Oxidative Stress and Free Radical Damage

Free Radicals The Body's Natural Antioxidants Overview Superoxide Dismutase (SOD !lutathione "eroxidase "eroxynitrite Formation #xcessive $ree radical (oxidative dama%e to the mitochondrial mem&rane 'ar(ers $or Oxidative Stress and Dama%e

Free Radicals: Free radicals are those particles and molecules that cause dama%e to the &ody's cells and essential $atty acids (e)%) #"A &y their ready reactivity and oxidisin% a&ility) This characteristic is de$ined &y their unpaired electron) Oxidative dama%e is o$ten associated with premature a%ein% and &iochemical and DNA dama%e) Some examples o$ oxidative dama%e to cells can &e $ound on the *denti$ication pa%e) Oxidative stress may not &e a primarly cause o$ +FS or related conditions in most su$$erers, &ut it is o$ten a contri&utary $actor) Oxidative dama%e is o$ten much hi%her in those su$$erin% $rom impaired liver $unction, heavy metal toxicity or who are heavily detoxi$yin% the &ody (releasin% heavy metals $rom the tissues ) http-..en)wi(ipedia)or%.wi(i.Antioxidant/Oxidative0stress0in0disease 'Oxidative stress is thou%ht to contri&ute to the development o$ a wide ran%e o$ diseases includin% Al1heimer's disease, "ar(inson's disease, the patholo%ies caused &y dia&etes, rheumatoid arthritis, and neurode%eneration in motor neurone diseases) *n many o$ these cases, it is unclear i$ oxidants tri%%er the disease, or i$ they are produced as a conse2uence o$ the disease and cause the disease symptoms)))The &rain is

uni2uely vulnera&le to oxidative in3ury, due to its hi%h meta&olic rate and elevated levels o$ polyunsaturated lipids, the tar%et o$ lipid peroxidation) +onse2uently, antioxidants are commonly used as medications to treat various $orms o$ &rain in3ury)' Free radicals dama%e the mitochondria (that produce the &ody's ener%y ) Free radical dama%e shorts the li$e o$ our &odies cells and contri&utes to premature a%ein%) The num&er o$ times our somatic cells can replicate or divide are $ixed or rather limited) The protective telomeres present at the end o$ chromosomes &ecome shorter each time a cell divides) The telomeres maintain the via&ility o$ &ody.somatic cells) 4hen they are too short they can no lon%er protect the chromosomes or provide the cell with the a&ility to divide) 4hen the telomeres o$ the chromosomes that ma(e up a cell are lost, the cell under%oes apoptosis or perish) Thus, increasin% the len%th o$ the li$e o$ each cell prior to division (&y consumin% enou%h antioxidants and minimisin% the num&er o$ oxidants consumed.&reathed in contri&utes to increasin% one's overall li$e expectancy and delays the onset o$ a%ein%) *ndeed, oxidative stress seen in various diseases is pro&a&ly itsel$ a symptom o$ poor liver $unction) *t is li(ely that impaired liver $unction is in $act closely associated with these diseases) Oxidants and $ree radicals, includin% in$lammatory and pro5oxidant cyto(ines o$ the immune system, have an adverse e$$ect on &lood vessel mana%ement and can promote the $ormation o$ atherosclerotic pla2ue) Dr Ray D) Strand's we& site &elow contains articles on oxidative stress) Below is also a lin( to an article a&out oxidative stress and +FS and F'S) www)&ionutrition)or%.de$ault)asp Oxidative Stress and +FS and F'S pd$ $ile Oxidative stress should &e o&vious $rom a variety o$ di$$erent &lood tests and &lood analyses, $or example, &lood serum vitamin levels (A, +, # , live &lood microscopy, and many others) For more in$ormation on Oxidative Stress and their e$$ect on &lood cells, please see the *denti$ication pa%e) Dr 'artin "all has theorised that tri%%ers o$ +FS and Fi&romyal%ia such as viral and &acterial in$ections (amon%st others actually cause an increase in Nitric Oxide levels, %reatly increasin% the oxidative stress on the &ody and worsenin% symptoms, in a &ody that may well have &een under considera&le oxidative stress anyway &ecause o$ dietary, li$estyle and other environmental causes) "lease see the 6iri pa%e $or more in$ormation) Free radicals come $rom a wide variety o$ sources, $rom pollution in the air we &reathe, heavy metals (which also multiply the num&ers o$ $ree radicals , air molecules ionised &y radiation, smo(e (ci%arettes, dru%s or $ires , chlorine in tap water, &ut mainly our diet)

The &i%%est source o$ in%ested $ree radicals is pro&a&ly $ried $oods and heated coo(in% oils, e)%) potato crisps.chips, $rench $ries, onion rin%s etc) ($ried in ve%eta&le oils which oxidises readily on account o$ the hi%h Ome%a 7 and 8 $atty acid content, into $ree radicals ) 9eated oil also tastes rather unpleasant compared to its unheated counterpart i$ one excludes the $ood taste $rom the e2uation) "lease see the Nutritional pa%e $or more in$ormation) *t should &e noted that most tap water is not neutral in p9) Blac(Spy's local tap water is &etween 8):; and 8);<, i)e) sli%htly acidic, on account o$ the chlorine that is added to it) +hlorine is an anti5micro&ial a%ent that (ills o$$ &acteria and other micro&es that mi%ht cause illness and in$ection otherwise) *t achieves this &ecause it is an oxidisin% a%ent) 4hen +hlorine %as dissolves in water, it produces hydrochloric acid and hydrochlorous acid (the oxidisin% a%ent ) This oxidisin% power is ta(en into the &ody and can add to the $ree radical &urden o$ the &ody as well as lowerin% one's p9) "ure water has a p9 o$ =) Some water authorities also add Fluoride to water, as descri&ed a&ove, to 'help with tooth decay') As already mentioned, it is possi&le to remove Fluoride and +hlorine $rom tap water as well as other potential contaminants and heavy metals, usin% a sophisticated water puri$ication and ionisation system) This can elevate the p9 $rom sli%htly acidic to sli%htly al(aline, i)e) a&ove p9 =) "lease see the Acidosis pa%e $or more in$ormation) As well as $rom external sources, $ree radicals also derive $rom the partial detoxi$ication products produced in the liver, as toxins are processed prior to excretion) *n addition, $ree radicals are produced inside the mitochondria o$ our cells, and their prouction is directly related to meta&olism, i)e) the rate o$ respiration and amount o$ ener%y we produce) The more ener%y we produce, the more $ree radicals we produced) 9owever, under normal, healthy circumstances, the &ody has its own mechanimsms to deal with these) As oxy%en and other compounds are &ro(en down to &e utilised &y the &ody (as part o$ meta&olism , certain molecules &ecome un&alanced, creatin% $ree radicals or oxidants) 4hen $ree radicals or oxidants are produced in excess, cells may su$$er $rom oxidative dama%e) One o$ the most harm$ul o$ these $ree radicals is the anion Superoxide) http-..en)wi(ipedia)or%.wi(i.Superoxide Superoxide is the anion O:5, i)e) the dioxy%en O: or O>O molecule with an additional electron, di$$erent $rom the Oxy%en anion O55) *t is important as the product o$ the one5 electron reduction o$ dioxy%en, which occurs widely in nature) 4ith one unpaired electron, the superoxide ion is a $ree radical, and, li(e dioxy%en, it is parama%netic)

*t should &e noted that some treatments $or dys&iosis include hydro%en peroxide and o1one, &oth o$ which are power$ul oxidisin% a%ents) O$ course, they may well oxidise harm$ul &acteria and yeasts etc), &ut they are not selective in what they oxidise and will cause oxidative dama%e.stress to everythin% they come into contact to varyin% extents) *$ consumed orally, then they will have a detrimental e$$ect on one's pro&iotic %ut $lora and also may well oxidise some o$ the tissues as well) Acidophilus &acteria do produce hydro%en peroxide, &ut in very small 2uantities and locally within the colon) &ac( to top The Body's Natural Antioxidants &ac( to top Overview http-..en)wi(ipedia)or%.wi(i.Antioxidant Antioxidants are molecules that protect the &ody a%ainst oxidative dama%e, which are themselves oxidised rather than &odily tissues &ein% oxidised) They also help to reduce the &uild up o$ atherosclerotic pla2ue in the arteries and help to protect the liver) A lac( o$ antioxidants as descri&ed a&ove will result in an increased level o$ oxidative dama%e, the &uild o$ up atherosclerotic pla2ue, premature a%ein% and put an excessive stress on the liver) Antioxidants protect the cells $rom dama%e $rom $ree radicals or oxidisin% a%ents and particles) Antioxidants in %eneral, and in particular the Superoxide Dismutase (SOD en1yme (discussed &elow have the a&ility to &rea( down Superoxide) They also help to reduce pla2ue that &uilds up inside our artery walls $rom hi%h ?D? cholesterol &lood levels) Some people have reported hu%e li$e chan%in% &ene$its $rom consumin% hi%h levels o$ antioxidants (e)%) drin(in% @an%o 3uice , &ut it is li(ely that such individuals were simply su$$erin% $rom excessive $ree radicals and not more complex &iochemical pro&lems) *n %eneral terms, the capacity to respond to oxidative stress has the potential to positively impact ener%y levels, vitality, health and the a&ility to cope with the physical and psycholo%ical stresses o$ modern li$e)

www)netdoctor)co)u(.$ocus.nutrition.$acts.oxidative0stress.oxidativestress)htm For an examination o$ %ood sources o$ external antioxidants, please see the Nutritional De$iciencies pa%e) The most power$ul antioxidants are the &ody's own internally produced antioxidants, (nown as "rimary Antioxidants, which tar%et speci$ic types o$ oxidative threats in the &ody, and are the most important down5re%ulators o$ oxidative stress in the &ody) They help to support proper liver $unction and the immune system) These "rimary Antioxidants are the $our in the list &elow) The most important o$ these are SOD, +atalase and !px) They are en1ymes that &rea( down oxidants, i)e) antioxidant en1ymes) 'elatonin is a antioxidant hormone and is also involved in the +ircadian Rhythm (awa(e.sleep cycle ) The external antioxidants (i)e) those consumed and in some cases in3ected (e)%) !lutathione , (nown as Secondary Antioxidants, are relatively less potent in their antioxidant capacity and are antioxidant chemicals) "erhaps the most e$$ective approach is to prime the &ody to produce its own extra stren%th internal (primary antioxidants, includin% SOD, +atalase and !px) These antioxidants provide the primary and most important level o$ de$ence a%ainst oxidative stress and $ree radical dama%e) O$ course, a healthy diet and in particular one that is rich in Ome%a 7 and 8 $atty acids and other nutritious $oods sources, with perhaps moderate amounts o$ %reen tea and al%ae, will also &e hi%h in antioxidants anyway) *t is %enerally %ood practice to eat a diet rich in antioxidants and to ta(e additional antioxidant supplement o$ one $orm or another) *n %eneral terms, "rimaryA and Secondary Antioxidants are listed in decreasin% order o$ potency &elow)

Superoxide Dismutase (SOD A +atalaseA !lutathione "eroxidase (!px A 'elatoninA !lutathione, +oBC< +arotenoids, 6itamin #

Flavonoids, 6itamins A and + 'inerals, "roteins

&ac( to top Superoxide Dismutase (SOD http-..en)wi(ipedia)or%.wi(i.Superoxide0dismutase SOD is in itsel$ not an antioxidant per se, &ut an en1yme that &rea(s down Superoxide speci$ically (i)e) a tar%etted antioxidant en1yme ) +ertain nutritional elements (i)e) those metals descri&ed a&ove ma(e up an essential part o$ the SOD molecule and su$$icient levels are essential in those with hi%h levels o$ oxidative stress or impaired liver $unction (or indeed those em&ar(in% on a detoxi$ication pro%ramme ) See also the section on liver $unction on the toxicity pa%e $or more in$ormation) http-..en)wi(ipedia)or%.wi(i.Antioxidant/Superoxide0dismutase):+0catalase0and0peroxi redoxins 'Superoxide dismutases (SODs are a class o$ closely related en1ymes that catalyse the &rea(down o$ the superoxide anion into oxy%en and hydro%en peroxide) SOD en1ymes are present in almost all aero&ic cells and in extracellular $luids) Superoxide dismutase en1ymes contain metal ion co$actors that, dependin% on the iso1yme, can &e copper, 1inc, man%anese or iron) *n humans, the copper.1inc SOD is present in the cytosol, while man%anese SOD is present in the mitochondrion) There also exists a third $orm o$ SOD in extracellular $luids, which contains copper and 1inc in its active sites) The mitochondrial iso1yme seems to &e the most &iolo%ically important o$ these three, since mice lac(in% this en1yme die soon a$ter &irth) *n contrast, the mice lac(in% copper.1inc SOD are via&le &ut have lowered $ertility, while mice without the extracellular SOD have minimal de$ects) *n plants, SOD iso1ymes are present in the cytosol and mitochondria, with an iron SOD $ound in chloroplasts that is a&sent $rom verte&rates and yeast)' As discussed on the *denti$ication Tests pa%e, %eneral cell protection $rom dama%e &y superoxide is provided &y intracellular Dinc-+opper SOD (Dn.+u5SOD ) 'itochondria are protected &y man%anese5dependent SOD ('n5SOD ) #xtracellular SOD (#+5SOD 5 another type o$ Dn.+u SODase protects the nitric oxide pathways that relax vascular smoother muscle tissue) For each $orm o$ SOD, %enetic variations are (nown, and mutations and polymorphisms can occur durin% excessive oxidative stress placed on the DNA) DNA adducts can chemically &loc( these %enes however) Dinc, +opper and 'an%anese are extremely important elements $or maintainin% healthy SOD levels, and patients should ensure that these mineral levels are supplemented i$ they drop &elow their re$erence ran%es) 'itochondrial $unction is limited in a sense &y the availa&le o$

SOD as without it extensive mitochondrial dama%e would occur (with elevated respiration rates &eyond the availa&le SOD and !lutathione that can &e produced) Su$$icient SOD levels, and indeed SOD supplementation, have &een lin(ed to the prevention and.or limitation o$ DNA dama%e.mutation $rom E6 exposure) "lease see the Nutritional De$iciencies pa%e, in particular the sections on Antioxidants and also 6itamin D and E6 ?i%ht #xposure) &ac( to top !lutathione "eroxidase http-..en)wi(ipedia)or%.wi(i.!lutathione0peroxidase !lutathione peroxidase (!px is the %eneral name o$ an en1yme $amily with peroxidase activity whose main &iolo%ical role is to protect the or%anism $rom oxidative dama%e) The &iochemical $unction o$ %lutathione peroxidase is to reduce lipid hydroperoxides to their correspondin% alcohols and to reduce $ree hydro%en peroxide to water) The reduced $orm o$ !lutathione (!S9 is one o$ the most important compounds involved in detoxi$ication and $or inter5 and extracellular Antioxidant protection in the &ody) !lutathione levels are $re2uently low in +FS patients) For more in$ormation a&out the role o$ !lutathione in "hase ** ?iver Function (+on3u%ation in the removal o$ toxins $rom the &ody, please see the "hase C and : #n1ymatic Function Summary section on the ?iver Function pa%e) For more in$ormation on !lutathione production, throu%h a process called 'ethylation, which is $re2uently impaired in individuals with +FS, please see the !lutathione and 'ethylation section on the ?iver Function pa%e) For more in$ormation %enerally on !lutathione "eroxidase and Superoxide, and their connection to mitochondrial $unction and cardiac $unction, please see the +ardiac *nsu$$iciency pa%e) &ac( to top Peroxynitrite Formation: "lease see the Nitric Oxide +ycle and "eroxynitrite pa%e $or a detailed review o$ the shi$t in the Nitric Oxide cycle in many +FS patients, and the e$$ect on overall oxidative stress) &ac( to top

xcessive !ree radical "oxidative# damage to the mitochondrial mem$rane: Reproduced $rom the 'itochondrial Dys$unction pa%eFree radicals damage the integrity of the mitochondrial membrane by attacking/oxidising the actual phospholipids that make up the majority of the mitochondrial membrane material. Free radicals are produced inside the mitochondria as a byproduct of energy production and respiration. The more energy you produce, the more free radicals you produce. The body has its own natural defence against such free radicals to prevent excessive free radical damage to the mitochondrial membranes. These are the antioxidant enzymes !" and to a somewhat lesser extent #lutathione. $itochondrial function is limited in a sense by the available of !" as without it extensive mitochondrial damage would occur %with elevated respiration rates beyond the available !" and glutathione that can be produced. & deficiency in the production of either of these primary antioxidant enzymes can of course result in excessive free radical damage to the mitochondrial membranes and excessive perforation and leaking of powerful free radicals like uperoxide out of the mitochondria, causing additional knock on problems. "amaged mitochondrial membranes are sometimes referred to as causing 'energy leaks', although this is rather a gross simplification. (n addition to excessive free radicals damaging the mitochondrial membranes, they may also cause damage to the actual mitochondrial ")& itself. $itochondrial ")& is completely separate from nuclear ")&. *nlike )uclear ")&, it is inherited solely from the mother in sexually reproducing organisms, e.g. humans. $itochondrial ")&, because of its close proximity to the inner mitochondrial membrane's respiratory chain, a primary source of free radical production, and also their limited capacity for self+repair and self+protection, are particularly susceptible to free radical damage. #eneral cell protection from damage by uperoxide is provided by intracellular ,inc-.opper !" %,n/.u+ !"/. $itochondria are protected by $anganese+dependent !" %$n+ !"/. 0xtracellular !" %0.+ !" + another type of ,n/.u !"ase/ protects the nitric oxide pathways that relax vascular smoother muscle tissue. For each form of !", genetic variations are known, and mutations and polymorphisms can occur during excessive oxidative stress placed on the ")&. ")& adducts %toxins that attach to ")& genes/ can chemically block these genes however. ,inc, .opper and $anganese are extremely important elements for maintaining healthy !" levels, and patients should ensure that these mineral levels are supplemented if they drop below their reference ranges. http-//en.wikipedia.org/wiki/$itochondrial1")& http-//ghr.nlm.nih.gov/chromosome2$T

(n addition, free radicals can also be produced in excess by the liver. 3iver function with regards to clearing undesired compounds from the blood involves a two step process. This is described in detail on the (nefficient 3iver function page. The first step is 4hase 5 6egulation, using the .ytochrome 4789 enzymes, which are largely a set of oxidase reactions, producing a large number of free radicals. ufficient antioxidant compounds and chemicals are re:uired by the liver in order to keep these from causing too much damage within the liver and outside of the liver, these are both endogenously produced antioxidants and dietary sources of antioxidants. The second step of liver function is the 4hase ; .onjugation step, whereby molecules are added to the toxins in order to make them easier to remove from the body. These processes work in a perfect balance in a healthy liver. (f antioxidant and conjugation steps are impaired, then a large number of free radicals will be produced which can cause oxidative damage within the liver and also spill out into the blood stream, flooding it with excessive free radicals. The role of antioxidants such as uperoxide "imutase and 6+3ipoic &cid are discussed on the .ardiac and )utritional pages. c/f Toxicity 5 page- The presence of heavy metals in the body is thought to hugely increase the burden of free radicals on the body. Free radicals tend to multiply <exponentially' %not mathematically correct/ in the body when they strike heavy metal complexes. & free radical hitting a toxic metal ion is thought to multiply by a factor of 5999 or even 5,999,999, producing betweens 5999s and millions of new free radicals. These free radicals will damage proteins in the body unless they are neutralised by the body's natural antioxidants or antioxidant nutrients. !ne way to avoid excessive free radical damage is to remove toxic metal elements from the body and of course to take enough antioxidants/simulate production of the body's natural antioxidants. 4lease see the &ntioxidants section of the )utrition page and the links below for more information. www.healingdaily.com/conditions/free+radicals.htm &ac( to top Other %ar&ers !or Oxidative Stress and Damage: Reproduced $rom the Tests pa%e (in italics 8-Oxo-2-Deoxyguanosine & 8-Oxo-Guanosine =+!xo+;+"eoxyguanosine %a.k.a. =+!>d#/ is a ")& oxidative damage marker, a byproduct of the oxidation of ")& by free radicals or 6eactive !xidative pecies %6! /. =+!xo+#uanosine %a.k.a. =+!>#/ is a cytoplasmic 6)& oxidative damage marker, a byproduct of the oxidation of 6)& by free

radicals or 6eactive !xidative pecies %6! /. .ellular concentrations of both of these compounds are a direct measurement or indication of oxidative stress in the body as a whole. !xidative stress may come from excessive free radical formation by the presence of heavy metals, or it may be related to excessive cellular immune activation response and inflammation %)eopterin production/ or indeed from free radicals escaping damaged mitochondrial membranes, etc. ?oth of these ")& and 6)& oxidative damage markers can be measured in this :uantitative urine test by 3aboratoire 4hilippe &uguste in France. ")& damage is one of the key mechanisms in the ageing process and the development of cardio+vascular diseases and cancer. 6)& oxidation is an early prominent feature of the main brain neurodegenerative diseases such as &lzheimer's "isease %&"/, 4arkinson's "isease %4"/, enile "ementia % "/, &myotrophic 3ateral clerosis %&3 / and $ultiple ystem &trophy %$ &/.

F2-Alpha Isoprostane F;+&lpha (soprostane %a.k.a. =+iso+4#F; alpha/ is a marker for oxidative damage of the lipid component of cell membranes. (t is a downstream oxidation production of membrane oxidation. (soprostanes as prostaglandin+like compounds created from the free radical attack of esterified of the !mega @ 0ssential Fatty &cid %0F&/ known as &rachidonic &cid %&6&/ inside the membrane phospholipid. (t is of course a very different molecule to a prostaglandin which is a lipid compound produced enyzmatically by the body using cyclooxygenase %.ox5+;/ from 0F&s and has nothing to do with free radical attack on cell membranes. (soprostanes in general are valuable markers in clinical biology as they are found in all biological fluids and tissues and are stable in vivo and ex vivo. There are 59 times more isoprostanes in atherosclerotic pla:ue compared with normal vascular tissue. They are also only dependent on their production %in this case free radical attack/ rather than metabolism or excretion without intraindividual variability. There are many studies validating (soprostanes as the most accurate and reliable indicator of oxidative stress in vitro and in vivo. http-..en)wi(ipedia)or%.wi(i.*soprostane Arachidonic Acid (ARA is particularly sensitive to peroxidation &y $ree radicals) F5iso5"!F: alpha is o$ course a very di$$erent

molecule to a prosta%landin which is a lipid compound produced eny1matically &y the &ody usin% cyclooxy%enase (+oxC5: $rom #FAs and has nothin% to do with $ree radical attac( on cell mem&ranes) F:5Alpha *soprostane levels can &e measured in one's urine and are a direct measurement o$ the extent o$ $ree radical oxidation o$ the mitochondrial mem&ranes)

%alondialdehyde and 'rotonaldehyde Two indicators (or downstream products o$ excessive (phospho lipid peroxidation (and mitochondrial mem&rane dama%e are the aldehyde derivates 'alondialdehyde ('DA and +rotonaldehyde, which can &e $ound attached to dama%ed mitochondrial mem&ranes under microscopy as part o$ the Translocator "rotein Studies &y the Acumen la&oratory) %ethemoglo$in ( Oxidised )emoglo$in #xcerpt $rom the Tissue Oxy%enation and +FS pa%e (in italics $ethemoglobinemia is a disorder characterised by the presence of elevated levels of oxidised hemoglobin in the blood, a.k.a. methemoglobin %met>b/. This results from the Ferrous %Fe;A/ (ron ion inside the >emoglobin molecule being oxidised by free radicals to Ferric %FeBA/ (ron. $ethemoglobin is a non+oxygen binding form of >emoglobin. !n average, a person will have 5C or less of his total >emoglobin count as $ethemoglobin, the remaining DDC present as >emoglobin. 0levated levels of $ethemoglobin can result in tissue hypoxia. pontaneous formation %oxidation/ of met>b by free radicals is normally mitigated by protective antioxidants in the 6?.s. .ontributary factors are oxidising agents or free radicals, including drugs, local anaesthetics, aniline dyes, metoclopramide, chlorates, bromates etc. ?lood high in met>b is a characteristic brown colour %i.e. rust presentE/ compared with the bright red colour of healthy blood. Treatments for $ethemoglobinemia include supplemental !; and administration of diluted methylene blue solution which reduces the Ferric (ron back to Ferrous (ron. !ther treatments may include other antioxidant %reducing agents/ for example Fitamin . %&scorbic &cid/. http-//en.wikipedia.org/wiki/$ethemoglobinemia

Gith regards to .F patients, it is likely to be slight but significant contributary factor, but a small part of a bigger picture. & study by 6. 6ichards, 3. Gang and >. Helinek, '0rythrocyte !xidative "amage in .hronic Fatigue yndrome', &rchives of $edical 6esearch, Folume B=, (ssue 5, pp D7+D=, examined B5 .F patients and 75 healthy control subjects and evidence of oxidative damage was present in the .F patients with statistically significant increases in ;,B+?4# %an indicator of long term low oxygenation + described above/, met>b and $"& %$alondialdehyde/. http-//linkinghub.elsevier.com/retrieve/pii/ 95==779D9@99;DD; met>b cannot be detected by using a 4ulse !ximeter, the usual pocket device for monitoring blood oxygen saturation levels, which only works with >emoglobin. !ne can view the colour of one's blood. There is a dedicated blood test however to detect the met>b levels as well as the levels of related non+!;+binding forms of >emoglobin F&I .!rg's article on 4ulse !ximetry in $ethemoglobinemia http-//www.ucsfhealth.org/adult/adam/data/99BBJ5.html