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l and smoke are major sources ofthepotent toxin acetaldehyde

IT'SHARD to look fetching with a

hangover. Curtains closed, you lie in

bed with a parched mouth, pounding

head and queasy stomach. On your way to the

kitchen for a glass of water you catch sight of

yoursel f in a mirror. Not a pretty sight. And if

you could witness the state of your insides

you'd be even more horrified .

Youare probably blaming your haggard

state on dehydration. or impurities in

whatever it was you drank last night, but

you're only partly right. Another big reasonfor your hangover is a simp le molecule called

acetaldehyde, produced by your liver as it

breaks down ethanol. Youcan take comfort

from the fact that once the acetaldehyde has

cleared from your system you will feel a lot

better, but your internal organs are n't so

lucky. They will be feeling the effects of

acetaldehyde for much longer.

Fora long time, acetaldehyde was

thought to be a harmless intermediate in the

breakdown of ethanol and was pretty much

ignored.Then its sinisteredge began to

emerge. It started in the 1980s when alcohol

researcher Victor Preedy of King's CollegeLondon found that acetaldehyde is a powerful

muscle poison. roughly 30 times more toxic

than ethanol itself.

It has since become clear that acetaldehyde

is the real demon in the demon drink. For

30 years researchers have known that excessive

alcohol intake causes serious long-term

damage to virtually every internal organ:

brain, kidneys, gonads, skeletal muscle, liver,

heart, uterus and digestive system. The

assumption was that ethanol itself was to

blame, but the mechanism was unclear.

Now,as we find out more about how drink

wreaks long-term havoc, the spotlight is

increasingly mo ving away from ethanol and

towards aceta ldehyde.

It's not just our boozing habits that are to

blame.Tobacco smoke. exhaust fumes and

foods all contribute to your acetaldehyde load.

The bacteria living in your mouth and guts

churn it ou t in bucket loads. The onslaught on

your body comes from within and without.

Measuring overall acetaldehyde exposure

is tricky as the molecule is quickly broken

down in the body, but researchers now believe

that acetaldehydeis at least partly responsible

for the rising incidence of cancer and liver

disease as well as, possibly,Alzheimer's.

Forsuch an innocuous-looking molecule,

acetaldehyde issurprisingly toxic. "With the

kind oflevels we take in, most of us should be

dead," says Richard Deitrich, a pioneer in

acetaldehyde research at the University of

Colorado Alcohol Research Center in Aurora.

Fortunately, the body has a battery of

detoxifying enzymes that specialise in

breaking the stuffdown .

10 february 20071 NewScientist 131



Almost every tissue in th e body is

quipped with the enz ymes known as

ldehyde dehydrogen ases (ALDHs), which

er t ace ta ldehyde to harmless acetic acid.

here are 19different ALDHsin humans bu t

e in partic ular, ALDH2, does most of th e

especially in the liver .

As soo n as you sta rt dr ink ing alcohol,

ur liver revs into ac tio n. First, it converts the

thanol into acetaldehyde using another

me, alcohol dehydrogen ase.

etaldehyde is then broken down by ALDH2n d th e resultin g acetica cid is burned as fue l

the muscles. The live r does a fantastic job:

ormally it elim ina tes over 99 per cent of the

cetaldehyde . Only minute amounts escape

th e bloodstream. But that 's where th e

ro blem s sta rt .

The ave rage liver can pr ocess about 7grams

ethanol a n hour - tho ugh in heavy dr inkers

figure can rise to 10 gr a m s - mean ing that

Skeletal m uscle is particularly badly

affected. Preedy has found that rats given a

single dose of ethanol end up with significant

muscle da mage as a result of acetald eh yde

at tacking proteins.The changes persist for

mo re th an 24 hours , long after the che mica l

itself has disappeared from thesystem

(Alcohol andAlcoholism, vol 40. p 485). "It 'sa

common mi sconcept ion that the brain an d

th e liver are the two organ s mo st a ffected by

alcoh ol abuse," says Preedy. "Muscle damage

is th e most common." Among alco holics,h esays , mu scle da mage is five times more

common th an cirrhosis of th e liver.

To make matters worse, the immune

system see s these adducts as foreign an d fires

off an in flamma to ry response .Around.ro per

cen t of patients with alcoholic liver disease

have anti-acetaldehyde ant ibodies in th eir

bloodstream . Drumming up an inflammatory

response is usually considered a bad om en as

akes about 12 hours to eliminate all th e

hanol in a bottle of win e.That's 12 ho urs of

ontinuous exposure to acetaldehyde,

ssibly longer. " It remains to be so lved how

st ace taldehyde disappe ars," says alcohol

esearche r Peter Eriksson from Finland's

Public Health Institute in Helsinki.

rreversible damage

is becoming increasingly clea r is that

most anyex

posure toacetalde

hyde can dou s damage. Aceta ldehyde attaches itself

amino groups in proteins to for m stable

mpounds called adducts. According to On ni

em ela of th e University ofTarnp ere in

inland, th ese cause irreversible da mage by

up protein structure an clfunctio n .

th e wake ofa dr inki ng bout , a whole range

adducts are formed in th e liver, muscles,

art, bra in and gastrointestinal tract.

NewS(ientislllOFebruary2007

it can resu lt in cell in jury an d persisten t

in flammation . It has been linked with a ho st

of diseases, includ ing rheu m atoid arthritis,

he art attacks,Alzheim er 's disease a nd cancer

(New Scientist, 22 May 2004, p40).

Acetaldehyde also attacks DNA.In 2005,

researchers at the US Nat ion al Institute on

Alcohol Abus e and Alcoholism in Bet hesda,

Maryland , reported that acetaldehyde ca n

attack DNAin m uch th e sa m e way it does

pro tei ns.The res ulting adducts dis rup t DNA's

st ructur e

and function. an dcan triggerm utations and chromosomal prob lems

(Nucleic Acids Research. vol 33 p 3513). These

ad ducts have shown up in th e organs of

rodent s fed alcohol and also in the white blood

cells of alcoholics. Little wonder, then, that

although ethanolitself is not considered a

carcinogen.acetaldehyde is- atleast in animals.

The re is growing eviclence that

aceta ldehyde isa hu m an carcinogen too.

Some of the bes t evidence come s from studying

people who canno t process the compound

norm ally.Rough ly 50 per cent of people of

Japan ese ,Chinese, Korean or Taiwanese origin

carry at least one faulty copy of th e ALDH 2

gene and can scarcely break down

acetaldehyde at all.The mutation is dominant

so even having on e copy causes problems.

Flushed faces

The immediate co nseq uences of having th e

faulty version of the ALDH2 gene are highly

visible. "You can see it in any restaurant in

Japan or China," Eriksson says. Almost as soon

thes e people have an alcoholi c dr ink.t he ir

acetalde hyde levels shoot up to between 6 an d

20 times th at found in people with normal

ALDH2.This acetaldehyde "rush" trigge rs

facial t1ush ing,elevated he art rate and dilated

blood vess els. Dizziness, headache, nausea

and vo mi ting soo n follow.

Not surprisingly, most flushers tend to

avoid alcohol , which is just as well s ince th e

long-term health consequences ar c turning

ou t to be serious. Among the m inority offlushers who are also heavy drinkers, th e

incidence of upperga strointestinal tract

cancer is about 50 times the normal rat e.

Gen e-deficient people also have high rates of

hea d an d neck cancer.

There's mo re. A recent study of 818 heavy

dr inkers in Germany found that those

individuals who ar e exposed to m ore

acetaldehyde as a result of a genetic defect

in this case, in the gene for alcohol

dehydrogenase - are at greater r isk of

developing can cers of the upper

gastrointestinal tract an d liver (Interna tional

Ioutnal a/Cancer, vol na , p 1998).Th ese and aho st of other results all add to th e growing

suspicion th at acetald ehyde is a human

carcinogen, says Helmut Seitz, profess or of

alcoh ol research at the Univ ersity of

Heidelbergin Germany. Mikko Salaspuro,a

gastroenterolo gist at the Universi ty Central

Hospital of Helsinki.agrees. " It is likely tha t

acet aldehyde will soon be considered to be

carcinogenicin humans," he says.

Acetaldehyde also seems to play a role in

breast cancer. with up to 5 per cent of all breast

cancers attributa ble to a lcohol consumption.

"The cells don 't forget. This will ini tiate

tu m our s 20 to 25yea rs later,"

says Seitz, who isconvinced that esca lating alcoh ol in take in th e

west is linked to rising rates of liver, colon and

rectal cancer.

There arc even sugges tions of a link

between ace ta ldehyde and Alzheim er's

disease. In 20 04, researchers at Nip pon

Medical School in Kawasaki, japan, reported

that amon g a group of peo ple with

Alzhe imer's. the faulty version of ALDH2 was

www .newsrientist.rom



gni ficantly mo re common than am ong a

en group of healthy peop le of

e same age (Annals of the New l'ork Academy

Sciences, vol 1011, P 36).

So who is at risk?As a general rul e, mo s t of

e excess acetaldehyde you encounter co me s

m alcoho l, and the more alcohol you drink

e m oreacetaldehyde you are exposed to.

no absolutely safe level of

m ptio n . "It is no t necessary to drink

am ou nt s of alcohol - even low amounts

et hanol taken regula rly in a sensitiven increases the ir risk." Seitz points out.

It 's a lso worth hearing in mind that m any

lic drinks conta in acetaldehyd e from

word go. Sherry producers, for instance.

ourage acetaldehyde product ion fo r its

y aroma. Calvados is particularly rich in

etaldehyde, and regular calvados dr inkers

ave twice th e incidence of oesophageal an d

al cancer compared with wine d rinkers who

sume the sam e amount of alcohol.

It gets worse. If you smoke , or are ex posed

ther people 's sm oke , you r acetaldehyde

rises furth er. Burning tobacco creates

dissolves in saliva, and

etaldehyde in saliva is a big problem. Unlike

e liver with its detoxifying enzyme s, the

mucous m em b ranes are pretty poor

breaking down acetaldehyde. Asa result,

toxic effect s persist for longer.

Among smoker s, the risk of oral cancer is

to 10 times higher than for people wh o have

There are , of course, downs of

gens in tobacco smoke, so

ldehyd e m ay well not be the on ly culprit.

ertheless , an individual smoker's cancer

s strongly as sociated with acetaldehyde

their saliva and some rese archers

ow believe th a t acetalde hyd e ma y be one of

e principal carcinogens in cigarette smoke .

Combine tobacco and alcoholand the

er multiplies. The effect is synergistic,

ing to Salaspuro,This could ex plain th e

-fold r ise in o ral cancers seen in people

o are both alco holics and smokers,

ed with those who ab stain fro m both .

don't know of any other cancers in which

e associations are so strong ,"Salaspuro says.

etaldehyde in saliva also comes from th e

tha t colonise th e mouth an d dig estive

ct. Many of these churn out acetaldehyde as

of their normal biochemistry. Others

ethanol from alcoholic drinks and turn

in to acetaldehyde.Some people harbour

rgan isms th at a re particularly good at

acetaldehyde. "It depends on the

of flora you h ave .There m ay be huge

at ions between individual s," says

aspuro. One mouth-dwelling bug,

ww.newscientisLcom

Strept ococcus salivarius, is particularly goo d at

tossing out acetaldeh yde. Another,Neisseria,

produces 100 ti m es more acetaldehyde when

exposed to ethanolcompared with ot her

m icroorganism s iso lated fro m the mouth.

Micro bial acetald ehyde produ ction coul d

also explain why people with poord en ta l

hygiene havean increased ris k of mouth

cancer.The Finnish researchers collected

saliva sam ples from 132 volunteers who

differed not on ly in their drink ing and

smoking habits but also in th e standardof their dent al hyg ien e. The result s show that

poor denta l hygiene comes with at wofold

increase in acetaldehyde leve ls (Oral

Oncology, vol 37p 153)·

Then t here is acet ald ehyde in th e diet. For

centur ies , peop les have used bacterial

fer me ntation to produce food -everything

from pickles an d yogur ts to bread and cheese.

Where th ere is fer m entation there is

Las t yea r the team released a study

showing tha t a piece of gu m containing jus t

5 mill igrams of t-cysteine could totally

eliminate acetaldehyde hom saliva if chewed

whil e smok ing (Cancer Epidemiology,

Biomarkers& Prevention , vol IS,p 146).

Salasp uro hopes the gum co uld help pr event

digestive tract cancers in those whoare most

at risk.The gu m is being com mercialise d by a

Finnish company ca lled Biohlt.

Germ -bu s ting mouthwash could also

help. Mouthwash contai ning the ant isepticchlorhexidine has be en shown to slash th e

numbers of acetaldehyde-p roducing

m icroo rganisms in t he mo u th , and in a st ud y

with 10 vo lunteers , the Finnish researchers

fo un d that t reatment with chlorhexidine for

th ree days cut acetaldehyde levels in drinkers '

saliva by 40 per cent.

i\nother solution proposed by th e Finnish

tea m is to tinkerwith th e bugs living in your

acetaldehyde. Acetaldehyde also occ urs

natu rally in r ipe fruit and coffee.

"Companies making da iry products

so meti mes try to increase the acetaldehyde

level to give it a specialaromat ic taste," says

Salaspuro, "Som e yog hur t producers are

searching for new bact eria that are even better

acetaldehyde p roducers." And if you live in a

city, there's more. Acetaldehyde is spewed out

by veh icle engines. Air pollution adds to the

to xic load, though no body is quite su re how

much this affects ou r health.

With ace ta ldehyde - and evidence of its

toxicity - coming at us from all sides, it 's not

surp rising that scientists are busy developing

ways to neutra lise the th reat. Salaspuroand

colleag ues at th e University of Helsinki , for

example, are developing a chewing gum tha t

mo ps up acetaldehyde.The gu m contain s a

harm less am ino acid , t-cysteine, wh ich reacts

with acetaldehyde and remo vesit from saliva.

intestines using preblotics or probiotics .

Lactulose - a ha rmless,indigestible sugar - is

one cand idate for th e job, says Salaspuro. In

experime nt s with rats , lactulosc appears to

inh ibit acetalde hyde production by m aking

th e colon more acidic.Alternatively,ingesting

a dose ofliving microorganisms that don 't

produce acetaldehyde, such as some

Lactobacillu s an d Bifidobact erium species,

cou ld als o help, say Seitz and Salaspu ro,

None of th ese interventions has been

shown to prevent cancer, so cannot as yet be

recommended as a substitute for a healthy

lifestyle. There is still only one sure route to an

acetaldehyde-free life : keep it clean. Scrub

yourteeth, avoid smoke,an d next time you 're

recovering from a ha ngover , remember to

promise your in ternal organs that this time

rea lly will be the las t. •

Lisa Melton isa science writerbased in London

10 February 10071 NewScientisllH

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