Aspartame in Diet Drinks Linked to Autism

There are many theories and much effort being made to understand increased autism, see http://www.ncbi.nlm.nih.gov/pubmed?term=autism%20increase. Though not an expert, I suspect the problem will be best resolved by looking at autism associated biochemistry. I noted the folate connection (http://www.ncbi.nlm.nih.gov/pubmed?term=autism%2Cfolate%20deficiency), but excluded a link to folate enzyme issues (called polymorphisms, see http://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase). This can be a big problem (see http://www.ncbi.nlm.nih.gov/pubmed?term=autism%2Cfolate%20polymorphisms and http://www.ncbi.nlm.nih.gov/pubmed/20468076.

Folate problems diminish transfer of methyl groups to homocysteine (http://en.wikipedia.org/wiki/Homocysteine) to form methionine (methylhomocyst eine, see the figure top of p 3000 here, http://download.cell.com/AJHG/pdf/PIIS0002929707614001.pdf?intermediate=true). Ultimate answers may also come from the autism and homocysteine linkage, http://www.ncbi.nlm.nih.gov/pubmed?term=autism%2Chomocysteine, or from the autism and B12 linkage, http://www.ncbi.nlm.nih.gov/pubmed?term=autism%2CB12. Note that 'the figure p 3000' shows how these issues are interrelated and suggest troubles with biological methylation in autism, be it general or very specific (http://www.ncbi.nlm.nih.gov/pubmed/15781839).

In 1998 mandatory folate fortification of grain products was required to prevent birth defects in offspring of deficient mothers. The folate deficiency problem has improved, but has not disappeared, perhaps because grain product consumption (and folate intake) amongst some has declined---pastries have weight consequences. Diabetes occurrence is on the increase and diabetes has similar correlations, see http://www.ncbi.nlm.nih.gov/pubmed?term=diabetes%2Cfolate%20deficiency.

John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition)

Formate and formaldehyde are [quoting another] “produced in the body during the endogenous demethylation of many compounds, including many foods and drugs. For example, the demethylation of the caffeine found in one cup of coffee produces 30 mg of formaldehyde (Imbus, 1988). Formaldehyde is essential in one-carbon pool intermediary metabolism. The metabolite of formaldehyde, formic acid, is a substrate for purine nucleotide synthesis (Sheehan and Tully, 1983). It can be calculated that more than 50,000 mg [that's 50 g] of formaldehyde is produced and metabolized in an adult human body daily and that an adult human liver will metabolize 22 mg of formaldehyde per minute (Clary and Sullivan, 1999). Consequently, it is quite clear that the formaldehyde from aspartame provides a trivial contribution to total formaldehyde exposure and metabolism in the body” (p 18 in and refs from http://www.fte.ugent.be/vlaz/Magnuson2007.pdf).

That metabolism requires folate/B12 vitamins. Many people are simply deficient in them. And forty percent of some populations have folate enzyme issues that require even more folate.

So all adverse side effects ever claimed from aspartame are really due to personal folate-related issues, not to this sweetener. And that probably includes migraines (see http://www.ncbi.nlm.nih.gov/pubmed/11121176). As to autism check out http://www.ncbi.nlm.nih.gov/pubmed?term=autism%2Cfolate%20deficiency . Aspartame is not associated with autism, but folate issues are clearly associated with it.

In people with these personal issues, these adverse risks exist whether one uses aspartame or not. Widespread overindulgence in ethanol (acetaldehyde is an inhibitor of the folate reactions) only exacerbates these risks, just as it exacerbates breast and other cancers and contributes to fetal alcohol syndrome.

John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition)