How too much fruc­tose can cause liver dam­age

Zambian Business Times - - LIFESTYLE - Source: The Econ­o­mist

FRUC­TOSE is the sweet­est of the nat­u­ral sug­ars. As its name sug­gests, it is found mainly in fruits. Its job seems to be to ap­peal to the sweet tooth’s of the ver­te­brates these fruit have evolved to be eaten by, the bet­ter to scat­ter their seeds far and wide. Fruc­tose is also, how­ever, of­ten added by man­u­fac­tur­ers of food and drink, to sweeten their prod­ucts and make them ap­peal to one species of ver­te­brate in par­tic­u­lar, namely Homo sapi­ens. And that may be a prob­lem, be­cause too much fruc­tose in the diet seems to be as­so­ci­ated with liver dis­ease and type 2 di­a­betes.

The na­ture of this as­so­ci­a­tion has been de­bated for years. Some ar­gue that the ef­fect is in­di­rect. They sug­gest that, be­cause sweet tastes sup­press the feel­ing of be­ing full (the rea­son why desserts, which come at the end of a meal, are sweet), con­sum­ing foods rich in fruc­tose en­cour­ages overeat­ing and the dis­eases con­se­quent upon that. Oth­ers think the ef­fect is more di­rect. They sus­pect that the cause is the way fruc­tose is metabolised. Ev­i­dence clearly

This week, how­ever, the meta­bolic hy­poth­e­sis has re­ceived a boost from a study pub­lished in Cell Me­tab­o­lism by Josh Rabi­nowitz of Prince­ton Univer­sity and his col­leagues. Specif­i­cally, Dr Rabi­nowitz’s work sug­gests that fruc­tose, when con­sumed in large enough quan­ti­ties, over­whelms the mech­a­nism in the small in­tes­tine that has evolved to han­dle it. This en­ables it to get into the blood­stream along with other di­gested mol­e­cules and travel to the liver, where some of it is con­verted into fat. And that is a process which has the po­ten­tial to cause long-term dam­age.

Dr Rabi­nowitz and his as­so­ciates came to this con­clu­sion by track­ing fruc­tose, and also glu­cose, the most com­mon nat­u­ral sugar, through the bod­ies of mice. They did this by mak­ing sugar mol­e­cules that in­cluded a rare but non-ra­dioac­tive iso­tope of car­bon, 13C. Some an­i­mals were fed fruc­tose doped with this iso­tope. Oth­ers were fed glu­cose doped with it. By look­ing at where the 13C went in each case the re­searchers could fol­low the fates of the two sorts of sugar.

The liver is the prime meta­bolic pro­cess­ing cen­tre in the body, so they ex­pected to see fruc­tose dealt with there. But the iso­topes told a dif­fer­ent story. When glu­cose was the doped sugar mol­e­cule, 13C was car­ried rapidly to the liver from the small in­tes­tine through the he­patic por­tal vein. This is a di­rect con­nec­tion be­tween the two or­gans that ex­ists to make such trans­fers of di­gested food mol­e­cules. It was then dis­trib­uted to the rest of the body through the gen­eral blood cir­cu­la­tion. When fruc­tose was doped, though, and ad­min­is­tered in small quan­ti­ties, the iso­tope gath­ered in the small in­tes­tine in­stead of be­ing trans­ported to the liver. It seems that the in­tes­tine it­self has the job of deal­ing with fruc­tose, thus mak­ing sure that this sub­stance never even reaches the liver. Hav­ing estab­lished that the two sorts of sugar are han­dled dif­fer­ently, Dr Rabi­nowitz and his col­leagues then upped the doses. Their in­ten­tion was to mimic in their mice the pro­por­tion­ate amount of each sugar that a hu­man be­ing would in­gest when con­sum­ing a small fruc­tose-en­hanced soft drink. As they ex­pected, all of the glu­cose in the dose was trans­ported ef­fi­ciently to the liver, whence it was re­leased into the wider blood­stream for use in the rest of the body. Also as ex­pected, the fruc­tose re­mained in the small in­tes­tine for pro­cess­ing. But not for­ever. About 30% of it es­caped, and was car­ried un­pro­cessed to the liver. Here, a part of it was con­verted into fat.

That is not a prob­lem in the short term. Livers can store a cer­tain amount of fat with­out fuss. And Dr Rabi­nowitz’s ex­per­i­ments are only short-term tri­als. But in the longer term chronic fat pro­duc­tion in the liver of­ten leads to dis­ease—and is some­thing to be avoided, if pos­si­ble.

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