Aspartame

You have no idea how many times I have overheard, heard, and been asked about aspartame. Most people I have heard discuss the subject tend to swing toward the belief that aspartame is an unhealthy substance most commonly found in diet drinks; while this is not entirely inaccurate, it seems clear to me that some education on subject is more than warranted – shall we start this scientific journey?

If you have read any of my other pieces, you know that I find it important to start at the foundation, the crux of the subject before we really get rolling and start knocking out the questions that plague the populace. Of course, as usual, I encourage you to educate yourself fully, but if time is an issue, this article is segmented for your convenience – read as much or as little as you’d like.


Understanding Aspartame

Let’s get chemical!

Okay, that was lame – I’ll give you that, but for us to understand aspartame, we should understand what makes up aspartame. It really is quite simple, honestly. Aspartame is made up of two amino acids called aspartic acid (also known as aspartate) and phenylalanine (1). Now, you might be a bit put off by this if you understand anything about protein build and for those of you who are unaware, you might be even more confused as to why I’m suddenly referencing protein in an aspartame article.

If you do not already know, amino acids are most well known for being “building blocks” for complete protein molecules. The same stuff that keeps you alive (protein) shares some of the same organic compounds as aspartame. While a complete protein has 20 amino acids, aspartame is made up of a concentration of only two.

As a side note, one of the breakdown products of aspartame, called 3-carboxymethyl-6-benzyl-2,5-diketopiperazine (we’ll stick to DKP.. easier to look at.. and pronounce.. and I can say it 10 times fast) is actually found in many natural nutritious environments such as many proteins, breads, cheeses, vegetables, and even in certain fungi (4). Bottom line, other than a chemist sticking phenylalanine and aspartic acid together in a lab, aspartame is an oddly “natural” substance.


What is Aspartame being used for?

That is a fundamentally important question for why we are even having this discussion. In essence, we know that sugar is a popular ingredient in a massive quantity of foods, and while it makes things taste delicious, it does not escape the fact that it is a carbohydrate and as such, per gram, consists of 4 calories – if you are drinking a soda with 70 grams of sugar, calories add up quickly. Due to this issue, enter aspartame.

However, aspartame, it too is 4 calories per gram.

Well, what gives? If they are the same on a caloric level, why substitute sugar with aspartame?

This is where things get a bit interesting (as if you weren’t already on the edge of your seat..). Our body is far more responsive to aspartame than it is to sugar. That means that it requires a minute amount of aspartame to elicit the same response in your taste buds as sugar. Quantitatively, it takes two teaspoons of sugar (32 calories) to elicit similar strength of reaction as one packet of aspartame (4 calories); it is estimated that aspartame is anywhere between 160-200x sweeter than sugar (2). So, again, where it would take a producer 100 grams of sugar to elicit a level of reaction in your mouth, it would take milligrams (note: not grams) to create the same reaction with aspartame – it is potent.

So, we can understand why aspartame has become an extremely popular additive to many drinks and foods, but is it acceptable to consume? Will you get cancer? Will you grow horns out of your butt? Will your eye balls fall out? Let’s find out.

 

Is Aspartame Safe?

I would guess this is what most people are concerned with, so let us get a detailed breakdown of the subject started.

Cancer

One of the greatest worries regarding aspartame is its impact as a carcinogen to our body. If we examine the numerous studies done on the subject, we can start making an educated decision on the matter.

In 2005, a study was published that did link (Note: link means correlation, not causation) aspartame consumption in rats to several cancers (pelvic cancer, leukemia, brain cancer, etc.)(3). While this study took a lot of heat from the FDA, among other critics (11), for various confounding variables (detailed in the “citations” of this article), there have been many studies that have had opposing conclusions. By the estimation of several other studies (increasing statistical reliability factor), cancer is not a risk from consuming various amounts of aspartame.

In children pre-diagnosed with cancer, as well as pregnant mothers, an epidemiological study concluded there is no relation between aspartame and cancer – in both cases; aspartame is safe to consume (6). Several reviews of past studies up to 1997 also concluded there is no link between aspartame and cancer in humans or rats (7)(9) while one study remained inconclusive (8).

Meanwhile, a comprehensive analysis on over 400,000 people concluded no connection between aspartame and ill health effects (10).

From a non-study perspective, the Food and Drug Administration (13), the National Cancer Institute (5), the Center of Disease Control (12) and American Cancer Society (13) have all proclaimed aspartame safe to consume at ADI (Acceptable Daily Intake – covered later), and in some cases, higher levels than ADI (114% ADI) have been studied in short term studies that found no connection between aspartame and cancer (4).

All in all, it is relatively safe to assume aspartame will not cause cancer.


 

General Health?

Now, while cancer is a worrisome disease and much research has been done on it, there are a plethora of other diseases that can be severely debilitating to our health. It is wise to see if aspartame has any impact on our health as a whole, so strap in, we’re going diving again.

I hope you like history.

In 1980, after much investigation, the FDA released their comprehensive study of the data collected by the United States Bureau of Foods (14) and while the FDA agreed with almost everything the Bureau had put together, there was some disagreement on one front that I feel is worthy of mention.

The Bureau compiled their conclusion on the toxicity of aspartic acid (one of the two amino acids that make up aspartame, remember?) based on 5 studies done with monkeys. In this case, 4 studies showed conclusive results that a toxicity level of Aspartic Acid could safely be placed at 120 umol/dl while the last study found conflicting results. These conflicting results were not resolved, yet the Bureau still put their recommendation at no more than 120 umol/dl. The FDA agreed that results were controversial, yet looked at toxicity levels of 100 umol/dl (as found in previous mice studies)(14).

I am mentioning this in full disclosure of conflicting results that were unresolved (otherwise, I would not mention it), but I need to make the perception of 100 umol/dl clear in relation to aspartame consumption. If a person consumes 200mg/kg of aspartame (well above the ADI), one’s baseline aspartic acid levels will increase between 3-7 umol/dl (3-7% of the projected toxicity level)(14); this means it is nearly impossible to consume enough aspartame to get remotely close to aspartic acid toxicity levels.

Moving on to other literature, according to The Critical Evaluation of a Food Additive: Assessment of Aspartame, there has been no reliable evidence against aspartame and DKP consumption looking at carcinogenic (as we covered before), genetic, reproductive (16), teratogenic (16), metabolic, acute, and chronic studies done on mice, rats, rabbits, guinea pigs, dogs, and humans fed up to, in some cases, 8 g/kg of aspartame (15).

A University of Mississippi and University of Alabama comprehensive analysis came to the same conclusion on all variables addressed in The Critical Evaluation of a Food Additive: Assessment of Aspartame as well as looking into acute toxicology (17). Repeating, on all fronts, high doses of aspartame and DKP showed no adverse effects.

Finally, even the stricter European Food Safety Authority (EFSA) has cleared aspartame as safe to consume at their ADI (18).

So, in regards to general health, aspartame seems to be clear for anyone in good standing.


Phenylketonuna

In the previous section, I covered general health and aspartame; in this section, I think it is important to note that aspartame can be unhealthy for a particular population.

Likely, you would know if you are suffering from this issue, but those with severe or moderate phenylketonuna are highly sensitive to one of principle pieces that make up aspartame structure; namely, phenylalanine (19)(20)(22). In short, people with phenylketonuna lack the digestive enzyme phenylalanine hydroxylase for the metabolism of phenylalanine and as phenylalanine is a component of aspartame, the consumption of aspartame at levels equivalent to a person without the disorder is believed to prove fatal (21). That being said, although this is a widely held belief, a few studies have been done on just how sensitive people with the disorder are and results were surprising.

According to certain studies that specifically examined toxicity of aspartame intake in various PKU (phenylketonuna) type participants, one would have to severely binge on aspartame to reach deleterious effects in certain individuals. Specifically, as certain people with retarded versions of PKU (stable 24-48 umol/dl blood phenylalanine concentrations) are not in toxic levels of phenylalanine concentration, they could consume minimal aspartame and remain fine. This may not be the case for severe PKU (stable 120-600 umol/dl phenylalanine concentrations). This same review looked at moderate PKU (16 umol/dl phenylalanine concentration) participants and single aspartame ingestion of 34mg/kg aspartame and found statistically higher phenylananine blood levels (+/-3umol/dl), but that statistical significant increase is still nowhere near toxic levels (23).

All that, re-stated, means that severe PKU should avoid aspartame completely while moderate PKU could possibly have a “forgiven” amount of aspartame and their body would handle it without disastrous effects. Essentially, a one time relative high dose (34mg/kg) of aspartame might be handled alright if one suffers from moderate PKU as the moderate PKU afflicted body metabolizes phenylalanine at a 1:2 rate compared to healthy persons (23). The biggest area of concern is the stacked intake of aspartame (ingesting aspartame several times in succession) as it does not allow the body enough time to dispose of phenylalanine when building in blood concentration.


Formaldehyde

A friend of mine brought up a point that aspartame breaks down to formaldehyde (yes, the stuff that is supposedly bad for you). Well, guess what? Aspartame does break down to formaldehyde (say whaaat!..).

There we have it, aspartame will instantly kill you -

- or not.

Who wants to bet we have to understand formaldehyde before we can understand why we are still kicking after drinking diet soda? You’d bet right.

Aspartame is actually broken up into the two amino acids we’ve been discussing the length of this article as well as methanol. Once those three agents are broken down, methanol is further broken down into formaldehyde which is then further broken into formic acid. Bunch of gibberish so far, right? Let’s take a look.

As methanol from aspartame breaks down to formaldehyde, it is actually breaking down into a particular source of formaldehyde known as exogenous formaldehyde (meaning, it came from outside the body). Now, before we go on, we have to understand why the difference between exogenous and endogenous (inside the body) is important.

While we receive exogenous formaldehyde from various sources (food, drink, air, etc.), our body actually creates endogenous formaldehyde (that’s right, you read that correctly). Our body needs formaldehyde, because endogenous formaldehyde exists in our body on a continuous basis as it acts as an essential intermediary in cellular metabolism (24)(25). So, the body uses formaldehyde (approximately 2.6 mg/L found in the blood) and then breaks it down further to formic acid and from that point on it either serves in nucleic acids and proteins or it is simply excreted through our urinary system (26).

Now that we have a general understanding of aspartame metabolism from the methanol pathway, we should understand that the body is fully equipped to deal with acceptable exogenous and natural endogenous formaldehyde.


What is an “acceptable” formaldehyde intake?

We know that the body has about 2.6 mg/L of formaldehyde in its circulatory system at any given time to fulfill its metabolic functions, but the body’s turnover rate is extremely quick running anywhere between .61-.91mg/kg/min which leads to a total turnover of 878-1310mg/kg/day. Endogenous formaldehyde total amount and turnover rate taken into consideration, one could consume 100mg/kg/day of exogenous formaldehyde and it would have negligible impact (<.001%) on our system (26).

How much aspartame would it take?

If a person were to consume 40mg/kg (I realize this number means little to you now, but once you get to the ADI section, you’ll piece things together nicely – I pinky promise) of aspartame, that person would still be consuming 2-9 times less formaldehyde than they will be consuming from their normal food sources in addition to their endogenous amounts (26).

How does diet soda compare to other foods?

Most people talk about diet soda when they are discussing aspartame, so I thought I’d add a quick section comparing a few figures to show things in perspective.

Methanol Amounts
Diet Drink (12oz): 55mg/L (28)
Milk: 1mg/kg (26)
Some Fish: 200mg/kg (27)
Various Fruit: 1-640mg/L (27)

 

What is the Acceptable Daily Intake (ADI) for Aspartame?

What will make this entire article come into perspective is knowing what the Acceptable Daily Intake recommendation is for you – this is where things tie together into a lovely bow.

The ADI, in the United States, is set to 50mg/kg/day of aspartame by the FDA while the World Health Organization (WHO) and European Food Safety Authority (EFSA) have their recommendation set to 40mg/kg/day of aspartame (4)(13).

What does this all mean?
Out of all the numbers I have thrown at your face, this one number (range) is the most important of them all: 2-10.

90% of the population consumes roughly 2-10 mg/kg/day of aspartame (29).

If you want me to make it clear why this is so crucial for you to understand, here it is:

The amount we consume is 5-25 times lower than what is considered safe by the FDA (4-20 times by the WHO and EFSA).

Not only that, we have proven that intakes 800-4000 times greater than we ingest have shown no adverse effects, either. You should, by now, realize the implications of those facts. Even the numbers of consumption in 99% of consumers at a higher range of 10-34mg/kg/day (15) is still below the ADI, which it itself is well below any projected toxicity levels.


SUMMARY

After everything outlined above, it seems evident that the research points the same direction logic dictates.

Aspartame is safe – if you are in standard health (non PKU, non-allergic, etc).

If you were to drown yourself in diet drinks, take aspartame tablets, and bathe in aspartame the likelihood of you hitting the ADI, let alone the projected toxicity levels are incredibly slim, especially in the latter scenario. So, have at it – enjoy your diet dews, diet cokes, and diet mochaccino latte espresso grande frappe extremes.


Writer: Nicolas Verhoeven
This is educational material only and not meant to be prescripton, consult your physician before making any changes.

                                                                                                              Citations
 


(1) Carter, J. (2014, January 14). Amino Acids and Protein. Retrieved May 9, 2015, from http://biology.clc.uc.edu/courses/bio104/protein.htm


(2) Anderson, J., & Young, L. (2010, May 1). Sugar and sweeteners. Retrieved May 9, 2015, from http://www.ext.colostate.edu/pubs/foodnut/09301.html


(3) Soffritti, M., Belpoggi, F., Esposti, D., Lambertini, L., Tibaldi, E., & Rigano, A. (2005, November 17). First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats. Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1392232/

Possible Limitations:
Experimental doses given were incorrect
Some data points missing
Experimental group findings were consistent with previous control groups

(4) Magnuson, B., Burdock, G., Doull, J., Kroes, R., Marsh, G., Pariza, M., . . . Williams, G. (2007). Result Filters. Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/17828671

 

(5) Artificial Sweeteners and Cancer. (2009, August 5). Retrieved May 9, 2015, from http://www.cancer.gov/cancertopics/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet
 

 (6) Gurney, J., Pogoda, J., Holly, E., Hecht, S., & Preston-Martin, S. (1997). Aspartame Consumption in Relation to Childhood Brain Tumor Risk: From a Case-Control Study. Journal of the National Cancer Institute, 89(14), 1072-1072.

Possible Limitations:
Epidemiological study
Quantity of Aspartame varied
Acute study without looking at chronic implications

(7) Flamm, W. (1997). Increasing brain tumor rates: Is there a link to aspartame? Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/8990134

Possible Limitations:
Speculative review

 

(8) Olney, J., Farber, N., Spitznagel, E., & LN, R. (1996, November 1). Increasing brain tumor rates: Is there a link to aspartame? Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/8939194
 

Possible Limitations:
Speculative review

(9) Koestner, A. (1997). Increasing brain tumor rates: Is there a link to aspartame? Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/8990135

Possible Limitations:
Speculative review

(10) Lim, U., Subar, A., Mouw, T., Hartge, P., Morton, L., Stolzenberg-Solomon, R., . . . Schatzkin, A. (2006, September 1). Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/16985027

Possible Limitations:
Was performed based on a database.
Questionnaire false reporting

(11) Magnuson, B., & Williams, G. (2008, June 1). Carcinogenicity of Aspartame in Rats Not Proven. Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430246/

 

(12) Evaluation of Consumer Complaints Related to Aspartame Use. (1984, November 2). Retrieved May 9, 2015, from http://www.cdc.gov/mmwr/preview/mmwrhtml/00000426.htm
 

(13) Aspartame. (2014, May 28). Retrieved May 9, 2015, from http://www.cancer.org/cancer/cancercauses/othercarcinogens/athome/aspartame


(14) Aspartame. (2014, May 28). Retrieved May 9, 2015, from http://www.cancer.org/cancer/cancercauses/othercarcinogens/athome/aspartame  


|Possible Limitations:
Extrapolation
Unable to resolve discrepancy in monkey studies

(15) Tschanz, C., Butchko, H., Stargel, W., & Kotsonis, F. (Eds.). (1996). Clinical Evaluation of a Food Additive: Assessment of Aspartame. Washington: CRC Press.  

Possible Limitations:
Not all studies performed in humans
Some studies performed strictly with DKP, not Aspartame

 

(16) Sturtevant, F. (1985). Use of aspartame in pregnancy. Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/2862125

(17) Et al, B. (2002). Aspartame: Review of Safety. Retrieved May 9, 2015, from http://www.dieteticai.ufba.br/Temas/ACUCARES/ASPARTAME.pdf

(18) EFSA completes full risk assessment on aspartame and concludes it is safe at current levels of exposure. (2013, December 10). Retrieved May 9, 2015, from http://www.efsa.europa.eu/en/press/news/131210.htm

 

(19) Phenylketonuria: MedlinePlus Medical Encyclopedia. (2013, June 9). Retrieved May 9, 2015, from http://www.nlm.nih.gov/medlineplus/ency/article/001166.htm
 

(20) Aspartame. (n.d.). Retrieved May 9, 2015, from https://www.food.gov.uk/science/additives/aspartame


(21) Beck, T. (n.d.). What is PKU? Retrieved May 9, 2015, from http://www.astro.sunysb.edu/tracy/whatis.html

Possible Limitations:
Astronomy Department PhD, not Nutrition


(22) Santana da Silva, L. (2000). Aspartame loading test in PKU heterozygous individuals bearing severe and moderate mutations. Retrieved May 9, 2015, from http://www.researchgate.net/profile/Maria-Luiza_Saraiva-Pereira/publication/249314244_Aspartame_loading_test_in_PKU_heterozygous_individuals_bearing_severe_and_moderate_mutations/links/0046351e429cc2c0f1000000.pdf

Possible Limitations:
Only applicable to certain PKU mutations

(23) Lewis, S. (1987). The aspartame story: A model for the clinical testing of a food additive”2. Retrieved May 9, 2015, from http://ajcn.nutrition.org/content/46/1/204.full.pdf html

Possible Limitations:
Does not address all PKU mutations

(24) Swenberg, J., Lu, K., Moeller, B., Gao, L., Upton, P., Nakamura, J., & Starr, T. (2011). Endogenous versus Exogenous DNA Adducts: Their Role in Carcinogenesis, Epidemiology, and Risk Assessment. Retrieved May 9, 2015, from http://toxsci.oxfordjournals.org/content/120/suppl_1/S130.full


(25) Frequently Asked Questions. (2011, April 6). Retrieved May 9, 2015, from http://www.americanchemistry.com/ProductsTechnology/Formaldehyde/Answers-to-FAQs-about-the-Health-Effects-of-Formaldehyde.PDF

(26) Endogenous formaldehyde turnover in humans compared with exogenous contribution from food sources1. (2014). Retrieved May 9, 2015, from http://www.efsa.europa.eu/en/efsajournal/doc/3550.pdf


(27) Methanol. (1997). Retrieved May 9, 2015, from http://www.inchem.org/documents/ehc/ehc/ehc196.htm#SubSectionNumber:5.1.3

(28) Kay, S. (2011, June 14). How Is Aspartame Digested? Retrieved May 9, 2015, from http://www.livestrong.com/article/470386-how-is-aspartame-digested/

(29) Butchko, H., & FN, K. (1991). Acceptable daily intake vs actual intake: The aspartame example. Retrieved May 9, 2015, from http://www.ncbi.nlm.nih.gov/pubmed/1894884

Possible Limitations:
Food survey reliability and accuracy are questionable, at best

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