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(The book While Science Sleeps is more about methanol than just aspartame.) August 24, 2013, original web page with responses I’m sorry to say you have been totally misinformed by the aspartame critics, who know nothing either about toxicology (the science of poisons) or about this sweetener. That alone accounts for the fact that aspartame is approved by the regulatory agencies of 90+ nations worldwide. Here is what you don’t know. Aspartame can react with water given heat and over time be converted (hydrolyzed) into its constituents–methanol and the parent dual amino acid aspartylphenylalanine; the latter may also be further hydrolyzed into its single amino acids (aspartate and phenylalanine). That said, methanol and these amino acids are perfectly stable in the soft-drink can, but this reaction with water removes aspartame’s sweetness, which is completely associated with the intact aspartame molecule. Upon human ingestion these same three products are produced by stomach hydrolysis. So where does the formaldehyde people mention come from? Formaldehyde and its further oxidation product formate arise in liver from oxidation of that methanol. Critics scream this is an issue, but it simply is not. Toxicology is all about dose. Everything is toxic, but that toxicity occurs only at a certain dose (concentration). Critics are trying to scare the public, but this fails with scientists, because screaming that something is toxic without recognition of the dose (concentration) factor is meaningless diatribe. And that is why trained scientists everywhere refuse to listen. The reality is that formaldehyde and formate pose little risk at the doses involved from aspartame; these substances [quoting another] are “produced in the body during the endogenous demethylation of many compounds, including many foods [fruit juices] 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). In fact the methyl groups produced from formaldehyde and formate by folate-B12 (see http://en.wikipedia.org/wiki/Vitamin_B12) are vital to our very existence. They are used to protect DNA and methylate the really toxic homocysteine (http://en.wikipedia.org/wiki/Homocysteine) into very valuable methionine. Now consider clear poisoning by methanol. It requires many milliliters of methanol, but poisoning is actually not due to the methanol or to the formaldehyde either—that formaldehyde becomes protein bound in the blood. The real poisoning is due to the production of formic acid (formate) faster than the often deficient folic acid/B12 vitamin systems can remove it. That causes accrual of formate and acidosis. Reducing the production of formate by inhibiting the enzyme making it, treatment of acidosis and enhancement by dietary folate (or related drugs) are the steps physicians take in methanol poisoning, http://www.ncbi.nlm.nih.gov/pubmed/12216995. John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition) ------------------------------ June 12, 2012, Concerning While Science Sleeps original web page with responses Aspartame is perfectly safe used as directed in healthy people I don't care whether the reader uses aspartame or not. But the people commenting about this need to know that the science just isn't there. There are NO acceptable and reproducible scientific papers to the contrary. But there are conspiracy theorists arguing this point, who profit from books (duh!), false treatments, and other misleading innuendo by claiming that there are accepted, reproducible scientific papers. Here are the facts. Only methanol amongst aspartame degradation products presents any risk to normal people---phenylalanine and aspartate are found in greater concentrations in normal foods, like milk and meat. Methanol is oxidized to formaldehyde and formate--both are chemically directly converted by the (tetrahydro)folate vitamin system into very valuable methyl groups. These methyl groups detoxify homocysteine and protect DNA (thymine). For more on its cycle see the figure at the top of p 3000 here, [...] 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 [...] Do these facts not make clear that any perceived problem is not with aspartame, methanol, formaldehyde or even formate, but metabolism issues in detoxifying them, which with folate (homocysteine and B12, see that cited p 3000) are potentially numerous? Up to 40% of some populations have folate polymorphisms, but most don't even know it. It is very uncommon to even test for this. For more read [...] And that doesn't include people with high blood concentrations of the true excitotoxin homocysteine or low concentrations of vitamin B12 (again see that figure on p 3000). All side effects that you suggest [cancer, neurological problems, and the many other dangerous side effects] are really due to these personal folate-related issues, not to aspartame. And in people with these issues, they likely exist whether one uses aspartame or not. And that is my real point! I think it likely that amongst the few people that respond to aspartame, they are at real risk from these issues. John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition) ------------------------------ February 1st, 2008, concerning bills in New Mexico and Hawaii original web page with responses John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, and Toxicology) New Mexico Aspartame is perfectly safe used as directed in healthy people. All this garbage about it not being safe is just that-garbage. The scientific community doesn’t believe these lies (see snopes.com, aspartame.net). If you want the real story on aspartame, read the full text of the latest comprehensive analysis (2007) by people with skill in toxicology (the science of poisons) at www.fte.ugent.be/vlaz/Magnuson2007.pdf.* Avoid websites by physicians with little training in this field and New Mexico activists that failed twice to get aspartame legislation even out of committee in New Mexico. *Apparently sponsored by Ajinomoto, the worlds largest manufacturer of MSG and aspartame. (pointed out in response by Patrick) Garst affiliations not discernable. He has 13 PubMed publications, two of them single-authored: The clinical relevance of the LD50. The effects of selected bulky substituents on the pulmonary toxicity of 3-furyl ketones in mice. Biological activity of phenolic compounds. Hepatic cytochrome P-450, cytochrome b5, and NADPH cytochrome c reductase in chicks and rats fed phenolic monomers, polymers, and glycosides. Species susceptibility to the pulmonary toxicity of 3-furyl isoamyl ketone (perilla ketone): in vivo support for involvement of the lung monooxygenase system. Arsenic-sulfur amino acid interactions in the chick. Accurate, wide-range, automated, high-performance liquid chromatographic method for the estimation of octanol/water partition coefficients II: Equilibrium in partition coefficient measurements, additivity of substituent constants, and correlation of biological data. Accurate, wide-range, automated, high-performance liquid chromatographic method for the estimation of octanol/water partition coefficients I: Effect of chromatographic conditions and procedure variables on accuracy and reproducibility of the method. Inhibition of separated forms of cyclic nucleotide phosphodiesterase from pig coronary arteries by 1,3-disubstituted and 1,3,8-trisubstituted xanthines. Perilla ketone: a potent lung toxin from the mint plant, Perilla frutescens Britton. Selective inhibition of cyclic nucleotide phosphodiesterases by analogues of 1-methyl-3-isobutylxanthine. Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthine. Preparation and Baeyer-Villiger Reaction of certain 2-carbalkoxycyclopropyl methyl ketones. Quaternary aminooxy congeners of acetyl gamma-homocholine. |