Comments on: Aspartame http://organichealthadviser.com/archives/aspartame Organic Health Tips, Guides And Information Wed, 08 Feb 2012 12:46:10 +0000 hourly 1 By: John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition) http://organichealthadviser.com/archives/aspartame/comment-page-1#comment-62 John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition) Sat, 23 May 2009 16:48:44 +0000 http://organichealthadviser.com/?p=245#comment-62 The information here about aspartame is very outdated and much of it has been rejected by science. In fact the first reality is that all aspartame research prior to 2009 is seriously and fatally flawed. It was all done in a scientifically unacceptable manner as was established in preliminary work presented at the Society of Toxicology (Seattle, USA) and the American Chemical Society (New Orleans, USA) national meetings in early 2008 and which is currently being preparing for regular publication. In those locations it was demonstrated that inappropriate controls were used in all aspartame research starting with the original Searle work and extending through the oft-cited Soffritti et al work published over the past several years (and even other work thereafter). The standard control-versus-treated animal experiments are simply invalid for aspartame, because aspartame is hydrolyzed to methanol and methanol (actually through its oxidation products formaldehyde and formate) has long been known to deplete a vitamin, namely folic acid. No properly done experiment can deplete a vitamin, but all experiments to date claiming problems have done just that! Hence, both controlled and treated groups of animals must be provided either the appropriate amounts of folic acid supplement to counter methanol-induced loss OR both controlled and treated groups of animals must be provided the same intake of methanol, one directly and the other from aspartame. However, the latter is an experimentally more challenging option. Various other studies found “no effect” from aspartame. Such animal studies were either of such short duration that folate depletion was not evident or more likely were performed with corn/soybean or other diets rich in folate and would not be expected to show any effect. The second reality is that this same underlying folate issue explains human problems attributed by critics to aspartame. The folate enzyme system metabolizes the common dietary ingredient methanol and methanol’s oxidation products formaldehyde and formate, which are innate metabolites of many substances. Although required only in 400-500 microgram quantities, many people are folate deficient both because some people refuse to take vitamin supplements and avoid folate fortified grain products (donuts, etc), but also because some people (~20%) have genetic problems that increase their need for folate above that required by others. You should realize the adverse effects claimed by antiaspartame critics can be systematically linked to shortage of this vitamin (and possibly also the connected B12). This includes “migraines, dizziness, shaking and tremors, seizures, mental confusion, change in mood, Alzheimer’s and permanent blindness or other issues” linked to aspartame. A simple review of the primary literature at http://www.ncbi.nlm.nih.gov/pubmed/ will show these issues are far better connected to folate and specifically folate deficiency, folate genetics issues, and homocysteine accrual than to aspartame [for example, type “folate,headache” without the quotes into the search line and find 43 references compared with “aspartame,headache” without the quotes for which there are 33 references.] Folate deficiency also underlies birth defects, many cancers (including breast cancer), and other conditions, so people susceptible to headaches from aspartame might actually be susceptible to many other more threatening health-related issues. But it is these underlying folate issues and not aspartame that explain much of this internet issue. The antiaspartame critics just don’t understand the issues involved, preferring instead to manufacture a controversy where none exists. For either animal or man the consequences of the folate deficiency that result are the incorporation of structurally weak uridylate (uracil, http://en.wikipedia.org/wiki/Uracil) bases in DNA in place of stronger thymidylate (methyluridylate called thymine, http://en.wikipedia.org/wiki/Thymine) and/or the accrual of toxic homocysteine (http://en.wikipedia.org/wiki/Homocysteine), most likely because of insufficient methylation of homocysteine to afford methionine (http://en.wikipedia.org/wiki/Methionine). Much has been written about the “excitotoxic” amino acids that form the aspartame framework (phenylalanine and aspartic acid) by aspartame critics. However, those excitotoxic amino acids occur at far greater concentrations in everyday food, so neither of these amino acids are issues for most people. However, what seems to be consistently missed by the antiaspartame critics is that homocysteine is a far stronger excitotoxin than any constituent of aspartame. In summary, there is no valid science questioning aspartame’s safety, but there is substantial direct and indirect evidence that any personal issues with aspartame reflect not aspartame per se, but a personal folate deficiency (see http://en.wikipedia.org/wiki/Folate_deficiency), folate polymorphism genetic issues, http://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase), and/or issues with related biochemistry linked to vitamin B12 (http://en.wikipedia.org/wiki/Vitamin_B12). There is no data suggesting any adverse effect for aspartame cannot simply and completely be explained by the folate deficiency, folate genetics, and homocysteine paradigm. This new information only suggests aspartame is even safer, now that what I have reported above is known to all the regulatory authorities. Given these new, stronger indications of safety, science no longer has any reason to doubt the safety of aspartame. And the European equivalent of the US FDA on April 20 just again validated the safety of aspartame, http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902454309.htm. John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition) (FYI, the author has absolutely no financial or biasing connection with the aspartame, the soft drink or their related industries and have made not one penny from my opposition, unlike many antiaspartame critics who sell books and offer irrelevant treatment. Their clearly stated goals are lawsuits, where none are justified. The author has an undergraduate degree in chemistry (with emphasis in organic and biological chemistry) from the University of Kansas, a Ph.D. in Medicinal Chemistry (Pharmacy) from the University of Iowa, postdoctoral experience at Yale University (Molecular Biophysics & Biochemistry) and two postdoctoral fellowships at Vanderbilt University (physiology-pharmacology (mentor moved), then nutritional toxicology) and taught nutritional toxicology at the University of Illinois (Champaign-Urbana, UIUC) besides having conducted federally funded research at Vanderbilt, UIUC, and at several other universities before recently entering into semi-retirement.) The information here about aspartame is very outdated and much of it has been rejected by science. In fact the first reality is that all aspartame research prior to 2009 is seriously and fatally flawed. It was all done in a scientifically unacceptable manner as was established in preliminary work presented at the Society of Toxicology (Seattle, USA) and the American Chemical Society (New Orleans, USA) national meetings in early 2008 and which is currently being preparing for regular publication. In those locations it was demonstrated that inappropriate controls were used in all aspartame research starting with the original Searle work and extending through the oft-cited Soffritti et al work published over the past several years (and even other work thereafter). The standard control-versus-treated animal experiments are simply invalid for aspartame, because aspartame is hydrolyzed to methanol and methanol (actually through its oxidation products formaldehyde and formate) has long been known to deplete a vitamin, namely folic acid. No properly done experiment can deplete a vitamin, but all experiments to date claiming problems have done just that! Hence, both controlled and treated groups of animals must be provided either the appropriate amounts of folic acid supplement to counter methanol-induced loss OR both controlled and treated groups of animals must be provided the same intake of methanol, one directly and the other from aspartame. However, the latter is an experimentally more challenging option. Various other studies found “no effect” from aspartame. Such animal studies were either of such short duration that folate depletion was not evident or more likely were performed with corn/soybean or other diets rich in folate and would not be expected to show any effect.

The second reality is that this same underlying folate issue explains human problems attributed by critics to aspartame. The folate enzyme system metabolizes the common dietary ingredient methanol and methanol’s oxidation products formaldehyde and formate, which are innate metabolites of many substances. Although required only in 400-500 microgram quantities, many people are folate deficient both because some people refuse to take vitamin supplements and avoid folate fortified grain products (donuts, etc), but also because some people (~20%) have genetic problems that increase their need for folate above that required by others. You should realize the adverse effects claimed by antiaspartame critics can be systematically linked to shortage of this vitamin (and possibly also the connected B12). This includes “migraines, dizziness, shaking and tremors, seizures, mental confusion, change in mood, Alzheimer’s and permanent blindness or other issues” linked to aspartame. A simple review of the primary literature at http://www.ncbi.nlm.nih.gov/pubmed/ will show these issues are far better connected to folate and specifically folate deficiency, folate genetics issues, and homocysteine accrual than to aspartame [for example, type “folate,headache” without the quotes into the search line and find 43 references compared with “aspartame,headache” without the quotes for which there are 33 references.] Folate deficiency also underlies birth defects, many cancers (including breast cancer), and other conditions, so people susceptible to headaches from aspartame might actually be susceptible to many other more threatening health-related issues. But it is these underlying folate issues and not aspartame that explain much of this internet issue. The antiaspartame critics just don’t understand the issues involved, preferring instead to manufacture a controversy where none exists.

For either animal or man the consequences of the folate deficiency that result are the incorporation of structurally weak uridylate (uracil, http://en.wikipedia.org/wiki/Uracil) bases in DNA in place of stronger thymidylate (methyluridylate called thymine, http://en.wikipedia.org/wiki/Thymine) and/or the accrual of toxic homocysteine (http://en.wikipedia.org/wiki/Homocysteine), most likely because of insufficient methylation of homocysteine to afford methionine (http://en.wikipedia.org/wiki/Methionine). Much has been written about the “excitotoxic” amino acids that form the aspartame framework (phenylalanine and aspartic acid) by aspartame critics. However, those excitotoxic amino acids occur at far greater concentrations in everyday food, so neither of these amino acids are issues for most people. However, what seems to be consistently missed by the antiaspartame critics is that homocysteine is a far stronger excitotoxin than any constituent of aspartame.

In summary, there is no valid science questioning aspartame’s safety, but there is substantial direct and indirect evidence that any personal issues with aspartame reflect not aspartame per se, but a personal folate deficiency (see http://en.wikipedia.org/wiki/Folate_deficiency), folate polymorphism genetic issues, http://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase), and/or issues with related biochemistry linked to vitamin B12 (http://en.wikipedia.org/wiki/Vitamin_B12). There is no data suggesting any adverse effect for aspartame cannot simply and completely be explained by the folate deficiency, folate genetics, and homocysteine paradigm. This new information only suggests aspartame is even safer, now that what I have reported above is known to all the regulatory authorities. Given these new, stronger indications of safety, science no longer has any reason to doubt the safety of aspartame. And the European equivalent of the US FDA on April 20 just again validated the safety of aspartame, http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902454309.htm.

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

(FYI, the author has absolutely no financial or biasing connection with the aspartame, the soft drink or their related industries and have made not one penny from my opposition, unlike many antiaspartame critics who sell books and offer irrelevant treatment. Their clearly stated goals are lawsuits, where none are justified. The author has an undergraduate degree in chemistry (with emphasis in organic and biological chemistry) from the University of Kansas, a Ph.D. in Medicinal Chemistry (Pharmacy) from the University of Iowa, postdoctoral experience at Yale University (Molecular Biophysics & Biochemistry) and two postdoctoral fellowships at Vanderbilt University (physiology-pharmacology (mentor moved), then nutritional toxicology) and taught nutritional toxicology at the University of Illinois (Champaign-Urbana, UIUC) besides having conducted federally funded research at Vanderbilt, UIUC, and at several other universities before recently entering into semi-retirement.)

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