Indeed. I think it helps to unpack the various claims being studied:
1) Carcinogenicity. Do certain sweeteners cause harmful mutations and increase cancer risk? This is one of the oldest and most frequent allegations, especially against saccharin and aspartame. Mostly inconclusive, though both sweeteners have been exonerated at least as often as they've been accused.
2) Insulin triggering. Artificial sweeteners may not bear the caloric load of sugars and starches -- but do they trigger the release of insulin, just the same? Again, the jury is still out, but certain sweeteners (aspartame, sucralose, and possibly saccharin) are looking suspect.
3) Caloric load. Some sweeteners and putatively indigestible molecules (sugar alcohols, "resistant starches," etc.) may contain more effective calories than in vitro studies predict them to contain. This is because the chemicals aren't digested in the traditional sense, but are fermented and absorbed in the gut. Caloric bioavailability is often different from nominal calorie count. (Indeed, this is the entire principle behind the supposed benefits of resistant sweeteners and starches; those benefits may have been overstated or misunderstood).
4) Disruption or adverse selection of gut microbiota. As detailed in this study. While not all sweeteners have been implicated here, this field of study is only just kicking into high gear. It seems reasonable to suspect that molecules fermented by / consumed by gut bacteria could have some effect on flora composition. Many sweeteners fit that criterion.
5) Other toxicities. Liver or kidney toxicity, neurotoxicity, endocrine disruption, etc. As with carcinogenicity, the jury is still out. Unlikely for some sweeteners that are not metabolized via these pathways. Possible for others. Most sweeteners (all?) on the market right now are generally recognized as safe in this respect, despite popular beliefs to the contrary. Notable exceptions exist for those with rare metabolic or genetic disorders, such as phenylketonuria (aspartame contains phenylalanine).
6) Side effects. Some sweeteners, particularly those in the sugar alcohol family (and sorbitol especially), can cause laxative effects and other GI-related issues. Individual tolerance can vary. Breaking this category out from #4 because the action here can be purely mechanical (i.e., increasing intestinal water absorption).
I'm not a doctor or medical researcher myself. Just an interested nerd. But I have been following this area for awhile. I welcome any corrections, comments, or additions from people more knowledgeable than I am. I assume there are many such people on HN. :)
Good list. Among the patients I see metabolic disturbances rank high on the list problems to manage. Some people complain of adverse effects of NAS such as headache, GI symptoms, but in the clinical setting, it's very hard to establish connections between NAS and metabolic syndrome manifestations like DM2.
The article says mouse fed any of 3 common NAS in water with/without glucose developed "glucose intolerance", which I take to mean above-normal glucose levels. That would point to either impaired insulin production or increased insulin resistance. I think the latter is much more likely.
This probably occurs in some humans too (among people genetically predisposed to develop DM2). Of course that's my extrapolation of the info, but seems a likely direction of future research. Getting insulin levels and measuring insulin resistance after NAS feeding are logical steps to take.
I agree with your comment and others that the role of colon microorganisms is a truly fascinating subject, and remains quite a mystery. Other research shows gut flora are distinct among host species. The evolution of these microbes appears intimately bound to the evolution of their host, but the nature of the link is unknown. Odds are unraveling the story of the numerous friends within (and all over) us will fill in important gaps in our knowledge in surprising ways.
1) Carcinogenicity. Do certain sweeteners cause harmful mutations and increase cancer risk? This is one of the oldest and most frequent allegations, especially against saccharin and aspartame. Mostly inconclusive, though both sweeteners have been exonerated at least as often as they've been accused.
2) Insulin triggering. Artificial sweeteners may not bear the caloric load of sugars and starches -- but do they trigger the release of insulin, just the same? Again, the jury is still out, but certain sweeteners (aspartame, sucralose, and possibly saccharin) are looking suspect.
3) Caloric load. Some sweeteners and putatively indigestible molecules (sugar alcohols, "resistant starches," etc.) may contain more effective calories than in vitro studies predict them to contain. This is because the chemicals aren't digested in the traditional sense, but are fermented and absorbed in the gut. Caloric bioavailability is often different from nominal calorie count. (Indeed, this is the entire principle behind the supposed benefits of resistant sweeteners and starches; those benefits may have been overstated or misunderstood).
4) Disruption or adverse selection of gut microbiota. As detailed in this study. While not all sweeteners have been implicated here, this field of study is only just kicking into high gear. It seems reasonable to suspect that molecules fermented by / consumed by gut bacteria could have some effect on flora composition. Many sweeteners fit that criterion.
5) Other toxicities. Liver or kidney toxicity, neurotoxicity, endocrine disruption, etc. As with carcinogenicity, the jury is still out. Unlikely for some sweeteners that are not metabolized via these pathways. Possible for others. Most sweeteners (all?) on the market right now are generally recognized as safe in this respect, despite popular beliefs to the contrary. Notable exceptions exist for those with rare metabolic or genetic disorders, such as phenylketonuria (aspartame contains phenylalanine).
6) Side effects. Some sweeteners, particularly those in the sugar alcohol family (and sorbitol especially), can cause laxative effects and other GI-related issues. Individual tolerance can vary. Breaking this category out from #4 because the action here can be purely mechanical (i.e., increasing intestinal water absorption).
I'm not a doctor or medical researcher myself. Just an interested nerd. But I have been following this area for awhile. I welcome any corrections, comments, or additions from people more knowledgeable than I am. I assume there are many such people on HN. :)