Aspartame Guilty (Again), This Time for Weight Gain

A new study from the Massachusetts General Hospital says Aspartame may retard weight loss because it blocks the function of an enzyme vital for the prevention of obesity, type 2 diabetes and cardiovascular disease.

Dec. 29, 2016
By Stav Dimitropoulos

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Aspartylpheny­lala­nine-methyl-ester, or Aspar­tame, is the by-prod­uct of an ulcer drug exper­i­men­ta­tion back in 1965, when a com­pany chemist found an inter­me­di­ate chem­i­cal to have a par­tic­u­larly sweet taste. About a decade later, Aspar­tame was approved by the FDA for restricted use in dry foods. Then it got on an exper­i­men­tal roller coaster of bans and re-approvals.

Today, Aspar­tame is a dietary hot potato.” Still in wide­spread use by weight-con­scious con­sumers, Aspar­tame has fer­vent fans but has not escaped the heavy crit­i­cism of sci­en­tific cir­cles, who asso­ciate it with headaches, mem­ory loss, seizures, vision loss, dia­betes, Alzheimer’s, chronic fatigue and depres­sion, even can­cer.

We stud­ied the impact of Aspar­tame on IAP and found it can indeed pre­dis­pose to obe­sity and dia­betes.- Kon­stan­ti­nos Economopou­los, Researcher

A new study from the Mass­a­chu­setts Gen­eral Hos­pi­tal (MGH) comes to fur­ther dis­tress the weight-con­scious group of peo­ple who use Aspar­tame as a sugar sub­sti­tute: Aspar­tame might actu­ally pro­hibit weight loss.

The report, Inhi­bi­tion of the gut enzyme intesti­nal alka­line phos­phatase may explain how Aspar­tame pro­motes glu­cose intol­er­ance and obe­sity in mice,” was pub­lished in Applied Phys­i­ol­ogy, Nutri­tion and Metab­o­lism. It found that Aspar­tame may not pro­mote weight loss because it blocks the func­tion of an enzyme vital for the pre­ven­tion of meta­bolic syn­drome (a group of symp­toms asso­ci­ated with type 2 dia­betes and car­dio­vas­cu­lar dis­ease).

Indeed, our study con­firms the obser­va­tion made by sci­en­tists in the late 1960s, that pheny­lala­nine (PHE) – a break­down prod­uct of Aspar­tame – specif­i­cally inhibits the action of intesti­nal alka­line phos­phatase (IAP),” said Kon­stan­ti­nos Economopou­los, Senior Research Sci­en­tist at the Organ Engi­neer­ing and Regen­er­a­tion Lab­o­ra­tory of the ‎Mass­a­chu­setts Gen­eral Hos­pi­tal, and researcher of the same study.


IAP is an enzyme, and when a sub­strate mol­e­cule inter­acts with the active site of IAP, an enzyme-sub­strate com­plex is formed and the enzyme is acti­vated. Thus, the enzyme and sub­strate are said to fit together and func­tion as a lock and a key. When pheny­lala­nine inter­acts with the IAP-sub­strate com­plex, it inac­ti­vates it by pro­duc­ing a more ther­mo­dy­nam­i­cally sta­ble IAP-PHE-sub­strate com­plex. The way you can pic­ture this is like the lock, the IAP, after the addi­tion of pheny­lala­nine can­not be opened any­more with the same key-sub­strate, because there is another key behind the door, pheny­lala­nine.”

Pre­vi­ously the team had found that feed­ing IAP to mice kept on a high-fat diet pre­vented the devel­op­ment of meta­bolic syn­drome and reduced symp­toms in ani­mals already inflicted with the con­di­tion. The knowl­edge that pheny­lala­nine impedes the action of IAP, and the fact that the for­mer is pro­duced upon Aspar­tame’s diges­tion urged the researchers to inves­ti­gate whether Aspar­tame might actu­ally retard weight loss.

The team fol­lowed four groups of mice for 18 weeks. Two groups were kept on a nor­mal diet, one on water with Aspar­tame, and the other on plain water. The other two groups were fed a high-fat diet, as well as Aspar­tame-infused or plain water.

The study found that the high-fat diet mice that received Aspar­tame gained more weight than those on the same diet that received plain water while the dif­fer­ence between the weights of the two groups fed a nor­mal diet was neg­li­gi­ble. What is more, Aspar­tame-receiv­ing mice in both diet groups were observed to have higher blood sugar lev­els than those fed the same diets with­out Aspar­tame, a fact that might point out glu­cose intol­er­ance. Finally, both Aspar­tame-receiv­ing groups had higher lev­els of the inflam­ma­tory pro­tein TNF-alpha in their blood, which reveals a kind of sys­temic inflam­ma­tion typ­i­cal of meta­bolic syn­drome.

What do these find­ings sug­gest for one of the most com­mer­cial (at least until ste­via) and con­tro­ver­sial arti­fi­cial sweet­en­ers? Can we imply that the ongo­ing anti-Aspar­tame polemic will ren­der it a sweet­ener of the yore?

We have no idea about whether sub­stances like Aspar­tame will get banned,” answered Economopou­los. They are in wide­spread use and gen­er­ally con­sid­ered safe for human con­sump­tion. We stud­ied the impact of Aspar­tame on IAP and found it can indeed pre­dis­pose to obe­sity and dia­betes.”

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