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newsucntut. "With the kind oflevels we take in." says Richard Deitrich. 10 february 20071 NewScientist 131 .Then its sinister edge began to emerge. The onslaught on your body comes from within and without. a pioneer in acetaldehyde research at the University of Colorado Alcohol Research Center in Aurora.Alcohol and smoke are major sources of thepotent toxin acetaldehyde www. Curtains closed. For a long time. roughly 30 times more toxic than ethanol itself. liver. For such an innocuous-looking molecule. Another big reason for your hangover is a simple molecule called acetaldehyde. And if you could witness the state of your insides you'd be even more horrified. most of us should be dead. the spotlight is increasingly mo ving away from ethanol and towards aceta ldehy de. the body has a battery of detoxifying enzymes that specialise in ~ breaking the stuff down . Measuring overall acetaldehyde exposure is tricky as the molecule is quickly broken down in the body. acetaldehyde was thought to be a harmless intermediate in the breakdown of ethanol and was pretty much ignored. The assumption was that ethanol itself was to blame. The bacteria living in your mouth and guts churn it out in bucket loads. possibly. but you're only partly right. but your internal organs are n't so lucky. For 30 years researchers have known that excessive alcohol intake causes serious long-term damage to virtually every internal organ: brain. Youcan take comfort from the fact that once the acetaldehyde has cleared from your system you will feel a lot better. gonads. They will be feeling the effects of acetaldehyde for much longer. exhaust fumes and foods all contribute to your acetaldehyde load. skeletal muscle.tom IT'SHARD to look fetching with a hangover. Fortunately. Not a pretty sight. Tobacco smoke. or impurities in whatever it was you drank last night. pounding head and queasy stomach. as we find out more about how drink wreaks long-term havoc. produced by your liver as it breaks down ethanol. you lie in bed with a parched mouth. Now. but researchers now believe that acet aldehyde is at least part ly responsible for the risin g incidence of can cer an d liver disease as well as. Youare probably blaming your haggard state on dehydration. kidneys. It's not just our boozing habits that are to blame. heart. uterus and digestive system. acetaldehyde is surprisingly toxic. It started in the 1980s when alcohol researcher Victor Preedy of King's College London found that acetaldehyde is a powerful muscle poison. but the mechanism was unclear. On your way to the kitchen for a glass of water you catch sight of yourself in a mirror. It has since become clear that acetaldehyde is the real demon in the demon drink. Alzh eimer's.

Irreversible damage What is becoming in creasingly clear is t hat al m os t any ex posu re to acetaldehyde can do seriou s da m age. resea rchers at Nipp on carcinogen. Th is w ill initiate stru ctur e and function." says Seitz . rodents fed alcohol and also in the white blood There arc eve n sugges tions of a link cells of alcoh oli cs. which is just as well sinc e the long-term health consequences ar c turni ng out to be serious. Dizzin ess. Hospital of Helsinki . vol 33 p 3513).mean ing that Skeletal m uscle is parti cu larly badly affected. Acetaldehyde also se em s to play a role in Maryland .atl east in animals. Heidelberg in Germany. In 2005. reported The re is growing eviclence that that among a group o f peo ple with aceta ldehyde is a hu m an carcinogen too." he says. In 2004. colon an d ad duc ts have shown up in th e organs of rectal cancer. "It's a common mi sconception that the brain and the liver ar e the two organs most a ffect ed by alcoh ol abuse. agrees. hea dach e.rom . a whole range of adducts are form ed in th e liver .ro per cent of patients with alcoholic liver disease have anti-ace talde hyde an tibodies in their bloodstream . acetaldehyde is . Gene-deficient people also have high rates of head and neck cancer." Among alco holics. elevated he art rate and dilated blo od vess els. with up to 5 per cent of all breast att ack DNA in m uch th e sam e way it do es cancers att ribu ta ble to alcohol consump tion. 321 N ewS(ientislllOF ebruary2007 The im m ediate consequences of havi ng the faulty vers ion of the ALDH2 gene are high ly visible. pro tei n s. vol 40. which convert ace ta ldehyde to harm less acetic acid. japan. Not surpri singly. Acetaldehyde is then broken down by ALDH2 an d the resultin g acetic acid is burned as fuel in the muscles. It has been linked with a ho st alcoh ol research at the Univ ersity of of diseases. lo ng after the che mical itself h as disappeared from th e system (Alcohol and Alcoholism. According to Onni Niemela of th e University of'Tarnpere in Finl and.Almost eve ry tis sue in th e bo dy is eq uip pe d with the enz ymes known as alde hyde dehydrogen ase s (ALDHs). reported that acetaldehyde can breast cancer. who is m u tation s and chromosomal problems co nvi nced that esca lating alcoh ol in take in th e (Nucle ic Acids Research. including rheu m atoid arthritis. On ly minute amounts escape into the bloodstream. But that 's where the p ro ble m s sta rt. and can trigger tu m ours 20 to 25 yea rs later. in the gene for alcohol dehydrogena se . says Helmut Seitz. Drumming up an in fla m m atory response is usually considered a bad omen as Some of the bes t evidence come s from studying people who can not process the compou nd norm ally. the incidence of upper ga strointestinal tract cancer is about 50 times the normal rat e. then. does most of th e work . p 40). Preedy has found that rats given a single dose of ethanol end up with signifi cant muscle damage as a resul t of acet ald ehyde attacking proteins. Korean or Taiwa nese origin carry at least one fau lty co py of th e ALDH2 gene and can sca rcely break down acetaldehyde at all. muscle s. Rough ly 50 per cent of people of Japanese . There's more. The re are 19 different ALDHs in humans but one in particular.newsrientist. First." Eriksson says.are at greater risk of developing can cers o f the upper gastrointestinal tract and liver (Interna tional Ioutnal a/Cancer. the faulty version of ALDH2 was www." says Preedy.especially in t he liver . he says . A recen t study of 818 heavy dr inkers in Germany found that those individuals who ar e exposed to m ore acet aldehyde as a result of a genetic defect ­ in this case. Medical School in Kawas ak i. Th at's 12 hou rs of con t inu ous ex posu re to acetaldehyde. Th ese west is linked to risin g ra tes of liver. The mutation is dominant so even having on e copy causes problems. In the wake ofa dr inki ng bout. the immune system see s these adducts as foreign and fires off an in flammato ry response. most flushers tend to avoid alcohol. Chinese. Among the m inority of flushers who are also heavy drinkers. acet aldehyde will soon be considered to be res ear ch ers at t he US Nat ion al Institute on ca rcin ogen ic in humans. Alcohol Abus e a n d Alcoholism in Bethesda. Alzhe im er 's. Alzheim er's disease a nd can cer gastroenterologist at the University Central (New Scient ist. Th e ch anges persist for mo re th an 24 hours. Aceta ldehyde att ac he s itself to am ino groups in protei n s to for m stable compounds called adducts. Aroun d. 22 May 2004. " It rem ains to be so lved how fast ace taldehyde disappe ars. yo ur liver revs into ac tio n. ALDH2. possib ly longer. As soon as you sta rt dr ink ing alcohol. "You can se e it in any restaurant in Japan or China. Little wonder. The resulting ad duc ts dis rupt DNA's "Th e cells don 't forget." says alcohol rese a rche r Pete r Eri ksson fro m Finland's National Public Health Institute in Helsinki. "Muscle damage is the most common. The live r does a fantastic job: normally it elim ina tes over 99 per cent of the acetaldehyde. Almost as soon thes e people have an alcoholic drin k. profess or of in flammation.though in heavy dr inkers that figure can rise to 10 gram s . he art. a he art att acks. The ave rage liver can pr ocess about 7 grams of ethanol a n hour . alcohol dehydrogenase. F lushed faces it takes abou t 12 hours to eliminate all th e et ha n ol ina bottle of win e. that between ace ta ldehyde and Alzheim er's although ethanol itsel f is no t considered a disease. Mikko Salaspu ro. t he ir acetal de hyde leve ls shoot up to between 6 and 20 times that found in people wit h norm al ALDH2 . " It is likely t ha t Acetaldehyde also attacks DNA. This acetaldehyde " ru sh " trig gers faci al t1ush ing. nausea an d vo mi ting soon follow. Th ese and a ~ host of other resu lts all add to the growi n g suspicion th at acetaldehyde is a human it can resu lt in cell in jury an d persistent car cin ogen. vol na. bra in an d gastrointes ti n al tract. To make matters worse. thes e cause irr ever sible damage by messing u p protein structure an clfu n ctio n. muscle da m age is five times more common than cirrh osis of th e liver. p 1998) . it converts the ethanol into aceta ldehyde u sing anot her enzyme. p 485).

None of th es e interventions has been shown to prevent canc er." says Salaspuro. As a result. "It is not necessary to drink huge am ou nts of alcohol . th ere's more. vol 37 p 153)· Then t her e is acet aldehyde in th e diet.coming at us from all sides. "Com pan ies m aking da iry products someti mes try to increase the acetaldehyde level to give it a spe cia l aromat ic taste. There are . and in a st ud y with 10 vo lunteers.and evidence of its toxicity . Salasp uro hopes the gum co uld help pr event d iges tive tr act ca ncers in th ose who are most at risk . says Salaspuro. the toxic effect s persist for longer. Many of these churn out acetaldehyde as part of their norm al biochemistry. "It depends on the kinds of flora you have . Biomarkers & Prevention . The gum is being commerciali se d by a Fin nis h company ca lled Bioh lt. or are exposed to other people's smoke. Nevertheless. For ce nt uries. so cannot as yet be recommended as a su bstit ute for a healthy lifestyle. avoid sm oke.even low amounts of ethanol taken regula rly in a se n sit ive per so n in cr eases their risk. wh ich reacts with acetaldehyde and rem oves it from saliva. and next time you 'r e recovering from a ha ngover . Salaspuro and colleagues at th e Unive rsity of Helsinki .signi ficantly more common than am ong a randomly chosen group of h ealthy people of the same age (Annals ofthe New l'ork Academy ofSciences. compared with those who ab sta in from both. and the more alcohol you drink the m ore ace taldehyde you are ex posed to. the Fin nish researchers foun d that t reat m ent wit h chlorhexidine for three days cut acetaldehyde leve ls in drinkers ' saliva by 40 per cent. most of the ex cess ace ta ldehyde you encounter co mes fro m alcohol. for ins tan ce." And if you live in a city. With ace taldehyde . is particularly goo d at to ss ing out aceta ldehyd e. it 's not surp rising that scientists are busy developing ways to neut ra lise the threat. Unlike th e liver with its detoxify ing en zy mes. Scrub your teeth. The Fin ni sh researchers collecte d saliva samples fro m 132 volunteers who differed not on ly in the ir drink ing and smoking habits but als o in th e standard of t heir dent al hyg iene. "Som e yog hu rt producers are searching for new bact eria that are even better acetaldehyde produ cers. according to Salaspuro. Sherry producers. such as some Lactobacillu s and Bifidobact erium species. The re m ay be huge vari ations between one ca n didate for th e job. Calvados is particularly rich in acetal dehyde. and regular calvados dr inkers h ave twice th e in ciden ce of oesophag eal and oral can cer compared with wine d rink ers who con sume the same amount of alcohol. lactulosc appea rs to inhibit acetalde hyde production by m ak in g the colon more acid ic.newscientisLcom aceta ldehyde . you r acetaldehyde load rises fu rth er. Among smoker s. It gets wors e . Germ -bus ting mouthwash co uld also help. P 36). The effect is synergistic. Strept ococcus salivarius. • Lisa Melton isa science writer based in London 10 F ebruary 10071 NewScientisllH . Combine tobacco and alcoho l and the danger multiplies. Another. are developing a chewing gum tha t mops up acetaldehyde. though no bo dy is q uite sure how much this affects our h ealth. Mouthwash contai nin g the ant isepti c chlorhexidine has be en shown to slash th e numbers of acetaldehyde-p roducing m icroo rganisms in t h e mou th . produces 100 ti m es more acetaldehyde wh en exp o sed to ethanol com pared with other m icro organism s iso lated from the mouth. Micro bial ace tald ehyde produ ction coul d also explain why people with poo r d enta l hygiene have an in creas ed ris k of mouth cancer. There is no abso lu tely sa fe level of consum p tio n . Others absorb ethanol from alcoholic d rinks and turn it in to aceta lde hyde . t -cysteine. intestines using preblotics or probiotics. www. If you smoke . so acetaldehyd e m ay well not be the only culprit. i\not her solution proposed by th e Fin n ish team is to tinker with th e bugs living in your Diet dilemma Acetaldehyde in saliva also comes fro m th e bugs that co lon ise th e mouth and dig estive tra ct. the ris k of oral canc er is 7 to 10 times higher than for people wh o have never smoked. So who is at risk? As a general rul e. p 146). say Seit z and Salaspuro. In experiment s with rats . in gestin g a dose ofliving microorganisms that don 't produce acetaldehyde. of course. Air pollution adds to the to xic load." says Salaspuro. Where th ere is fer m en tation there is Las t yea r the team releas ed a study showing t ha t a piece of gum co n tai ni ng jus t 5 mill igram s of t-cysteine coul d totally eliminate aceta ldehyde hom saliva if che wed whil e smoking (Cancer Epidemiology. This co uld ex plai n th e Iso -fold rise in oral cancers seen in people who are both alco ho lics and sm oker s. Burning tobacco creates acetaldehyde that dissolves in saliva. cou ld als o help. the mouth's mucous m embranes are pretty poor at bre ak ing down acetald ehyde. Some people harbour o rganisms th at are particularly good at producing acetaldehyde. and acetaldehyde in saliva is a big problem. It's a lso worth hearing in m ind that m any alcoholic drin ks conta in acet aldehyd e from t he word go. " I don't know of any other cancers in which the associations are so strong. There is still only one sure route to a n acetaldehyde-free life : keep it clean. Acetalde hyde is spewed out by veh icle engines. " Seitz points out. vol IS. for example. remember to promise yo ur in tern al organs that this ti me rea lly will be the las t. an indi vidu al sm oker 's can cer risk is stro ngly as sociated with acetaldehyde levels in their saliva and some rese ar chers n ow believe that acetaldehyde may be one of the prin cipal carcinogens in cigarette smoke. Neisseria. downs of carci no gens in tobacco smoke. vol 1011.The gum contain s a harmless am ino acid." Salaspuro says. Lactulose . The result s show that poor denta l hygien e comes with at wofold in crea se in ace taldehyde leve ls (Oral Oncology. Alternatively.a ha rmless. encourage acetaldehyde product ion fo r its fruity arom a. peoples have used bacte rial fer mentation to produce food -eve ryth ing from p ickles an d yogurts to bread and cheese. indigestible sugar . Aceta lde hyde also occ urs natu rally in ripe fr u it and coffee. One mouth-dwelling bug.