[HN Gopher] Microbiome-driven effects of non-nutritive sweetener...
___________________________________________________________________
Microbiome-driven effects of non-nutritive sweeteners on human
glucose tolerance
Author : masonhipp
Score : 115 points
Date : 2022-08-20 12:45 UTC (10 hours ago)
(HTM) web link (www.cell.com)
(TXT) w3m dump (www.cell.com)
| edwnj wrote:
| no free lunch
| clearwind wrote:
| Anecdotally, as a type 1 diabetic it's very interesting to
| observe different effects of sugars and sweeteners on my
| continuous blood glucose sensor over time.
|
| For example DASH is a zero-calorie but sweet drink I have tried a
| couple of times and it makes my body chart a course for the moon.
|
| Another drink called Gusto seems to have replaced sugars with
| Agave syrup, which works well at first but after several days
| builds up intolerance or something.
|
| Modern regular orange juice is like a load of TNT with a 4 minute
| fuse.
|
| Recently white wine and sparkling white wine instantly start
| making my sugar readings hop around erratically, moment by
| moment. (Not something I saw before about 4 months ago - before
| that it would be more like a steady incline.
|
| The disruptors have made their way over to food and drink, it
| seems.
| inetsee wrote:
| Somewhat unrelated to the article: I am a LADA diabetic (Latent
| Autoimmune Diabetes in Adults, sometimes referred to as Type
| 1.5). I am insulin dependent, but I didn't become symptomatic
| until my early 40s.
|
| Lately, I have been experimenting with the "grazing diet".
| Instead of eating three meals a day one would eat a dozen or
| more really small meals; basically snacks.
|
| The motivation was that the glucose response profile of my
| insulin was poorly matched with the glucose response profile of
| the foods I eat. My insulin (Humalog), has a profile lasting
| three to four hours, while most of my foods have a much shorter
| profile, some with a profile of an hour or less. By spreading
| my carbohydrate intake over more time I get a better match to
| my insulin response. For example, I spend two or more hours
| eating lunch. So far, it seems to be helping noticeably.
| stjohnswarts wrote:
| have you ever tested diet soda with the various artificial
| sweeteners? I've tried it personally and never seen the
| slightest notch above what would random noise whereas sugar is
| "straight to the moon, lois" a half hour to hour later.
| clearwind wrote:
| I have a similar effect to you usually with diet soda, maybe
| a slight rise. Only some of the newer ones caused my readings
| to funk up.
| wdwvt1 wrote:
| Microbiome researcher here - I feel like this is the time I get
| to shine in HN threads.
|
| The Segal and Elinav labs are powerhouses in computational and
| gnotobiotic microbiome study. They've published several highly
| cited papers around interactions between diet, the microbiome,
| and various host parameters. A couple highlights include this [1]
| 2015 Cell paper predicting host glycemic response from microbial
| and dietary information, and this [2] 2014 Nature paper
| identifying artificial sweeteners as a source of glucose
| intolerance (mediated through the microbiome).
|
| In the current work, they show that two non-nutritive sweeteners
| (NNS, saccharin and sucralose) impair glucose tolerance, and that
| the microbiome of individuals most susceptible to NNS-induced
| glucose-intolerance can transmit some of the phenotype to mice.
| These data are generated with human cohorts of good size (n=20
| per sweetener) over a reasonable time frame (2 weeks of daily NNS
| administration). Importantly, the levels of NNS that are
| administered are well below the acceptable daily intake (ADI).
| For example, sucralose is given at 102 mg/day, about 34% of the
| ADI of 5 mg/kg, and reasonably close to an estimate of 1.6 mg/kg
| as average daily consumption in humans (reference in [3]). The
| strongest data for the paper is with sucralose (and saccharin).
| The researchers show that consumption of sucralose causes a shift
| in glycemic response: participants consuming sucralose had higher
| glucose excursion in a glucose tolerance test (GTT) than those
| consuming either control diet (Fig 2A, E, F). In addition to GTT
| changes, sucralose-consuming participants had altered level of 9
| identified metabolites (Fig 4B-D).
|
| After establishing these baseline results, the researchers search
| for mechanism by stratifying the sucralose cohort in the top and
| bottom responders. These are, respectively, the individuals who
| show most change from baseline in GTT at the end of intervention
| (2 weeks) and those that show the least. There are differences in
| metabolites, as well as the biochemical pathways those
| metabolites come from (TCA cycle) in these two groups (Fig 4E,
| F). There are correlations between changes in the microbiome
| (both specific taxa and functional gene categories) and the
| changes in measured metabolite levels as well (Fig 5).
|
| In figure 6, the researchers present their strongest data. The
| researchers inoculate groups of germ-free mice with fecal samples
| from the sucralose participants from either the baseline or end
| of intervention. 4 groups of mice receive the feces of the top
| 1-4 responders (most perturbed GTT), 3 groups receive feces from
| the bottom 1-3 responders, and each of these is compared to a
| group receiving baseline feces. The purpose of this test is to
| see if the microbiome, altered by sucralose administration, can
| cause impaired glucose tolerance in mice that have never been
| exposed to sucralose. The researchers show that indeed there is
| significant glucose-tolerance impairment in mice that receive
| post-sucralose feeding feces, though interetingly they show that
| both bottom- and top-responder feces causes this (Fig 6A, G).
| They show that baseline samples from bottom- and top-responders
| do not cause differences in glucose tolerance (Fig 8C), showing
| that something about the sucralose treatment changes microbial
| composition to promote glucose intolerance. The researchers
| attempt to find a mechanistic explanation for the differences by
| comparing groups of mice colonized with top- and bottom-responder
| (grouped by baseline or end of intervention) feces.
|
| Ultimately, this is an extremely impressive paper representing a
| lot of work (and many storied I haven't recapped). Like many
| microbiome papers, I think it oversells the mechanistic and
| physiologically relevant aspects of the research.
|
| 1. The data is presented in ways that maximize statistical
| significance with very little reference to the scale of the
| actual change. a. Fig 4 B-D and Fig 5 B, D, F show significant
| metabolite differences but give no reference to actual changes in
| blood concentration (also Fig 5 metabolites not significant after
| FDR correction). Without isotope-dilution mass spectrometry
| (which this is not), it's hard to tell how large the changes are
| in the blood metabolites. The relationship between concentration
| of a metabolite and measured area on a mass spec is a power
| function (for different metabolites exponents can be less or
| greater than 1), and so this data may represent a lot of change
| in concentration or very little. In addition, the authors rely on
| GTT differences to tell the story, but what is the scale of these
| changes? It is not clear that there is physiological relevance to
| this scale of change. b. Many of the metrics used are hard to
| relate to physiologically relevant quantities and allow
| researcher degrees of freedom. As an example Fig 3 ordinates the
| participant samples using a principal components projection of
| the microbial gene annotations. The loadings determining the
| ordination - and selected for highlight are shown in Fig 3 G-J.
| The researchers group several of these loadings into super
| pathways (e.g. purine metabolism) but it's very hard to tell if
| this kind of difference reflects a functional capacity change in
| the microbiome (and certainly gives no data about the actual
| transcription of these genes). Any of these groupings could be
| highlighted, allowing a lot of flexibility in the storytelling
| with no penalization for multiple hypotheses. c. Fig 8J "Spearman
| correlation of sucrose degradation pathway fold change abundance
| (day 21/baseline) with fold difference in GTT-AUC of each of the
| conventionalized mouse groups." This is so far away from
| physiology it's hard to say what it means.
|
| 2. Both Eran Segal and Eran Elinav are co-founders of the company
| DayTwo - a personalized microbiome company that helps diabetics
| manage their symptoms with microbiome based analytics and
| treatments. The paper feels like it explores the 'personalization
| angle' and the expense of other mechanistic studies. For example,
| the importance of osmolarity on the microbiome and how phenotypes
| around osmostress might be contributing to the resulting host
| phenotypes.
|
| [1]
| https://www.sciencedirect.com/science/article/pii/S009286741...
| [2] https://www.nature.com/articles/nature13793?tdc_uid=921043
| [3] https://foodinsight.org/everything-you-need-to-know-about-
| su...
| tejohnso wrote:
| They indicate:
|
| > Notably, all four tested NNS (saccharin, sucralose, aspartame,
| and stevia) significantly and distinctly altered the human
| intestinal and oral microbiome, as would be expected for these
| chemically diverse compounds.
|
| But also:
|
| > Non-nutritive sweeteners (NNS) are commonly integrated into
| human diet and presumed to be inert
|
| So they are presumed to be inert, but also significantly alter
| microbiome, _as would be expected_ since they are chemically
| diverse compounds.
|
| They indicate it should be obvious that they are not inert at the
| same time as they are presumed to be inert? And if it's obvious
| that they are not inert then why are there so many unanswered
| questions while they're still allowed into our food system? Is it
| unreasonable to expect that some newly popular food additive is
| properly studied before it stats to gain massive adoption in
| prepared foods?
| Tagbert wrote:
| The assertion of them being "inert" is probably in terms of
| interaction with the human metabolism. That is likely what is
| studied when deciding if a compound is safe for ingestion.
|
| What you are calling out is the wider impact to our internal
| ecology and that is s much more complex thing to measure and
| something that we are only beginning to understand. There are
| no regulatory frameworks that take that into account.
| anjel wrote:
| Just wondering why sugar alcohols like sorbitol and erythritol
| were excluded from this study.
| mirekrusin wrote:
| ...or xylitol?
| heisenbit wrote:
| By messing with part of the fructose transport mechanisms sugar
| alcohols are messing with the microbiome so likely would have
| stood out. There is a reason at least here there are labels
| warning of too much consumption.
| anjel wrote:
| Erythritol as a NNS is claimed/marketed not to effect the gut
| biome, indeed to pass through the body unmetabolized.
| ta988 wrote:
| This is a bit more complicated, it is not really
| metabolized but it does have a big impact because it is
| absorbed by the gut and also change bacterial
| populations... https://academic.oup.com/advances/article/10
| /suppl_1/S31/530...
| petra wrote:
| According to the article in the link, erythritol doesn't
| change bacterial populations.
| dataangel wrote:
| generally any alternative sugar that isn't metabolized by
| you is metabolized by bacteria
| vanilla-almond wrote:
| I use stevia as a replacement for sugar. This research is
| difficult to understand for a layperson like me (I'm too thick).
| Is anyone able to answer the questions below?
|
| ---
|
| _Extract_ : "non-nutritive sweeteners (NNS), such as saccharin,
| sucralose, aspartame, acesulfame-K, and stevia, that do not
| contain calories and are thereby presumed to be inert and not
| elicit a postprandial glycemic response."
|
| _Question_ : Does this research confirm that stevia elicits a
| postprandial glycemic response? (Does stevia stimulate insulin?).
|
| ---
|
| _Extract_ : "Notably, all four tested NNS (saccharin, sucralose,
| aspartame, and stevia) significantly and distinctly altered the
| human intestinal and oral microbiome, as would be expected for
| these chemically diverse compounds."
|
| _Extract_ : "Degradation of steviol glycosides by gut bacteria
| is an established component of their metabolism although some
| species may be more proficient than others in performing this
| task and thus, pre-exposure microbiome heterogeneity may conduce
| to differential responses to stevia."
|
| _Question_ : So stevia alters the human intestinal and oral
| microbiome. Are these changes a negative outcome and thus a
| concern for anyone using stevia?
| clusterhacks wrote:
| I just skimmed this study but other RCTs say no to your first
| question:
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103435/#:~:tex...
| .
|
| You can go down a rabbit hole with the references in this paper
| - I think a generally interested layperson is definitely
| capable of understanding papers like this. My instinct is that
| the hardest to understand papers are often actually so special-
| area related that those papers don't contain useful information
| except for researchers. So you can skip them.
|
| Don't know about the second question and suspect no one else
| does either.
|
| As an aside - how did you manage that transition to stevia? I
| _despise_ non-sugar sweeteners and can detect them in very
| small amounts. For "reasons" I don't eat meat and I supplement
| protein intake with whey. If it wasn't for a small number of
| high-quality unflavored (and thus lacking artificial
| sweeteners) whey isolates I would probably re-introduce meat
| into my diet.
| vanilla-almond wrote:
| Thank you for the answers. I didn't find it difficult to
| transition to stevia. At first, it had a different taste from
| sugar (not unpleasant, much sweeter) but I got used to the
| taste. Some people find stevia has a bitter aftertaste. Lots
| of stevia products are a mixture of stevia and erythritol
| (like 'Truvia') to mask any bitter aftertaste. I use less
| stevia than sugar (about half of the sugar amount).
| mod wrote:
| Are you using stevia in all places you would use sugar?
|
| Are there any things/situations you can't use stevia for?
| sillystuff wrote:
| > Are there any things/situations you can't use stevia
| for?
|
| Unrefined ground dried stevia leaf can be quite bitter
| depending on what it is mixed into. I find it works well
| in baked goods like cinnamon rolls and corn bread, but
| makes berry smoothies too bitter to drink.
|
| The refined version is much less bitter-- e.g., it works
| in berry smoothies (but, there is a very noticeable fake
| sugar taste/after taste with smoothies).
|
| In either case, mixing with a little regular sugar
| (naturally occurring sugar content in e.g., berry
| smoothies is sufficient), generally improves the favor.
|
| And, stevia does not caramelize like sugar when cooked.
| E.g., replacing most of the sugar in pancake/waffle
| batter will result in pancakes/waffles that do not brown
| when cooked.
| vanilla-almond wrote:
| Yes, I have replaced sugar completely with stevia. I have
| tried different stevia brands and found them fairly
| similar - they are a mixture of stevia blends with
| erythritol.
|
| I found one stevia brand with a 1:8 ratio (1g of stevia =
| 8g of Sugar i.e. 1:8 ratio). Found that too sweet for me
| and had a bitter aftertaste. I usually buy stevia with a
| 1:2 ratio (i.e. 1g of stevia = 2g of Sugar).
|
| I use stevia in tea and coffee. Have also used stevia
| successfully to make cakes, cookies, and ice cream.
| kekebo wrote:
| Not OP but what did the trick for me was a combination of the
| following sweeteners, listed from largest to least amount:
|
| - erythritol (~0 calories, ~2/3s as sweet as sugar),
|
| - xylitol (~60% of sugar calories, improves oral biome,
| inhibits enamel demineralization),
|
| - stevia or sucralose for added sweetness.
|
| After experimenting with different ratios I now rarely crave
| sugar at all anymore.
|
| Another thing to consider is that the initial dopamine
| response to sweeteners seems to generally be lower than with
| sugar, but there are indications that this gap may lessen
| with continued use over a matter of weeks (at least in mice
| in a small number of studies). Andrew Huberman from Stanford
| brought it up in a recent episode about nutrition:
| https://hubermanlab.com/how-foods-and-nutrients-control-
| our-...
| temeritatis wrote:
| I'd like to add monk fruit to that list. Usually you wanna
| combine: (monk fruit OR stevia) + (erythritol OR xylitol)
| to get a very nice flavor. Stevia or monk fruit on their
| own are "flat" in sweetness but very strong. The xylitol or
| erythritol gives some fullness, or body.
| sillystuff wrote:
| PSA: xylitol is extremely toxic for dogs.
|
| https://pubmed.ncbi.nlm.nih.gov/20473849/
| bigtex wrote:
| Also it can give some people gastric problems. I don't
| have an issue but know people who do.
| bjelkeman-again wrote:
| Gastric problems to me, in other words are, a problem for
| my intestinal microbiome which my health depends on.
| kekebo wrote:
| [Disclaimer: Not a doctor or nutrition expert]
|
| From what I've read about postprandial glucose levels, the
| question seems less about _whether or not_ something elicits a
| glycemic response, but by how much and how that compares to
| glucose /fructose.
|
| Another useful measure would be comparing satiation after
| consumption of sugar vs non-caloric sweeteners, to determine if
| the significant drop in calories leads to more food ingested
| overall.
|
| Stevia in particular seems to be one of the lesser studied
| sweeteners, based on a handful of papers postprandial glucose
| levels doesn't seem to differ a lot compared to sugar. But
| there seem to be somewhat consistent findings that satiety
| levels remain largely the same given the same mass of ingested
| food ( e.g. [0][1]).
|
| To your second question, from my view the understanding of the
| human microbiome is still rather poor, especially in terms of
| health implications on various physiological systems (including
| neurological), optimal composition and applicable ways to
| maintain it. Although the last time I checked was probably 1-2
| years ago, if anyone is aware of useful new data here I would
| welcome a link.
|
| [0] https://sci-hub.ee/10.3390/nu11123036
|
| [1] https://sci-
| hub.ee/https://www.sciencedirect.com/science/art...
| TheSpiceIsLife wrote:
| I'd argue both those studies are insufficient to come to any
| conclusions because people do not exist for only one day, and
| they do not exist in only a healthy state.
|
| A healthy subject, say in their mid twenties, should be able
| to consume 60g glucose almost instantaneously and have little
| to no affect on blood glucose. That same subject, if they
| were to repeatedly do that, multiple times a day, for four
| decades, is highly likely to have Type 2 diabetes and a heart
| condition, also likely to have a kidney condition, peripheral
| neuropathy, macular degeneration, etc take your pick.
|
| The interesting question is what are the long term effects.
| There are no positive outcomes for a long term high sugar
| content diet, and _I argue_ that taking any one plant
| derived, or synthetic chemical, concentrating it and
| consuming it, is either nutritively, or medically,
| beneficial, or, if not beneficial, will work, at least to
| some extent, to tax the body by making healthy homeostatic
| more difficult.
|
| As an aside, and this isn't directed at you in particular,
| but at the HN community, if such a thing can be said to
| exist, more broadly: _frameworks_.
|
| What frameworks exist within which do make sense of
| nutritional / health information. How are we to live? What
| are some (any?) of these frameworks, and where should we go
| to read about them?
| xorcist wrote:
| It's a baffling thought that so much research is spent on
| which _type_ of sugar water might cause the least amount of
| bad long term effects.
|
| It's not like there is any medical need for the body to
| consume sugar water at all.
|
| As recreation, sure, but doing something daily is routine,
| not recreation. That last part is the strange bit. Consume
| it every tenth meal and you can pick any type of sugar, an
| otherwise healthy individual would suffer no long term
| effects. Consume it every meal and you will.
|
| As a though experiment, it would be interesting to think
| about how much research would be made into finding out
| which alcohol we could ingest 50 g of to every meal while
| minimizing long term damage.
| kekebo wrote:
| It's good you point that out. Two studies should almost
| never sufficient for a conclusive argument, especially not
| in a field where physiological variability may be more
| decisive than probability distributions derived from group
| studies (On average peanuts don't kill people but that's
| not a useful metric if you happen to be allergic).
|
| In terms of informational frameworks regarding nutrition I
| have to say the landscape is quite bleak. Understanding
| broccoli or its effects on the human body make big pharma
| no money, publications are only slowly picking up speed
| with new (crowd-) funding options. Even worse, the lack of
| funding and publishing set a rather low barrier for food
| industry players to manipulate the field in their favor,
| which makes for even less solid ground (e.g.
| https://www.nytimes.com/2016/09/13/well/eat/how-the-sugar-
| in... ).
|
| But there are exceptions, Rhonda Patrick comes to mind,
| she's mostly or fully crowdfunded, including her papers
| iirc. She can go very deep but is usually aimed at non
| specialists:
| https://www.youtube.com/c/FoundMyFitness/videos
|
| And Andrew Huberman who finances his podcast through
| sponsors, quite dense but always trying to explain medical
| terms and concepts he brings up:
| https://www.youtube.com/c/AndrewHubermanLab
|
| As for "how are we to live" I think a good starting point
| nutritionally is to try and watch/feel the body reacting to
| different foods and maybe reading up after something feels
| really good or bad to maybe gain some theoretical insights.
| There are no studies for your body in particular but you
| have full production test access pretty much all of the
| time (I would try to prevent restarts though).
| vanilla-almond wrote:
| Thank you for the links. I agree, it would be really useful
| to see more research. Newer products likes monkfruit
| sweetener and allulose have even less research.
| 41b696ef1113 wrote:
| While it does not address the root question, one benefit of
| sugar substitutes is that they are many times sweeter than
| sugar: stevia is 200-300x sweeter, resulting in less total mass
| consumed. My hopelessly-naive-because-biology thought is that
| each molecule would be metabolized a single time (by your own
| liver or your microbiome), resulting in less total impact on
| your body.
| vanilla-almond wrote:
| I also find using less stevia than the equivalent sugar
| amount. I still have a sweet tooth but I don't buy sweet
| foods (make my own sweet foods with stevia).
| hedora wrote:
| Not answering your questions directly, but it has been known
| for decades that fake sugars (NNS in the abstract) cause weight
| gain.
|
| Since you asked about insulin response; (some?) artificial
| sweeteners seem to be safe for diabetics. There is no other
| group of people I can think of that should consider using these
| products.
|
| On a somewhat related note, the soft drink industry has
| replaced some "diet" drinks with "light" versions that contain
| sugar and NNS.
|
| I've found that this causes (intentional?) confusion,
| especially at restaurants, and multiple servers have
| inadvertently tried to serve our kids that stuff when we
| ordered things like "lemonade".
|
| In addition to all the above, consuming NNS causes migraines
| for some people, and they interact badly with some medications.
| I disagree with the abstract's use of the term "presumed
| inert", but I suppose they are trying to be diplomatic.
| api wrote:
| A glance suggests that Saccharine and Sucralose may be
| problematic. The others may be "complicated" but the effect also
| looks close to noise. They should have included some non-
| sweetener molecules of a similar nature as controls.
|
| Sucralose was an instant no to me when I saw the molecule. "Here
| let's hang a chlorine off this here sugar." Nope. I recall seeing
| similar sentiments in a thread over at Reddit where a biochemist
| remarked that it looked like a pesticide.
|
| The weird complicated molecules in Stevia and Monk Fruit seem
| safe precisely because they look like something the body is going
| to hack apart right away and look like all the other complicated
| molecules found in plants that the body is used to dealing with.
| Things like blueberries and onions are just loaded with random
| baroque carbon sculptures like this.
| GekkePrutser wrote:
| Hmm,"let's hang a chlorine of this here sodium" seems to work
| out pretty well for us in moderation. I guess it's all about
| the molecule's properties.
| ta988 wrote:
| you can't just read a molecule and say "oh it looks like
| something safe". Digitalin and the cardiac glycosides [1a,1b]
| may look like completely innocuous compounds (just have to
| remove a group and they are inactive). Some hormones look like
| cholesterol. Some steroisomers [2] (think of it as just
| changing the order atoms are connected in space but not what
| they are connected to) of molecules kill you while some other
| forms are safe and that's even harder to grasp on a 2d
| representation of the structure.
|
| [1a] https://en.m.wikipedia.org/wiki/Cardiac_glycoside
|
| [1b] https://en.m.wikipedia.org/wiki/Steroid
|
| [2] https://en.m.wikipedia.org/wiki/Enantiopure_drug
| matheusmoreira wrote:
| The presence of chlorine does not necessarily imply toxicity.
| Widely used medications like sertraline and loratadine have
| chlorine atoms.
| balderdash wrote:
| As someone that is relying on a single high school chemistry
| class as a base of knowledge, why would Cl here give you pause?
| In other words why is the Cl here bad, but ok in say salt?
| refurb wrote:
| Alkyl halides (carbon chains with halogens off of them) can
| be alkylating agents - basically they can bond to molecules
| within your body and if it's things like DNA, can cause
| mutations and other bad stuff.
|
| Nitrogen mustards (highly reactive alkyl halides) are used in
| chemotherapy. They basically damage DNA which is used to kill
| off fast reproducing cancer cells (but they also kill off
| normal cells).
|
| I was a little surprised when I first saw the structure of
| sucralose. Chlorides aren't that reactive (bromides and
| iodides are much more reactive), but a person might consume
| grams of sucralose so concentrations are high.
|
| That said, many experiments have been done and sucralose
| isn't reactive at all. Due to the shape of the molecule and
| steric interactions, the chlorines are very difficult to
| knock off.
|
| I wouldn't be concerned with taking it.
| hinoki wrote:
| As another person with only high school chemistry, sucralose
| does look a bit like DDT.
|
| https://en.m.wikipedia.org/wiki/DDT
| https://en.m.wikipedia.org/wiki/Sucralose
| simias wrote:
| Am I supposed to find that this https://upload.wikimedia.or
| g/wikipedia/commons/e/e9/Sucralos... looks like this https:
| //upload.wikimedia.org/wikipedia/commons/0/0b/P%2Cp%27... ?
|
| Because I'm not seeing it.
| photochemsyn wrote:
| The fundamental difference is between the sugar ring
| (flexible, which each carbon having tetrahedral geometry,
| and localized electron density) and the aromatic benzene
| ring (flat trigonal geometry, with electrons delocalized
| over the ring).
|
| If you attach chlorine to the latter, you end up with
| something that's very hard to break down (very persistent)
| and which will often (depending on exact structure) stick
| tightly to many biological molecules. Thus they can cause
| developmental disruption, odd forms of cancer, liver
| damage, etc. For example, TCDD (dioxin, a side product of
| many herbicide synthesis routes, a notorious component of
| Agent Orange formulations in Vietnam, etc.):
|
| https://en.wikipedia.org/wiki/2,3,7,8-Tetrachlorodibenzodio
| x...
|
| The chlorinated sugar ring is probably easier to break down
| but if this produces an activated chlorine species during
| metabolism, say in your liver, it might bind to who-knows-
| what and cause problems. Or it might just get excreted as a
| chlorine ion, no different from NaCl (table salt). I'd
| avoid it myself.
|
| Some organo-chlorines (and -bromines) also occur in small
| amounts in many edible seaweeds, apparently often with the
| halide attached to fatty acids and lipids. Hence consuming
| large amounts of seaweed might not be the best idea either.
| kortex wrote:
| In the grand scheme of molecules, they look nothing alike.
|
| DDT is what we call a "greasy brick", while sucralose is a
| highly water soluble sugar.
| FollowingTheDao wrote:
| I saw someone who looked like my brother. But it was not my
| brother.
| kortex wrote:
| Chlorine-carbon (or halocarbons in general) bonds are
| somewhat rare in nature. That is not to say they don't exist,
| but they are a bit unusual. The problem with halocarbons
| (aside from fluorine, which has its own issues) is they are
| generally not very reactive, so they can bioaccumulate. But
| when they do react with biological systems, it tends to be in
| unwanted and toxic ways.
|
| That said, as a former chemist, I consume sucralose, and I am
| not worried by it. Unlike most halocarbons, It's very water
| soluble, so it does not react in the ways the bad halocarbons
| do.
| adrian_b wrote:
| In salts and in sea water, the chlorine is in the form of
| free chloride ions, which is also the normal form of chlorine
| in your body.
|
| In sucralose, chlorine substitutes a hydroxy group and it is
| covalently bonded to a carbon atom.
|
| Most of the organic substances where hydroxy groups are
| substituted with chlorine atoms are more or less toxic and
| some are carcinogenic.
|
| For example, substituting the hydroxy groups in carbonic acid
| with chlorine yields the toxic phosgene, which has been used
| as a chemical weapon in WWI.
| naasking wrote:
| > Most of the organic substances where hydroxy groups are
| substituted with chlorine atoms are more or less toxic and
| some are carcinogenic.
|
| This kind of argument is so... "weird" to put it politely.
| H2O also becomes toxic if you add an oxygen atom. The
| safety of chemical compounds does not follow from a naive
| classification of bonds.
| dataangel wrote:
| It's a heuristic. If you haven't done a randomized
| placebo controlled double blind exhaustive study of the
| compound and all you have to go on is the layout of the
| molecule, is it a bad guess?
| naasking wrote:
| > If [...] all you have to go on is the layout of the
| molecule, is it a bad guess?
|
| Yes, almost certainly. Like I pointed out, one atom is
| the difference between a toxin and water.
| parineum wrote:
| Guess all you want I suppose but there are fairly
| exhaustive studies on artificial sweeteners.
| naasking wrote:
| > Sucralose was an instant no to me when I saw the molecule.
| "Here let's hang a chlorine off this here sugar." Nope. I
| recall seeing similar sentiments in a thread over at Reddit
| where a biochemist remarked that it looked like a pesticide.
|
| If you could infer the properties of a compound by making vague
| analogies to other similar looking molecules, chemistry would
| be easy. Changing a single atom can completely change the
| safety properties of a compound, ie. H2O->H2O2, Hg2Cl2->HgCl2.
|
| > The weird complicated molecules in Stevia and Monk Fruit seem
| safe precisely because they look like something the body is
| going to hack apart right away and look like all the other
| complicated molecules found in plants that the body is used to
| dealing with.
|
| Yeah, like the atropa belladonna, the deadly nightshade? I'm
| sure that's chock full of "baroque carbon sculptures". Maybe
| biochemistry just isn't so easy.
| seanhandley wrote:
| Isn't bleach just a water molecule with an extra oxygen atom?
| I'm not a chemist but I didn't think you could make assumptions
| about the effect of a substance in the way you describe. Am I
| missing something?
| SAI_Peregrinus wrote:
| Hydrogen peroxide is H2O2 (SMILES `OO`).
|
| "Bleach" can refer to any chemical that makes things whiter.
| Common laundry bleach is usually a chlorine bleach, most
| often Sodium Hypochlorite (NaClO, SMILES `[Na+].[O-]Cl`).
|
| There are a bunch of other bleaches[1].
|
| [1] https://en.wikipedia.org/wiki/Bleach
| FollowingTheDao wrote:
| Everyone always with this "noise"! Of course there is noise!
| They are looking at the "noise" and telling you what it is
| from! Genetics!
|
| If you average any trial out in a large population there will
| be "noise", but these people who live with the "noise" are the
| ones affected and suffering.
|
| Does everyone have microbiome-driven effects of non-nutritive
| sweeteners? Probably not, but what about the ones that do?
| mlyle wrote:
| > If you average any trial out in a large population there
| will be "noise", but these people who live with the "noise"
| are the ones affected and suffering.
|
| If you do a trial in a large population of a drug, device, or
| clinical practice that does _nothing_ - a perfect placebo-
| you'll see a variety of effects: statistical noise.
|
| If you do a trial in a large population of a drug, device, or
| clinical practice that has an effect-- you'll measure that
| effect, plus the statistical noise.
|
| You can't generally tell for any individual whether the drug
| helped or hurt. But you can tell that more people did well
| (or badly) in group A than group B.
|
| You can't even really know exactly how big the effect is
| precisely: just a range of likely effect sizes.
|
| The more things you try to measure to more precisely zero in
| on an effect, the greater the chance that statistical noise
| spuriously makes one of these look important (and the larger
| the effect must be to be reliably measured).
| https://xkcd.com/882/
| FollowingTheDao wrote:
| > You can't generally tell for any individual whether the
| drug helped or hurt. But you can tell that more people did
| well (or badly) in group A than group B.
|
| That is what they found in this study, but the OP said it
| was likely "noise" and had no scientific basis for saying
| that. My point; saying something is "noise" is a way to
| look cool on HN and dismiss any finding that does not fit
| your world view.
| mlyle wrote:
| > That is what they found in this study, but the OP said
| it was likely "noise" and had no scientific basis for
| saying that.
|
| It's a small finding in both effect size and statistical
| significance, and prior probabilities count.
|
| Barely statistically significant findings don't change my
| beliefs much, because the base rate and prior knowledge
| matter.
|
| E.g. if you show me a p<0.05 finding that ESP exists, I'm
| going to dismiss it as statistical noise-- even if the
| study methodology is perfect it's only 10-20x more likely
| that ESP works than before, and 20x my prior belief of
| very near 0 is still very near 0.
|
| If you show me a p<0.05 finding that green jelly beans
| cause acne, after studying all colors-- I don't care at
| all.
|
| Here, the commenter you replied to-- api-- suggested that
| the study clearly indicates that there's reason to be
| concerned about saccharine and sucralose. It raises a
| general level of concern about other NNS's, but the data
| is ambiguous and weak. This is a reasonable reading of
| the study.
| simias wrote:
| If you manage to model the "noise" and make it somewhat
| deterministic then it's not noise any more. If genetic
| variations really are the reason for these variations and
| some people are indeed measurably harmed by these compounds
| then it would be a very interesting and somewhat alarming
| result, but that's not what the study says or what we can
| conclude from it.
| FollowingTheDao wrote:
| > If you manage to model the "noise" and make it somewhat
| deterministic then it's not noise any more.
|
| Yes. That is called doing science.
|
| > If genetic variations really are the reason for these
| variations and some people are indeed measurably harmed by
| these compounds then it would be a very interesting and
| somewhat alarming result, but that's not what the study
| says or what we can conclude from it.
|
| What would make me not think that? Maybe we should
| investigate it. That is also called science. Saying
| anything is noise only disregards the response of that part
| of the sample as useless. It is not useless.
|
| It is why some of us are more sensitive to to certain
| diets: https://www.chop.edu/conditions-
| diseases/carbohydrate-malabs...
| parineum wrote:
| You know what isn't science? Not doing any of that and
| just going off on a study that's led to more questions
| (aka, science) in the comments of Hacker News.
|
| Their study had a scope, they did the study and found
| some results then drew some conclusions. They also found
| the study wasn't large enough to draw all conclusions
| because of noise, something they didn't know before the
| study.
|
| > Saying anything is noise only disregards...
|
| Saying something is noise indicates that the data isn't
| clear enough to draw a conclusion and more specific and
| targeted studies are needed to draw said conclusion.
|
| It certainly doesn't mean that they're ignoring the
| plight of... you.
| FollowingTheDao wrote:
| I was commenting on how the original commenter was using
| the term noise. Not how scientists use it.
|
| Listen, the term noise is probably the worst term for
| this data. Because we don't know if it's noise until we
| examine to see if it is noise. So until we know it's
| noise we can't call it noise. It's like you're walking
| into a crowded room and you're trying to hear one thing
| but there is too much "noise". This assumes we know what
| we're looking for in the first place.
| TaupeRanger wrote:
| Yikes. When someone makes a comment about "noise" in this
| context, they simply mean "we can't tell whether the effect
| observed is due to the thing we're measuring". You'd need a
| much larger study with totally different design to even begin
| to approach the question of "do non-nutritive sweeteners make
| peoples' lives worse or shorten their lives compared to
| whatever else they might be ingesting". No need for the
| confrontational angle.
| FollowingTheDao wrote:
| > You'd need a much larger study with totally different
| design to even begin to approach the question
|
| Yes, that is my point. As the OP remarked; "The others may
| be "complicated" but the effect also looks close to noise.
| " is disregarding that data.
|
| When one thinks of the word "noise" one hears something
| that bothers them, like "there is too much noise in here".
| This is the problem with research. By getting rid of the
| "noise" they will only zero in to the thing they wish to
| hear clearly.
| stjohnswarts wrote:
| does hanging a chloride off of sodium scare you as well? sodium
| alone scares me a lot more...
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