Aspartame and PTSD

Young man sitting at kitchen table with hands on face
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PTSD and Its Symptoms
Post-traumatic stress disorder (PTSD) is characterized by a number of symptoms. According to the May 2013 revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), these symptoms may include alterations in cognition and mood, as well as alterations in arousal and reactivity. Manifestations of these alterations can include negative beliefs about oneself; negative emotions such as fear, anger and shame; diminished interest in significant pre-traumatic activities; feelings of alienation; the inability to experience positive emotion; irritable behavior; problems concentrating; and difficulty sleeping.



History of Aspartame Approval
Aspartame is an artificial, non-saccharide sweetener used as a sugar substitute, which is approximately 200 times sweeter than sucrose. When metabolized by the body it breaks down into three components: two amino acids (aspartic acid and phenylalanine) and a small amount of methanol (methyl alcohol).
Discovered in 1965, aspartame was initially given restricted approval for use in dry foods by the Food and Drug Administration (FDA) in 1974. The following year, the FDA placed a stay on the approval due to questions surrounding the validity and thoroughness of the studies submitted by GD Searle (the manufacturer of aspartame) during the initial application process. In 1980, a Public Board of Inquiry (PBOI), created by the FDA, heard testimony regarding concerns about purported links between aspartame and brain damage as well as aspartame’s effects on developing fetuses.

  While the PBOI disagreed with the claims brought forth, the Board did have further questions about the link between aspartame and brain cancer. As a result of the questions brought forth at the PBOI, the Board revoked the approval of aspartame, pending further inquiry. In 1981, newly appointed FDA Commissioner Arthur Hull Hayes, in consultation with FDA scientists, cited analysis errors made by the PBOI regarding the safety of aspartame.

After a review of additional studies, including those addressing the possible brain cancer link, aspartame was reapproved for dry good use in 1981.

The following year, Searle filed a petition with the FDA to allow aspartame to be approved as a sweetener in carbonated beverages and other liquids. In July 1983, aspartame was approved for inclusion in liquids despite objections from the National Soft Drink Association (NSDA), which was concerned about the stability of aspartame in liquid form  and concerned because at temperatures exceeding 85 degrees Fahrenheit, methanol breaks down into formaldehyde and Diketopiperazine (DKP), which can be toxic at high levels of ingestion.

The Function and Sources of the Components of Aspartame
Aspartic acid (also known as asparaginic acid) helps regulate hormone production and release and also helps maintain normal nervous system function, in part by stimulating the synapses in the central nervous system. Aspartic acid also helps convert carbohydrates into energy.

It is known as a conditional or “non-essential” amino acid because we do not need to consume food in order to obtain it; it is naturally synthesized by our bodies. However, we do ingest it when we eat peanuts, soybeans, lentils, salmon, oysters, asparagus and several other high-protein foods.

Phenylalanine is an amino acid that plays a critical role in the formation of protein and several neurochemicals, including dopamine and adrenaline. As an indispensable or “essential” amino acid, it cannot be produced by our bodies and therefore must be obtained from food sources such as meat, fish and dairy products as well as nuts and legumes.

Methyl alcohol (frequently referred to as wood alcohol) is found in windshield cleaner, shellac, paint remover, deicing fluids and antifreeze. Exposure can cause dizziness, vomiting, convulsions and blindness. As little as 2oz can kill an adult. However, a number of food products contain trace amounts of methyl alcohol, including wine; orange juice and grapefruit juice; fruits, especially apples, black currants and tomatoes; vegetables such as potatoes, brussels sprouts, celery and parsnips; and smoked meats and fish. In a typical day, the average person consumes approximately 10mg of methanol per day as part of their regular diet. A can of diet soda flavored with aspartame will contribute approximately 20mg of methyl alcohol to their intake.

Formaldehyde is a strong-smelling chemical used in building materials and insulation. It is also used as a preservative in laboratories and mortuaries and can be found in auto emissions. It has been labeled a “known human carcinogen” by the International Agency for Research on Cancer and as a “probable human carcinogen” by the Environmental Protection Agency. Formaldehyde is usually present in the air (both indoor and outdoor) at less than 0.03 parts per million (ppm). When present in the air at levels exceeding 0.1ppm, irritation to the eyes, nose, throat, and skin may occur. However, formaldehyde is also naturally produced by the body in quantities much greater than is produced in the breakdown of aspartame – and the formaldehyde is essential to the formation of several compounds, including DNA. There is also formaldehyde present in a variety of foods, including bananas, pears, cauliflower, kohlrabi, dried shitake mushrooms, ham, sausage and several edible species of crustaceans. A single jelly bean releases 45 times more formaldehyde than an entire can of diet soda – and no one eats just one jelly bean.

Diketopiperazine (DKP), also known as dioxopiperazine or piperazinedione, is not a single chemical. Rather, DKP refers to a class of organic molecule isomers. It is the 2,5 isomer of DKP that becomes present in the body as a breakdown product of the small amount of methyl alcohol in aspartame.  DKP can be found in many foods including cereals, cheese, chocolate, coffee, beer and milk. DKP has also been linked to neuroprotective activity, showing significantly reduced cell death associated with necrosis (premature cell death), apoptosis (preprogrammed cell death) or injury.
 

The Safety of Aspartame

The three components of aspartame (aspartic acid, phenylalanine, and methyl alcohol) as well as the formaldehyde and DKP which methanol can break down into at high storage temperatures, have been causes of concern for some people since the introduction of aspartame. According to Ann Louise Gittleman, Ph.D., in Get the Sugar Out, nearly75 percent of all complaints to the FDA about food are regarding aspartame.

However, the FDA, the European Food Safety Authority (EFSA) and even the American Cancer Society state that aspartame poses no risks when it is consumed in quantities in line with acceptable daily intake amounts (ADI). An ADI is calculated to be 1/100th of the no-observed-effect level (NOEL). The NOEL is the greatest concentration of a substance that does not cause any change to the growth, development or lifespan of the organism.


The FDA has set the ADI for aspartame at 50 milligrams per kilogram (mg/kg) of body weight per day. The EFSA’s ADI for aspartame is slightly lower, at 40 milligrams per kilogram (mg/kg) of body weight per day. To put this in perspective, an adult weighing 165lbs. would have to drink nearly 20 cans of diet soda or eat over 100 packets of straight sweetener to consume the ADI of aspartame for a single day. One 12oz. can of diet soda contains approximately 190mg of aspartame, which breaks down into 90mg of phenylalanine, 72mg of aspartic acid and 18mg of methanol.

By comparison, 8oz. of milk contains 404mg of phenylalanine and 592mg of aspartic acid. Chocolate, rye bread, plain cheese pizza, eggs, Parmesan cheese, lobster, tuna, chicken, lamb, and turkey all contain more phenylalanine per serving than diet soda. A single banana contains more methanol than a can of diet soda, as does an 8oz glass of tomato juice.

It is important to note, however, that most methanol found in foods is bound to pectin, which the human body cannot digest because it lacks the proper enzymes and therefore the methanol is not released. These foods often also contain ethanol, which counteracts the effects of methanol. This is not the case for the methanol component of aspartame, which is considered “free methanol.”

An ADI of 7.5 milligrams per kilogram (mg/kg) of body weight per day was established for DKP by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the FDA and the UK Committee on Toxicity in the 1980s. In 1987, FDA Toxicologist Dr. Jacqueline Verrett testified before congress that DKP has been implicated as a cause of uterine polyps and changes in blood cholesterol. However, in 2012, as part of its reevaluation of artificial food sweeteners, the European Food Safety Authority (EFSA) requested additional data on DKP, which it ultimately found to be safe in levels of typical consumption. The following year, the EFSA concluded that the amount of potential exposure to DKP from all food sources averaged 1/75th to 1/4th of the ADI for DKP and therefore recognized no consumer safety risk from exposure to DKP.



Phenylketonuria
There is one population for which aspartame has been proven to be highly dangerous: people who suffer from the genetic condition phenylketonuria (PKU). PKU is a rare autosomal recessive disorder, meaning a child would have to inherit a copy of the non-functioning allele from each parent. Children born with PKU lack the ability to metabolize phenylalanine, one of the components in aspartame. The build-up of phenylalanine can cause seizures, behavior problems and developmental and cognitive delays. While the consumption of aspartame (as well as any other foods containing phenylalanine) could have catastrophic consequences for a person with PKU, it is important to remember that PKU is a rare genetic condition, for which babies are tested at birth. It is not something to be concerned about unless you have a diagnosis of PKU.

Aspartame and PTSD
After all the data has been presented in this article showing that aspartame (and its components) has been deemed safe by multiple international and national oversight organizations, why should there then be any concern about people with PTSD consuming aspartame? A 2014 month-long University of North Dakota study showed that otherwise healthy adults who consumed a high-aspartame diet (25 mg/kg of body weight/day, which is still half the ADI for aspartame) exhibited increased irritability, worsening depression and difficulty with spatial orientation. Working memory (which is the application of short-term memory to cognitive tasks) was not impacted. After eight days on the high-aspartame diet, the subjects had a two-week washout period (where the subjects were not actively being studied for aspartame consumption) followed by eight days on a low-aspartame diet (10 mg/kg of body weight/day).

These instances of worsening depression recorded during the University of North Dakota study lend further credence to an earlier study of 80 patients, half of which had unipolar depression. The participants were given 30 mg/kg of body weight/day of aspartame (60% of the ADI) or a placebo for seven days. While the subjects with no history of depression showed no symptoms regardless of which group they were assigned to, those with a history of depression exhibited a number of symptoms, some of which were severe. In fact, the Institutional Review Board stopped the project because of the reactions of those participants with depression.

One of aspartic acid’s main functions is gluconeogenesis (the generation of glucose). Its other main function is that of a neurotransmitter agonist. An agonist helps facilitate the action of a receptor. As aspartate (the conjugate base of aspartic acid), it stimulates NMDA receptors, as does glutamate. Aspartate can also form the neurotransmitter NMDA, by bonding with a methyl group from a donor compound. Aspartate, therefore, acts as both a neurotransmitter itself and as a building block for another neurotransmitter.

The NMDA receptor is primarily responsible for controlling memory functions and for regulating synaptic plasticity (the changing strength or weakness of a synapse over time, as well as the number of receptors on a synapse). In order for the NMDA receptor to work properly, it needs to bind with either glycine or D-serine, as well as with glutamate (or NMDA). Glycine-site NMDA receptor agonists hold promise for new drugs to help mediate anxiety, depression, and pain.

However, certain receptors, including NMDA, can become overexcited and cause neuronal excitotoxicity. This can lead to cell damage and death, including to the hippocampus, which plays a major role in encoding fear conditioning. The hippocampus in people with PTSD is already hypoactive; further damage from neuronal excitotoxicity could exacerbate the already abnormal fear response. Dopamine can help protect cells against neurotoxicity but people with depression (frequently a comorbid condition with PTSD) often suffer from abnormal dopamine levels. Consuming food and beverages with high levels of aspartame can lead to increased levels of NMDA which then can cause neuronal excitotoxicity.

Conclusions
Given that recent studies have shown a correlation between increased rates of depression and high-aspartame diets, it seems advisable that people who are more likely to develop depressive episodes (including those with PTSD) should limit their intake of aspartame to well below the ADI of 50 mg/kg of body weight/day, despite the additive’s seeming safety for the general public. This becomes clearer when considering that the same study also noted increased irritability and pronounced cognition deficits, symptoms people diagnosed with PTSD already struggle with. Finally, taking into account the potential damage done to the hippocampus by the excitotoxin NMDA, consideration should be taken about consumption of aspartame for those with PTSD or other mental health conditions such as major depressive disorder.

Aspartame is marketed under the brand names NutraSweet, Equal and Sugar Twin.

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