Taste is one of the ways the body determines which foods to eat. Does aspartame taste right to you?

Multiple opposing heuristics can exist and one can be stronger than another. Aspartame may taste weird, but, when metabolized, it's broken down into three molecules that already exist in the body in larger concentrations in normal situations. The latter reason seems stronger than the former reason.

You could argue the bad taste is related (via not being available to our ancestors during natural selection) to the fact aspartame has no nutritional value, and it might in fact harm you by confusing the way you use taste to evaluate what food to eat, or something. That's covered in

I am not including potential 'taste-based diet change' effects here - if the sweet taste that doesn't correspond to sugar intake causes some homeostasis on sugar intake to be knocked slightly off or something, that doesn't count. That is, imo, a marginal reason to not consume aspartame if you aren't already overweight!

though

IARC review of evidence expected to publish 14th July, see here. I will post here any relevant outcomes of that. I think it stands a chance of raising your confidence to at least high single figures.

@WXTJ IARC published their review.

IARC blog/announcement:

The Working Group classified both aspartame and isoeugenol as possibly carcinogenic to humans (Group 2B). Neither aspartame nor isoeugenol had previously been evaluated by the IARC Monographs programme. Aspartame was classified as Group 2B on the basis of limited evidence for cancer in humans, limited evidence for cancer in experimental animals, and limited mechanistic evidence."

Full analysis (Lancet, paywalled). I can't find this without a paywall, this will have more detail on the mechanistic studies with some evidence of cancer-causing mechanisms in humans (hepatocellular carcinomas, I think).

Slightly more detailed committee team announcement:

"“JECFA also considered the evidence on cancer risk, in animal and human studies, and concluded that the evidence of an association between aspartame consumption and cancer in humans is not convincing,” said Dr Moez Sanaa, WHO’s Head of the Standards and Scientific Advice on Food and Nutrition Unit. “We need better studies with longer follow-up and repeated dietary questionnaires in existing cohorts. We need randomized controlled trials, including studies of mechanistic pathways relevant to insulin regulation, metabolic syndrome and diabetes, particularly as related to carcinogenicity.”"

okay, i'll try to get the full text

also: m$100 manalink bounty on any of the following:

point out a specific factual error i made below

state that 'i am an expert and i think you (jackson) are doing something conceptually wrong here that looks like <a sentence or two> but actually convincing you of that would be too much effort'

evidence that moves my position a little bit or i think is interesting

@jacksonpolack appreciate your analysis of the review.

c&s's paper intro mentions methanol so I did a shitty google scholar search. i haven't checked this so i think there's a good chance something in one of the papers or (more likely) they way I'm about to infer is wrong, but:

serum methanol levels after 99th percentile aspartame intake "assuming aspartame were to replace all sucrose sweeteners in the diet" (so that's still significantly above the actual 99th percentile aspartame intake)

https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/0278691586902279

breath methanol levels after fruit consumption

http://more.coulditbeformaldehyde.info/refs/Lindinger1997EndogenousMethanolFromFruit.pdf

just from graph-staring (always a reliable method) as far as I can tell aspartame-produced methanol is much less than fruit-produced methanol

This peer-reviewed analysis in a relatively high IF journal would make me resolve it to not-NO, probably around 20%:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227014/

(also: placing limit orders that low seems self-evidently counterproductive)

Not having read it yet since you posted 7 seconds ago:

My sense is that aspartame has been studied a lot and that most of the big reviews find that it is fine. I spend a lot of time reading random papers, and a lot of papers are just bad, and in fields like bio this includes some papers in good journals. So when you combine that this is one review that coexists with a hundred reviews saying 'it is fine', it's not obvious that pushes us above 1% before I read the review and compare its claims to the ones that say its fine.

(also: placing limit orders that low seems self-evidently counterproductive)

The idea is that I "actually believe that the probability is <1%, so if I'm wrong then I want to lose money as proof that I'm wrong". Like I'd rather the CMV markets as a whole lose me money and find me things I'm wrong about than I be super-careful on them and not lose money (sorta).

also whenever I see claims that something causes like 20 different diseases I instantly think 'lol no'

The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed

like there's no way it does all of those right? That has to just be a bunch of bad studies. Maybe there's one good study in there but...

@jacksonpolack yeah, the issue is that the limit order was taken before I got here, thus (assuming a YES-side resolution) profiting somebody who didn't contribute to finding an answer. A limit order higher would allow the person presenting evidence to take it (you could offer to review the evidence privately first to eliminate associated risk), aligning the incentives better

i put up some higher orders

also I've asked the manifold admins for q&a markets where i give the reward directly to the best answers, which solves the incentives problem, and they indicated they might do it

@CodeandSolder they don't conclude it does all that stuff lol, but there are possible pathways presented and some evidence

Okay, randomly diving into the first study that review cites is:

Aspartame has also been blamed for causing type 2 diabetes mellitus (T2DM) and may not meet the expectation of being healthy alternative to sugar in sweetened beverages [35]. A recent study investigating the effect of sucrose-sweetened and artificially (aspartame) sweetened food and drinks on inflammatory markers in overweight subjects found that consumption of sweetened items significantly increased plasma haptoglobin and transferrin but did not significantly increase the C-reactive protein level. This study corroborates findings from others that suggest that the pro-inflammatory process underlying the greater risk of diabetes may be exacerbated by a high intake of rapidly digested and absorbed carbohydrates and artificial sweetener [36].

not expecting anyone to read all the quotes here there are many

36

Background: Observational studies have found that dietary glycemic load is positively associated with C-reactive protein (CRP) concentrations in healthy humans, which suggests that the type of carbohydrate ingested influences inflammatory activity.

Objective: We investigated the effect of a diet with a high content of sucrose or artificial sweeteners on the inflammatory markers CRP, haptoglobin, and transferrin in overweight subjects.

Design: Overweight men and women consumed daily food and drink supplements containing either sucrose [n = 21; body mass index (BMI, in kg/m2): 28.0] or artificial sweeteners (n = 20; BMI: 27.6), predominantly from soft drinks (70%; average ≈1.3 L/d) for 10 wk.

Results: During the intervention, sucrose intake increased by 151% in the sucrose group and decreased by 42% in the sweetener group, resulting in a 1.6-kg weight gain in the sucrose group and a 1.2-kg weight loss in the sweetener group over 10 wk (P < 0.001). Concentrations of haptoglobin, transferrin, and CRP increased by 13%, 5%, and 6%, respectively, in the sucrose group and decreased by 16%, 2%, and 26%, respectively, in the sweetener group (between-group differences: P = 0.006, P = 0.01, and P = 0.1, respectively). Adjustment for changes in body weight and energy intake did not substantially influence this outcome.

Conclusions: The study shows that in the present group of overweight subjects a high consumption of sugar-sweetened foods and drinks increased haptoglobin and transferrin but had, at best, only a limited influence on CRP.

So they find that for sucrose vs artificial sweeteners, modulo significance, haptoglobin and transferrin are lower for artificial sweeteners.

In the present study the sucrose diet produced a nonsignificant 6% increase and the sweetener diet produced a 26% decrease in CRP concentrations (P = 0.1). This trend toward an association between a diet high in rapidly digested and absorbed carbohydrates and CRP supports the findings of an earlier observational study (10). In the observational study the CRP concentrations were measured in 244 apparently healthy women, and the association between the subjects' dietary glycemic load and CRP concentrations was examined (10). It was found that the median CRP concentration for the lowest quintile of dietary glycemic load was significantly lower than the CRP concentration for the highest quintile. This result remained after adjusting for several confounders such as age, BMI, history of hypertension, high cholesterol or diabetes mellitus, and lifestyle factors.

The lack of statistical significance in the present study may be due to a type II error as a result of the small number of subjects, which was only 19 and 18, respectively, in the 2 groups. However, the changes in CRP were relatively small, and, by taking into consideration that the reliability of CRP is poor (17), the results suggest that sucrose has little effect on CRP.

The sucrose diet increased concentrations of haptoglobin, and changes in haptoglobin concentrations were positively associated with changes in sucrose intake. This finding could indicate increased inflammation in the sucrose group and decreased inflammation in the artificial sweetener group. However, changes in haptoglobin concentrations were positively correlated with changes in energy intake, which suggests that haptoglobin may respond to the body’s energy flux rather than to the sucrose intake. However, it is not possible to reach a firm conclusion on this aspect because of the close covariation between energy and sucrose intakes.

Transferrin is a negative acute-phase protein, and a drop in transferrin concentrations therefore reflects increased inflammation. It was therefore contrary to our expectations that transferrin increased in the sucrose group and decreased in the sweetener group. Changes in transferrin concentrations were also positively associated with changes in energy intake, which could indicate that transferrin responds to the body’s energy flux. Adjusting for changes in energy intake did not eliminate the difference between the 2 groups, in either haptoglobin or transferrin, although the differences became less significant.

In conclusion, this study shows that, apart from causing weight gain and increasing blood pressure, a high consumption of sugar-sweetened drinks and foods may increase inflammatory activity in overweight subjects. This finding was independent of weight changes. The relative changes in inflammatory markers in the present study were small. Even though the between-group differences in haptoglobin and transferrin were statistically significant, it is doubtful that these differences are biologically important.

Roughly, they measured sucrose vs sweeteners on CRP, transferrin, and haptoglobin. More CRP and haptoglobin are bad, and more transferrin is good, inflammation wise. Artificial sweeteners decreased haptoglobin and transferrin, and had a null effect on crp. So, net here, the sweeteners had one good effect, one bad effect, and one null effect. And even the two non-null effects were "doubtful that ... biologically important".

From the original review:

This study corroborates findings from others that suggest that the pro-inflammatory process underlying the greater risk of diabetes may be exacerbated by a high intake of rapidly digested and absorbed carbohydrates and artificial sweetener

This sentence feels like it's saying the study corroborates that artificial sweeteners may be bad. It does not do that though.

Without a deep dive, I don't find the '6. Impact of Aspartame on Children and Fetuses' to move me at all

I don't find the "7. Genotoxicity" section to move me at all

Although the safety of use of aspartame has been assessed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA), among others, few studies have tested its genotoxic properties in vivo and in vitro [67,68,69,70,71,72,73,74]. Unfortunately, none of these studies were conducted according to GLP [74,75]. Despite the lack of pharmaceutical studies in the GMP system, publications state that aspartame is not genotoxic [68,71,72,75,76]. In addition, research techniques have developed over the years and current methods are more accurate and reliable [75].

However, GLP-based studies on the genotoxicity and mutagenicity of aspartame based on bacterial reverse mutation and in vivo murine micronucleus testing found aspartame to have neither genotoxic nor mutagenic effects [75]. Other genotoxicity and mutagenicity studies were performed by Najam et al. with aspartamine alone and in combination with sitagliptin, which is an oral antidiabetic drug [81,82]. The results of the performed Comet assay were similar to the positive dose-dependent chromosome aberration test [67,82], while aspartame demonstrated significant mutagenic effects in Ames assay for TA100. In addition, aspartame with sitagliptin did not demonstrate greater effects than sitagliptin alone [82]. Unfortunately, opposite results have been obtained in more recent studies [75,82].

For industrial purposes, aspartame is often combined with other substances to obtain a desired taste. Genotoxicity studies found the combination of aspartame with another frequently used sweetener, acesulfame-K, to result in an increase in genotoxic activity conditioned by a dose-response relationship. Since the same studies also showed no genotoxic effects in acesulfame-K, it can be expected that it is aspartame that increases genotoxicity [68].

"all the good studies got null results but we'll nitpick some technical issue with them. here are some bad studies on somewhat-related things that don't meet our technical nitpicks from before, but if I twist their data a bit then here's a suggestive result!!!!"

That last paragraph especially about aspartame + acesulfame-K does not belong in a serious review.

I do not find "8. Behavioral Disorders" convincing. Reference 83 does not appear to have anything to do with aspartame. 17 and 99 are, at a glance, not impressive either. The remaining text is speculation on mechanisms - there are probably 100,000 semi-plausible-sounding mechanisms for every actually existing and important interaction in biology.

Same for '9. Autism Spectrum Disorder (ASD)'

The rise in autism increased significantly in 1983 with the rise in consumption of aspartame in carbonated beverages, also known as diet soda [105], and has continued to do so as aspartame consumption has grown [106]

I think writing this kind of sentence should lead to fines, at least, if not prison time. Decade-long time trends in the modern world all correlate! Lots of things go up, and lots of things go down! Vaccines cause autism! Immigrants cause alzheimers!

Also, 105 does not appear to mention aspartame, and 106 is a crank book with lovely quotes like

Please try to imagine flocks of formaldehyde hawk fledglings emerging from these blood vessels into the circuitry of the brain. Imagine wave after wave of hungry hawks looking for protein to attack, having to go further and further as protein landing sites are lost to competitors and then eventually consumed by macrophages, slowly but surely expanding the plaque as the years go by (Figure 7). It is worth noting that a single drop of diet cola sweetened with aspartame contains sufficient methanol to produce well over a hundred trillion of these damaging crazy hawks. What exactly are the crazy hawks attacking?

There's also an obviously confounded observational study

I am not convinced by '10. Neurodegeneration Due to Long Term Use of Aspartame' because again it's just a bunch of mechanism hypotheses without good evidence spanning the entire way from aspartame to harm (other than a few shitty p-hacked mouse studies on various biomarkers)

I am not convinced by "11. Allergies and Skin Problems". The evidence that a few people have individual negative reactions to aspartame is plausible, but that is something that happens with most foods. I bounced off the last paragraph about 'similar analgesic and anti-inflammatory properties to nonsteroidal anti-inflammatory drugs', but it seems to contradict itself about whether aspartame is anti inflammatory?

I agree with the '12. Phenyloketonuria' section, but as described in the description individuals with PKU need to avoid many kinds of healthy foods.

Not moved by '13. Cancer Properties'

Although studies performed on rodents in vivo and in vitro and research on the expression of proto-oncogenes and tumor suppressor genes suggest that aspartame may have carcinogenic properties [139,140,143], it is not possible to conclusively determine that aspartame is carcinogenic for humans. Indeed, most research fails to identify any such association [73,144].

Overall I don't think it's a high-quality review and am not at all convinced by it.

Not your fault, and I enjoy doing this kind of thing anyway

Do any of you three plan to present evidence, or do you just think 1/2% is too low as a prior

@jacksonpolack I had intended to read about this, but wasn't sure I'd get around to it, so this gives me incentive to. Also, yes, I think 2% is too low a prior. I'm least confident in your assertion that the methanol production is insignificant compared to other sources in the body (but 10 minutes of actual research will probably significant solidify or shift my view here)

@jacksonpolack too low, doesn't jive with my experience. aspartame, at least anecdotally, fucks up your digestion. I might dive into research, but mostly waiting.