Aspartame Study From Spain

The Trocho study is a general study on artificial sweeteners' toxicity supported through the Bosch & Gimpera Foundation, Barcelona, Spain. (See original research report)

The researchers determined the extent of conversion of aspartame methanol to formaldehyde and its eventual effect on the overall physiologic function of the rat. The results suggest that the conversion of aspartame methanol into formaldehyde adducts (The complex that forms when a chemical binds to a biological molecule, such as DNA or a protein.) should to be taken into account because of the widespread utilization of this sweetener. The study concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts.

Adult male rats were given an oral dose of 10 mg/kg aspartame (referred to in this report as 14C-"labeled") in the methanol carbon. At timed intervals up to six hours, the radioactivity in blood plasma and in several organs was investigated. Most of the radioactivity found (>98 % in plasma, >75% in the liver) was bound to protein. The "label" present in the liver, blood plasma and in the kidney was in the range of 1-2% of total radioactivity administered per gram or milligram, changing little with time. Other organs (brown and white adipose tissues, muscle, brain, cornea and retina) contained levels of the label in the range of 1/12 to 1/10th of that of liver. In all, the rat retained six hours after administration, about 5% of the label, half of it was in the liver.

The binding of methanol-derived carbon to tissue proteins was widespread in the study, affecting all body systems, fully reaching even sensitive targets such as the brain and retina. In all groups studied, the label bound found in blood plasma and body tissues corresponded to the aspartame injected, since there was no other source of radioactivity available.

Most of the label found in the tissues is the result of the formation of formaldehyde or (in smaller proportion because of its lower reactivity), formate adducts. Methanol is highly volatile. The above behavioural results were also found in formaldehyde-protein adducts as a long-lived species difficult to eliminate, in which the protein was denatured and its original function altered.

The nature of the tissue in which the label accumulated was a direct consequence of the formaldehyde binding to the tissue structures. The amount of formaldehyde adducts coming from aspartame in the tissue proteins and nucleic acids appeared to be cumulative.

In several tissues, methanol was primarily oxidized to formaldehyde and formic acid, the main metabolites responsible for the poisonous effects of acute methanol intoxication in man and experimental animals

The presence of label in other molecules strongly supports the adduct formation claim, attributing formaldehyde as the main responsibility for the appearance of aspartame-
methanol label in the tissue components. The evidence presented, then, proves that a significant portion of the methanol carbon of aspartame finds its way into adducts of proteins and nucleic acids under the conditions tested, both in normal and cirrhotic rats (those with a chronic progressive disease of the liver).

Formaldehyde induces severe functional alterations, including the development of cancer. The small amounts of formaldehyde, which can be potentially produced from dietary use of aspartame, have been often overlooked in its potential toxicity precisely because of the limited amount eventually produced. However, the administration of labeled aspartame to experimental animals resulted in the incorporation of a significant proportion of the label to proteins. The study results show that the carbon adducts of protein and DNA may have been generated only from formaldehyde derived from aspartame methanol.

The amount of label recovered in tissue components was quite high in all the groups, but especially in the NA-study rats. In this group, the liver alone retained for a long period of time more than 2% of the methanol carbon given in a single oral dose of aspartame, and the rest of the body stored an additional 2% or more. These are indeed extremely high levels for adducts of formaldehyde, a substance responsible of chronic poisonous effects that has also been considered carcinogenic.

The repeated occurrence of claims that aspartame produces headache and other neurological and psychological secondary effects may be explained in the permanence of this formaldehyde label, since formaldehyde intoxication can induce similar effects.

The cumulative effects derived from the incorporation of label in the chronic administration model in the study suggests that regular intake of aspartame may result in the progressive accumulation of formaldehyde adducts. It may be further speculated that the formation of adducts can help to explain the chronic effects aspartame consumption may induce on sensitive tissues such as the brain.

Posted February 2006 | Permanent Link

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