Aspartame: Once More Unto the Breach

I fundamentally couldn't much care less about the supposed effects of one synthetic sweetener over another versus highly processed sugars, if it were't for the fact that as soon as I taste whatever synthetic sweetener it is, it tastes disgusting to me.

I just don't get how people are content to consume this stuff - they markedly change the taste, indelibly affecting the thing they're sweetening. Heck, even stevia adds its own distinct nastiness to whatever it flavours.

So, I stick with sugar, and just consume waay less of it than I used to. Though this somewhat limits the choice of soft drinks I can enjoy consuming when it comes to a treat.

>one of the most exhaustively studied substances in the human food supply

About a year ago, this single fact changed my mind about it being 'very bad' for you. If given a choice between a sugar drink (cola) and an aspartame flavored drink ('zero' cola), I will take the aspartame.

> If you look on Wikipedia, you’ll see that aspartame is a methyl ester of the aspartic acid phenylalanine dipeptide, which isn’t, like, comforting.

The aversion most people have to anything sounding chemical is crazy.

Chemically speaking, this is a relatively simple molecule. „Dipeptide“ means it consists of two amino acids, which are ubiquitous and make up every protein. „Methyl ester“ is the product of a reaction between an acid, in this case the amino acid phenylalanine, and an alcohol, in this case methanol. Also very common throughout chemistry and biology.

IMO more damaging fact is that it doesn't work. The evidence is pretty clear it doesn't actually help you lose weight and in some cases there is actually an increase in weight, obesity, and type-2 diabetes. (https://pubmed.ncbi.nlm.nih.gov/28716847/, https://pubmed.ncbi.nlm.nih.gov/27129676/)

For me this can be pretty easily observed eating a meal with water vs with diet soda. Especially if it's like a 'bad' meal with fast/fried food. There is definitely something that causes you to crave/eat more.

It frankly just tastes weird. I can't understand why people want to eat it. Americans need to retrain their palette to not need a sweet deluge every day, and just enjoy heavy sugar items as an occasional treat.

And I say this as someone who cooks with MSG daily.

This article does not address the cognitive aspect of aspartame.

What is the impact of 'faking out' the sugar processing components of our metabolism? Specifically is there anything bad associated with our brains thinking that we're getting sugar and some, perhaps incomplete, chain of reactions taking place to prepare the body for sugar processing, and then the sugar never showing up?

I haven't read any of the literature on it but I imagine that some of those metabolic components stay "flipped on" for longer than they would if they had real sugar exposure, because they never get what they are prepared to receive by our brains upon consumption.

Disclosure: my grandfather died of pancreatic cancer and was a heavy consumer of artificial sweeteners (daily, in tea).

Aspartame and pickled vegetables share the same carcinogen designation. If you are concerned about one then logically you must share the same concern about the other.

https://www.bbc.com/future/article/20230630-aspartame-what-e...

Interestingly enough it’s the same conclusion that this guy came to (1). He also reads and summarizes a lot of papers.

Bottom line of the article above and (1): aspartame is not a health concern you should have.

(1) https://physiqonomics.com/aspartame/

I love this article! It is not the first time I hear the bad reputation of aspartame is unfounded.

AFAIK, there was only one study which said aspartame was dangerous: they fed a rat with a HUGE amount of it (like way more than a human could consume, in proportion) and the rat got ill or died I don't remember. That "study" was obviously flawed yet the media kept talking about it everywhere.

At that point, it wouldn't surprise me if the sugar industry is behind this.

It seems like the heart of the problem is that idea that anything can be proven to be safe.

Some people have a hard time understanding that this can be impossible.

I had a person trying to tell me that aspartame is dangerous because it decomposed into aspartic acid, which is a toxin. Apparently an amino acid can be a toxin even when your body makes it and the proteins in your body contain about a kilogram of it.

I have some beef with the methodology for excluding analyses from the lit review. If authors being from “obscure institutions” is a problem, then so too should authors employed by companies that manufacture aspartame or funded by companies that manufacture aspartame. 2 of the 3 reviews that the author considers very high quality have this problem.

The WHO recently published a recommendation essentially condemning all non-sugar sweeteners. I've read through much of the 200 page report (https://www.who.int/publications/i/item/9789240046429), and what I found was really troubling: time and time again, the report takes a longitudinal study whose authors note "likely confounding", omits that information, and then includes the study's conclusions stripped of that context. In one case I saw, the WHO report implied that the authors had adequately controlled for confounding factors even though the authors had specifically called them out as a weakness.

Even more puzzling, the WHO announcement (https://www.who.int/news/item/15-05-2023-who-advises-not-to-...) explicitly lists essentially every commonly known artificial sweetener, even though the evidence the report cites is extremely uneven and has very little to say about many of them. The studies on long term health effects, in particular, are almost entirely based on studies which examine soft drink consumption. Aside from the obvious, difficult-to-control biases is that approach (e.g. people who drink diet drinks are disproportionately people who are trying to lose weight, are diabetic, have been told to switch by their doctor, etc.), this means that virtually all of the data is primarily about aspartame, since that's the primary sweetener in most diet drinks.

The cherry on top is that the WHO announcement suggests that people try to shift to "naturally occurring sugars" despite the fact that multiple studies cited by the report specifically note that the health impact of fruit juice consumption is not distinguishable from any other sugar consumption.

That said, from my non-expert point of view, the one thing that does seem to be pretty consistent is evidence on gut biome effects. It kind of seems like there's some mechanism involving sweetness itself and gut biome interference, and I'm not sure what's going on there.

But the WHO report is disturbing. A meta-analysis is supposed to pull together large numbers of studies in order to smooth out biases and find broader trends, but what this report seems to have done instead is to launder biases that were reported with integrity. Taken together with the WHO recommendation, a large number of sporadic and often suspicious results have been put together into a wildly sweeping conclusion which does not look to me like it's at all scientifically justified.

This article is well-written to appeal to people who want to be "scientific."

I found it convincing. My wife did not. She found this far more credible source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227014/

To summarize:

- Aspartame is linked to premature menarche in girls aged 9 and 10

- Aspartame, especially when used with another common sweetener is linked to genotocixity.

- Aspartame causes increases in behavioral disorders

- Aspartame causes neurodegeneration with long-term use

- Aspartame can induce contact dermatitis

> Safety studies have found the metabolic products of aspartame (aspartic acid, phenylalanine, and methanol) to be more harmful to the body than the original substance itself...

> ...In humans, there have been reports of premature birth as well as allergic reactions and weight gain in the newborns. Studies involving girls aged 9–10 have shown that aspartame increases the risk of an early first menstruation (<11 years).

So for me... I have to think that there remains a high likelihood that aspartame is harmful, and this article draws wrong conclusions.

I find it a bit odd that this review only discusses the things it's metabolized into and not either of the things that seem more relevant (at this point: the effect of tasting it psychologically, and then whatever it is in your gut that does the metabolizing.

Like, great, I believe that if you inject those chemicals into me in the right spot I'll be fine. But didn't you skip a few steps?

Not that I care much either way. It sounds like it's safe, toxicologically and epidemiologically speaking. But there's still a difference between eating things that taste sweet and not doing it at all-- beyond the molecules that end up in your blood.

The effect aspartame has on the gut biome before it breaks down into the safer constituents is still a large gap. As we learn more and more about the importance of our gut biome as a living system parallel to the much more rigorously studied blood and lymphatic systems, I think deeper understanding of wholistic effects could emerge.

I'm intolerant to aspartame in particular (it causes me migraines) and most artificial sweeteners (upset stomach).

But that doesn't mean no one else should have them.

At face value, it's far from clear how this molecule was discovered. Nothing about the structure indicates that it would taste sweet. Wikipedia offers this account:

> Aspartame was discovered in 1965 by James M. Schlatter, a chemist working for G.D. Searle & Company. Schlatter had synthesized aspartame as an intermediate step in generating a tetrapeptide of the hormone gastrin, for use in assessing an anti-ulcer drug candidate. He discovered its sweet taste when he licked his finger, which had become contaminated with aspartame, to lift up a piece of paper.

https://en.wikipedia.org/wiki/Aspartame

But the Washington Post seems to disagree:

> It has been 17 years since chemist James M. Schlatter, who was tinkering with an anti-ulcer drug at the time, dipped his finger into a mixture of asparatic acid and phenylalanine and, for reasons that remain unclear, brought the result into contact with his tongue. Now, after a long legal and scientific struggle, the stuff that was on Schlatter's finger that fateful day in 1965 can be on your finger too, or dissolved in your coffee, or stirred into your yogurt, or sprinkled over your cinnamon toast.

https://www.washingtonpost.com/archive/lifestyle/food/1982/0...

There was a time when reporting the taste of a newly-synthesized organic molecule was not uncommon in the literature. It's possible that Schlatter was just doing something that was not unusual at the time.

An account of the discovery, written by one of the authors of the original research paper reporting the discovery (Mazur), and reportedly based on an affidavit gives this account:

> In December 1965 I was working with Dr. Mazur on the synthesis of the C-terminal tetrapeptide of gastrin. We were making intermediates and trying to purify them. In particular, on an occasion in December, 1965, I was recrystallizing aspartylphenylalanine methyl ester (aspartame) ... when the mixture bumped [spilled over while boiling] onto the outside of the flask. As a result, some of the powder got onto my fingers. At a slightly later stage, when licking my finger to pick up a piece of paper, I noticed a very strong, sweet taste. Initially, I thought that I mush have still had some sugar o. my hands from earlier in the day. However, I quickly realized this could not be so, since I had washed my hands in the meantime. I, therefore, traced the power on my hands back to the container into which I had placed the crystallized apsartyl-phenylalanine methyl ester. I felt that this ... was not likely to be toxic and I therefore tasted a little of it and found that it was the substance which I had previously tasted on my finger.

- Aspartame: Physiology and Biochemistry, edited by Stegink and Filer

"Note that this study was funded by Ajinomoto via some kind of blind-trust arrangement"

Tells you everything about that all important often cited paper

My general feeling regarding phenylalanine is there anything that turns my bowels into Jackson Pollock cannot be good for me.

Though Donald Rumsfeld is mentioned once in the article, his part in the approval of aspartame should be more generally known. Aspartame is equally as toxic as Rumsfeld was.

"Dr. John Olney, who founded the field of neuroscience called excitotoxicity, attempted to stop the approval of aspartame with Attorney James Turner back in 1996. The FDA's own toxicologist, Dr. Adrian Gross told Congress that without a shadow of a doubt, aspartame can cause brain tumors and brain cancer and that it violated the Delaney Amendment, which forbids putting anything in food that is known to cause cancer." [0]

[0] https://www.huffpost.com/entry/donald-rumsfeld-and-the-s_b_8...