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Aspartame's Cancer Producing Mechanism


Aspartame, the artificial sweetener made of a combination of two amino acids and methanol, has been found by a recent study on rats, to produce cancers over the lifetime of these laboratory animals. The study was conducted by the European Ramazzini Foundation of Oncology and Environmental Sciences.

Although the European Union's Food Safety Authority in Parma has stated that the study results are inconclusive and should not make us stop taking aspartame, the Scientific Director of the Foundation and primary author of the aspartame study, Dr. Morando Soffritti, M.D., stands by the study's results and announces further studies not only on aspartame but on other widely used sweeteners as well.

As for a possible mechanism on how aspartame promotes the appearance of cancers in those who consume the sweetener, here is a recent article by Beldeu Singh, a Malaysian researcher.

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by Beldeu Singh

Phenylalanine is an essential amino acid which means that the human body cannot synthesize it and it must be obtained from the diet. The primary dietary sources of phenylalanine are high protein foods such as fish, eggs, meat and dairy products.

L-aspartic acid is another natural amino acid. Natural amino acids are the building blocks of proteins in the body. Of the more than 80 amino acids which have been found in living organisms, about 20 serve as the building blocks for the proteins. In mammals, aspartic acid is non-essential, which means it is produced in the body and it is involved in the excitatory neurotransmission activity in the brain.

There are two acidic amino acids - aspartic acid and glutamic acid and both play important roles as general acids in enzyme active centers and in maintaining the solubility and ionic character of proteins. Aspartic acid is used in metabolic activity for the biochemical building of other amino acids and biochemicals in the citric acid cycle. Some of the biochemicals that are synthesized from aspartic acid are asparagine, arginine, lysine, methionine, threonine, isoleucine and several nucleotides.

The mammalian biological system is an intelligent system that has the biochemical engineering to use biomolecules for more than one beneficial purpose to maintain health. The same applies to its protein-building system based on amino acids as the buidilg blocks of proteins. In addition to protein synthesis, amino acids have other biologically-important roles. Glycine and glutamate are neurotransmitters as well as standard amino acids in proteins and many amino acids are used to synthesize other molecules, such as tryptophan, a precursor of the neurotransmitter serotonin and glycine which is one of the reactants in the synthesis of porphyrins such as heme. This system is engineered for biochemical efficiency and is protected by its antioxidant defense mechanism so that free radicals are prevented from damaging the biomolecules and affecting the rates of the biochemical pathways that support life. Minerals from food sources form a part of this biochemistry.

Minerals form a unique chelate with aspartic acid to form aspartates. Aspartates are required in the tricarboxylic acid cycle (Krebs cycle), from which most of the energy is produced by metabolism. The potassium and magnesium forms of the aspartates appear to be agents that promote the efficiency of aerobic energy production for use as cellular energy and consequently they enhance muscular work. Hence, they can be used to overcome fatigue.

Aspartic acid is also known as an ammonia dextoxifier as it facilitates removal of excess ammonia from the liver. The ammonia enters the bloodstream for excretion from the body via the urine. Eating excess can be bad for health, if too much ammonia enters the bloodstream before it is excreted from the body as ammonia is toxic.

Ammonia is produced in the human body and is essential in the body as a building block for making proteins and other complex molecules. In excess, ammonia reacts with strong oxidizers, zinc, copper, and heavy metals in the body. Sudden excess amounts of ammonia in the bloodstream could react with zinc and copper and possibly other minerals, all of which are involved in the metallothionein protein system that helps remove hydroxyl radicals from the cells and are excreted in the urine. If the metallothionein proteins lose the sequestered minerals they become dysfunctional and that can produce many symptoms, from vasoconstriction or breathing problems to symptoms of cellular damage.

Since metallothionein proteins are in cells throughout the body, a rapid compromising effect on the metallothionein protein system explains the wide variety of problems associated with ammonia poisoning from eye irritations to stomach problems, all depending on the concentration of ammonia and corresponding damage to the metallothionein protein system in cells. "Exposure to high concentrations of ammonia in air causes immediate burning of the eyes, nose, throat and respiratory tract and can result in blindness, lung damage or death. Inhalation of lower concentrations can cause coughing, and nose and throat irritation while swallowing ammonia can cause burns to the mouth, throat and stomach" (Department of Health, NY, April 2006).

Ammonia has not been classified for carcinogenic effects but its reaction with minerals and the tandem effect of compromising the metallothionein protein system must be studied for possible carcinogenicity in the long term consumption of aspartame. The effect is produced over the long term because its toxic effects are mediated through reacting with minerals utilized in the metallothionein protein system instead of the type of damage produced by superoxide radicals that can increase the acidity of the cytoplasm and inactivate the enzymes involved in aerobic respiration and the highly reactive hydroxyl radical that causes cellular injury at a faster rate. Additionally, there is strong individual variability, due largely on account of nutritional status, including mineral intake from fruits and vegetables.

The compromise of the metallothionein protein system through aspartame consumption as a route to carcinogenesis is much slower and is in harmony with the recent Italian study that showed that rats fed with aspartame over their lifetime produced cancers at a higher rate than rats in the control group.

Since minerals form a unique chelate with aspartic acid to form aspartates that are required in the tricarboxylic acid cycle (Krebs cycle), and if excess ammonia reacts with the chelated minerals, the level of aspartate declines as does the amount of aerobic energy. In some cells, the aerobic energy production may be shut down by this process, leading to the rerouting of the glucose molecule into the toxic pathway for energy production found in cancer cells. Interesting as it may sound, experimental evidence from biomolecular studies is required to validate it.

Aspartic acid is found in sprouting seeds, oat flakes, avocado, asparagus, sugar cane and molasses. Aspartic acid can be easily converted to glucose when demand for glucose exceeds supply.

Aspartame is a sweetener that is formed by combining phenylalanine with another amino acid called aspartic acid.

Amino acids come in two forms, designated as "L-" and "D-" forms. The "L-" form is the naturally occurring form in foods, whereas the "D-" form is the synthetic. For industrial use amino acids are normally synthesized as it is many times cheaper to synthesize. When an amino acid is synthesized commercially, there is usually a mixture of the L- and D- forms. Sometimes the D- form is removed, but in the case of phenylalanine, the combination of the two forms is used to take advantage of the unique characteristics of both forms. The combined form of the supplement is known as D, L-phenylalanine or DLPA. DLPA was found to be as effective as a drug in treating depressive
symptoms, indicating that DLPA has powerful antidepressant properties.

In the manufacture of aspartame, the most desirable starting material is one comprising purely the L-isomer form of phenylalanine. Phenylalanine is conventionally made either through chemical synthesis, enzymatic synthesis or fermentation. Most of these methods result in a racemic mixture of the D and L isomers which must either be separated or resolved, to yield a pure L-phenylalanine fraction but the separation or resolution steps are costly.

Biocatalytic processes resulting in the formation of a specific isomer are known to scientists. Also there is a patented process for producing L-amino acids by transamination but I do not know which process is actually used for the commercial production of aspartame. Usually, the most economical processes and methods are used. (A healthy corporate bottom line is more important than the nation's health).

Aspartame, used as artificial sweetener (NutraSweet, Equal) aspartyl-phenylalanine, is 200 times sweeter than sucrose. Aspartame is a chemical compound consisting of 50% phenylalanine (PHE), 40% aspartic acid and 10% methyl alcohol (or methanol, wood alcohol). Methanol is readily converted to the immune suppressing toxic substance formaldehyde (Rich Sources Of Nutrients, Jurriaan Plesman BA(Psych), Post Grad Dip Clin Nutr., updated 3 June, 2006). The other problem from aspartame, therefore arises from methanol and its toxic metabolite - formaldehyde.

Since 1980, the National Cancer Institute (NCI) has conducted studies to determine if there is a link between occupational exposure to formaldehyde and an increase in the incidence of cancer and possibly a risk to cancer. Several NCI studies show a link to exposure to formaldehyde and an increased risk for leukemia and brain cancer compared with the general population. Another study by the National Institute for Occupational Safety and Health (NIOSH) also found an association between the duration of exposure to formaldehyde and leukemia deaths.

In 1995, the International Agency for Research on Cancer (IARC) concluded that formaldehyde is a probable human carcinogen and upon reevaluation of the existing data in June 2004, the IARC reclassified formaldehyde as a known human carcinogen (International Agency for Research on Cancer (June 2004). IARC Classifies Formaldehyde as Carcinogenic to Humans. Retrieved June 30, 2004; see

Several case-control studies and cohort studies, including analysis of the large NCI cohort, have reported an association between formaldehyde exposure and nasopharyngeal cancer but formaldehyde appears to affect at sites other than the upper respiratory tract.

Since formaldehyde is water soluble and highly reactive with biological macromolecules, adverse effects resulting from exposure are observed in those tissues or organs with which formaldehyde first comes into contact (i.e., the respiratory and aerodigestive tract, including oral and gastrointestinal mucosa, following inhalation or ingestion, respectively). There are also case reports for some individuals that formaldehyde-induced asthma. In laboratory animals, formaldehyde causes degenerative non-neoplastic effects in mice and monkeys and nasal tumours in rats (Monticello et al., 1989). In vitro, formaldehyde induced DNA-protein crosslinks, DNA single-strand breaks, chromosomal aberrations, sister chromatid exchange, and gene mutations in human and rodent cells (Reuzel et al., 1990; Cassee et al., 1996; Woutersen et al., 1987).

Formaldehyde produces intramolecular and intermolecular crosslinks within proteins and nucleic acids upon absorption at the site of contact (Swenberg et al., 1983). It is also rapidly metabolized to formate by a number of widely distributed cellular enzymes, the most important of which is NAD+-dependent formaldehyde dehydrogenase. Metabolism by formaldehyde dehydrogenase occurs subsequent to formation of a formaldehyde-glutathione conjugate. Formaldehyde dehydrogenase has been detected in human liver and red blood cells and in a number of tissues (e.g., respiratory and olfactory epithelium, kidney, and brain) in the rat. The conjugation of glutathione with formaldehyde serves to stop its toxicity and to facilitate its removal from the body and that contributes to the depletion of glutathione - an antioxidant enzyme in the human and mammalian biochemical system.

The mechanisms by which formaldehyde induces tumours appears to be slow and is unlikely to be mediated directly by free radical damage or direct oxidative stress. The evidence of glutathione-mediated detoxification of formaldehyde within nasal tissues becomes saturated in rats at inhalation exposures above 4 ppm (4.8 mg/m3) (Casanova & Heck, 1987) and the detection of the formaldehyde-glutathione conjugate in human liver points to an indirect process that first depletes glutathione in cells sufficiently to allow the accumulation of hydrogen peroxide levels in cells, and the reaction of hydrogen peroxide with superoxide creates the hydroxyl radical that aids the development and progression of cancers. This process is accelerated when in certain cells or tissues, excess ammonia compromises the metallothionein protein system but overall, it is a rather slow process that does not develop within two or three years in most individuals.