MITOXIC-Why Aspartame may not be good for any of us, especially Mitochondrial Disease patients

I have never liked diet drinks. Never, ever. The taste of artificial sweetener makes me sick to my stomach.
When we gave up artificial colors and flavors at our house, though, the artificial sweetener also went in the trash (in the hidden sources we discovered).  I didn’t think much about it until the other day an on-line friend posted that her daughter (who is suspected of mito) was having severe behavioral changes to a reflux medicine that my daughter had been on (Prevacid). A few of the other moms online suggested it may be the fillers or sweeteners rather than the actual medicine itself. Which is the conclusion we had come to (thinking it was the soy derived flavoring and dye in the Prevacid) when Lady A was around 10 month old. Lo and behold my friend did some research of her own and began to suspect Aspartame as the culprit to her daughters severe personality and behavioral changes.
She posted this LINK to the research she had found on the internet.

What is Aspartame:

Some notes from Wikipedia:

Metabolism and phenylketonuria

Upon ingestion, aspartame breaks down into natural residual components, including aspartic acid, phenylalanine, methanol,^[25] and further breakdown products including formaldehyde^[26] and formic acid, accumulation of the latter being suspected as the major cause of injury in methanol poisoning. Human studies show that formic acid is excreted faster than it is formed after ingestion of aspartate. In some fruit juices, higher concentrations of methanol can be found than the amount produced from aspartame in beverages.^[13]

High levels of the naturally-occurring essential amino acid phenylalanine are a health hazard to those born with phenylketonuria (PKU), a rare inherited disease that prevents phenylalanine from being properly metabolized. Since individuals with PKU must consider aspartame as an additional source of phenylalanine, foods containing aspartame sold in the United States must state “Phenylketonurics: Contains Phenylalanine” on their product labels.^[27]

In the UK, foods that contain aspartame are legally required by the country’s Food Standards Agency to list the chemical among the product’s ingredients and carry the warning “Contains a source of phenylalanine” – this is usually at the foot of the list of ingredients. Manufacturers are also required to print ‘”with sweetener(s)” on the label close to the main product name’ on foods that contain “sweeteners such as aspartame” or “with sugar and sweetener(s)” on “foods that contain both sugar and sweetener”.^[28]

Under the trade names Equal, NutraSweet, and Canderel, aspartame is an ingredient in approximately 6,000 consumer foods and beverages sold worldwide, including (but not limited to) diet sodas and other soft drinks, instant breakfasts, breath mints, cereals, sugar-free chewing gum, cocoa mixes, frozen desserts, gelatin desserts, juices, laxatives, chewable vitamin supplements, milk drinks, pharmaceutical drugs and supplements, shake mixes, tabletop sweeteners, teas, instant coffees, topping mixes, wine coolers and yogurt.

As I read it, I was reminded of all the information I had read I the last 3 years about the dangers of aspartame not to mention aspartame’s direct negative effect on individuals with another metabolic disorder I have been learning more and more about recently: PKU.  In addition, I was reminded of a book called Excitotoxins: The Taste That Kills. It is a fairly technical read and while I have not read it cover to cover, I have skimmed it – and the main point of the doctor who wrote it is: Aspartame (and MSG) disrupt brain chemistry in harmful ways. Here is the cliff notes version of the book on video (my favorite way to “read”):

Aspartame is WIDESPREAD in our society, here is a LIST of products where Aspartame can be found.

Aspartame Consumer Safety Network  which includes a PILOT HOTLINE… why a hotline for pilots and aspartame  you may ask? … read this.  Why may pilots be more affected by Aspartame? Here is one possible theory.

What happens when you combine 2 Mitotoxic substances: Aspartame Plus Artificial Colors

Inhibition of neurite (neuron) outgrowth was found at concentrations of additives theoretically achievable in plasma by ingestion of a typical snack and drink. In addition, Trypan Blue dye exclusion was used to evaluate the cellular toxicity of food additives on cell viability of NB2a cells; both combinations had a straightforward additive effect on cytotoxicity (toxicity to cells).

To see a photo this toxic effect on Neurons (with MSG in photo, but experiment also done with Aspartame) scroll to the 6th bullet point picture..

LAYMAN and LAYWOMEN’s VERSION

So… why should those with mito beware (as well as the rest of us?)…here is the 2 minute Non- technical version:

From My last Mitotoxic post about Acetaminophen you may remember the chemical Glutathione {G}. This chemical is one of the major detoxifying chemicals in your body. As I have mentioned before,  It has been shown that children with autism and those withmitochondrial disease have lower levels of {G} to begin with. In the scientific articles below, research points to the fact that Aspartame disrupts the antioxidant status of the brain… SPECIFICALLY the Glutathione {G} dependant system. So if you are low to begin with in {G} and then you consume Aspartame, you reduce this crucial antioxidant even further..in a place where you really don’t want to have oxidative stress or damage YOUR BRAIN!  (Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system’s ability to readily detoxify the reactive intermediates or easily repair the resulting damage.)  So do you know what your Glutathione {G} levels are? Probably not, unless you have had them specifically tested and sought out a test for {G}, because this is not a routine blood test that your doctor will order for your yearly physical…. but maybe it should be?? Here is an option to ask your doctor about at your next visit:  Spectracell Micronutrient Panel

In addition to disrupting {G} levels, and lowering your ability to detoxify, many of the the chemicals that Aspartame breaks down to in your body can be very TOXIC…including methanol (causes blindness when ingested), formaldehyde (chemical used to preserve deceased bodies), formic acid (occurrs naturally in bee sting venom), phenylalanine (amino acid, can be toxic to those who cannot break it down- like those with PKU) and aspartic acid (amino acid).  The levels of these chemicals may build up and cause more damage in your body if you are not able to rid (or detoxify) yourself from them.

Just a little Drink for THOUGHT…the next time you reach for the Diet Cola or hand your child a glass of Crystal Lite… which are filled with this neuron altering chemical called ASPARTAME (deemed “safe” by the FDA)

Here is just some of  THE SCIENCE

Aspartame and glutathione

Long-term consumption of aspartame and brain antioxidant defense status.

Abstract

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Aspartame and Glutathione #2

The effect of L-cysteine and glutathione on inhibition of Na+, K+-ATPase activity by aspartamemetabolites in human erythrocyte membrane.

BACKGROUND:

Reports have implicated Aspartame (N-L-a-aspartyl-L-phenylalanine methyl ester, ASP) in neurological problems.

RESULTS:

Membrane Mg(2+)-ATPase activity was not altered. The sum of ASP metabolite concentrations corresponding to 34, 150 or 200 mg/kg of the sweetener ingestion resulted in an inhibition of the membrane Na(+), K(+)-ATPase by -30, -40, -48%, respectively. MeOH concentrations of 0.14, 0.60 or 0.80 mM decreased the enzyme activity by -25, -38, -43%, respectively. Asp concentrations of 2.80, 7.60 or 10.0 mM inhibited membrane Na(+), K(+)-ATPase by -26, -40, -46%, respectively. Phe concentrations of 0.14, 0.35 or 0.50 mM reduced the enzyme activity by -24, -44, -48%, respectively. Preincubation with L-cysteine or reduced glutathione (GSH) completely or partially restored the inhibited membrane Na(+), K(+)-ATPase activity by high or toxic ASP metabolite concentrations.

CONCLUSIONS:

Low concentrations of ASP metabolites had no effect on Na(+), K(+)-ATPase activity. High or abuse concentrations of ASP hydrolysis products significantly decreased the membrane enzyme activity, which was completely or partially prevented by L-cysteine or reduced GSH.

Methanol and Aspartame

Methanol: a chemical Trojan horse as the root of the inscrutable U.

Abstract

Until 200 years ago, methanol was an extremely rare component of the human diet and is still rarely consumed in contemporary hunter and gatherer cultures. With the invention of canning in the 1800s, canned and bottled fruits and vegetables, whose methanol content greatly exceeds that of their fresh counterparts, became far more prevalent. The recent dietary introduction of aspartame, an artificial sweetener 11% methanol by weight, has also greatly increased methanol consumption. Moreover, methanol is a major component of cigarette smoke, known to be a causative agent of many diseases of civilization (DOC). Conversion to formaldehyde in organs other than the liver is the principal means by which methanol may cause disease. The known sites of class I alcohol dehydrogenase (ADH I), the only human enzyme capable of metabolizing methanol to formaldehyde, correspond to the sites of origin for many DOC. Variability in sensitivity to exogenous methanol consumption may be accounted for in part by the presence of aldehyde dehydrogenase sufficient to reduce the toxic effect of formaldehyde production in tissue through its conversion to the much less toxic formic acid. The consumption of small amounts of ethanol, which acts as a competitive inhibitor of methanol’s conversion to formaldehyde by ADH I, may afford some individuals protection from DOC.

Can Aspartame trigger a metabolic crisis in a child?

Metabolic acidosis mimicking diabetic ketoacidosis after use of calorie-free mineral water.

Abstract

A previously healthy boy was admitted with fever, tachycardia, dyspnea, and was vomiting. A blood test showed a severe metabolic acidosis with pH 7.08 and an anion gap of 36 mmol/L. His urine had an odor of acetone. The serum glucose was 5.6 mmol/L, and no glucosuria was found. Diabetic ketoacidosis could therefore be eliminated. Lactate level was normal. Tests for the most common metabolic diseases were negative. Because of herpes stomatitis, the boy had lost appetite and only been drinking Diet Coke and water the last days. Diet Coke or Coca-Cola Light is sweetened with a blend containing cyclamates, aspartame, and acesulfame potassium, all free of calories. The etiology of the metabolic acidosis appeared to be a catabolic situation exaggerated by fasting with no intake of calories. The elevated anion gap was due to a severe starvation ketoacidosis, mimicking a diabetic ketoacidosis. Pediatricians should recommend carbohydrate/calorie-containing fluids for rehydration of children with acute fever, diarrhea, or illness.

 Aspartame and Seizures

Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study.

Abstract

There are anecdotal reports of increased seizures in humans after ingestion of aspartame. We studied 10 children with newly diagnosed but untreated generalized absence seizures. Ambulatory cassette recording of EEG allowed quantification of numbers and length of spike-wave discharges in a double-blind study on two consecutive days. On one day the children received 40 mg/kg aspartame and on the other day, a sucrose-sweetened drink. Baseline EEG was the same before aspartame and sucrose. Following aspartame compared with sucrose, the number of spike-wave discharges per hour and mean length of spike-wave discharges increased but not to a statistically significant degree. However, the total duration of spike-wave discharge per hour was significantly increased after aspartame (p = 0.028), with a 40% +/- 17% (SEM) increase in the number of seconds per hour of EEG recording that the children spent in spike-wave discharge. Aspartame appears to exacerbate the amount of EEG spike wave in children with absence seizures. Further studies are needed to establish if this effect occurs at lower doses and in other seizure types.

Formic Acid, Methanol and Mitochondrial

Acquired mitochondrial impairment as a cause of optic nerve disease.

Abstract

BACKGROUND:

Blindness from an optic neuropathy recently occurred as an epidemic affecting 50,000 patients in Cuba (CEON) and had clinical features reminiscent of both tobacco-alcohol amblyopia (TAA) and Leber’s hereditary optic neuropathy (Leber’s; LHON). Selective damage to the papillomacular bundle was characteristic, and many patients also developed a peripheral neuropathy. Identified risk factors included vitamin deficiencies as well as exposure to methanol and cyanide. In all 3 syndromes, there is evidence that singular or combined insults to mitochondrial oxidative phosphorylation are associated with a clinically characteristic optic neuropathy.

PURPOSE:

First, to test the hypothesis that a common pathophysiologic mechanism involving impairment of mitochondria function and, consequently, axonal transport underlies both genetic optic nerve diseases such as Leber’s and acquired toxic and nutritional deficiency optic neuropathies. According to this hypothesis, ATP depletion below a certain threshold leads to a blockage of orthograde axonal transport of mitochondria, which, in turn, leads to total ATP depletion and subsequent cell death. Second, to address several related questions, including (1) How does impaired energy production lead to optic neuropathy, particularly since it seems to relatively spare other metabolically active tissues, such as liver and heart? (2) Within the nervous system, why is the optic nerve, and most particularly the papillomacular bundle, so highly sensitive? Although there have been previous publications on the clinical features of the Cuban epidemic of blindness, the present hypothesis and the subsequent questions have not been previously addressed.

METHODS:

Patients in Cuba with epidemic optic neuropathy were personally evaluated through a comprehensive neuro-ophthalmologic examination. In addition, serum, lymphocytes for DNA analysis, cerebrospinal fluid (CSF), sural nerves, and eyes with attached optic nerves were obtained from Cuban patients, as well as from Leber’s patients, for study. Finally, we developed an animal model to match the low serum folic acid and high serum formate levels found in the CEON patients, by administering to rats low doses of methanol after several months of a folic acid-deficient diet. Optic nerves and other tissues obtained from these rats were analyzed and compared with those from the Cuban patients.

RESULTS:

Patients from the Cuban epidemic of optic neuropathy with clinical evidence of a selective loss of the papillomacular bundle did much better once their nutritional status was corrected and exposure to toxins ceased. Patients with CEON often demonstrated low levels of folic acid and high levels of formate in their blood. Histopathologic studies demonstrated losses of the longest fibers (in the sural nerve) and those of smallest caliber (papillomacular bundle) in the optic nerve, with intra-axonal accumulations just anterior to the lamina cribrosa. Our animal model duplicated the serologic changes (low folic acid, high formate) as well as these histopathologic changes. Furthermore, ultrastructural examination of rat tissues demonstrated mitochondrial changes that further matched those seen on ultrastructural examination of tissues from patients with Leber’s.

CONCLUSION:

Mitochondria can be impaired either genetically (as in Leber’s) or through acquired insults (such as nutritional or toxic factors). Either may challenge energy production in all cells of the body. While this challenge may be met through certain compensatory mechanisms (such as in the size, shape, or number of the mitochondria), there exists in neurons a threshold which, once passed, leads to catastrophic changes. This threshold may be that point at which mitochondrial derangement leads to such ATP depletion that axonal transport is compromised, and decreased mitochondrial transport results in even further ATP depletion. Neurons are singularly dependent on the axonal transport of mitochondria.