This study will contribute to our understanding of the relationship between the human microbiome and CFS. It may also lead to new treatment options, including the use of probiotics.

-- Dikoma Shungu, PhD, of Weill Medical College of Cornell University, who will use a brain scanning technique called magnetic resonance spectroscopy to confirm earlier findings that brain fluid of CFS patients contains significantly elevated levels of lactate, a substance important in metabolism. Shungu's team will also investigate the reason for this phenomenon, exploring whether lactate levels are higher in CFS patients because their brains contain high levels of toxic compounds that cause a condition called oxidative stress (which could implicate chronic inflammation), or because mitochondrial dysfunction is causing malfunctions in the production of brain energy. If this study is successful, brain lactate levels could provide an objective diagnostic biomarker for CFS.

The Accelerate CFS Research Initiative was made possible by the successful completion of a yearlong, million-dollar fundraising campaign, the largest research campaign for CFS to date in the United States. The CFIDS Association has funded more than $5.4 million in CFS research since 1987, making it second only to the federal government in CFS research spending.

"This was a real grassroots campaign, with most contributions coming not from major corporations or foundations, but from ordinary people whose lives have been affected by the illness," said Kimberly McCleary, president and CEO of the CFIDS Association. "Patients, their family, friends and doctors stepped up to give donations large and small to fuel the research initiative."

"While support from individual American citizens is vital for research progress," McCleary noted, "more funding from the government, from biotech firms and from the pharmaceutical industry is desperately needed. CFS affects more Americans than many other well-known diseases, but receives far less research funding."

About the CFIDS Association of America

The CFIDS Association was founded in 1987 to stimulate high-quality CFS research, improve the ability of health care professionals to diagnose and manage the illness, provide educational information for patients and their families, and build widespread public awareness of CFS. The organization has invested more than $26 million in research, education and public policy and is the largest charitable funder and advocate of CFS research in the U.S.

Create A Story II

From our games board - The Three Word Story - If you'd like to participate it's as easy as joining up and posting!

"In the Beginning, there was a tiny little house with a red little hat and a giant brick chimney. Sometimes, it blew a big spiraling poof of lightly rainbow flavored lollipops. The big chimney was twisted and contorted in loop de loops of great complexity and incredible flexibility. This allowed for two very important messengers from a totally different dimension!"

Serum antioxidants and nitric oxide levels in fibromyalgia: a controlled study.

Taken from here


Serum antioxidants and nitric oxide levels in fibromyalgia: Rheumatol Int. 2008 Oct 14. [Epub ahead of print] Sendur OF, Turan Y, Tastaban E, Yenisey C, Serter M.

Department of Physical Medicine and Rehabilitation, Adnan Menderes University Medicine School Hospital, Aydin, Turkey. PMID: 18853166



We proposed to assess antioxidant status and nitric oxide in fibromyalgia (FM) patients in comparison to healthy controls. Additionally, the association between the serum antioxidant levels and clinical findings in FM patients was also investigated.

Thirty-seven FM patients and 37 healthy controls were enrolled in this study. Severity of fatigue and pain were determined by Visual Analogue Scale. Functional capacity in daily living activities was evaluated by fibromyalgia impact questionnaire. Serum NO, catalase and glutathione were measured.

Serum glutathione and catalase levels were significantly lower in FM patients than controls. However, no significant difference was seen in serum NO levels between the two groups. A significant correlation was evident between serum NO level and pain. Additionally, the correlation between glutathione level and morning stiffness was found to be significant.

These findings support other studies, we assume that these two antioxidants might have impact on the pathogenesis of FM disease.

Create A Story I

From our games board - The Three Word Story - If you'd like to participate it's as easy as joining up and posting!

The little spider had hairy legs that made squeaky noises like tiny out-of-tune violins.

From atop the largest building in the whole world he decided to do a backflip and trail webbing all about the tower's shiny glass viewing windows, next to the open stellar wormhole leading all the pixies to the fantastic plastic yellow submarine sinking into oblivion.

Hypothesis: ME/CFS caused by dysregulation of hydrogen sulfide metabolism

Article source


Chronic fatigue syndrome (CFS), which is also known as myalgic
encephalomyelitis (ME), is a debilitating, multi-system disease
whose etiology is unclear, and for which there are as yet no reliable
treatments. Here the hypothesis is advanced that the multi-system
disturbances in CFS/ME are caused by disturbances in the homeostasis
of endogenous hydrogen sulfide (H2S) and result in mitochondrial
dysfunction.

Research on H2S -- the gas that causes the characteristic smell of
rotten eggs -- dates to the 1700‚s and has shown a remarkable
range of effects in both animals and humans. At high concentrations,
H2S has a variety of biological toxicities including being
instantaneously deadly; at low concentrations some evidence suggests
that H2S has beneficial effects and can act as an endogenous
biological mediator the third such gaseous mediator discovered
(after nitric oxide and carbon monoxide). The brain, pancreas and
the gastrointestinal tract produce H2S. Endogenous H2S plays a role
in regulating blood pressure, body temperature, vascular smooth
muscle, cardiac function, cerebral ischemia, and in modulating
the hypothalamus/pituitary/adrenal axis. It even has been called
a "master metabolic regulator."

Recent research has demonstrated that at low, non-toxic doses,
exogenous H2S produces a reversible state of hibernation-like deanimation
in mice, causing a decrease in core body temperature,
an apnea-like sleep state, reduced heart and respiration rates,
and a severe metabolic drop [1]. These characteristics are not unlike
the symptoms and extreme "de-animation" experienced by
CFS/ME patients. Moreover, H2S affects biological networks that
are disrupted by CFS including neurologic, endocrine and immunologic
systems. Therefore, a plausible etiology of CFS is an increase
in the activity of endogenous H2S, thereby inhibiting mitochondrial
oxygen utilization.

H2S and Mitochondria
In this view, fatigue and the other CFS/ME symptoms could be
due to diminished physiological and cellular energy due to reduction
in the capacity of mitochondria to utilize oxygen and synthesize
ATP. Specifically, H2S binds to the mitochondrial enzyme
cytochrome c oxidase, which is part of Complex IV of the electron
transport chain, and attenuates oxidative phosphorylation and ATP
production.

Consistent with this finding, recent research on low levelH2S toxicity
points to increased formation of free radicals and depolarization
of the mitochondrial membrane, a condition that would
decrease ATP synthesis [2]. If poisoning renders mitochondria inefficient,
one would expect cells to shift to anaerobic mechanisms, a
shift that has been reported for CFS patients. Also consistent with
this hypothesis is the fact that mitochondria are organelles descended
from ancient eukaryotic sulfur-utilizing microbes. Thus, it
is not surprising that they show a very high affinity for sulfide.
Of course, H2S or sulfide may not directly affect mitochondria
by binding to them. Genomic changes could mediate some of the
effects of H2S. Some studies have found evidence for the involvement
of the cytochrome c oxidase gene in CFS/ME. Also, investigators
have found CFS abnormalities in genes related to fatty acid
metabolism, apoptosis, mitochondrial membrane function, and
protein production in mitochondria. Given a predisposing genetic
background, H2S may lead to genomic instability or cumulative
mutations in the mitochondrial DNA [3].

Alternatively, the effects of H2S could be initially mediated by
changes in the redox potential of cells or changes in their sulfur
metabolism, especially in glutathione. Another possible mechanism
is a direct effect of H2S on the immune system. Recent research
indicates that exogenous hydrogen sulfide induces
functional inhibition and cell death of cytotoxic lymphocyte subsets
of CD8 (+) T cells and NK cells.

Finally, H2S plays a pivotal role in both aerobic and non-anaerobic
organisms as a signaling molecule. Bacteria in the gut both produce
H2S and utilize it as a substrate alternative to oxygen. This is of
particular relevance in the gastrointestinal tract, where unusually
high levels of gram-negative bacteria, which increase intestinal permeability,
have been found in patients with CFS/ME [4]. In addition
to bacteria, yeast, mold and other fungi also emit H2S.
CFS/ME is a model disease for multisystem disturbance. It is my
hypothesis that mitochondria, organelles required by every cell to
sustain life, are unable to adequately utilize oxygen. This mitochondrial
disturbance could be due to the combined effects of
anaerobic conditions known to occur in CFS and associated low-level
H2S toxicity. This increase in H2S alters fine signaling necessary
for body homeostasis, and causes CFS. Understanding the role of
H2S in the body, and, in particular, in mitochondrial function,
may provide a unifying lens through which to view the diverse
manifestations of this complex disease.


References
[1] Blackstone Eric, Morrison Mike, Roth Mark B. H2S induces a suspended
animation-like state in mice. Science Magazine 2005;308(5721):518.
doi:10.1126/science.110858.
[2] Eghbal MA, Pennefather PS, O‚Brien PJ. H2S cytotoxicity mechanism involves
reactive oxygen species formation and mitochondrial depolarisation.
Toxicology 2004;203(13):6976. PMID: 15363583.
[3] Attene-Ramos MS, Wagner ED, Gaskins HR, Plewa MJ. Hydrogen sulfide induces
direct radical-associated DNA damage. Mol Cancer Res 2007 [PMID: 17475672].
[4] Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of
enterobacteria in chronic fatigue syndrome (CFS): indication for the
involvement of gram-negative enterobacteria in the etiology of CFS and for
the presence of an increased gut-intestinal permeability. J Affect Disord
2007;99(13):23740. PMID: 17007934

Announcment: Live Chat Session

Blue Butterflies is having a live chat session this weekend. For now it is members only so if you would like to participate please sign up!

If you are interested but don't wish to sign up until you get to know what we are about better then let us know. If there is enough interest we may hold a public live chat session.

Following are the times but if you don't see your timezone and would like to participate either leave a comment here or log into the forum and post in this thread

The live chat times are;

Cananda (Toronto) Sunday 7th at 7:30pm
US (St Paul) Sunday 7th at 6:30pm
Syd/Melb Monday 8th 9:30am