Dr Pall: Nitric Oxide Cycle Theory: Will It Explain CFS, FM, and Other ‘Unexplained’ Illnesses?

[Guest guest]

Nitric Oxide Cycle Theory: Will It Explain CFS, FM, and Other ‘Unexplained’ Illnesses? - Q & A with L. Pall, PhD

http://www.prohealth.com//library/showArticle.cfm?libid=12896

First things first, I was glad to see that Dr. Pall says the origin of many "unexplained" illnesses is probably viral and bacterial.

It feels like "deja vu all over again"...like we're going in circles here. But this theory does pique my interest because my tests with Dr. Gleuck, identified a genetic inabily to process Nitric Oxide properly. This nitric oxide dysregulation in my body is almost certainly a major cause of pain and fatigue symptoms.

Dr. Gleuck's recommendation for me was to supplement with Arginaid, a supplement primarily used in hospitals. I take it off and on, and it seems to help, but I find it difficult to be consistent with it. I'm not sure why he doesn't recommend regular arginine supplements. I have heard mixed reports on arginine. If you do think NO could be an issue for you and want to try Arginaid, you can get it from Walgreen's on-line (I recommend the lemon flavor).

High Level athletes have trainers who use various therapies to deal with nitric oxide buildup so that they can perform again quickly. (I heard one coach say that one of the reasons Phelps was able to accomplish all those gold medals, was because he has very little difficulty with Nitric Oxide the way other athletes do, and he doesn't need to rest between races the way others do). Many athletes get daily massage (wouldn't that be great?) but I doubt if most of us could afford it, and ice baths, right after they've finished their sporting or athletic events. Tony talks about ice a lot but I don't think I could handle ice baths at this stage. Would probably pass out.

Anyway, maybe we pwc should be looking into this a bit more. Dr. Pall seems to think so, here's a link to his theory and protocol for reducing NO (near the end of the article):

http://chronicfatigue.about.com/gi/dynamic/offsite.htm?zi=1/XJ & sdn=chronicfatigue & cdn=health & tm=108 & gps=375_1951_1219_568 & f=10 & su=p736.8.336.ip_ & tt=2 & bt=1 & bts=1 & zu=http%3A//sprident.com/martin-pall/

A lot of his supplements sound familiar, but I also notice a number of them I've taken in the past that have been somewhat beneficial.

penny

p.s. I also found another article which I'm pasting below. I'm not sure of the source (newtreatments.org). It does explain a lot about nitric oxide dysregulation in pwcs. Sounds very familiar, like the story of most of our lives. I don't know if they're just making the theory fit the symptoms, or if this really is a better understanding of how our illness works. Fingers crossed some good will come of it.

http://www.newtreatments.org/Adrenals/ga/123

NITRIC OXIDEIf the topic of nitric oxide is new to you, it will help a lotif you take the time to review some generalbackground on this toxic agent. Click here for nitric oxidebasics!An increase in nitric oxide during immune activation lowersoverall adrenal output and, coupled withlow DHEA, will cause the same clinical picture now evident inchronic fatigue syndrome andfibromyalgia (abstracts). Read a few of the abstracts and youwill see that increased levels of NO willnot only lower cortisol, but also lower aldosterone, DHEA,pregnenolone and catecholaminesecretion.The most direct evidence that NO alter adrenal function comesfrom work with rats. Dr. CBCymeryng, et al, at the University of Buenos Aires found thatNO significantly decreasedcorticosterone (the same as cortisol in man) production bothin unstimulated and incorticotropin-stimulated zone fasciculate adrenal cells, in

adose-dependent manner. The productionof pregnenolone from cholesterol was also significantlyreduced. This effect was reversed by ferroushemoglobin (abstract).But primary hypoadrenalism due to weakened adrenal glands isnot as much in evidence in CFS andFM, as is secondary hypoadrenalism (defect inpituitary-hypothalmus axis). The evidence in chronicfatigue syndrome and fibromyalgia all point to a reduced ACTHresponse to CRH and vasopressin.But it does not matter in this theory whether you have primaryor secondary hypoadrenalism!Upregulated nitric oxide due to hyperimmunity (coupled withanother toxic gas, carbon monoxide)also alters hypothalmus-pituitary function and would createthe exact same pattern now evidenced inthese illnesses (abstract).A vicious circle begins to form! Low cortisol and DHEA allowsthe immune system to becomehyper; hyper immune response (upregulated nitric oxide

andother cytokines) alters HPA axisfunction, resulting in low cortisol.If one were looking for a single factor that would completelyexplain chronic fatigue syndrome,including every single crazy symptoms known to occur in thisillness, you would need only look atupregulated nitric oxide (NO).Dr. AM Levin (Link) has examined this nitric oxide theory andis able to tie it in seamlessly with yeastinfections. I suspect that he is on target, but I would alsoadd that I believe many other pathogens canalso connect and cause the same situation. Still, I do likehis work in this area. He is the first MD tojump on the bandwagon of upregulated NO as a major factor inCFS.As mentioned earlier, Tumor Necrosis Factor-alpha (TNF-a) isknown to be increased in CFS.(Taking DHEA supplements helps down-regulates TNF.(abstracts))Tumor necrosis factor-alpha and other Th1 cytokinesupregulates the production of

nitric oxide (NO)and nitric oxide synthase (NOS) (abstracts) therefore, it issafe to say nitric oxide is upregulated inCFS (abstract).Even though no studies have been done to date about the strongconnection between TNF-alpha(known to be increased in CFS) and NO, there is evidenceshowing a strong possibility ofupregulated NO is CFS. As a matter of fact, evidence suggestthat autoimmune pathogenesis initiatedby inflammatory responses within the CNS may result in partfrom a vicious cycle in whichTNF-alpha and NO mutually provoke each other's production(abstract).Another important body of evidence is that fact that naturalkiller cell cytotoxicity, found low is CFS(abstract) (abstract), is also shown dose-dependently low whenchemical NO donors are addedduring afferent phase of NK stimulation with IL-12 andTNF-alpha. Conversely, when an inhibitor ofNO synthase was added, a subsequent increase in

thecytotoxicity of the effector cells towards theNK-sensitive target cells (K562) was observed (abstract). Inother words, upregulated nitric oxidelowers natural killer cell activity and accounts for theevidence found in CFS.In support of this view of upregulated nitric oxide in CFS,other medical researchers are alsobeginning to suspect this simple gas in playing a major rolein CFS. One theory involvesN-methyl-D-aspartate (NMDA) receptors in the brain. When brainfunction is balanced, GABA andNMDA receptor activity is balanced. In CFS, however, NMDAreceptors become substantiallymore active than GABA receptors. HealthComm Internationalfeels that a key component in theupregulation of NMDA receptors in CFS involves theoverproduction of nitric oxide. They state,"This molecule, itself a neurotransmitter, has been associatedwith stimulation of the NMDA receptorsystem when released into the nervous system

(Link).HealthComm is using an aspect of nitric oxide'sfunction in the brain to show evidence of upregulation in CFS.It look's like they could be on to partof the problem in CFS--nitric oxide does upregulate NMDAreceptors (abstract). However, Isuggest this is a pattern that is more closely associated withthe symptoms of hypoadrenalism, than itis a single cause of CFS.Here is were the valium every 3 days can help. The drugenhances GABA binding and increasesGABA receptors (abstract), which, like a see saw, will lowerNMDA receptors, but tolerance doeshappen rapidly so dosing every third day is mandatory in thebenefit is to be continued.One might also try low dose trazodone every day as a way ofdown-regulating the NMDA receptors(abstract). This could also be the manner in which low dosesof selective serotonin reuptakeinhibitors (SSRIs) help some with CFS since these drugs alsodown regulate NMDA

receptors, atleast in the rat (abstract).Recent research also shows that the amino acid homocysteine iselevated in the spinal fluid and brainof PWC (abstract). This evidence supports the view that nitricoxide is also elevated in CFS sincenitric oxide inhibits the enzyme that breaks downhomocysteine.Nitric oxide is the most potent vasodilator known. Excessiveproduction of this simple moleculecauses the drastic fall in blood pressure during shock. Nitricoxide is also now known to drasticallyreduce the pain threshold and to be responsible for increasedsensitivity to pain, especiallyfibromyalgia-like pain (references). Nitric oxide ismanufactured in cartilage cells (chondrocytes)(abstracts). Since nitric oxide stimulates the reception ofpain (abstracts), there can be little doubt thatNO is responsible for fibromyalgia pain in CFS!NO also can stimulate insulin secretion by

deenergizingmitochondria (abstract). Insulin also increasethe release of NO in the vascular system (abstract)(abstract).Since NO is a potent vasodilator,insulin produced in response to a high carbohydrate meal willcause increased vasodilation making aPWCs with neurally mediated hypotension feel much worse. Inother words, insulin and NO have aclose association that will lead to hypoglycemic reactions inPWCs, making a high protein dietmandatory in treating CFS. The activated immune system inchronic fatigue syndrome andfibromyalgia also reduces the manufacture of new healthy redblood cells (erythropoiesis) (abstract).A strong connection exist between the local activation of bonemarrow T-lymphocytes, increasedproduction of cytokines, and reduced levels of red bloodcells.In additon, both inflammatory cytokines and nitric oxide (NO)interfere with the way the bodymetabolizes iron (references) (abstract).

Not only does NOcause problems with iron metabolism,but defects in iron utilization and reutilization results inreduced performance of many iron-requiringenzymes and proteins (references).Research has found that when the immune system is activatedthe critical period in the developmentof nutritional iron deficiency occurs after 30 to 40 dayswithout iron supplementation. The person isunable to maintain hemoglobin levels without endangering theiron-requiring enzyme groups which areessential for life (abstract). This indicates that any singleillness or combinations of factors that canstimulate the immune system and increase nitric oxideproduction for longer than 30 to 40 days, couldprogress into CFS in selected individuals.A similar iron metabolizing problem exist in AIDS. As HIVinfection advances, progressive anemia isestablished. The study of iron metabolism in these patientsshows a pattern similar to

that of theAnemia of Chronic Disease (see below). A group of Spanishresearchers think that these changes inAIDS might be due to iron sequestration in phagocytic cellsinduced by release of cytokines from theimmune system (abstract).Red cell hemoglobin is the most important iron-requiringprotein likely defective in CFS.Hemoglobin is the MAJOR scavenger of excessive NO, therefore,an inability to remove this toxicimmune agent quickly before it vasodilates blood vesselsexcessively and over reacts with healthycells can result in many of the symptoms, particularlyfatigue, neurally mediated hypotension, and jointpain. In addition, if nitric oxide is not being properlyscavenged, then problems with excessive NOcan occur even if NO is not upregulated.As unbelievable as all this sounds, the very latest evidenceindicates that nitric oxide also controls theamount of oxygen reaching the cells. If you do not read

anylink in this article, you shouldstruggle to read this one (Link) . The researchers found thatthe loss of oxygen flips a switch thatreleases nitric oxide in the arteries to dilate blood vesselsand increase blood flow so that theremaining oxygen can be delivered to tissue. On the returntrip to the lungs, the oxygen that was lostin the arteries is recaptured in the veins, giving theappearance of inefficient oxygen delivery. Theresearchers measured blood flow and oxygen concentration inseveral regions of rat brain while therats breathed air with varying oxygen levels. They showed thathemoglobin releases a form of nitricoxide in the small arteries that regulate blood flow, thuspromoting oxygen delivery. When the animalsbreathed oxygen under higher air pressure, oxygen levelsincreased in tissue, and hemoglobincompensated by halting NO release and contracting bloodvessels.The finding also clears up another

puzzle. In test tubeexperiments, hemoglobin scavenges NO andconstricts blood vessels. Yet in the body, hemoglobin does nothave this effect under normalconditions. "This tendency to constrict blood vessels seems tooppose hemoglobin's job of deliveringoxygen," one researcher said. "Our findings explain whyhemoglobin doesn't constrict blood vesselsin the body. It releases NO in the arteries to counteract theNO it scavenges."But what if something goes wrong with this system? Asmentioned above, cortisol reversesmacrophage activation, therefore, it can be assumed that lowcortisol will allow macrophages to bemore easily activated by stimuli. Since these white cells dumploads of NO into the system when theyare activated, maybe one major problem with chronic fatiguesyndrome is activated macrophages.Release of NO from macrophages has been visualized in themouse (abstract). Their activation inchronic

fatigue syndrome is theorized to be similar to themanner in which a cancer drug (Taxol)primes macrophages in cancer patients (abstract).Nitric oxide primed macrophages are ready to dump their NO atthe least disturbance. This theorysuggest that increased stress of the faster blood flow throughthe vessels, after isoproterenol isinjected in the TTT, releases this "primed" nitric oxide,intensifying the effects of the drug causing theperson with activated macrophages to go into syncope rathereasily. The increased NO stimulates therelease of large amounts of prostacylin, which causesbradycardia (slowing of heart rate)(references).Physical activity would increased the release of NO fromprimed macrophages simply because thestress of muscle activity would put pressure on the primedmacrophages causing them to dump theirNO. The action of the heart muscle would also placealternating pressure on the

macrophages. Flowstress of the blood flowing more rapidly through the vascularsystem during exercise would alsorelease a lot of NO. So would a sudden drop in barometricpressure. These factors would explainwhy chronic fatigue syndrome and fibromyalgia are noted for anincrease in symptoms after physicalactivity. Some with CFS and FM swear they feel worse justbefore a weather front moves in, whichwould agree with the release of NO due to a drop inatmospheric pressure.Hemoglobin is not the only iron-requiring enzyme likelydefective in chronic fatigue syndrome andfibromyalgia. The cytochrome p450 liver enzyme system(abstract) is also likely defective. Theseenzymes are responsible for metabolizing toxic chemicals anddrugs (most antidepressants) intometabolites that can then be removed from the body in the bileor by the kidneys (link).As mentioned earlier, inflammatory stimuli, such as

TNF-alpha,are increased in chronic fatiguesyndrome. TNF-alpha increases nitric oxide production andnitric oxide reacts with the ironcomplexes in the cytochrome p450 enzymes thereby inhibitingthe action of these important liverenzymes. (abstracts) (abstract).Defects in cytochrome p450 liver enzymes due to excessivenitric oxide (abstract) will result in abuild up of environmental chemicals in the body and asuper-sensitivity to certain drugs. (references)Most chemicals use in food processing do not cause problemsfor healthy people simply becausehealthy people have normal liver enzymes and can metabolizethese chemicals and flush them out ofthe body. But in people with defective cytochrome p450enzymes, these chemicals can build up inthe body to the point where they become toxic. Most chemicalscan cause this toxicity. (link)The normal dosage of certain drugs can also cause toxicreactions if

they are not being properlymetabolized due to a defect in the p450 enzymes. (link) Aperson with this illness might have toreduce dosages of certain drugs to as low as 1/10th of thenormal dose to avoid reactions. Otherdrugs might not work simply because they must be metabolizedinto their bioactive metabolite inorder to become effective.Fact is, the failure of the cytochrome p450 liver enzymes todetoxify the body is likely somewhatresponsible for multiple chemical sensitivity and may even berelated indirectly to what is now thoughtto be responsible for Gulf War Syndrome. Researchers at theUniversity of Texas believe they knowwhat causes Gulf War Syndrome. A long term study of members ofan Alabama Seabee unit thatserved in the Persian Gulf War strongly indicated that manyveterans who became ill do not carry aspecific gene that attempts to neutralize the nerve gas Sarin.That lends more support to the claim

thatsoldiers in the Gulf War were exposed to small amounts ofnerve gas. (link) The genetic defect couldexplain why some soldiers were afflicted with the syndrome --which has a wide range of symptomsresembling chronic fatigue syndrome. The biggest questionsabout Gulf War syndrome has been whyone person got sick when the person next to him didn't. Butnow experts suspect a genetic reasonwhy some people got sick, linking the illness to damage fromcertain chemicals.Writing in the journal Toxicology and Applied Pharmacology,the research team said a gene thatcontrols production of an enzyme known as type Q paraoxonase,or PON-Q, which helps the bodydestroy toxins, might be responsible.It is highly specific for the chemical nerve agents sarin andsoman as well as for the common pesticidediazinon. Fact is, several organophosphorus insecticides aredetoxified through the cytochromeP450/paraoxonase (PON1) pathway

(abstract). The reaserchersfound strong statistical linksbetween Gulf War syndrome and veterans' reports of exposure tocombinations of chemicals likepesticides and low-level chemical nerve agents. They predictedin 1997 that it might be due to aPON-Q deficiency, and now that's what they have found. Humanserum paraoxonase (PON 1)exists in 2 major forms (Q and R), which differ in the aminoacid glutamine and arginine, respectively.These PON allozymes hydrolyze organophosphates and aromaticesters, and both also protect LDLfrom copper ion-induced oxidation.The group had linked three different neurological syndromes tothe use of pesticide-containing fleacollars, highly concentrated insect repellent and pillsformulated with pyridostigmime bromide tocounteract the effects of nerve gas, as well as exposure tolow-level chemical nerve agents.Other researchers have theorized about a similar mechanism

inchronic fatigue syndrome (abstract)involving toxicity through the GABAa receptor. Corrigan, etal, discuss the possible involvement oforganochlorine compounds which are widespread in theenvironment and may have similar toxiceffects through damaged cholinergic input to the dentate gyrusof the hippocampus where cholinergicand GABAergic transmission are closely linked.Researchers in Australia also found a close assoicationbetween organochlorines and chronic fatiguesyndrome(abstract) (abstract).A defect in iron-requiring P450 liver enzymes might alter thecytochrome P450/paraoxonase(PON1) pathway, affecting paraoxonase-Q in people with chronicfatigue syndrome, but it will likelytake decades before researchers answer this question.Liver enzymes might also play the major role in many foodallergies due to certain toxic compoundscontained naturally in some foods.Food allergies are also

likely due to Leaky Gut Syndrome(link). In this illness, the stomach wall isweakened and allows tiny particles of undigested food and foodchemicals to enter into the bloodstream where they are picked up by immune cells as pathogens.The immune reaction following theintrusion of food particles and food chemicals can causesevere migraine type headaches, depressionand insomnia (link). The likely cause of this problem inchronic fatigue syndrome is hyperimmunity,including upregulated IL-6 and nitric oxide.The way it appears, anything that can activated the immunesystem over a long period of time canlead to cytochrome p450 liver enzyme dysfunction and result inchronic fatigue syndrome andfibromyalgia!Since pregnenolone, progesterone, and DHEA are allbiosynthesized from cholesterol by p450iron-requiring enzymes, the failure of this enzyme system dueto an iron metabolizing problem causedby hyperimmunity

can lead to low levels of these neurohormones(abstracts). Low levels of theseneurosteroids are know to cause brain fog, especiallypregnenolone.Problems with iron metabolism can also contribute to loss ofenergy, reduced oxygen utilization,reduced blood pressure control, altered sleep, reduced brainperfusion, difficulty in concentration,and many other symptoms noted in CFS.At least one researcher is interested in the associationbetween a defect in iron metabolism andincreased nitric oxide production. (link)The secondary and/or primary hypoadrenalism found in CFScauses dehydration, decreasing thewater content in the blood by up to 40% in some individuals(reference). When there is less water inthe body, there is an equal less amount of water in the bloodand the blood thickened! Since RBCand hemoglobin measurements are based on a percentage of drawnblood, hemoconcentrated bloodis

artificially increase in red cell numbers and hemoglobin,causing an elevated reading in the drawnblood of a person with chronic fatigue syndrome. This falseincrease in RDC indices prevents anyiron related blood problem from being detected. People withchronic fatigue syndrome andfibromyalgia are anemic and neither they nor their doctor areaware of it!The type of anemia is called, Anemia of Chronic Disease (ACD)(link) . ACD is common in patientswho have a long standing disease in which the immune system isactivated. The causes are complexand incompletely understood, but probably involve inflammatorycytokines and nitric oxide. (link)In ACD the production of new red cells is insufficient for thedegree of anemia and RBC length ofsurvival is shortened and there is an impaired re-utilizationof iron.ACD is fairly easy to diagnose if iron deficiency anemia (IDA)can be ruled out, and

it is easy todiagnose IDA in an otherwise healthy person. But thedifferential diagnosis of ACD and IDA in apatient who has a chronic disease like chronic fatiguesyndrome, who also has an iron metabolizingproblem, is extremely difficult. The differential diagnosisrequires assessment of iron status, but thatassessment is complicated by the fact that ACD causes changesin the parameters of iron status.With chronic disease, Total Iron Binding Capacity (TIBC)decreases, counteracting the usualincrease due to iron deficiency. Serum iron decreases,mimicking iron deficiency.The single most important diagnostic mark of iron deficiencyis low serum ferritin, but ferritin ismarkedly elevated as an acute phase protein in a chronicdiseases, reaching many fold higher than thediagnostic point, even in clearly iron deficient patients.Recent clinical studies demonstrate that serum transferrinreceptor (sTfR), an

independent parameterof iron status, adds to the power of existing diagnostic testsin diagnosis of iron deficiency in patientswith chronic disease. It is, in fact, comparable to marrowaspiration, the gold standard for irondeficiency, in evaluating iron status.Most doctors will not know how to diagnose borderline anemiain CFS, and may simply dismiss it asnot possible. To get iron status properly evaluated, referyour doctor to this web site (click here).One other point should be made before leaving the subject ofiron in chronic fatigue syndrome andfibromyalgia. Not only does dehydration and low blood volumemask the presents of anemia, it alsoalters the flexibility of red blood cells and their ability todeform and travel through the tiny capillariesin the brain. Dehydrated red blood cells show signs of reduceelasticity (abstract) and could be thecause of reduced blood flow in the brain noted in CFS.

TiltTable TestThe results of Tilt Table Tests (TTT) in which 95% of CFSpatients are positive for neurally mediatedhypotension is likely due to increased nitric oxide productionin CFS coupled with certain factorsduring the administration of the TTT. The beta-adrenergicagonist, isoproterenol, is injected toincrease heart rate and decrease the amount of time spent inthe tilted position. In healthy folks withnormal nitric oxide levels, the drug vasodilates the bloodvessels and speeds the heart rate. But thisvasodilation is nitric oxide dependent so that when NO isinhibited, the vasodilation is decreased(abstracts). Conversely, when NO is upregulated as istheorized here, the response to isoproterenolis greatly exaggerated and syncope can occur.Many PWCs complain that the TTT cause the same type of flarebrought on by a period of intenseexercise. This is understandable since the same release of NOby

primed macrophages would occurwhen the heart rate increases during exercise. The flare frompost-exercise fatigue and a TTT wouldbe similar since they are both caused by the same phenomena.The Aspirin Test High doses of aspirin is also known torelieve a severe flare in symptoms afterexercise. Aspirin not only inhibits prostacylins, the drug isalso a nitric oxide inhibitor (abstracts).Taking 3-4 aspirin during a severe case of fatigue shouldcause you to recover about 30 minuteslater. The aspirin test should reveal to you that your NO isupregulated and causing your fatigue.Taking aspirin when you feel fine will do nothing so wait tillyou feel your worse to conduct this test.Taking aspirin before having a TTT would likely insurenegative results for NMH. Aspirin can alsohelp you reduce post-exercise fatigue.But one caution here: If you suffer a lot of headaches thatseemed food related, you likely

leaky gutsyndrome and taking aspirin can aggravate this condition andbring on more headaches. Why AreSo Many Women Affected?Chronic Fatigue syndrome and fibromyalgia are predominatelydiseases of women because femalesnaturally have ~20% less red blood cells and ~20% lesshemoglobin than men. They also suffer a fargreater iron loss than men due to monthly blood loss. To makematters worse for women, recentresearch shows that whole-body production of nitric oxide is20+% greater in healthy women than inmen (abstract).Estrogen is the likely culprit because this hormone alsostimulates nitric oxide production. Fact is,estrogen's upregulation of nitric oxide, a potent vasodilator,is likely the reason estrogen preventsheart attacks. (abstracts) I don't know how much comforting itis to tell a women with chronic fatiguesyndrome that she is less likely to have a heart attack due toher illness. I would

suppose that mostwould rather have the heat attack risk and manage it withexercise.In support of this theory, a recent correlation of serummeasures of nitric oxide production with lupusdisease activity has been discovered (abstracts). Lupus isanother mostly female illness, likely for thesame reasons above. Maybe a nitric oxide study in CFS/FM isnot far off? Certainly if Lupus wasshown to be associated with NO, some CFS researcher will soonput two and two together.Blacks and CFSHow many black people you know with CFS? None likely. Someresearchers says this is becauseblacks don't complain to doctors, but that's not true. Truthis, blacks do not suffer CFS and FMnearly as often as whites simply because they respond muchdifferently to increased levels of nitricoxide (Link) (abstract) (abstract). Blacks also have higherblood pressure and generally have highercortisol

levels.SerotoninPeople with chronic fatigue syndrome may or may not bedeficient in serotonin. Upregulated nitricoxide does decreases serotonin levels by inactivatingtryptophan hydroxylase, the initial enzyme in thebiosynthesis of this important neurotransmitter (abstract).And, since serotonin plays an importantrole in inhibiting the level of TNF-alpha (abstract), reducedserotonin levels could explain the increasein this potent cytokine found in some with CFS.But the serotonin picture is muddle. Many people with chronicfatigue syndrome respond negativelyto antidepressants taken to increase serotonin levels. Severalresearchers have also found evidence ofhigh serotonin levels in chronic fatigue syndrome. There isalso minor evidence that an allergicreaction to serotonin could be going on in some.Taking 5-HTP (link), the amino acid precursor to serotonin,might help restore serotonin and

downregulate TNF-alpha is some PWCs. It should also improve sleepand having a calming effect.Serotonin is an extremely important agent in chronic fatiguesyndrome and may or may not play a rolein many symptoms (link). This hypothesis takes the view ofindividual need when it comes toserotonin. Try it, but don't hesitate to stop taking serotoninboosters if you feel worse.Improving Red Cell HealthEating calves liver and/or taking various vitamins andsupplements to improve red cell health after youhave been successful at lowering cytokine/nitric oxide outputwith hydrocortisone (Every Third DayTherapy) will improve overall health. However, one must firstmakes sure that they have controlledthe upregulated nitric oxide, before taking iron supplements.The iron is sequestered away from nitricoxide in CFS for a reason. Iron forms potent and dangerousoxygen radicals when exposed to highlevels of NO. Therefore,

iron supplements are not recommendeduntil NO is brought under control.DopamineDopamine likely plays a big part in the symptoms of CFSbecause phentermine and other dopaminestimulates (ritalin, cylert) are know to provide fantasticshort term relief of chronic fatigue syndromeand fibromyalgia symptoms. But this research effort has notyet try to unravel anything meaningfulfrom the study of dopamine in these illnesses. Dopamine andnitric oxide are mentioned associatedwith each other in over 100 recent medical abstracts so anyoneinterested in looking into this mightfind some great info.B-12Vitamin B-12, especially hydroxocobalamin (B-12a), is known toreduce the symptoms of chronicfatigue syndrome and fibromyalgia. B-12, especiallyhydroxocobalamin, is also know as a nitric oxidescavenger (abstracts).In summaryIf you've got chronic fatigue syndrome, you have low

cortisoland DHEA due to a blunted ACTHresponse to CRH. You also suffer from increased cytokineproduction, upregulated nitric oxide, poorred cell health, defective iron-requiring enzymes and proteinsand low pregnenolone. Due to youractivated immunity and liver enzyme problems, you also sufferfrom chemical exposure and selectivedeficiency of certain amino acids and nutrients. Theseproblems are collectively responsible for allyour symptoms.Since there are many different root causes, no particulardrug, herb, or nutrient by itself can addressall the problems. This wide variety of symptoms coming frommany different aspects of the sameillness has also made this an extremely difficult syndrome forthe medical community and your friendsand relatives to accept. They will tend to think you arefaking it simply because you suffer from somany different, seemingly unrelated, symptoms.The average person (and

doctor) does not realize thatdysregulated nitric oxide can cause so manydifferent medical problems!The best things you can do to recover is increase yourcortisol bioactivity in order to lower cytokinesand nitric oxide, while at the same time slowly addressing allthe other medical problems. Not an easytask! You will need to go slow and by extremely patient.Remember, you could begin one drug ornutrient to address one problem and, at the same time, sufferan increase in symptoms from adifferent problem, causing you to think the new nutrient youjust started is not for you. Just theopposite could happen and likely has. You could try a newproduct and have a natural reduction insymptoms not related to the new product, causing you to thinkthe new product is a wonder drug.Pay close attention to the nutrients that have a proven tractrecord for helping others. If you triedthem once and failed to improve--go

back and try them again.Spending the extra time to learn about the broad consequencesof increased nitric oxide activity willhelp you to understand you illness and accept this recoveryprogram. Click here for more nitric oxideinfo and links. http://www.newtreatments.org/