typical hubris of man sort of thing. everyone thinks science is a blessing while completely ignoring the human cost. how many collective years of misery did victims of science have to suffer? cancers and such. terrible fates, all justified by progress.
is it worth a slightly better standard of living? is any of this making us happier?
Germ theory is due to science. This led to some of the most significant interventions that extended the human lifespan. It isn't all luxury.
However, i doubt there is any artificial sweetener that is healthy. There really isn't a free lunch in life, and if something tastes sweet, it will cause insulin release, and if it isn't accompanied with glucose, you will release less insulin over time to maintain homeostasis.
This is not to mention compound specific issues like erythritol causing increased clotting at doses used by humans.
The paper discussed (open access, so anybody can read it there) has a number of flaws and more general weaknesses. If it were a better paper it would be published somewhere stronger than the Journal of Toxicology and Environmental Health, Part B. (the part B refers to the papers being a kind of hybrid between primary research and review article. Reviews are good to find pertinent papers, but often ignore pretty severe flaws in methods. I generally don't trust them other than an index of what work is in the field, and the conclusions of the papers contained).
Many of the experiments were performed only with sucralose 6 acetate (S6a), rather than sucralose itself (i assume to maximize this effect. Considering this, concentrations used in the experiments are rather high.
In experiment 1 using human lymphoblast cells, DNA damaging effects were only found in the mM (millimolar) range of S6A. For comparison the blood alcohol limit to drive corresponds to about 5.4 millimoles, and is reached between 2 and 3 standard drinks, or 20 to 30 grams of pure ethanol.
These seemingly high doses required for toxicity occur in many of these experiments, especially considering that they are done with the metabolite rather than the parent compound.
Experiment 2 finds micronuclei at about 2 mM of S6A in the same cells and not below.
Experiment 3 is an
in silico projection of toxicity/mutagenicity which predicts that but in the results they mentioned that it is not substantiated by the ames test performed in experiment 4 (the gold standard assay for mutagenicity). Thus, the
in silico data is worthless.
Experiment 5 demonstrates an increase in intestinal permeability at concentrations between 5 and 10 mM of the metabolite sucralose 6 acetate. This effect was not significant at the 2.5 mM concentration. Sucralose itself was tested and found significant at increasing permeability at 80 mM.
Experiment 6 finds alterations in the RNA expression of 34 genes when the same intestinal cells from experiment 4 treated with S6A at 10 mM, and 2 genes when treated with sucralose at 80 mM.
Experiment 7 finds that sucralose 6 acetate is cleared from human liver microsomes with a half life of 36.6 minutes, and sucralose is not cleared to an extent to calculate a half life (>186.4 minutes). This corresponds with initial studies of sucralose finding it not to be cleared by the liver (and not studying s6a).
Experiment 8 looks at liver enzyme inhibition by S6a and not sucralose. Inhibition levels were in the micromolar (uM) level (1000 fold lower than millimolar), as the enzymes purified liver microsomes are more exposed to the metabolite than when in intact cells. S6a inhibited CYP1A2 at 42.9 uM (compared to 0.111 uM for the positive control) and CYP2C19 at 89.3 uM (compared to 4.19 uM for the positive control). These potencies are much lower than compounds found in common food inhibitors of liver enzymes such as the furanocoumarins in grapefruits.
Overall this paper seems to report alarming effects at much higher concentrations than would be consumed sucralose is ~600 times as sweet as sugar, so will be in much lower concentrations than sucrose, with incomplete biotransformation of sucralose to s6a.
However, i am not saying sucralose is without negative effects, just that this study is a bit shit.
This study (also open access) published in nature medicine (one of the best journals for biomedical research) is much better.
The study shows little effect of chronic free access to sucralose in mouse weight, insulin responses/glucose tolerance, and inconsistent changes to gut microbiota.
They show decreased T cell (cytotoxic adaptive immune cell) responses and proliferation in mice after being given unlimited access to sucralose, leading to concentrations near what humans reach after sucralose consumption, 1uM (thousands fold lower than levels of the sucralose 6 acetate metabolite in the previous study). This paper goes further and characterizes the molecular mechanisms of these in multiple cell lines to be impaired pholipase C based calcium signaling (phospholipases cleave cell membrane phospholipids, to lipid fragments and the phosphate head groups which open up intracellular calcium stores. This pathway is present in all Gq coupled receptors such as a favorite of mine and many other blue lighters, the serotonin 2a receptor which produces psychadelic effects).
This paper used multiple models to confirm their findings and found a functional role where mice implanted with tumors rejected some less when treated with sucralose, which is definately a reason in my book to avoid the compound.
They also found impaired responses to infection in mice and in cells treated with sucralose, but they found a reduction in autoimmune disease symptoms in mouse models, which oddly they suggest sucralose as a treatment for.
I feel this is a much better paper because of their detailed analysis of molecular mechanisms, plus use of animal models to get closer to human relevance. It also seems there is more nuance where they don't ignore random positive effects of the t cell suppression on auto-immune symptoms.
There are plenty of unstudied nuances, and i kind of just want this post to convey the message that not all science is equal, and analysis of the contents of the papers is required to judge the validity of their claims.
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