Oxidative Stress and Fatigue
in [Fibromyalgia]
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From: ironjustice on 8 Aug 2008 00:13 On Aug 7, 11:39 am, ironjustice <teamtan...(a)hotmail.com> wrote:oxidative stress in CFS << Chronic Fatigue Syndrome: Oxidative Stress and Dietary Modifications Alternative Medicine Review 2001 (Oct); 6 (5): 450459 ~ FULL TEXT Alan C. Logan, ND, Cathy Wong, ND (Cand.) Introduction Chronic fatigue syndrome (CFS) is a relatively common disorder, particularly in women, affecting 522 women and 291 men per 100,000. [ 1 ] In addition to the characteristic persistent fatigue, CFS patients often complain of a number of symptoms including headache, joint pain, gastrointestinal (GI) disturbance, cognitive dysfunction, visual disturbance, and paresthesia. [ 2,3 ] Pathological changes have been observed in CFS patients, including white matter lesions in the CNS [ 4-6 ] and cerebral hypoperfusion. [ 7-9 ] Other findings that suggest CNS involvement include vestibular dysfunction [ 10,11 ] and gait abnormalities. [ 12,13 ] Immune response also appears to be impaired; specifically, elevated levels of interferon alpha, transforming growth factor beta, interleukin-4, interleukin-6, interleukin-1 alpha, and tumor necrosis factor alpha (TNF-a) have been observed. [ 14-19 ] The purpose of this paper is to integrate various branches of current research in an effort to highlight the importance of antioxidant capacity and food intolerance in CFS. First, recent studies will be reviewed that indicate oxidative stress is involved in the pathogenesis of CFS. This suggests antioxidants may be beneficial in the management of CFS. Glutathione (GSH), N-acetylcysteine (NAC), a- lipoic acid, oligomeric proanthocyanidins (OPCs), Ginkgo biloba, and Vaccinium myrtillus (bilberry) would therefore be dietary supplements with potential therapeutic benefit. Second, the literature will be reviewed that suggests food intolerance may be involved in CFS symptom presentation and in oxidation via cytokine induction. Although food intolerance can be an important consideration in the presentation of this heterogeneous disorder, evidence also suggests celiac disease should be included in the differential diagnosis of CFS. Celiac disease may present primarily with neurological symptoms in the absence of gastrointestinal symptoms. Current Research on Oxidative Stress in CFS The role of oxidative stress in CFS is an emerging focus of research. Although it is uncertain whether oxidative stress is a cause or a result of this illness, recent studies have demonstrated that oxidative stress contributes to the pathology and clinical symptoms of CFS. Theoretically, oxidative stress can be caused by an increase in the generation of reactive oxygen species, of which mitochondrial dysfunction is believed to be a main source, or it can be caused by a decline in the efficiency of antioxidant enzyme systems. [ 20 ] Recent studies have examined both of these possibilities by looking for markers of oxidative stress and protective antioxidant systems. Fulle et al observed evidence of oxidative damage to the DNA and lipids of biopsy samples from the vastus lateralis muscles of CFS patients. [ 20 ] In addition, they found an increase in the activity of antioxidant enzyme systems, including glutathione peroxidase, an increase they suggest is a compensatory measure in response to oxidative stress. The researchers noted a similarity between increased oxidative damage in CFS patients and age-related changes in healthy individuals, concluding that antioxidants have therapeutic potential to reduce oxidative damage. Pall suggests the level of the oxidant peroxynitrite is important in CFS patients. [ 21 ] He contends elevated peroxynitrite causes mitochondrial dysfunction, lipid peroxidation, and, by way of positive feedback, elevated cytokine levels. The cytokines, in turn, cause the formation of nitric oxide that combines with superoxide to form the potent oxidant peroxynitrite, thus continuing the cycle. Peroxynitrite targets the mitochondria and Pall notes this may help explain mitochondrial dysfunction in CFS. As support for the peroxynitrite theory, Pall cites evidence that the mitochondrial enzymes succinic dehydrogenase and cis-aconitase are inactivated by peroxynitrite. [ 22,23 ] This makes for an interesting finding because decreased succinic dehydrogenase activity has been found in CFS patients [ 24,25 ] and urine levels of the intermediates metabolized by these enzymes have been found to be elevated in CFS patients. [ 26,27 ] Pall proposes a number of nutritional and botanical interventions that may reduce peroxynitrite and cytokine levels; among them, the soy isoflavone genistein, epigallocatechin-3-gallate from green tea, and vitamins C and E. Keenoy et al found impaired antioxidant capacity in a sample of CFS patients with "subclinical" or moderate magnesium deficiency. [ 28 ] The impaired capacity involved both the total antioxidative capacity of plasma, as measured by Trolox Equivalents Antioxidant Capacity (TEAC), and the antioxidant component dependent on albumin. While no improvement was observed in these parameters after oral or intravenous magnesium supplementation, some patients demonstrated increased serum vitamin E and an associated decrease in lipid peroxidation. This finding, according to the authors, is likely due to the sparing effect of magnesium on vitamin E by preventing its in vivo oxidation. In addition, the researchers postulated that an elevated concentration of inflammatory cytokines might indirectly cause diminished antioxidant capacity by inhibiting albumin transcription in the liver. A subset of patients whose magnesium body stores did not improve after supplementation also had lower blood glutathione levels, suggesting a relationship might exist between intractable magnesium deficiency and low glutathione. [ 28 ] Interestingly, RBC magnesium levels have previously been reported to be decreased in CFS patients, some of whom had adequate dietary intake of magnesium. [ 29 ] Some of these same researchers further examined the role of oxidative stress in CFS. They found an increased susceptibility of LDL and VLDL to copper-induced peroxidation in CFS patients. [ 30 ] They conclude this might indicate the impaired lipoprotein antioxidant capacity in CFS, causing accelerated lipid peroxidation. Richards et al found CFS patients had elevated levels of methemoglobin (MetHb), a marker of oxidative stress. [ 31 ] Formation of MetHb, a product of iron oxidation, is regulated by NADH-MetHb reductase. Consequently, levels of MetHb may increase when there is an alteration in this reducing system within the erythrocyte. The researchers reported the increase in MetHb correlates with the presence and severity of several CFS symptoms, including photophobia, irritability, and GI complaints. MetHb also requires glutathione and cysteine to be reduced in normal cells. It is interesting to note that both glutathione [ 28 ] and cysteine [ 32 ] levels have been found in decreased levels in CFS patients. Additional evidence supporting the role of free radical damage in CFS patients and the efficacy of antioxidant treatment comes from a recent study. [ 33 ] In a three-month, double-blind, placebo-controlled crossover study, 22 CFS patients were given a Swedish pollen extract high in antioxidant polyphenols. Statistically significant improvement was observed in the treatment group, notably in fatigue, sleep disturbance, GI complaints, and hypersensitivity. In addition, there was a highly significant improvement in erythrocyte fragility, a marker of oxidative damage. The researcher acknowledged the synergistic effect of antioxidants, as in the Swedish pollen extract, and suggests future research using antioxidant combinations. Implications for Antioxidant Treatment The above findings on oxidative stress suggest that supplementing with certain antioxidants, in addition to vitamins C and E, may be valuable in a CFS treatment protocol (Table 1). A number of supplements should be considered for potential therapeutic intervention, including selenium (necessary to support glutathione peroxidase activity), [ 34 ] GSH, NAC, and a-lipoic acid. Although there is conflicting evidence, a number of studies have shown oral administration of GSH can directly increase plasma and tissue GSH concentration. [ 35-37 ] Alternately, NAC and a-lipoic acid can increase GSH concentration indirectly; [ 38,39 ] NAC provides cysteine for GSH synthesis, and a- lipoic acid is believed to increase intracellular GSH levels by reducing extracellular cystine to cysteine, bypassing the cystine transporter. [ 40 ] GSH is neuroprotective and may play a role in preventing additional CNS lesions. [ 41 ] a-Lipoic acid is also neuroprotective, scavenges nitric oxide and peroxynitrite, and may be especially promising as an antioxidant against mitochondrial dysfunction.40 The supplement coenzyme Q10 has similar neuroprotective qualities and has the ability to improve mitochondrial function. [ 42 ] The botanical antioxidants OPCs and Ginkgo biloba should also be considered. Bagchi et al found that OPCs are highly bioavailable and provide significantly greater protection against free radical damage than beta carotene and vitamins C and E. [ 43 ] These authors also reported the ability of OPCs to provide protection from radical- induced lipid peroxidation and DNA damage, which is of particular importance to CFS patients. Ginkgo biloba is a powerful antioxidant, [ 44 ] demonstrating strong neuroprotective properties in animals. It has been shown to reduce mitochondrial reactive oxygen species, in particular peroxynitrite. [ 45 ] The capacity of Ginkgo to increase cerebral blood flow [ 46 ] and improve memory and cognition associated with cerebral insufficiency [ 47 ] suggests it may be useful for CFS symptoms related to hypoperfusion. Plant-based antioxidant support should be maximized through dietary intake. Cao et al found that a diet high in fruits and vegetables can increase plasma antioxidant capacity in humans, as measured by oxygen radical absorbance capacity (ORAC) assay. [ 48 ] Blueberries have the highest ORAC scores among thirty fruits and vegetables tested, [ 49,50 ] and may be of significant benefit due to their high potential antioxidant activity, [ 51 ] neuroprotective properties, [ 52 ] and specific ability to protect red blood cells from in vivo oxidative damage. [ 53 ] Of the blueberry species, Vaccinium myrtillus has the highest combined anthocyanidin, phenol, and ORAC scores. [ 51 ] In a recent double-blind, placebo-controlled, crossover study, administration of pure anthocyanidins (80 mg daily) showed a small but statistically significant benefit in a group of patients with the related disorder of fibromyalgia. [ 54 ] The trial was three months in duration for active treatment and involved an anthocyanidin combination derived from grape seed, bilberry, and cranberry. Improvements were observed in sleep quality and fatigue. Based on these findings a similar trial is warranted in CFS patients. Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > "Oxidative stress may offer a common explanation" > > Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):181-3. > In vivo magnetic resonance spectroscopy in chronic fatigue syndrome. > > Chaudhuri A, Behan PO. > > Division of Clinical Neurosciences, Institute of Neurological > Sciences, > Southern General Hospital, University of Glasgow, 1345 Govan Road, > Glasgow G51 > 4TF, UK. > > The pathogenic mechanisms of chronic fatigue syndrome (CFS) are not > clearly known. > Fatigue, poor short-term memory and muscle pain are the most disabling > symptoms in CFS. Research data on magnetic resonance spectroscopy > (MRS) of muscles and brain in CFS patients suggest a cellular > metabolic abnormality in > some cases. (31)P MRS of skeletal muscles in a subset of patients > indicate early intracellular acidosis in the exercising muscles. > (1)H MRS of the regional brain areas in CFS have shown increased peaks > of choline derived from the cell membrane phospholipids. Cell membrane > oxidative stress may offer a common explanation for the observed MRS > changes in the muscles and brain of CFS > patients and this may have important therapeutic implications. > As a research tool, MRS may be used as an objective outcome measure in > the intervention studies. > In addition, regional brain (1)H MRS has the potential for wider use > to substantiate a clinical diagnosis of CFS from other disorders of > unexplained chronic fatigue. > > PMID: 15253888 [PubMed - in process] > > ----------------------- > > Who loves ya. > Tom > > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh > > Man Is A Herbivore!http://tinyurl.com/4rq595 > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
From: LoriB.o.B. on 8 Aug 2008 00:26 Ah, so he also has some prejudices against both the mentally disabled ("morons") (not meaning any posters btw, just against the Americans w/ Disabilities Act) & those poor folks who've suffered massive head injuries or strokes ("brain dead"). LoriBoB Reporting because I'm sick of this a-hole & ignoring doesn't do it. So, if everyone reports him for every post, perhaps we shall once again be rid of him at least for awhile. ******************** On Aug 7, 4:27 pm, ironjustice <teamtan...(a)hotmail.com> wrote: > On Aug 7, 4:11 pm, High Miles <2Blue...(a)comcast.net> wrote:But who > would believe anything a ranter like that posts << > > Obviously not brain dead morons .. > > Who loves ya. > Tom
From: ironjustice on 8 Aug 2008 01:09 On Aug 7, 9:26 pm, "LoriB.o.B." <banjob...(a)comcast.net> wrote: snip << What did I tell you about brain dead morons .. ? Stay off my threads .. You got a problem with English .. ? Comeon .. give us some more of your putrid .. spew .. You can doooo .. it .. Comeon .. do .. what .. you .. do .. best .. Whine .. and leave .. Understand .. fruitcake .. ? Do ya .. ? This is a thread about oxidative stress and fatigue .. you don't like it .. ? There's the door .. fruitcake .. You make other fruitcakes look .. bad .. and chuck is looking bad enough .. already .. Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > Ah, so he also has some prejudices against both the mentally disabled > ("morons") (not meaning any posters btw, just against the Americans w/ > Disabilities Act) & those poor folks who've suffered massive head > injuries or strokes ("brain dead"). > LoriBoB > Reporting > because I'm sick of this a-hole > & ignoring doesn't do it. > So, if everyone reports him for every post, perhaps we shall once > again be rid of him at least for awhile. > ******************** > > On Aug 7, 4:27 pm, ironjustice <teamtan...(a)hotmail.com> wrote: > > > > > On Aug 7, 4:11 pm, High Miles <2Blue...(a)comcast.net> wrote:But who > > would believe anything a ranter like that posts << > > > Obviously not brain dead morons .. > > > Who loves ya. > > Tom- Hide quoted text - > > - Show quoted text -
From: LoriB.o.B. on 8 Aug 2008 01:40 O, & I repeat myself on purpose because he didn't "get it" . Prejudiced pedoph. > > Ah, so he also has some prejudices against both the mentally disabled > > ("morons") (not meaning any posters btw, just against the Americans w/ > > Disabilities Act) & those poor folks who've suffered massive head > > injuries or strokes ("brain dead"). > > LoriBoB > > Reporting > > because I'm sick of this a-hole > > & ignoring doesn't do it. > > So, if everyone reports him for every post, perhaps we shall once > > again be rid of him at least for awhile. > > ******************** > > > On Aug 7, 4:27 pm, ironjustice <teamtan...(a)hotmail.com> wrote: > > > > On Aug 7, 4:11 pm, High Miles <2Blue...(a)comcast.net> wrote:But who > > > would believe anything a ranter like that posts << > > > > Obviously not brain dead morons .. > > > > Who loves ya. > > > Tom- Hide quoted text - > > > - Show quoted text -
From: Chuck on 8 Aug 2008 07:49
On Aug 7, 5:57�pm, jay <jaym1...(a)hotmail.com> wrote: > Actually, ironjustice has found a prominent characteristic common in > many pathologies. Reducing iron levels in such cases is prudent. Of course it is. Unfortunately the messenger has no ability or desire to extrapolate that biochemistry into real world applicable explanations. Just cut, paste, and be obnoxious to anyone who probes further. Firstly, individuals should stop taking any supplements with iron unless they have been *clearly* diagnosed with iron deficiency. ex physical, Include blood tests on iron levels; ferritin, serum iron, iron saturation, hematocrit, MCV.................. if any of these are abnormal, ask your physician / healthcare provider about ways of decreasing sytemic iron levels. CB |